endocrine emergencies: recognition and management · ross et al. thyroid. 2016oct;26(10):1343-1421....
TRANSCRIPT
Endocrine Emergencies
Recognition and
Management
Outline
1 Adrenal Crisis
2 Thyroid Storm
3 Myxedema Coma
Clinical Case
24 yo female with a hx of addisonrsquos disease and hypothyroidism who is
28 weeks pregnant develops acute infection with influenza
1 Admitted of obstetric service at OSH
2 Continues to Receive home doses of hydrocortisone and
fludrocortisone
3 Requires 12 L of normal saline over next 36 hours to maintain BP
4 Recovers uneventfully and is discharged from the hospital
Adrenal Insufficiency (AI)
It is the clinical SS of a deficiency of the hormone cortisol
Primary AI (adrenal gland) affects about 100-1401 million people
Secondary AI(HPA axis) affects about 150-2801 million people
This mean that in alabama (49M) mississippi (3M) and
Louisiana(47M)
- there are approximately 1800 people with primary AI
- up to twice that number with secondary AI
NIDDKhttpswwwniddknihgovhealth-informationendocrine-diseasesadrenal-insufficiency-addisons-diseasedefinition-facts
Puar et al The American Journal of
Medicine Vol 129 No 3 March
2016
80ndash90 of cases of
primary adrenal
insufficiency are
caused by
autoimmune
adrenalitis which can
be isolated (40) or
part of an autoimmune
polyendocrinopathy
syndrome (60)
Adrenal insufficiency related to
Immune Checkpoint inhibitors (ICI)
1 ICI related hypophysitisa Incidence from nivolumab and pembrolizumab is low at 05 and 11
b incidence for ipilimumab alone is is 56
c Highest incidence is in combination therapy with an incidence ranging from 88-
105 (ipilimumab and Nivolumab most common)
2 ICI related primary adrenal failurea incidence of 08-2 on monotherapy
b combination therapy estimations ranged from 52 to 76 for ipilimumab with
nivolumab or pembrolizumab respectively
Filette et al Horm Metab Res 2019 51 145ndash156
Clinical Case
This is a patient who is been on ipinivo for extensive small cell lung cancer that was progressing
Prior to his third dose he received routine TFTs which showed a low TSH and a low free T4
the patient presents to the hospital with a one-week history of hypotension fatigue nausea and poor
appetite
Na 134-----gt 146 (lt3 days)
BP 8658
New Engl J Med 1996335(16)1207
Delay in Diagnosis
Due to the fact the these symptoms are non-specific common and
can be quite vague there is often a delay in diagnosis with many
being diagnosed in the hospital
Papierska et al found that 44 of their primary AI patients were
diagnosed with AC or while admitted with impending AC
Erichsen et al in a norwegian PAI registry survery found that 62
were diagnosed during an acute hospital admission
Definition of Adrenal Crisis
ldquoAn Acute deterioration in a patient with adrenal
Insufficiency The principal manifestation of adrenal
crises is hypotension or hypovolemic shock but other
symptoms such as weakness anorexia nausea
abdominal pain fever vomiting fatigue electrolyte
abnormalities confusion coma and marked laboratory
abnormalities can also occurrdquoPuar et al The American Journal of Medicine (2016) 129 339e1-339e9
Adrenal Crisis
An acute deterioration in health that is associated with absolute (SBP lt 100 mmHg) or
relative hypotension
the features of which resolve following parenteral glucocorticoid administration
demonstrated by a marked resolution of hypotension within 1 h
and improvement of clinical symptoms over 2 h
Added details to the Definition
acute abdominal symptoms
deliriumobtundation
hyponatraemiahyperkalaemia hypoglycaemia
pyrexia
Rushworth et al Endocrine (2017) 55336ndash
345
Dineen et al Ther Adv
Endocrinol Metab
2019 Vol 10 1ndash12
Incidence and Mortality of Adrenal Crises
1 Most studies have shown an incidence of between 5-10 ACrsquos100
patient years with adrenal insufficiency
2 In treated AI Adrenal crises contributes significantly to the increased
mortality
a Up to 15 of patients with autoimmune AI
b 42 of those with CAH
3 The associated mortality rate from adrenal crisis in treated adrenal
insufficiency is 05100 PY
Rushworth et al Endocrine (2017) 55336ndash
345Hahner et al J Clin Endocrinol Metab 100
407ndash 416 2015
Hahner et al J Clin Endocrinol Metab 100
407ndash 416 2015
- 423 patients followed
prospectively for 2 years
- 64 adrenal crisis
during follow up
- Ten patients died in
follow up 4 due to
AC
Risk Factors
I All patients with AI are at risk when the requirements for cortisol
exceed what is available
II Prior episode of AC
III Primary AI gt Secondary AI
A Complete loss of adrenal function specifically aldosterone
B More likely to have type 1 DM which is a risk factor
IV Diabetes insipidus
V Social isolation
VI Psychological stress
Glucocorticoid induced AI-- Risk of AC in
chronic glucocorticoid therapy
- SAI due to sustained glucocorticoid exposure is common but AC events tend to be rare
or mild
- probably due to incomplete HPA axis suppression in many treated patients
- a prospective study was conducted in 40 renal transplant patients admitted with
significant physiologic stress
- patients received only their baseline prednisone immunosuppression (5-10
mgday) and no stress doses of glucocorticoids
- The clinical course of the patients revealed no evidence of adrenal insufficiency
There was no mortality increase in hospital stay or eosinophilia
Rushworth et al Endocrine (2017) 55336ndash
345
Bromberg JSTransplantation 1991
Feb51(2)385-90
Precipitating factors
73 51 48
Hahner et al
Prospective Study of Adrenal Crisis
J Clin Endocrinol Metab February 2015 100(2)407ndash416
J Clin Endocrinol Metab 100 407ndash 416 2015
Clinical Presentation of Adrenal Crisis
Work Up of Possible Adrenal Crises
1 In patient with known AI presenting with symptoms cw AC therapy
should be instituted immediately
2 In those wo a prior dx of AI
a Serum Cortisol gt 20 ugdl usually excludes AI while an AM
cortisolstressed state cortisol lt 5 ugdl is supportive
b Draw a cortisol ACTH Renin Aldosterone and DHEA-S and
then give 100 mg of hydrocortisone
Puar et al The American Journal of
Medicine Vol 129 No 3 March
2016
Treatment of Adrenal Crisis
1 100 mg of parenteral (IV or IM) hydrocortisone or 4 mg
dexamethasone IV in patients without a known diagnosis
2 This to be follow by 200 mg of parenteral hydrocortisone over the
next 24 hours or 4 mg of dexamethasone every 12 hours
a Can be 50 mg q 6 hours or as a continuous infusion
3 Fluid administrations as clinically indicated
Neiman Treatment of adrenal
insufficiency in adults UpToDate
Hyponatremia
1 Due to AI can correct rapidly due to free water excretion and
suppression of ADH so be careful for overly rapid Na correction and
Osmotic demyelination syndrome
Prevention of adrenal Crisis
1 Appropriate management of patient with adrenal insufficiency
includes extensive management of stress dosing of steroids for
febrile illness emotional stress increased physical stress etc
1 All patients should be instructed on stress dosing and parenteral
glucocorticoid administration
1 carry a steroid dependency card
1 wear a MedicAlert bracelet or similar identification
Thyroid Storm
Thyroid storm is an endocrine emergency that is characterized by
rapid deterioration of a patient with thyrotoxicosis within days or hours
of presentation and is associated with high mortality
Thyroid Storma rare life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis
Epidemiology of Thyroid Storm
Incidence of thyroid storm 057-076 100000 persons per year in
the US
Incidence among hospitalized patients 48-56 cases100000
persons per year
142-184 of patients hospitalized for thyrotoxicosis
Hospital mortality was 12-36 (higher in japanese series)
Galindo RJ et al Thyroid 2019 29 36-43
Akamizu et al Thyroid 2018 Jan28(1)32-40
Precipitants of Thyroid Storm
Akamizu et al Thyroid 2018 Jan28(1)32-40
Galindo RJ et al Thyroid 2019 29 36-43
Why does storm develop Is this a reasonable
question
Clinical manifestations of Thyroid Storm
Fever 42 in
japanese survey
56 reported in
literature
Tachycardia (76
gt130)
CHF (70)
CNS manifestations
(84)
agitation restlessness
delirium mental
aberrationpsychosis
somnolencelethargy
convulsion or coma
GI symptoms (70)
abdominal pain
Diarrhea
nauseavomiting
jaundice with liver
dysfunction
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Outline
1 Adrenal Crisis
2 Thyroid Storm
3 Myxedema Coma
Clinical Case
24 yo female with a hx of addisonrsquos disease and hypothyroidism who is
28 weeks pregnant develops acute infection with influenza
1 Admitted of obstetric service at OSH
2 Continues to Receive home doses of hydrocortisone and
fludrocortisone
3 Requires 12 L of normal saline over next 36 hours to maintain BP
4 Recovers uneventfully and is discharged from the hospital
Adrenal Insufficiency (AI)
It is the clinical SS of a deficiency of the hormone cortisol
Primary AI (adrenal gland) affects about 100-1401 million people
Secondary AI(HPA axis) affects about 150-2801 million people
This mean that in alabama (49M) mississippi (3M) and
Louisiana(47M)
- there are approximately 1800 people with primary AI
- up to twice that number with secondary AI
NIDDKhttpswwwniddknihgovhealth-informationendocrine-diseasesadrenal-insufficiency-addisons-diseasedefinition-facts
Puar et al The American Journal of
Medicine Vol 129 No 3 March
2016
80ndash90 of cases of
primary adrenal
insufficiency are
caused by
autoimmune
adrenalitis which can
be isolated (40) or
part of an autoimmune
polyendocrinopathy
syndrome (60)
Adrenal insufficiency related to
Immune Checkpoint inhibitors (ICI)
1 ICI related hypophysitisa Incidence from nivolumab and pembrolizumab is low at 05 and 11
b incidence for ipilimumab alone is is 56
c Highest incidence is in combination therapy with an incidence ranging from 88-
105 (ipilimumab and Nivolumab most common)
2 ICI related primary adrenal failurea incidence of 08-2 on monotherapy
b combination therapy estimations ranged from 52 to 76 for ipilimumab with
nivolumab or pembrolizumab respectively
Filette et al Horm Metab Res 2019 51 145ndash156
Clinical Case
This is a patient who is been on ipinivo for extensive small cell lung cancer that was progressing
Prior to his third dose he received routine TFTs which showed a low TSH and a low free T4
the patient presents to the hospital with a one-week history of hypotension fatigue nausea and poor
appetite
Na 134-----gt 146 (lt3 days)
BP 8658
New Engl J Med 1996335(16)1207
Delay in Diagnosis
Due to the fact the these symptoms are non-specific common and
can be quite vague there is often a delay in diagnosis with many
being diagnosed in the hospital
Papierska et al found that 44 of their primary AI patients were
diagnosed with AC or while admitted with impending AC
Erichsen et al in a norwegian PAI registry survery found that 62
were diagnosed during an acute hospital admission
Definition of Adrenal Crisis
ldquoAn Acute deterioration in a patient with adrenal
Insufficiency The principal manifestation of adrenal
crises is hypotension or hypovolemic shock but other
symptoms such as weakness anorexia nausea
abdominal pain fever vomiting fatigue electrolyte
abnormalities confusion coma and marked laboratory
abnormalities can also occurrdquoPuar et al The American Journal of Medicine (2016) 129 339e1-339e9
Adrenal Crisis
An acute deterioration in health that is associated with absolute (SBP lt 100 mmHg) or
relative hypotension
the features of which resolve following parenteral glucocorticoid administration
demonstrated by a marked resolution of hypotension within 1 h
and improvement of clinical symptoms over 2 h
Added details to the Definition
acute abdominal symptoms
deliriumobtundation
hyponatraemiahyperkalaemia hypoglycaemia
pyrexia
Rushworth et al Endocrine (2017) 55336ndash
345
Dineen et al Ther Adv
Endocrinol Metab
2019 Vol 10 1ndash12
Incidence and Mortality of Adrenal Crises
1 Most studies have shown an incidence of between 5-10 ACrsquos100
patient years with adrenal insufficiency
2 In treated AI Adrenal crises contributes significantly to the increased
mortality
a Up to 15 of patients with autoimmune AI
b 42 of those with CAH
3 The associated mortality rate from adrenal crisis in treated adrenal
insufficiency is 05100 PY
Rushworth et al Endocrine (2017) 55336ndash
345Hahner et al J Clin Endocrinol Metab 100
407ndash 416 2015
Hahner et al J Clin Endocrinol Metab 100
407ndash 416 2015
- 423 patients followed
prospectively for 2 years
- 64 adrenal crisis
during follow up
- Ten patients died in
follow up 4 due to
AC
Risk Factors
I All patients with AI are at risk when the requirements for cortisol
exceed what is available
II Prior episode of AC
III Primary AI gt Secondary AI
A Complete loss of adrenal function specifically aldosterone
B More likely to have type 1 DM which is a risk factor
IV Diabetes insipidus
V Social isolation
VI Psychological stress
Glucocorticoid induced AI-- Risk of AC in
chronic glucocorticoid therapy
- SAI due to sustained glucocorticoid exposure is common but AC events tend to be rare
or mild
- probably due to incomplete HPA axis suppression in many treated patients
- a prospective study was conducted in 40 renal transplant patients admitted with
significant physiologic stress
- patients received only their baseline prednisone immunosuppression (5-10
mgday) and no stress doses of glucocorticoids
- The clinical course of the patients revealed no evidence of adrenal insufficiency
There was no mortality increase in hospital stay or eosinophilia
Rushworth et al Endocrine (2017) 55336ndash
345
Bromberg JSTransplantation 1991
Feb51(2)385-90
Precipitating factors
73 51 48
Hahner et al
Prospective Study of Adrenal Crisis
J Clin Endocrinol Metab February 2015 100(2)407ndash416
J Clin Endocrinol Metab 100 407ndash 416 2015
Clinical Presentation of Adrenal Crisis
Work Up of Possible Adrenal Crises
1 In patient with known AI presenting with symptoms cw AC therapy
should be instituted immediately
2 In those wo a prior dx of AI
a Serum Cortisol gt 20 ugdl usually excludes AI while an AM
cortisolstressed state cortisol lt 5 ugdl is supportive
b Draw a cortisol ACTH Renin Aldosterone and DHEA-S and
then give 100 mg of hydrocortisone
Puar et al The American Journal of
Medicine Vol 129 No 3 March
2016
Treatment of Adrenal Crisis
1 100 mg of parenteral (IV or IM) hydrocortisone or 4 mg
dexamethasone IV in patients without a known diagnosis
2 This to be follow by 200 mg of parenteral hydrocortisone over the
next 24 hours or 4 mg of dexamethasone every 12 hours
a Can be 50 mg q 6 hours or as a continuous infusion
3 Fluid administrations as clinically indicated
Neiman Treatment of adrenal
insufficiency in adults UpToDate
Hyponatremia
1 Due to AI can correct rapidly due to free water excretion and
suppression of ADH so be careful for overly rapid Na correction and
Osmotic demyelination syndrome
Prevention of adrenal Crisis
1 Appropriate management of patient with adrenal insufficiency
includes extensive management of stress dosing of steroids for
febrile illness emotional stress increased physical stress etc
1 All patients should be instructed on stress dosing and parenteral
glucocorticoid administration
1 carry a steroid dependency card
1 wear a MedicAlert bracelet or similar identification
Thyroid Storm
Thyroid storm is an endocrine emergency that is characterized by
rapid deterioration of a patient with thyrotoxicosis within days or hours
of presentation and is associated with high mortality
Thyroid Storma rare life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis
Epidemiology of Thyroid Storm
Incidence of thyroid storm 057-076 100000 persons per year in
the US
Incidence among hospitalized patients 48-56 cases100000
persons per year
142-184 of patients hospitalized for thyrotoxicosis
Hospital mortality was 12-36 (higher in japanese series)
Galindo RJ et al Thyroid 2019 29 36-43
Akamizu et al Thyroid 2018 Jan28(1)32-40
Precipitants of Thyroid Storm
Akamizu et al Thyroid 2018 Jan28(1)32-40
Galindo RJ et al Thyroid 2019 29 36-43
Why does storm develop Is this a reasonable
question
Clinical manifestations of Thyroid Storm
Fever 42 in
japanese survey
56 reported in
literature
Tachycardia (76
gt130)
CHF (70)
CNS manifestations
(84)
agitation restlessness
delirium mental
aberrationpsychosis
somnolencelethargy
convulsion or coma
GI symptoms (70)
abdominal pain
Diarrhea
nauseavomiting
jaundice with liver
dysfunction
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Clinical Case
24 yo female with a hx of addisonrsquos disease and hypothyroidism who is
28 weeks pregnant develops acute infection with influenza
1 Admitted of obstetric service at OSH
2 Continues to Receive home doses of hydrocortisone and
fludrocortisone
3 Requires 12 L of normal saline over next 36 hours to maintain BP
4 Recovers uneventfully and is discharged from the hospital
Adrenal Insufficiency (AI)
It is the clinical SS of a deficiency of the hormone cortisol
Primary AI (adrenal gland) affects about 100-1401 million people
Secondary AI(HPA axis) affects about 150-2801 million people
This mean that in alabama (49M) mississippi (3M) and
Louisiana(47M)
- there are approximately 1800 people with primary AI
- up to twice that number with secondary AI
NIDDKhttpswwwniddknihgovhealth-informationendocrine-diseasesadrenal-insufficiency-addisons-diseasedefinition-facts
Puar et al The American Journal of
Medicine Vol 129 No 3 March
2016
80ndash90 of cases of
primary adrenal
insufficiency are
caused by
autoimmune
adrenalitis which can
be isolated (40) or
part of an autoimmune
polyendocrinopathy
syndrome (60)
Adrenal insufficiency related to
Immune Checkpoint inhibitors (ICI)
1 ICI related hypophysitisa Incidence from nivolumab and pembrolizumab is low at 05 and 11
b incidence for ipilimumab alone is is 56
c Highest incidence is in combination therapy with an incidence ranging from 88-
105 (ipilimumab and Nivolumab most common)
2 ICI related primary adrenal failurea incidence of 08-2 on monotherapy
b combination therapy estimations ranged from 52 to 76 for ipilimumab with
nivolumab or pembrolizumab respectively
Filette et al Horm Metab Res 2019 51 145ndash156
Clinical Case
This is a patient who is been on ipinivo for extensive small cell lung cancer that was progressing
Prior to his third dose he received routine TFTs which showed a low TSH and a low free T4
the patient presents to the hospital with a one-week history of hypotension fatigue nausea and poor
appetite
Na 134-----gt 146 (lt3 days)
BP 8658
New Engl J Med 1996335(16)1207
Delay in Diagnosis
Due to the fact the these symptoms are non-specific common and
can be quite vague there is often a delay in diagnosis with many
being diagnosed in the hospital
Papierska et al found that 44 of their primary AI patients were
diagnosed with AC or while admitted with impending AC
Erichsen et al in a norwegian PAI registry survery found that 62
were diagnosed during an acute hospital admission
Definition of Adrenal Crisis
ldquoAn Acute deterioration in a patient with adrenal
Insufficiency The principal manifestation of adrenal
crises is hypotension or hypovolemic shock but other
symptoms such as weakness anorexia nausea
abdominal pain fever vomiting fatigue electrolyte
abnormalities confusion coma and marked laboratory
abnormalities can also occurrdquoPuar et al The American Journal of Medicine (2016) 129 339e1-339e9
Adrenal Crisis
An acute deterioration in health that is associated with absolute (SBP lt 100 mmHg) or
relative hypotension
the features of which resolve following parenteral glucocorticoid administration
demonstrated by a marked resolution of hypotension within 1 h
and improvement of clinical symptoms over 2 h
Added details to the Definition
acute abdominal symptoms
deliriumobtundation
hyponatraemiahyperkalaemia hypoglycaemia
pyrexia
Rushworth et al Endocrine (2017) 55336ndash
345
Dineen et al Ther Adv
Endocrinol Metab
2019 Vol 10 1ndash12
Incidence and Mortality of Adrenal Crises
1 Most studies have shown an incidence of between 5-10 ACrsquos100
patient years with adrenal insufficiency
2 In treated AI Adrenal crises contributes significantly to the increased
mortality
a Up to 15 of patients with autoimmune AI
b 42 of those with CAH
3 The associated mortality rate from adrenal crisis in treated adrenal
insufficiency is 05100 PY
Rushworth et al Endocrine (2017) 55336ndash
345Hahner et al J Clin Endocrinol Metab 100
407ndash 416 2015
Hahner et al J Clin Endocrinol Metab 100
407ndash 416 2015
- 423 patients followed
prospectively for 2 years
- 64 adrenal crisis
during follow up
- Ten patients died in
follow up 4 due to
AC
Risk Factors
I All patients with AI are at risk when the requirements for cortisol
exceed what is available
II Prior episode of AC
III Primary AI gt Secondary AI
A Complete loss of adrenal function specifically aldosterone
B More likely to have type 1 DM which is a risk factor
IV Diabetes insipidus
V Social isolation
VI Psychological stress
Glucocorticoid induced AI-- Risk of AC in
chronic glucocorticoid therapy
- SAI due to sustained glucocorticoid exposure is common but AC events tend to be rare
or mild
- probably due to incomplete HPA axis suppression in many treated patients
- a prospective study was conducted in 40 renal transplant patients admitted with
significant physiologic stress
- patients received only their baseline prednisone immunosuppression (5-10
mgday) and no stress doses of glucocorticoids
- The clinical course of the patients revealed no evidence of adrenal insufficiency
There was no mortality increase in hospital stay or eosinophilia
Rushworth et al Endocrine (2017) 55336ndash
345
Bromberg JSTransplantation 1991
Feb51(2)385-90
Precipitating factors
73 51 48
Hahner et al
Prospective Study of Adrenal Crisis
J Clin Endocrinol Metab February 2015 100(2)407ndash416
J Clin Endocrinol Metab 100 407ndash 416 2015
Clinical Presentation of Adrenal Crisis
Work Up of Possible Adrenal Crises
1 In patient with known AI presenting with symptoms cw AC therapy
should be instituted immediately
2 In those wo a prior dx of AI
a Serum Cortisol gt 20 ugdl usually excludes AI while an AM
cortisolstressed state cortisol lt 5 ugdl is supportive
b Draw a cortisol ACTH Renin Aldosterone and DHEA-S and
then give 100 mg of hydrocortisone
Puar et al The American Journal of
Medicine Vol 129 No 3 March
2016
Treatment of Adrenal Crisis
1 100 mg of parenteral (IV or IM) hydrocortisone or 4 mg
dexamethasone IV in patients without a known diagnosis
2 This to be follow by 200 mg of parenteral hydrocortisone over the
next 24 hours or 4 mg of dexamethasone every 12 hours
a Can be 50 mg q 6 hours or as a continuous infusion
3 Fluid administrations as clinically indicated
Neiman Treatment of adrenal
insufficiency in adults UpToDate
Hyponatremia
1 Due to AI can correct rapidly due to free water excretion and
suppression of ADH so be careful for overly rapid Na correction and
Osmotic demyelination syndrome
Prevention of adrenal Crisis
1 Appropriate management of patient with adrenal insufficiency
includes extensive management of stress dosing of steroids for
febrile illness emotional stress increased physical stress etc
1 All patients should be instructed on stress dosing and parenteral
glucocorticoid administration
1 carry a steroid dependency card
1 wear a MedicAlert bracelet or similar identification
Thyroid Storm
Thyroid storm is an endocrine emergency that is characterized by
rapid deterioration of a patient with thyrotoxicosis within days or hours
of presentation and is associated with high mortality
Thyroid Storma rare life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis
Epidemiology of Thyroid Storm
Incidence of thyroid storm 057-076 100000 persons per year in
the US
Incidence among hospitalized patients 48-56 cases100000
persons per year
142-184 of patients hospitalized for thyrotoxicosis
Hospital mortality was 12-36 (higher in japanese series)
Galindo RJ et al Thyroid 2019 29 36-43
Akamizu et al Thyroid 2018 Jan28(1)32-40
Precipitants of Thyroid Storm
Akamizu et al Thyroid 2018 Jan28(1)32-40
Galindo RJ et al Thyroid 2019 29 36-43
Why does storm develop Is this a reasonable
question
Clinical manifestations of Thyroid Storm
Fever 42 in
japanese survey
56 reported in
literature
Tachycardia (76
gt130)
CHF (70)
CNS manifestations
(84)
agitation restlessness
delirium mental
aberrationpsychosis
somnolencelethargy
convulsion or coma
GI symptoms (70)
abdominal pain
Diarrhea
nauseavomiting
jaundice with liver
dysfunction
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Adrenal Insufficiency (AI)
It is the clinical SS of a deficiency of the hormone cortisol
Primary AI (adrenal gland) affects about 100-1401 million people
Secondary AI(HPA axis) affects about 150-2801 million people
This mean that in alabama (49M) mississippi (3M) and
Louisiana(47M)
- there are approximately 1800 people with primary AI
- up to twice that number with secondary AI
NIDDKhttpswwwniddknihgovhealth-informationendocrine-diseasesadrenal-insufficiency-addisons-diseasedefinition-facts
Puar et al The American Journal of
Medicine Vol 129 No 3 March
2016
80ndash90 of cases of
primary adrenal
insufficiency are
caused by
autoimmune
adrenalitis which can
be isolated (40) or
part of an autoimmune
polyendocrinopathy
syndrome (60)
Adrenal insufficiency related to
Immune Checkpoint inhibitors (ICI)
1 ICI related hypophysitisa Incidence from nivolumab and pembrolizumab is low at 05 and 11
b incidence for ipilimumab alone is is 56
c Highest incidence is in combination therapy with an incidence ranging from 88-
105 (ipilimumab and Nivolumab most common)
2 ICI related primary adrenal failurea incidence of 08-2 on monotherapy
b combination therapy estimations ranged from 52 to 76 for ipilimumab with
nivolumab or pembrolizumab respectively
Filette et al Horm Metab Res 2019 51 145ndash156
Clinical Case
This is a patient who is been on ipinivo for extensive small cell lung cancer that was progressing
Prior to his third dose he received routine TFTs which showed a low TSH and a low free T4
the patient presents to the hospital with a one-week history of hypotension fatigue nausea and poor
appetite
Na 134-----gt 146 (lt3 days)
BP 8658
New Engl J Med 1996335(16)1207
Delay in Diagnosis
Due to the fact the these symptoms are non-specific common and
can be quite vague there is often a delay in diagnosis with many
being diagnosed in the hospital
Papierska et al found that 44 of their primary AI patients were
diagnosed with AC or while admitted with impending AC
Erichsen et al in a norwegian PAI registry survery found that 62
were diagnosed during an acute hospital admission
Definition of Adrenal Crisis
ldquoAn Acute deterioration in a patient with adrenal
Insufficiency The principal manifestation of adrenal
crises is hypotension or hypovolemic shock but other
symptoms such as weakness anorexia nausea
abdominal pain fever vomiting fatigue electrolyte
abnormalities confusion coma and marked laboratory
abnormalities can also occurrdquoPuar et al The American Journal of Medicine (2016) 129 339e1-339e9
Adrenal Crisis
An acute deterioration in health that is associated with absolute (SBP lt 100 mmHg) or
relative hypotension
the features of which resolve following parenteral glucocorticoid administration
demonstrated by a marked resolution of hypotension within 1 h
and improvement of clinical symptoms over 2 h
Added details to the Definition
acute abdominal symptoms
deliriumobtundation
hyponatraemiahyperkalaemia hypoglycaemia
pyrexia
Rushworth et al Endocrine (2017) 55336ndash
345
Dineen et al Ther Adv
Endocrinol Metab
2019 Vol 10 1ndash12
Incidence and Mortality of Adrenal Crises
1 Most studies have shown an incidence of between 5-10 ACrsquos100
patient years with adrenal insufficiency
2 In treated AI Adrenal crises contributes significantly to the increased
mortality
a Up to 15 of patients with autoimmune AI
b 42 of those with CAH
3 The associated mortality rate from adrenal crisis in treated adrenal
insufficiency is 05100 PY
Rushworth et al Endocrine (2017) 55336ndash
345Hahner et al J Clin Endocrinol Metab 100
407ndash 416 2015
Hahner et al J Clin Endocrinol Metab 100
407ndash 416 2015
- 423 patients followed
prospectively for 2 years
- 64 adrenal crisis
during follow up
- Ten patients died in
follow up 4 due to
AC
Risk Factors
I All patients with AI are at risk when the requirements for cortisol
exceed what is available
II Prior episode of AC
III Primary AI gt Secondary AI
A Complete loss of adrenal function specifically aldosterone
B More likely to have type 1 DM which is a risk factor
IV Diabetes insipidus
V Social isolation
VI Psychological stress
Glucocorticoid induced AI-- Risk of AC in
chronic glucocorticoid therapy
- SAI due to sustained glucocorticoid exposure is common but AC events tend to be rare
or mild
- probably due to incomplete HPA axis suppression in many treated patients
- a prospective study was conducted in 40 renal transplant patients admitted with
significant physiologic stress
- patients received only their baseline prednisone immunosuppression (5-10
mgday) and no stress doses of glucocorticoids
- The clinical course of the patients revealed no evidence of adrenal insufficiency
There was no mortality increase in hospital stay or eosinophilia
Rushworth et al Endocrine (2017) 55336ndash
345
Bromberg JSTransplantation 1991
Feb51(2)385-90
Precipitating factors
73 51 48
Hahner et al
Prospective Study of Adrenal Crisis
J Clin Endocrinol Metab February 2015 100(2)407ndash416
J Clin Endocrinol Metab 100 407ndash 416 2015
Clinical Presentation of Adrenal Crisis
Work Up of Possible Adrenal Crises
1 In patient with known AI presenting with symptoms cw AC therapy
should be instituted immediately
2 In those wo a prior dx of AI
a Serum Cortisol gt 20 ugdl usually excludes AI while an AM
cortisolstressed state cortisol lt 5 ugdl is supportive
b Draw a cortisol ACTH Renin Aldosterone and DHEA-S and
then give 100 mg of hydrocortisone
Puar et al The American Journal of
Medicine Vol 129 No 3 March
2016
Treatment of Adrenal Crisis
1 100 mg of parenteral (IV or IM) hydrocortisone or 4 mg
dexamethasone IV in patients without a known diagnosis
2 This to be follow by 200 mg of parenteral hydrocortisone over the
next 24 hours or 4 mg of dexamethasone every 12 hours
a Can be 50 mg q 6 hours or as a continuous infusion
3 Fluid administrations as clinically indicated
Neiman Treatment of adrenal
insufficiency in adults UpToDate
Hyponatremia
1 Due to AI can correct rapidly due to free water excretion and
suppression of ADH so be careful for overly rapid Na correction and
Osmotic demyelination syndrome
Prevention of adrenal Crisis
1 Appropriate management of patient with adrenal insufficiency
includes extensive management of stress dosing of steroids for
febrile illness emotional stress increased physical stress etc
1 All patients should be instructed on stress dosing and parenteral
glucocorticoid administration
1 carry a steroid dependency card
1 wear a MedicAlert bracelet or similar identification
Thyroid Storm
Thyroid storm is an endocrine emergency that is characterized by
rapid deterioration of a patient with thyrotoxicosis within days or hours
of presentation and is associated with high mortality
Thyroid Storma rare life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis
Epidemiology of Thyroid Storm
Incidence of thyroid storm 057-076 100000 persons per year in
the US
Incidence among hospitalized patients 48-56 cases100000
persons per year
142-184 of patients hospitalized for thyrotoxicosis
Hospital mortality was 12-36 (higher in japanese series)
Galindo RJ et al Thyroid 2019 29 36-43
Akamizu et al Thyroid 2018 Jan28(1)32-40
Precipitants of Thyroid Storm
Akamizu et al Thyroid 2018 Jan28(1)32-40
Galindo RJ et al Thyroid 2019 29 36-43
Why does storm develop Is this a reasonable
question
Clinical manifestations of Thyroid Storm
Fever 42 in
japanese survey
56 reported in
literature
Tachycardia (76
gt130)
CHF (70)
CNS manifestations
(84)
agitation restlessness
delirium mental
aberrationpsychosis
somnolencelethargy
convulsion or coma
GI symptoms (70)
abdominal pain
Diarrhea
nauseavomiting
jaundice with liver
dysfunction
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Puar et al The American Journal of
Medicine Vol 129 No 3 March
2016
80ndash90 of cases of
primary adrenal
insufficiency are
caused by
autoimmune
adrenalitis which can
be isolated (40) or
part of an autoimmune
polyendocrinopathy
syndrome (60)
Adrenal insufficiency related to
Immune Checkpoint inhibitors (ICI)
1 ICI related hypophysitisa Incidence from nivolumab and pembrolizumab is low at 05 and 11
b incidence for ipilimumab alone is is 56
c Highest incidence is in combination therapy with an incidence ranging from 88-
105 (ipilimumab and Nivolumab most common)
2 ICI related primary adrenal failurea incidence of 08-2 on monotherapy
b combination therapy estimations ranged from 52 to 76 for ipilimumab with
nivolumab or pembrolizumab respectively
Filette et al Horm Metab Res 2019 51 145ndash156
Clinical Case
This is a patient who is been on ipinivo for extensive small cell lung cancer that was progressing
Prior to his third dose he received routine TFTs which showed a low TSH and a low free T4
the patient presents to the hospital with a one-week history of hypotension fatigue nausea and poor
appetite
Na 134-----gt 146 (lt3 days)
BP 8658
New Engl J Med 1996335(16)1207
Delay in Diagnosis
Due to the fact the these symptoms are non-specific common and
can be quite vague there is often a delay in diagnosis with many
being diagnosed in the hospital
Papierska et al found that 44 of their primary AI patients were
diagnosed with AC or while admitted with impending AC
Erichsen et al in a norwegian PAI registry survery found that 62
were diagnosed during an acute hospital admission
Definition of Adrenal Crisis
ldquoAn Acute deterioration in a patient with adrenal
Insufficiency The principal manifestation of adrenal
crises is hypotension or hypovolemic shock but other
symptoms such as weakness anorexia nausea
abdominal pain fever vomiting fatigue electrolyte
abnormalities confusion coma and marked laboratory
abnormalities can also occurrdquoPuar et al The American Journal of Medicine (2016) 129 339e1-339e9
Adrenal Crisis
An acute deterioration in health that is associated with absolute (SBP lt 100 mmHg) or
relative hypotension
the features of which resolve following parenteral glucocorticoid administration
demonstrated by a marked resolution of hypotension within 1 h
and improvement of clinical symptoms over 2 h
Added details to the Definition
acute abdominal symptoms
deliriumobtundation
hyponatraemiahyperkalaemia hypoglycaemia
pyrexia
Rushworth et al Endocrine (2017) 55336ndash
345
Dineen et al Ther Adv
Endocrinol Metab
2019 Vol 10 1ndash12
Incidence and Mortality of Adrenal Crises
1 Most studies have shown an incidence of between 5-10 ACrsquos100
patient years with adrenal insufficiency
2 In treated AI Adrenal crises contributes significantly to the increased
mortality
a Up to 15 of patients with autoimmune AI
b 42 of those with CAH
3 The associated mortality rate from adrenal crisis in treated adrenal
insufficiency is 05100 PY
Rushworth et al Endocrine (2017) 55336ndash
345Hahner et al J Clin Endocrinol Metab 100
407ndash 416 2015
Hahner et al J Clin Endocrinol Metab 100
407ndash 416 2015
- 423 patients followed
prospectively for 2 years
- 64 adrenal crisis
during follow up
- Ten patients died in
follow up 4 due to
AC
Risk Factors
I All patients with AI are at risk when the requirements for cortisol
exceed what is available
II Prior episode of AC
III Primary AI gt Secondary AI
A Complete loss of adrenal function specifically aldosterone
B More likely to have type 1 DM which is a risk factor
IV Diabetes insipidus
V Social isolation
VI Psychological stress
Glucocorticoid induced AI-- Risk of AC in
chronic glucocorticoid therapy
- SAI due to sustained glucocorticoid exposure is common but AC events tend to be rare
or mild
- probably due to incomplete HPA axis suppression in many treated patients
- a prospective study was conducted in 40 renal transplant patients admitted with
significant physiologic stress
- patients received only their baseline prednisone immunosuppression (5-10
mgday) and no stress doses of glucocorticoids
- The clinical course of the patients revealed no evidence of adrenal insufficiency
There was no mortality increase in hospital stay or eosinophilia
Rushworth et al Endocrine (2017) 55336ndash
345
Bromberg JSTransplantation 1991
Feb51(2)385-90
Precipitating factors
73 51 48
Hahner et al
Prospective Study of Adrenal Crisis
J Clin Endocrinol Metab February 2015 100(2)407ndash416
J Clin Endocrinol Metab 100 407ndash 416 2015
Clinical Presentation of Adrenal Crisis
Work Up of Possible Adrenal Crises
1 In patient with known AI presenting with symptoms cw AC therapy
should be instituted immediately
2 In those wo a prior dx of AI
a Serum Cortisol gt 20 ugdl usually excludes AI while an AM
cortisolstressed state cortisol lt 5 ugdl is supportive
b Draw a cortisol ACTH Renin Aldosterone and DHEA-S and
then give 100 mg of hydrocortisone
Puar et al The American Journal of
Medicine Vol 129 No 3 March
2016
Treatment of Adrenal Crisis
1 100 mg of parenteral (IV or IM) hydrocortisone or 4 mg
dexamethasone IV in patients without a known diagnosis
2 This to be follow by 200 mg of parenteral hydrocortisone over the
next 24 hours or 4 mg of dexamethasone every 12 hours
a Can be 50 mg q 6 hours or as a continuous infusion
3 Fluid administrations as clinically indicated
Neiman Treatment of adrenal
insufficiency in adults UpToDate
Hyponatremia
1 Due to AI can correct rapidly due to free water excretion and
suppression of ADH so be careful for overly rapid Na correction and
Osmotic demyelination syndrome
Prevention of adrenal Crisis
1 Appropriate management of patient with adrenal insufficiency
includes extensive management of stress dosing of steroids for
febrile illness emotional stress increased physical stress etc
1 All patients should be instructed on stress dosing and parenteral
glucocorticoid administration
1 carry a steroid dependency card
1 wear a MedicAlert bracelet or similar identification
Thyroid Storm
Thyroid storm is an endocrine emergency that is characterized by
rapid deterioration of a patient with thyrotoxicosis within days or hours
of presentation and is associated with high mortality
Thyroid Storma rare life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis
Epidemiology of Thyroid Storm
Incidence of thyroid storm 057-076 100000 persons per year in
the US
Incidence among hospitalized patients 48-56 cases100000
persons per year
142-184 of patients hospitalized for thyrotoxicosis
Hospital mortality was 12-36 (higher in japanese series)
Galindo RJ et al Thyroid 2019 29 36-43
Akamizu et al Thyroid 2018 Jan28(1)32-40
Precipitants of Thyroid Storm
Akamizu et al Thyroid 2018 Jan28(1)32-40
Galindo RJ et al Thyroid 2019 29 36-43
Why does storm develop Is this a reasonable
question
Clinical manifestations of Thyroid Storm
Fever 42 in
japanese survey
56 reported in
literature
Tachycardia (76
gt130)
CHF (70)
CNS manifestations
(84)
agitation restlessness
delirium mental
aberrationpsychosis
somnolencelethargy
convulsion or coma
GI symptoms (70)
abdominal pain
Diarrhea
nauseavomiting
jaundice with liver
dysfunction
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Adrenal insufficiency related to
Immune Checkpoint inhibitors (ICI)
1 ICI related hypophysitisa Incidence from nivolumab and pembrolizumab is low at 05 and 11
b incidence for ipilimumab alone is is 56
c Highest incidence is in combination therapy with an incidence ranging from 88-
105 (ipilimumab and Nivolumab most common)
2 ICI related primary adrenal failurea incidence of 08-2 on monotherapy
b combination therapy estimations ranged from 52 to 76 for ipilimumab with
nivolumab or pembrolizumab respectively
Filette et al Horm Metab Res 2019 51 145ndash156
Clinical Case
This is a patient who is been on ipinivo for extensive small cell lung cancer that was progressing
Prior to his third dose he received routine TFTs which showed a low TSH and a low free T4
the patient presents to the hospital with a one-week history of hypotension fatigue nausea and poor
appetite
Na 134-----gt 146 (lt3 days)
BP 8658
New Engl J Med 1996335(16)1207
Delay in Diagnosis
Due to the fact the these symptoms are non-specific common and
can be quite vague there is often a delay in diagnosis with many
being diagnosed in the hospital
Papierska et al found that 44 of their primary AI patients were
diagnosed with AC or while admitted with impending AC
Erichsen et al in a norwegian PAI registry survery found that 62
were diagnosed during an acute hospital admission
Definition of Adrenal Crisis
ldquoAn Acute deterioration in a patient with adrenal
Insufficiency The principal manifestation of adrenal
crises is hypotension or hypovolemic shock but other
symptoms such as weakness anorexia nausea
abdominal pain fever vomiting fatigue electrolyte
abnormalities confusion coma and marked laboratory
abnormalities can also occurrdquoPuar et al The American Journal of Medicine (2016) 129 339e1-339e9
Adrenal Crisis
An acute deterioration in health that is associated with absolute (SBP lt 100 mmHg) or
relative hypotension
the features of which resolve following parenteral glucocorticoid administration
demonstrated by a marked resolution of hypotension within 1 h
and improvement of clinical symptoms over 2 h
Added details to the Definition
acute abdominal symptoms
deliriumobtundation
hyponatraemiahyperkalaemia hypoglycaemia
pyrexia
Rushworth et al Endocrine (2017) 55336ndash
345
Dineen et al Ther Adv
Endocrinol Metab
2019 Vol 10 1ndash12
Incidence and Mortality of Adrenal Crises
1 Most studies have shown an incidence of between 5-10 ACrsquos100
patient years with adrenal insufficiency
2 In treated AI Adrenal crises contributes significantly to the increased
mortality
a Up to 15 of patients with autoimmune AI
b 42 of those with CAH
3 The associated mortality rate from adrenal crisis in treated adrenal
insufficiency is 05100 PY
Rushworth et al Endocrine (2017) 55336ndash
345Hahner et al J Clin Endocrinol Metab 100
407ndash 416 2015
Hahner et al J Clin Endocrinol Metab 100
407ndash 416 2015
- 423 patients followed
prospectively for 2 years
- 64 adrenal crisis
during follow up
- Ten patients died in
follow up 4 due to
AC
Risk Factors
I All patients with AI are at risk when the requirements for cortisol
exceed what is available
II Prior episode of AC
III Primary AI gt Secondary AI
A Complete loss of adrenal function specifically aldosterone
B More likely to have type 1 DM which is a risk factor
IV Diabetes insipidus
V Social isolation
VI Psychological stress
Glucocorticoid induced AI-- Risk of AC in
chronic glucocorticoid therapy
- SAI due to sustained glucocorticoid exposure is common but AC events tend to be rare
or mild
- probably due to incomplete HPA axis suppression in many treated patients
- a prospective study was conducted in 40 renal transplant patients admitted with
significant physiologic stress
- patients received only their baseline prednisone immunosuppression (5-10
mgday) and no stress doses of glucocorticoids
- The clinical course of the patients revealed no evidence of adrenal insufficiency
There was no mortality increase in hospital stay or eosinophilia
Rushworth et al Endocrine (2017) 55336ndash
345
Bromberg JSTransplantation 1991
Feb51(2)385-90
Precipitating factors
73 51 48
Hahner et al
Prospective Study of Adrenal Crisis
J Clin Endocrinol Metab February 2015 100(2)407ndash416
J Clin Endocrinol Metab 100 407ndash 416 2015
Clinical Presentation of Adrenal Crisis
Work Up of Possible Adrenal Crises
1 In patient with known AI presenting with symptoms cw AC therapy
should be instituted immediately
2 In those wo a prior dx of AI
a Serum Cortisol gt 20 ugdl usually excludes AI while an AM
cortisolstressed state cortisol lt 5 ugdl is supportive
b Draw a cortisol ACTH Renin Aldosterone and DHEA-S and
then give 100 mg of hydrocortisone
Puar et al The American Journal of
Medicine Vol 129 No 3 March
2016
Treatment of Adrenal Crisis
1 100 mg of parenteral (IV or IM) hydrocortisone or 4 mg
dexamethasone IV in patients without a known diagnosis
2 This to be follow by 200 mg of parenteral hydrocortisone over the
next 24 hours or 4 mg of dexamethasone every 12 hours
a Can be 50 mg q 6 hours or as a continuous infusion
3 Fluid administrations as clinically indicated
Neiman Treatment of adrenal
insufficiency in adults UpToDate
Hyponatremia
1 Due to AI can correct rapidly due to free water excretion and
suppression of ADH so be careful for overly rapid Na correction and
Osmotic demyelination syndrome
Prevention of adrenal Crisis
1 Appropriate management of patient with adrenal insufficiency
includes extensive management of stress dosing of steroids for
febrile illness emotional stress increased physical stress etc
1 All patients should be instructed on stress dosing and parenteral
glucocorticoid administration
1 carry a steroid dependency card
1 wear a MedicAlert bracelet or similar identification
Thyroid Storm
Thyroid storm is an endocrine emergency that is characterized by
rapid deterioration of a patient with thyrotoxicosis within days or hours
of presentation and is associated with high mortality
Thyroid Storma rare life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis
Epidemiology of Thyroid Storm
Incidence of thyroid storm 057-076 100000 persons per year in
the US
Incidence among hospitalized patients 48-56 cases100000
persons per year
142-184 of patients hospitalized for thyrotoxicosis
Hospital mortality was 12-36 (higher in japanese series)
Galindo RJ et al Thyroid 2019 29 36-43
Akamizu et al Thyroid 2018 Jan28(1)32-40
Precipitants of Thyroid Storm
Akamizu et al Thyroid 2018 Jan28(1)32-40
Galindo RJ et al Thyroid 2019 29 36-43
Why does storm develop Is this a reasonable
question
Clinical manifestations of Thyroid Storm
Fever 42 in
japanese survey
56 reported in
literature
Tachycardia (76
gt130)
CHF (70)
CNS manifestations
(84)
agitation restlessness
delirium mental
aberrationpsychosis
somnolencelethargy
convulsion or coma
GI symptoms (70)
abdominal pain
Diarrhea
nauseavomiting
jaundice with liver
dysfunction
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Clinical Case
This is a patient who is been on ipinivo for extensive small cell lung cancer that was progressing
Prior to his third dose he received routine TFTs which showed a low TSH and a low free T4
the patient presents to the hospital with a one-week history of hypotension fatigue nausea and poor
appetite
Na 134-----gt 146 (lt3 days)
BP 8658
New Engl J Med 1996335(16)1207
Delay in Diagnosis
Due to the fact the these symptoms are non-specific common and
can be quite vague there is often a delay in diagnosis with many
being diagnosed in the hospital
Papierska et al found that 44 of their primary AI patients were
diagnosed with AC or while admitted with impending AC
Erichsen et al in a norwegian PAI registry survery found that 62
were diagnosed during an acute hospital admission
Definition of Adrenal Crisis
ldquoAn Acute deterioration in a patient with adrenal
Insufficiency The principal manifestation of adrenal
crises is hypotension or hypovolemic shock but other
symptoms such as weakness anorexia nausea
abdominal pain fever vomiting fatigue electrolyte
abnormalities confusion coma and marked laboratory
abnormalities can also occurrdquoPuar et al The American Journal of Medicine (2016) 129 339e1-339e9
Adrenal Crisis
An acute deterioration in health that is associated with absolute (SBP lt 100 mmHg) or
relative hypotension
the features of which resolve following parenteral glucocorticoid administration
demonstrated by a marked resolution of hypotension within 1 h
and improvement of clinical symptoms over 2 h
Added details to the Definition
acute abdominal symptoms
deliriumobtundation
hyponatraemiahyperkalaemia hypoglycaemia
pyrexia
Rushworth et al Endocrine (2017) 55336ndash
345
Dineen et al Ther Adv
Endocrinol Metab
2019 Vol 10 1ndash12
Incidence and Mortality of Adrenal Crises
1 Most studies have shown an incidence of between 5-10 ACrsquos100
patient years with adrenal insufficiency
2 In treated AI Adrenal crises contributes significantly to the increased
mortality
a Up to 15 of patients with autoimmune AI
b 42 of those with CAH
3 The associated mortality rate from adrenal crisis in treated adrenal
insufficiency is 05100 PY
Rushworth et al Endocrine (2017) 55336ndash
345Hahner et al J Clin Endocrinol Metab 100
407ndash 416 2015
Hahner et al J Clin Endocrinol Metab 100
407ndash 416 2015
- 423 patients followed
prospectively for 2 years
- 64 adrenal crisis
during follow up
- Ten patients died in
follow up 4 due to
AC
Risk Factors
I All patients with AI are at risk when the requirements for cortisol
exceed what is available
II Prior episode of AC
III Primary AI gt Secondary AI
A Complete loss of adrenal function specifically aldosterone
B More likely to have type 1 DM which is a risk factor
IV Diabetes insipidus
V Social isolation
VI Psychological stress
Glucocorticoid induced AI-- Risk of AC in
chronic glucocorticoid therapy
- SAI due to sustained glucocorticoid exposure is common but AC events tend to be rare
or mild
- probably due to incomplete HPA axis suppression in many treated patients
- a prospective study was conducted in 40 renal transplant patients admitted with
significant physiologic stress
- patients received only their baseline prednisone immunosuppression (5-10
mgday) and no stress doses of glucocorticoids
- The clinical course of the patients revealed no evidence of adrenal insufficiency
There was no mortality increase in hospital stay or eosinophilia
Rushworth et al Endocrine (2017) 55336ndash
345
Bromberg JSTransplantation 1991
Feb51(2)385-90
Precipitating factors
73 51 48
Hahner et al
Prospective Study of Adrenal Crisis
J Clin Endocrinol Metab February 2015 100(2)407ndash416
J Clin Endocrinol Metab 100 407ndash 416 2015
Clinical Presentation of Adrenal Crisis
Work Up of Possible Adrenal Crises
1 In patient with known AI presenting with symptoms cw AC therapy
should be instituted immediately
2 In those wo a prior dx of AI
a Serum Cortisol gt 20 ugdl usually excludes AI while an AM
cortisolstressed state cortisol lt 5 ugdl is supportive
b Draw a cortisol ACTH Renin Aldosterone and DHEA-S and
then give 100 mg of hydrocortisone
Puar et al The American Journal of
Medicine Vol 129 No 3 March
2016
Treatment of Adrenal Crisis
1 100 mg of parenteral (IV or IM) hydrocortisone or 4 mg
dexamethasone IV in patients without a known diagnosis
2 This to be follow by 200 mg of parenteral hydrocortisone over the
next 24 hours or 4 mg of dexamethasone every 12 hours
a Can be 50 mg q 6 hours or as a continuous infusion
3 Fluid administrations as clinically indicated
Neiman Treatment of adrenal
insufficiency in adults UpToDate
Hyponatremia
1 Due to AI can correct rapidly due to free water excretion and
suppression of ADH so be careful for overly rapid Na correction and
Osmotic demyelination syndrome
Prevention of adrenal Crisis
1 Appropriate management of patient with adrenal insufficiency
includes extensive management of stress dosing of steroids for
febrile illness emotional stress increased physical stress etc
1 All patients should be instructed on stress dosing and parenteral
glucocorticoid administration
1 carry a steroid dependency card
1 wear a MedicAlert bracelet or similar identification
Thyroid Storm
Thyroid storm is an endocrine emergency that is characterized by
rapid deterioration of a patient with thyrotoxicosis within days or hours
of presentation and is associated with high mortality
Thyroid Storma rare life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis
Epidemiology of Thyroid Storm
Incidence of thyroid storm 057-076 100000 persons per year in
the US
Incidence among hospitalized patients 48-56 cases100000
persons per year
142-184 of patients hospitalized for thyrotoxicosis
Hospital mortality was 12-36 (higher in japanese series)
Galindo RJ et al Thyroid 2019 29 36-43
Akamizu et al Thyroid 2018 Jan28(1)32-40
Precipitants of Thyroid Storm
Akamizu et al Thyroid 2018 Jan28(1)32-40
Galindo RJ et al Thyroid 2019 29 36-43
Why does storm develop Is this a reasonable
question
Clinical manifestations of Thyroid Storm
Fever 42 in
japanese survey
56 reported in
literature
Tachycardia (76
gt130)
CHF (70)
CNS manifestations
(84)
agitation restlessness
delirium mental
aberrationpsychosis
somnolencelethargy
convulsion or coma
GI symptoms (70)
abdominal pain
Diarrhea
nauseavomiting
jaundice with liver
dysfunction
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
New Engl J Med 1996335(16)1207
Delay in Diagnosis
Due to the fact the these symptoms are non-specific common and
can be quite vague there is often a delay in diagnosis with many
being diagnosed in the hospital
Papierska et al found that 44 of their primary AI patients were
diagnosed with AC or while admitted with impending AC
Erichsen et al in a norwegian PAI registry survery found that 62
were diagnosed during an acute hospital admission
Definition of Adrenal Crisis
ldquoAn Acute deterioration in a patient with adrenal
Insufficiency The principal manifestation of adrenal
crises is hypotension or hypovolemic shock but other
symptoms such as weakness anorexia nausea
abdominal pain fever vomiting fatigue electrolyte
abnormalities confusion coma and marked laboratory
abnormalities can also occurrdquoPuar et al The American Journal of Medicine (2016) 129 339e1-339e9
Adrenal Crisis
An acute deterioration in health that is associated with absolute (SBP lt 100 mmHg) or
relative hypotension
the features of which resolve following parenteral glucocorticoid administration
demonstrated by a marked resolution of hypotension within 1 h
and improvement of clinical symptoms over 2 h
Added details to the Definition
acute abdominal symptoms
deliriumobtundation
hyponatraemiahyperkalaemia hypoglycaemia
pyrexia
Rushworth et al Endocrine (2017) 55336ndash
345
Dineen et al Ther Adv
Endocrinol Metab
2019 Vol 10 1ndash12
Incidence and Mortality of Adrenal Crises
1 Most studies have shown an incidence of between 5-10 ACrsquos100
patient years with adrenal insufficiency
2 In treated AI Adrenal crises contributes significantly to the increased
mortality
a Up to 15 of patients with autoimmune AI
b 42 of those with CAH
3 The associated mortality rate from adrenal crisis in treated adrenal
insufficiency is 05100 PY
Rushworth et al Endocrine (2017) 55336ndash
345Hahner et al J Clin Endocrinol Metab 100
407ndash 416 2015
Hahner et al J Clin Endocrinol Metab 100
407ndash 416 2015
- 423 patients followed
prospectively for 2 years
- 64 adrenal crisis
during follow up
- Ten patients died in
follow up 4 due to
AC
Risk Factors
I All patients with AI are at risk when the requirements for cortisol
exceed what is available
II Prior episode of AC
III Primary AI gt Secondary AI
A Complete loss of adrenal function specifically aldosterone
B More likely to have type 1 DM which is a risk factor
IV Diabetes insipidus
V Social isolation
VI Psychological stress
Glucocorticoid induced AI-- Risk of AC in
chronic glucocorticoid therapy
- SAI due to sustained glucocorticoid exposure is common but AC events tend to be rare
or mild
- probably due to incomplete HPA axis suppression in many treated patients
- a prospective study was conducted in 40 renal transplant patients admitted with
significant physiologic stress
- patients received only their baseline prednisone immunosuppression (5-10
mgday) and no stress doses of glucocorticoids
- The clinical course of the patients revealed no evidence of adrenal insufficiency
There was no mortality increase in hospital stay or eosinophilia
Rushworth et al Endocrine (2017) 55336ndash
345
Bromberg JSTransplantation 1991
Feb51(2)385-90
Precipitating factors
73 51 48
Hahner et al
Prospective Study of Adrenal Crisis
J Clin Endocrinol Metab February 2015 100(2)407ndash416
J Clin Endocrinol Metab 100 407ndash 416 2015
Clinical Presentation of Adrenal Crisis
Work Up of Possible Adrenal Crises
1 In patient with known AI presenting with symptoms cw AC therapy
should be instituted immediately
2 In those wo a prior dx of AI
a Serum Cortisol gt 20 ugdl usually excludes AI while an AM
cortisolstressed state cortisol lt 5 ugdl is supportive
b Draw a cortisol ACTH Renin Aldosterone and DHEA-S and
then give 100 mg of hydrocortisone
Puar et al The American Journal of
Medicine Vol 129 No 3 March
2016
Treatment of Adrenal Crisis
1 100 mg of parenteral (IV or IM) hydrocortisone or 4 mg
dexamethasone IV in patients without a known diagnosis
2 This to be follow by 200 mg of parenteral hydrocortisone over the
next 24 hours or 4 mg of dexamethasone every 12 hours
a Can be 50 mg q 6 hours or as a continuous infusion
3 Fluid administrations as clinically indicated
Neiman Treatment of adrenal
insufficiency in adults UpToDate
Hyponatremia
1 Due to AI can correct rapidly due to free water excretion and
suppression of ADH so be careful for overly rapid Na correction and
Osmotic demyelination syndrome
Prevention of adrenal Crisis
1 Appropriate management of patient with adrenal insufficiency
includes extensive management of stress dosing of steroids for
febrile illness emotional stress increased physical stress etc
1 All patients should be instructed on stress dosing and parenteral
glucocorticoid administration
1 carry a steroid dependency card
1 wear a MedicAlert bracelet or similar identification
Thyroid Storm
Thyroid storm is an endocrine emergency that is characterized by
rapid deterioration of a patient with thyrotoxicosis within days or hours
of presentation and is associated with high mortality
Thyroid Storma rare life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis
Epidemiology of Thyroid Storm
Incidence of thyroid storm 057-076 100000 persons per year in
the US
Incidence among hospitalized patients 48-56 cases100000
persons per year
142-184 of patients hospitalized for thyrotoxicosis
Hospital mortality was 12-36 (higher in japanese series)
Galindo RJ et al Thyroid 2019 29 36-43
Akamizu et al Thyroid 2018 Jan28(1)32-40
Precipitants of Thyroid Storm
Akamizu et al Thyroid 2018 Jan28(1)32-40
Galindo RJ et al Thyroid 2019 29 36-43
Why does storm develop Is this a reasonable
question
Clinical manifestations of Thyroid Storm
Fever 42 in
japanese survey
56 reported in
literature
Tachycardia (76
gt130)
CHF (70)
CNS manifestations
(84)
agitation restlessness
delirium mental
aberrationpsychosis
somnolencelethargy
convulsion or coma
GI symptoms (70)
abdominal pain
Diarrhea
nauseavomiting
jaundice with liver
dysfunction
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Delay in Diagnosis
Due to the fact the these symptoms are non-specific common and
can be quite vague there is often a delay in diagnosis with many
being diagnosed in the hospital
Papierska et al found that 44 of their primary AI patients were
diagnosed with AC or while admitted with impending AC
Erichsen et al in a norwegian PAI registry survery found that 62
were diagnosed during an acute hospital admission
Definition of Adrenal Crisis
ldquoAn Acute deterioration in a patient with adrenal
Insufficiency The principal manifestation of adrenal
crises is hypotension or hypovolemic shock but other
symptoms such as weakness anorexia nausea
abdominal pain fever vomiting fatigue electrolyte
abnormalities confusion coma and marked laboratory
abnormalities can also occurrdquoPuar et al The American Journal of Medicine (2016) 129 339e1-339e9
Adrenal Crisis
An acute deterioration in health that is associated with absolute (SBP lt 100 mmHg) or
relative hypotension
the features of which resolve following parenteral glucocorticoid administration
demonstrated by a marked resolution of hypotension within 1 h
and improvement of clinical symptoms over 2 h
Added details to the Definition
acute abdominal symptoms
deliriumobtundation
hyponatraemiahyperkalaemia hypoglycaemia
pyrexia
Rushworth et al Endocrine (2017) 55336ndash
345
Dineen et al Ther Adv
Endocrinol Metab
2019 Vol 10 1ndash12
Incidence and Mortality of Adrenal Crises
1 Most studies have shown an incidence of between 5-10 ACrsquos100
patient years with adrenal insufficiency
2 In treated AI Adrenal crises contributes significantly to the increased
mortality
a Up to 15 of patients with autoimmune AI
b 42 of those with CAH
3 The associated mortality rate from adrenal crisis in treated adrenal
insufficiency is 05100 PY
Rushworth et al Endocrine (2017) 55336ndash
345Hahner et al J Clin Endocrinol Metab 100
407ndash 416 2015
Hahner et al J Clin Endocrinol Metab 100
407ndash 416 2015
- 423 patients followed
prospectively for 2 years
- 64 adrenal crisis
during follow up
- Ten patients died in
follow up 4 due to
AC
Risk Factors
I All patients with AI are at risk when the requirements for cortisol
exceed what is available
II Prior episode of AC
III Primary AI gt Secondary AI
A Complete loss of adrenal function specifically aldosterone
B More likely to have type 1 DM which is a risk factor
IV Diabetes insipidus
V Social isolation
VI Psychological stress
Glucocorticoid induced AI-- Risk of AC in
chronic glucocorticoid therapy
- SAI due to sustained glucocorticoid exposure is common but AC events tend to be rare
or mild
- probably due to incomplete HPA axis suppression in many treated patients
- a prospective study was conducted in 40 renal transplant patients admitted with
significant physiologic stress
- patients received only their baseline prednisone immunosuppression (5-10
mgday) and no stress doses of glucocorticoids
- The clinical course of the patients revealed no evidence of adrenal insufficiency
There was no mortality increase in hospital stay or eosinophilia
Rushworth et al Endocrine (2017) 55336ndash
345
Bromberg JSTransplantation 1991
Feb51(2)385-90
Precipitating factors
73 51 48
Hahner et al
Prospective Study of Adrenal Crisis
J Clin Endocrinol Metab February 2015 100(2)407ndash416
J Clin Endocrinol Metab 100 407ndash 416 2015
Clinical Presentation of Adrenal Crisis
Work Up of Possible Adrenal Crises
1 In patient with known AI presenting with symptoms cw AC therapy
should be instituted immediately
2 In those wo a prior dx of AI
a Serum Cortisol gt 20 ugdl usually excludes AI while an AM
cortisolstressed state cortisol lt 5 ugdl is supportive
b Draw a cortisol ACTH Renin Aldosterone and DHEA-S and
then give 100 mg of hydrocortisone
Puar et al The American Journal of
Medicine Vol 129 No 3 March
2016
Treatment of Adrenal Crisis
1 100 mg of parenteral (IV or IM) hydrocortisone or 4 mg
dexamethasone IV in patients without a known diagnosis
2 This to be follow by 200 mg of parenteral hydrocortisone over the
next 24 hours or 4 mg of dexamethasone every 12 hours
a Can be 50 mg q 6 hours or as a continuous infusion
3 Fluid administrations as clinically indicated
Neiman Treatment of adrenal
insufficiency in adults UpToDate
Hyponatremia
1 Due to AI can correct rapidly due to free water excretion and
suppression of ADH so be careful for overly rapid Na correction and
Osmotic demyelination syndrome
Prevention of adrenal Crisis
1 Appropriate management of patient with adrenal insufficiency
includes extensive management of stress dosing of steroids for
febrile illness emotional stress increased physical stress etc
1 All patients should be instructed on stress dosing and parenteral
glucocorticoid administration
1 carry a steroid dependency card
1 wear a MedicAlert bracelet or similar identification
Thyroid Storm
Thyroid storm is an endocrine emergency that is characterized by
rapid deterioration of a patient with thyrotoxicosis within days or hours
of presentation and is associated with high mortality
Thyroid Storma rare life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis
Epidemiology of Thyroid Storm
Incidence of thyroid storm 057-076 100000 persons per year in
the US
Incidence among hospitalized patients 48-56 cases100000
persons per year
142-184 of patients hospitalized for thyrotoxicosis
Hospital mortality was 12-36 (higher in japanese series)
Galindo RJ et al Thyroid 2019 29 36-43
Akamizu et al Thyroid 2018 Jan28(1)32-40
Precipitants of Thyroid Storm
Akamizu et al Thyroid 2018 Jan28(1)32-40
Galindo RJ et al Thyroid 2019 29 36-43
Why does storm develop Is this a reasonable
question
Clinical manifestations of Thyroid Storm
Fever 42 in
japanese survey
56 reported in
literature
Tachycardia (76
gt130)
CHF (70)
CNS manifestations
(84)
agitation restlessness
delirium mental
aberrationpsychosis
somnolencelethargy
convulsion or coma
GI symptoms (70)
abdominal pain
Diarrhea
nauseavomiting
jaundice with liver
dysfunction
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Definition of Adrenal Crisis
ldquoAn Acute deterioration in a patient with adrenal
Insufficiency The principal manifestation of adrenal
crises is hypotension or hypovolemic shock but other
symptoms such as weakness anorexia nausea
abdominal pain fever vomiting fatigue electrolyte
abnormalities confusion coma and marked laboratory
abnormalities can also occurrdquoPuar et al The American Journal of Medicine (2016) 129 339e1-339e9
Adrenal Crisis
An acute deterioration in health that is associated with absolute (SBP lt 100 mmHg) or
relative hypotension
the features of which resolve following parenteral glucocorticoid administration
demonstrated by a marked resolution of hypotension within 1 h
and improvement of clinical symptoms over 2 h
Added details to the Definition
acute abdominal symptoms
deliriumobtundation
hyponatraemiahyperkalaemia hypoglycaemia
pyrexia
Rushworth et al Endocrine (2017) 55336ndash
345
Dineen et al Ther Adv
Endocrinol Metab
2019 Vol 10 1ndash12
Incidence and Mortality of Adrenal Crises
1 Most studies have shown an incidence of between 5-10 ACrsquos100
patient years with adrenal insufficiency
2 In treated AI Adrenal crises contributes significantly to the increased
mortality
a Up to 15 of patients with autoimmune AI
b 42 of those with CAH
3 The associated mortality rate from adrenal crisis in treated adrenal
insufficiency is 05100 PY
Rushworth et al Endocrine (2017) 55336ndash
345Hahner et al J Clin Endocrinol Metab 100
407ndash 416 2015
Hahner et al J Clin Endocrinol Metab 100
407ndash 416 2015
- 423 patients followed
prospectively for 2 years
- 64 adrenal crisis
during follow up
- Ten patients died in
follow up 4 due to
AC
Risk Factors
I All patients with AI are at risk when the requirements for cortisol
exceed what is available
II Prior episode of AC
III Primary AI gt Secondary AI
A Complete loss of adrenal function specifically aldosterone
B More likely to have type 1 DM which is a risk factor
IV Diabetes insipidus
V Social isolation
VI Psychological stress
Glucocorticoid induced AI-- Risk of AC in
chronic glucocorticoid therapy
- SAI due to sustained glucocorticoid exposure is common but AC events tend to be rare
or mild
- probably due to incomplete HPA axis suppression in many treated patients
- a prospective study was conducted in 40 renal transplant patients admitted with
significant physiologic stress
- patients received only their baseline prednisone immunosuppression (5-10
mgday) and no stress doses of glucocorticoids
- The clinical course of the patients revealed no evidence of adrenal insufficiency
There was no mortality increase in hospital stay or eosinophilia
Rushworth et al Endocrine (2017) 55336ndash
345
Bromberg JSTransplantation 1991
Feb51(2)385-90
Precipitating factors
73 51 48
Hahner et al
Prospective Study of Adrenal Crisis
J Clin Endocrinol Metab February 2015 100(2)407ndash416
J Clin Endocrinol Metab 100 407ndash 416 2015
Clinical Presentation of Adrenal Crisis
Work Up of Possible Adrenal Crises
1 In patient with known AI presenting with symptoms cw AC therapy
should be instituted immediately
2 In those wo a prior dx of AI
a Serum Cortisol gt 20 ugdl usually excludes AI while an AM
cortisolstressed state cortisol lt 5 ugdl is supportive
b Draw a cortisol ACTH Renin Aldosterone and DHEA-S and
then give 100 mg of hydrocortisone
Puar et al The American Journal of
Medicine Vol 129 No 3 March
2016
Treatment of Adrenal Crisis
1 100 mg of parenteral (IV or IM) hydrocortisone or 4 mg
dexamethasone IV in patients without a known diagnosis
2 This to be follow by 200 mg of parenteral hydrocortisone over the
next 24 hours or 4 mg of dexamethasone every 12 hours
a Can be 50 mg q 6 hours or as a continuous infusion
3 Fluid administrations as clinically indicated
Neiman Treatment of adrenal
insufficiency in adults UpToDate
Hyponatremia
1 Due to AI can correct rapidly due to free water excretion and
suppression of ADH so be careful for overly rapid Na correction and
Osmotic demyelination syndrome
Prevention of adrenal Crisis
1 Appropriate management of patient with adrenal insufficiency
includes extensive management of stress dosing of steroids for
febrile illness emotional stress increased physical stress etc
1 All patients should be instructed on stress dosing and parenteral
glucocorticoid administration
1 carry a steroid dependency card
1 wear a MedicAlert bracelet or similar identification
Thyroid Storm
Thyroid storm is an endocrine emergency that is characterized by
rapid deterioration of a patient with thyrotoxicosis within days or hours
of presentation and is associated with high mortality
Thyroid Storma rare life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis
Epidemiology of Thyroid Storm
Incidence of thyroid storm 057-076 100000 persons per year in
the US
Incidence among hospitalized patients 48-56 cases100000
persons per year
142-184 of patients hospitalized for thyrotoxicosis
Hospital mortality was 12-36 (higher in japanese series)
Galindo RJ et al Thyroid 2019 29 36-43
Akamizu et al Thyroid 2018 Jan28(1)32-40
Precipitants of Thyroid Storm
Akamizu et al Thyroid 2018 Jan28(1)32-40
Galindo RJ et al Thyroid 2019 29 36-43
Why does storm develop Is this a reasonable
question
Clinical manifestations of Thyroid Storm
Fever 42 in
japanese survey
56 reported in
literature
Tachycardia (76
gt130)
CHF (70)
CNS manifestations
(84)
agitation restlessness
delirium mental
aberrationpsychosis
somnolencelethargy
convulsion or coma
GI symptoms (70)
abdominal pain
Diarrhea
nauseavomiting
jaundice with liver
dysfunction
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Adrenal Crisis
An acute deterioration in health that is associated with absolute (SBP lt 100 mmHg) or
relative hypotension
the features of which resolve following parenteral glucocorticoid administration
demonstrated by a marked resolution of hypotension within 1 h
and improvement of clinical symptoms over 2 h
Added details to the Definition
acute abdominal symptoms
deliriumobtundation
hyponatraemiahyperkalaemia hypoglycaemia
pyrexia
Rushworth et al Endocrine (2017) 55336ndash
345
Dineen et al Ther Adv
Endocrinol Metab
2019 Vol 10 1ndash12
Incidence and Mortality of Adrenal Crises
1 Most studies have shown an incidence of between 5-10 ACrsquos100
patient years with adrenal insufficiency
2 In treated AI Adrenal crises contributes significantly to the increased
mortality
a Up to 15 of patients with autoimmune AI
b 42 of those with CAH
3 The associated mortality rate from adrenal crisis in treated adrenal
insufficiency is 05100 PY
Rushworth et al Endocrine (2017) 55336ndash
345Hahner et al J Clin Endocrinol Metab 100
407ndash 416 2015
Hahner et al J Clin Endocrinol Metab 100
407ndash 416 2015
- 423 patients followed
prospectively for 2 years
- 64 adrenal crisis
during follow up
- Ten patients died in
follow up 4 due to
AC
Risk Factors
I All patients with AI are at risk when the requirements for cortisol
exceed what is available
II Prior episode of AC
III Primary AI gt Secondary AI
A Complete loss of adrenal function specifically aldosterone
B More likely to have type 1 DM which is a risk factor
IV Diabetes insipidus
V Social isolation
VI Psychological stress
Glucocorticoid induced AI-- Risk of AC in
chronic glucocorticoid therapy
- SAI due to sustained glucocorticoid exposure is common but AC events tend to be rare
or mild
- probably due to incomplete HPA axis suppression in many treated patients
- a prospective study was conducted in 40 renal transplant patients admitted with
significant physiologic stress
- patients received only their baseline prednisone immunosuppression (5-10
mgday) and no stress doses of glucocorticoids
- The clinical course of the patients revealed no evidence of adrenal insufficiency
There was no mortality increase in hospital stay or eosinophilia
Rushworth et al Endocrine (2017) 55336ndash
345
Bromberg JSTransplantation 1991
Feb51(2)385-90
Precipitating factors
73 51 48
Hahner et al
Prospective Study of Adrenal Crisis
J Clin Endocrinol Metab February 2015 100(2)407ndash416
J Clin Endocrinol Metab 100 407ndash 416 2015
Clinical Presentation of Adrenal Crisis
Work Up of Possible Adrenal Crises
1 In patient with known AI presenting with symptoms cw AC therapy
should be instituted immediately
2 In those wo a prior dx of AI
a Serum Cortisol gt 20 ugdl usually excludes AI while an AM
cortisolstressed state cortisol lt 5 ugdl is supportive
b Draw a cortisol ACTH Renin Aldosterone and DHEA-S and
then give 100 mg of hydrocortisone
Puar et al The American Journal of
Medicine Vol 129 No 3 March
2016
Treatment of Adrenal Crisis
1 100 mg of parenteral (IV or IM) hydrocortisone or 4 mg
dexamethasone IV in patients without a known diagnosis
2 This to be follow by 200 mg of parenteral hydrocortisone over the
next 24 hours or 4 mg of dexamethasone every 12 hours
a Can be 50 mg q 6 hours or as a continuous infusion
3 Fluid administrations as clinically indicated
Neiman Treatment of adrenal
insufficiency in adults UpToDate
Hyponatremia
1 Due to AI can correct rapidly due to free water excretion and
suppression of ADH so be careful for overly rapid Na correction and
Osmotic demyelination syndrome
Prevention of adrenal Crisis
1 Appropriate management of patient with adrenal insufficiency
includes extensive management of stress dosing of steroids for
febrile illness emotional stress increased physical stress etc
1 All patients should be instructed on stress dosing and parenteral
glucocorticoid administration
1 carry a steroid dependency card
1 wear a MedicAlert bracelet or similar identification
Thyroid Storm
Thyroid storm is an endocrine emergency that is characterized by
rapid deterioration of a patient with thyrotoxicosis within days or hours
of presentation and is associated with high mortality
Thyroid Storma rare life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis
Epidemiology of Thyroid Storm
Incidence of thyroid storm 057-076 100000 persons per year in
the US
Incidence among hospitalized patients 48-56 cases100000
persons per year
142-184 of patients hospitalized for thyrotoxicosis
Hospital mortality was 12-36 (higher in japanese series)
Galindo RJ et al Thyroid 2019 29 36-43
Akamizu et al Thyroid 2018 Jan28(1)32-40
Precipitants of Thyroid Storm
Akamizu et al Thyroid 2018 Jan28(1)32-40
Galindo RJ et al Thyroid 2019 29 36-43
Why does storm develop Is this a reasonable
question
Clinical manifestations of Thyroid Storm
Fever 42 in
japanese survey
56 reported in
literature
Tachycardia (76
gt130)
CHF (70)
CNS manifestations
(84)
agitation restlessness
delirium mental
aberrationpsychosis
somnolencelethargy
convulsion or coma
GI symptoms (70)
abdominal pain
Diarrhea
nauseavomiting
jaundice with liver
dysfunction
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Dineen et al Ther Adv
Endocrinol Metab
2019 Vol 10 1ndash12
Incidence and Mortality of Adrenal Crises
1 Most studies have shown an incidence of between 5-10 ACrsquos100
patient years with adrenal insufficiency
2 In treated AI Adrenal crises contributes significantly to the increased
mortality
a Up to 15 of patients with autoimmune AI
b 42 of those with CAH
3 The associated mortality rate from adrenal crisis in treated adrenal
insufficiency is 05100 PY
Rushworth et al Endocrine (2017) 55336ndash
345Hahner et al J Clin Endocrinol Metab 100
407ndash 416 2015
Hahner et al J Clin Endocrinol Metab 100
407ndash 416 2015
- 423 patients followed
prospectively for 2 years
- 64 adrenal crisis
during follow up
- Ten patients died in
follow up 4 due to
AC
Risk Factors
I All patients with AI are at risk when the requirements for cortisol
exceed what is available
II Prior episode of AC
III Primary AI gt Secondary AI
A Complete loss of adrenal function specifically aldosterone
B More likely to have type 1 DM which is a risk factor
IV Diabetes insipidus
V Social isolation
VI Psychological stress
Glucocorticoid induced AI-- Risk of AC in
chronic glucocorticoid therapy
- SAI due to sustained glucocorticoid exposure is common but AC events tend to be rare
or mild
- probably due to incomplete HPA axis suppression in many treated patients
- a prospective study was conducted in 40 renal transplant patients admitted with
significant physiologic stress
- patients received only their baseline prednisone immunosuppression (5-10
mgday) and no stress doses of glucocorticoids
- The clinical course of the patients revealed no evidence of adrenal insufficiency
There was no mortality increase in hospital stay or eosinophilia
Rushworth et al Endocrine (2017) 55336ndash
345
Bromberg JSTransplantation 1991
Feb51(2)385-90
Precipitating factors
73 51 48
Hahner et al
Prospective Study of Adrenal Crisis
J Clin Endocrinol Metab February 2015 100(2)407ndash416
J Clin Endocrinol Metab 100 407ndash 416 2015
Clinical Presentation of Adrenal Crisis
Work Up of Possible Adrenal Crises
1 In patient with known AI presenting with symptoms cw AC therapy
should be instituted immediately
2 In those wo a prior dx of AI
a Serum Cortisol gt 20 ugdl usually excludes AI while an AM
cortisolstressed state cortisol lt 5 ugdl is supportive
b Draw a cortisol ACTH Renin Aldosterone and DHEA-S and
then give 100 mg of hydrocortisone
Puar et al The American Journal of
Medicine Vol 129 No 3 March
2016
Treatment of Adrenal Crisis
1 100 mg of parenteral (IV or IM) hydrocortisone or 4 mg
dexamethasone IV in patients without a known diagnosis
2 This to be follow by 200 mg of parenteral hydrocortisone over the
next 24 hours or 4 mg of dexamethasone every 12 hours
a Can be 50 mg q 6 hours or as a continuous infusion
3 Fluid administrations as clinically indicated
Neiman Treatment of adrenal
insufficiency in adults UpToDate
Hyponatremia
1 Due to AI can correct rapidly due to free water excretion and
suppression of ADH so be careful for overly rapid Na correction and
Osmotic demyelination syndrome
Prevention of adrenal Crisis
1 Appropriate management of patient with adrenal insufficiency
includes extensive management of stress dosing of steroids for
febrile illness emotional stress increased physical stress etc
1 All patients should be instructed on stress dosing and parenteral
glucocorticoid administration
1 carry a steroid dependency card
1 wear a MedicAlert bracelet or similar identification
Thyroid Storm
Thyroid storm is an endocrine emergency that is characterized by
rapid deterioration of a patient with thyrotoxicosis within days or hours
of presentation and is associated with high mortality
Thyroid Storma rare life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis
Epidemiology of Thyroid Storm
Incidence of thyroid storm 057-076 100000 persons per year in
the US
Incidence among hospitalized patients 48-56 cases100000
persons per year
142-184 of patients hospitalized for thyrotoxicosis
Hospital mortality was 12-36 (higher in japanese series)
Galindo RJ et al Thyroid 2019 29 36-43
Akamizu et al Thyroid 2018 Jan28(1)32-40
Precipitants of Thyroid Storm
Akamizu et al Thyroid 2018 Jan28(1)32-40
Galindo RJ et al Thyroid 2019 29 36-43
Why does storm develop Is this a reasonable
question
Clinical manifestations of Thyroid Storm
Fever 42 in
japanese survey
56 reported in
literature
Tachycardia (76
gt130)
CHF (70)
CNS manifestations
(84)
agitation restlessness
delirium mental
aberrationpsychosis
somnolencelethargy
convulsion or coma
GI symptoms (70)
abdominal pain
Diarrhea
nauseavomiting
jaundice with liver
dysfunction
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Incidence and Mortality of Adrenal Crises
1 Most studies have shown an incidence of between 5-10 ACrsquos100
patient years with adrenal insufficiency
2 In treated AI Adrenal crises contributes significantly to the increased
mortality
a Up to 15 of patients with autoimmune AI
b 42 of those with CAH
3 The associated mortality rate from adrenal crisis in treated adrenal
insufficiency is 05100 PY
Rushworth et al Endocrine (2017) 55336ndash
345Hahner et al J Clin Endocrinol Metab 100
407ndash 416 2015
Hahner et al J Clin Endocrinol Metab 100
407ndash 416 2015
- 423 patients followed
prospectively for 2 years
- 64 adrenal crisis
during follow up
- Ten patients died in
follow up 4 due to
AC
Risk Factors
I All patients with AI are at risk when the requirements for cortisol
exceed what is available
II Prior episode of AC
III Primary AI gt Secondary AI
A Complete loss of adrenal function specifically aldosterone
B More likely to have type 1 DM which is a risk factor
IV Diabetes insipidus
V Social isolation
VI Psychological stress
Glucocorticoid induced AI-- Risk of AC in
chronic glucocorticoid therapy
- SAI due to sustained glucocorticoid exposure is common but AC events tend to be rare
or mild
- probably due to incomplete HPA axis suppression in many treated patients
- a prospective study was conducted in 40 renal transplant patients admitted with
significant physiologic stress
- patients received only their baseline prednisone immunosuppression (5-10
mgday) and no stress doses of glucocorticoids
- The clinical course of the patients revealed no evidence of adrenal insufficiency
There was no mortality increase in hospital stay or eosinophilia
Rushworth et al Endocrine (2017) 55336ndash
345
Bromberg JSTransplantation 1991
Feb51(2)385-90
Precipitating factors
73 51 48
Hahner et al
Prospective Study of Adrenal Crisis
J Clin Endocrinol Metab February 2015 100(2)407ndash416
J Clin Endocrinol Metab 100 407ndash 416 2015
Clinical Presentation of Adrenal Crisis
Work Up of Possible Adrenal Crises
1 In patient with known AI presenting with symptoms cw AC therapy
should be instituted immediately
2 In those wo a prior dx of AI
a Serum Cortisol gt 20 ugdl usually excludes AI while an AM
cortisolstressed state cortisol lt 5 ugdl is supportive
b Draw a cortisol ACTH Renin Aldosterone and DHEA-S and
then give 100 mg of hydrocortisone
Puar et al The American Journal of
Medicine Vol 129 No 3 March
2016
Treatment of Adrenal Crisis
1 100 mg of parenteral (IV or IM) hydrocortisone or 4 mg
dexamethasone IV in patients without a known diagnosis
2 This to be follow by 200 mg of parenteral hydrocortisone over the
next 24 hours or 4 mg of dexamethasone every 12 hours
a Can be 50 mg q 6 hours or as a continuous infusion
3 Fluid administrations as clinically indicated
Neiman Treatment of adrenal
insufficiency in adults UpToDate
Hyponatremia
1 Due to AI can correct rapidly due to free water excretion and
suppression of ADH so be careful for overly rapid Na correction and
Osmotic demyelination syndrome
Prevention of adrenal Crisis
1 Appropriate management of patient with adrenal insufficiency
includes extensive management of stress dosing of steroids for
febrile illness emotional stress increased physical stress etc
1 All patients should be instructed on stress dosing and parenteral
glucocorticoid administration
1 carry a steroid dependency card
1 wear a MedicAlert bracelet or similar identification
Thyroid Storm
Thyroid storm is an endocrine emergency that is characterized by
rapid deterioration of a patient with thyrotoxicosis within days or hours
of presentation and is associated with high mortality
Thyroid Storma rare life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis
Epidemiology of Thyroid Storm
Incidence of thyroid storm 057-076 100000 persons per year in
the US
Incidence among hospitalized patients 48-56 cases100000
persons per year
142-184 of patients hospitalized for thyrotoxicosis
Hospital mortality was 12-36 (higher in japanese series)
Galindo RJ et al Thyroid 2019 29 36-43
Akamizu et al Thyroid 2018 Jan28(1)32-40
Precipitants of Thyroid Storm
Akamizu et al Thyroid 2018 Jan28(1)32-40
Galindo RJ et al Thyroid 2019 29 36-43
Why does storm develop Is this a reasonable
question
Clinical manifestations of Thyroid Storm
Fever 42 in
japanese survey
56 reported in
literature
Tachycardia (76
gt130)
CHF (70)
CNS manifestations
(84)
agitation restlessness
delirium mental
aberrationpsychosis
somnolencelethargy
convulsion or coma
GI symptoms (70)
abdominal pain
Diarrhea
nauseavomiting
jaundice with liver
dysfunction
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Hahner et al J Clin Endocrinol Metab 100
407ndash 416 2015
- 423 patients followed
prospectively for 2 years
- 64 adrenal crisis
during follow up
- Ten patients died in
follow up 4 due to
AC
Risk Factors
I All patients with AI are at risk when the requirements for cortisol
exceed what is available
II Prior episode of AC
III Primary AI gt Secondary AI
A Complete loss of adrenal function specifically aldosterone
B More likely to have type 1 DM which is a risk factor
IV Diabetes insipidus
V Social isolation
VI Psychological stress
Glucocorticoid induced AI-- Risk of AC in
chronic glucocorticoid therapy
- SAI due to sustained glucocorticoid exposure is common but AC events tend to be rare
or mild
- probably due to incomplete HPA axis suppression in many treated patients
- a prospective study was conducted in 40 renal transplant patients admitted with
significant physiologic stress
- patients received only their baseline prednisone immunosuppression (5-10
mgday) and no stress doses of glucocorticoids
- The clinical course of the patients revealed no evidence of adrenal insufficiency
There was no mortality increase in hospital stay or eosinophilia
Rushworth et al Endocrine (2017) 55336ndash
345
Bromberg JSTransplantation 1991
Feb51(2)385-90
Precipitating factors
73 51 48
Hahner et al
Prospective Study of Adrenal Crisis
J Clin Endocrinol Metab February 2015 100(2)407ndash416
J Clin Endocrinol Metab 100 407ndash 416 2015
Clinical Presentation of Adrenal Crisis
Work Up of Possible Adrenal Crises
1 In patient with known AI presenting with symptoms cw AC therapy
should be instituted immediately
2 In those wo a prior dx of AI
a Serum Cortisol gt 20 ugdl usually excludes AI while an AM
cortisolstressed state cortisol lt 5 ugdl is supportive
b Draw a cortisol ACTH Renin Aldosterone and DHEA-S and
then give 100 mg of hydrocortisone
Puar et al The American Journal of
Medicine Vol 129 No 3 March
2016
Treatment of Adrenal Crisis
1 100 mg of parenteral (IV or IM) hydrocortisone or 4 mg
dexamethasone IV in patients without a known diagnosis
2 This to be follow by 200 mg of parenteral hydrocortisone over the
next 24 hours or 4 mg of dexamethasone every 12 hours
a Can be 50 mg q 6 hours or as a continuous infusion
3 Fluid administrations as clinically indicated
Neiman Treatment of adrenal
insufficiency in adults UpToDate
Hyponatremia
1 Due to AI can correct rapidly due to free water excretion and
suppression of ADH so be careful for overly rapid Na correction and
Osmotic demyelination syndrome
Prevention of adrenal Crisis
1 Appropriate management of patient with adrenal insufficiency
includes extensive management of stress dosing of steroids for
febrile illness emotional stress increased physical stress etc
1 All patients should be instructed on stress dosing and parenteral
glucocorticoid administration
1 carry a steroid dependency card
1 wear a MedicAlert bracelet or similar identification
Thyroid Storm
Thyroid storm is an endocrine emergency that is characterized by
rapid deterioration of a patient with thyrotoxicosis within days or hours
of presentation and is associated with high mortality
Thyroid Storma rare life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis
Epidemiology of Thyroid Storm
Incidence of thyroid storm 057-076 100000 persons per year in
the US
Incidence among hospitalized patients 48-56 cases100000
persons per year
142-184 of patients hospitalized for thyrotoxicosis
Hospital mortality was 12-36 (higher in japanese series)
Galindo RJ et al Thyroid 2019 29 36-43
Akamizu et al Thyroid 2018 Jan28(1)32-40
Precipitants of Thyroid Storm
Akamizu et al Thyroid 2018 Jan28(1)32-40
Galindo RJ et al Thyroid 2019 29 36-43
Why does storm develop Is this a reasonable
question
Clinical manifestations of Thyroid Storm
Fever 42 in
japanese survey
56 reported in
literature
Tachycardia (76
gt130)
CHF (70)
CNS manifestations
(84)
agitation restlessness
delirium mental
aberrationpsychosis
somnolencelethargy
convulsion or coma
GI symptoms (70)
abdominal pain
Diarrhea
nauseavomiting
jaundice with liver
dysfunction
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Risk Factors
I All patients with AI are at risk when the requirements for cortisol
exceed what is available
II Prior episode of AC
III Primary AI gt Secondary AI
A Complete loss of adrenal function specifically aldosterone
B More likely to have type 1 DM which is a risk factor
IV Diabetes insipidus
V Social isolation
VI Psychological stress
Glucocorticoid induced AI-- Risk of AC in
chronic glucocorticoid therapy
- SAI due to sustained glucocorticoid exposure is common but AC events tend to be rare
or mild
- probably due to incomplete HPA axis suppression in many treated patients
- a prospective study was conducted in 40 renal transplant patients admitted with
significant physiologic stress
- patients received only their baseline prednisone immunosuppression (5-10
mgday) and no stress doses of glucocorticoids
- The clinical course of the patients revealed no evidence of adrenal insufficiency
There was no mortality increase in hospital stay or eosinophilia
Rushworth et al Endocrine (2017) 55336ndash
345
Bromberg JSTransplantation 1991
Feb51(2)385-90
Precipitating factors
73 51 48
Hahner et al
Prospective Study of Adrenal Crisis
J Clin Endocrinol Metab February 2015 100(2)407ndash416
J Clin Endocrinol Metab 100 407ndash 416 2015
Clinical Presentation of Adrenal Crisis
Work Up of Possible Adrenal Crises
1 In patient with known AI presenting with symptoms cw AC therapy
should be instituted immediately
2 In those wo a prior dx of AI
a Serum Cortisol gt 20 ugdl usually excludes AI while an AM
cortisolstressed state cortisol lt 5 ugdl is supportive
b Draw a cortisol ACTH Renin Aldosterone and DHEA-S and
then give 100 mg of hydrocortisone
Puar et al The American Journal of
Medicine Vol 129 No 3 March
2016
Treatment of Adrenal Crisis
1 100 mg of parenteral (IV or IM) hydrocortisone or 4 mg
dexamethasone IV in patients without a known diagnosis
2 This to be follow by 200 mg of parenteral hydrocortisone over the
next 24 hours or 4 mg of dexamethasone every 12 hours
a Can be 50 mg q 6 hours or as a continuous infusion
3 Fluid administrations as clinically indicated
Neiman Treatment of adrenal
insufficiency in adults UpToDate
Hyponatremia
1 Due to AI can correct rapidly due to free water excretion and
suppression of ADH so be careful for overly rapid Na correction and
Osmotic demyelination syndrome
Prevention of adrenal Crisis
1 Appropriate management of patient with adrenal insufficiency
includes extensive management of stress dosing of steroids for
febrile illness emotional stress increased physical stress etc
1 All patients should be instructed on stress dosing and parenteral
glucocorticoid administration
1 carry a steroid dependency card
1 wear a MedicAlert bracelet or similar identification
Thyroid Storm
Thyroid storm is an endocrine emergency that is characterized by
rapid deterioration of a patient with thyrotoxicosis within days or hours
of presentation and is associated with high mortality
Thyroid Storma rare life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis
Epidemiology of Thyroid Storm
Incidence of thyroid storm 057-076 100000 persons per year in
the US
Incidence among hospitalized patients 48-56 cases100000
persons per year
142-184 of patients hospitalized for thyrotoxicosis
Hospital mortality was 12-36 (higher in japanese series)
Galindo RJ et al Thyroid 2019 29 36-43
Akamizu et al Thyroid 2018 Jan28(1)32-40
Precipitants of Thyroid Storm
Akamizu et al Thyroid 2018 Jan28(1)32-40
Galindo RJ et al Thyroid 2019 29 36-43
Why does storm develop Is this a reasonable
question
Clinical manifestations of Thyroid Storm
Fever 42 in
japanese survey
56 reported in
literature
Tachycardia (76
gt130)
CHF (70)
CNS manifestations
(84)
agitation restlessness
delirium mental
aberrationpsychosis
somnolencelethargy
convulsion or coma
GI symptoms (70)
abdominal pain
Diarrhea
nauseavomiting
jaundice with liver
dysfunction
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Glucocorticoid induced AI-- Risk of AC in
chronic glucocorticoid therapy
- SAI due to sustained glucocorticoid exposure is common but AC events tend to be rare
or mild
- probably due to incomplete HPA axis suppression in many treated patients
- a prospective study was conducted in 40 renal transplant patients admitted with
significant physiologic stress
- patients received only their baseline prednisone immunosuppression (5-10
mgday) and no stress doses of glucocorticoids
- The clinical course of the patients revealed no evidence of adrenal insufficiency
There was no mortality increase in hospital stay or eosinophilia
Rushworth et al Endocrine (2017) 55336ndash
345
Bromberg JSTransplantation 1991
Feb51(2)385-90
Precipitating factors
73 51 48
Hahner et al
Prospective Study of Adrenal Crisis
J Clin Endocrinol Metab February 2015 100(2)407ndash416
J Clin Endocrinol Metab 100 407ndash 416 2015
Clinical Presentation of Adrenal Crisis
Work Up of Possible Adrenal Crises
1 In patient with known AI presenting with symptoms cw AC therapy
should be instituted immediately
2 In those wo a prior dx of AI
a Serum Cortisol gt 20 ugdl usually excludes AI while an AM
cortisolstressed state cortisol lt 5 ugdl is supportive
b Draw a cortisol ACTH Renin Aldosterone and DHEA-S and
then give 100 mg of hydrocortisone
Puar et al The American Journal of
Medicine Vol 129 No 3 March
2016
Treatment of Adrenal Crisis
1 100 mg of parenteral (IV or IM) hydrocortisone or 4 mg
dexamethasone IV in patients without a known diagnosis
2 This to be follow by 200 mg of parenteral hydrocortisone over the
next 24 hours or 4 mg of dexamethasone every 12 hours
a Can be 50 mg q 6 hours or as a continuous infusion
3 Fluid administrations as clinically indicated
Neiman Treatment of adrenal
insufficiency in adults UpToDate
Hyponatremia
1 Due to AI can correct rapidly due to free water excretion and
suppression of ADH so be careful for overly rapid Na correction and
Osmotic demyelination syndrome
Prevention of adrenal Crisis
1 Appropriate management of patient with adrenal insufficiency
includes extensive management of stress dosing of steroids for
febrile illness emotional stress increased physical stress etc
1 All patients should be instructed on stress dosing and parenteral
glucocorticoid administration
1 carry a steroid dependency card
1 wear a MedicAlert bracelet or similar identification
Thyroid Storm
Thyroid storm is an endocrine emergency that is characterized by
rapid deterioration of a patient with thyrotoxicosis within days or hours
of presentation and is associated with high mortality
Thyroid Storma rare life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis
Epidemiology of Thyroid Storm
Incidence of thyroid storm 057-076 100000 persons per year in
the US
Incidence among hospitalized patients 48-56 cases100000
persons per year
142-184 of patients hospitalized for thyrotoxicosis
Hospital mortality was 12-36 (higher in japanese series)
Galindo RJ et al Thyroid 2019 29 36-43
Akamizu et al Thyroid 2018 Jan28(1)32-40
Precipitants of Thyroid Storm
Akamizu et al Thyroid 2018 Jan28(1)32-40
Galindo RJ et al Thyroid 2019 29 36-43
Why does storm develop Is this a reasonable
question
Clinical manifestations of Thyroid Storm
Fever 42 in
japanese survey
56 reported in
literature
Tachycardia (76
gt130)
CHF (70)
CNS manifestations
(84)
agitation restlessness
delirium mental
aberrationpsychosis
somnolencelethargy
convulsion or coma
GI symptoms (70)
abdominal pain
Diarrhea
nauseavomiting
jaundice with liver
dysfunction
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Precipitating factors
73 51 48
Hahner et al
Prospective Study of Adrenal Crisis
J Clin Endocrinol Metab February 2015 100(2)407ndash416
J Clin Endocrinol Metab 100 407ndash 416 2015
Clinical Presentation of Adrenal Crisis
Work Up of Possible Adrenal Crises
1 In patient with known AI presenting with symptoms cw AC therapy
should be instituted immediately
2 In those wo a prior dx of AI
a Serum Cortisol gt 20 ugdl usually excludes AI while an AM
cortisolstressed state cortisol lt 5 ugdl is supportive
b Draw a cortisol ACTH Renin Aldosterone and DHEA-S and
then give 100 mg of hydrocortisone
Puar et al The American Journal of
Medicine Vol 129 No 3 March
2016
Treatment of Adrenal Crisis
1 100 mg of parenteral (IV or IM) hydrocortisone or 4 mg
dexamethasone IV in patients without a known diagnosis
2 This to be follow by 200 mg of parenteral hydrocortisone over the
next 24 hours or 4 mg of dexamethasone every 12 hours
a Can be 50 mg q 6 hours or as a continuous infusion
3 Fluid administrations as clinically indicated
Neiman Treatment of adrenal
insufficiency in adults UpToDate
Hyponatremia
1 Due to AI can correct rapidly due to free water excretion and
suppression of ADH so be careful for overly rapid Na correction and
Osmotic demyelination syndrome
Prevention of adrenal Crisis
1 Appropriate management of patient with adrenal insufficiency
includes extensive management of stress dosing of steroids for
febrile illness emotional stress increased physical stress etc
1 All patients should be instructed on stress dosing and parenteral
glucocorticoid administration
1 carry a steroid dependency card
1 wear a MedicAlert bracelet or similar identification
Thyroid Storm
Thyroid storm is an endocrine emergency that is characterized by
rapid deterioration of a patient with thyrotoxicosis within days or hours
of presentation and is associated with high mortality
Thyroid Storma rare life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis
Epidemiology of Thyroid Storm
Incidence of thyroid storm 057-076 100000 persons per year in
the US
Incidence among hospitalized patients 48-56 cases100000
persons per year
142-184 of patients hospitalized for thyrotoxicosis
Hospital mortality was 12-36 (higher in japanese series)
Galindo RJ et al Thyroid 2019 29 36-43
Akamizu et al Thyroid 2018 Jan28(1)32-40
Precipitants of Thyroid Storm
Akamizu et al Thyroid 2018 Jan28(1)32-40
Galindo RJ et al Thyroid 2019 29 36-43
Why does storm develop Is this a reasonable
question
Clinical manifestations of Thyroid Storm
Fever 42 in
japanese survey
56 reported in
literature
Tachycardia (76
gt130)
CHF (70)
CNS manifestations
(84)
agitation restlessness
delirium mental
aberrationpsychosis
somnolencelethargy
convulsion or coma
GI symptoms (70)
abdominal pain
Diarrhea
nauseavomiting
jaundice with liver
dysfunction
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Hahner et al
Prospective Study of Adrenal Crisis
J Clin Endocrinol Metab February 2015 100(2)407ndash416
J Clin Endocrinol Metab 100 407ndash 416 2015
Clinical Presentation of Adrenal Crisis
Work Up of Possible Adrenal Crises
1 In patient with known AI presenting with symptoms cw AC therapy
should be instituted immediately
2 In those wo a prior dx of AI
a Serum Cortisol gt 20 ugdl usually excludes AI while an AM
cortisolstressed state cortisol lt 5 ugdl is supportive
b Draw a cortisol ACTH Renin Aldosterone and DHEA-S and
then give 100 mg of hydrocortisone
Puar et al The American Journal of
Medicine Vol 129 No 3 March
2016
Treatment of Adrenal Crisis
1 100 mg of parenteral (IV or IM) hydrocortisone or 4 mg
dexamethasone IV in patients without a known diagnosis
2 This to be follow by 200 mg of parenteral hydrocortisone over the
next 24 hours or 4 mg of dexamethasone every 12 hours
a Can be 50 mg q 6 hours or as a continuous infusion
3 Fluid administrations as clinically indicated
Neiman Treatment of adrenal
insufficiency in adults UpToDate
Hyponatremia
1 Due to AI can correct rapidly due to free water excretion and
suppression of ADH so be careful for overly rapid Na correction and
Osmotic demyelination syndrome
Prevention of adrenal Crisis
1 Appropriate management of patient with adrenal insufficiency
includes extensive management of stress dosing of steroids for
febrile illness emotional stress increased physical stress etc
1 All patients should be instructed on stress dosing and parenteral
glucocorticoid administration
1 carry a steroid dependency card
1 wear a MedicAlert bracelet or similar identification
Thyroid Storm
Thyroid storm is an endocrine emergency that is characterized by
rapid deterioration of a patient with thyrotoxicosis within days or hours
of presentation and is associated with high mortality
Thyroid Storma rare life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis
Epidemiology of Thyroid Storm
Incidence of thyroid storm 057-076 100000 persons per year in
the US
Incidence among hospitalized patients 48-56 cases100000
persons per year
142-184 of patients hospitalized for thyrotoxicosis
Hospital mortality was 12-36 (higher in japanese series)
Galindo RJ et al Thyroid 2019 29 36-43
Akamizu et al Thyroid 2018 Jan28(1)32-40
Precipitants of Thyroid Storm
Akamizu et al Thyroid 2018 Jan28(1)32-40
Galindo RJ et al Thyroid 2019 29 36-43
Why does storm develop Is this a reasonable
question
Clinical manifestations of Thyroid Storm
Fever 42 in
japanese survey
56 reported in
literature
Tachycardia (76
gt130)
CHF (70)
CNS manifestations
(84)
agitation restlessness
delirium mental
aberrationpsychosis
somnolencelethargy
convulsion or coma
GI symptoms (70)
abdominal pain
Diarrhea
nauseavomiting
jaundice with liver
dysfunction
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Clinical Presentation of Adrenal Crisis
Work Up of Possible Adrenal Crises
1 In patient with known AI presenting with symptoms cw AC therapy
should be instituted immediately
2 In those wo a prior dx of AI
a Serum Cortisol gt 20 ugdl usually excludes AI while an AM
cortisolstressed state cortisol lt 5 ugdl is supportive
b Draw a cortisol ACTH Renin Aldosterone and DHEA-S and
then give 100 mg of hydrocortisone
Puar et al The American Journal of
Medicine Vol 129 No 3 March
2016
Treatment of Adrenal Crisis
1 100 mg of parenteral (IV or IM) hydrocortisone or 4 mg
dexamethasone IV in patients without a known diagnosis
2 This to be follow by 200 mg of parenteral hydrocortisone over the
next 24 hours or 4 mg of dexamethasone every 12 hours
a Can be 50 mg q 6 hours or as a continuous infusion
3 Fluid administrations as clinically indicated
Neiman Treatment of adrenal
insufficiency in adults UpToDate
Hyponatremia
1 Due to AI can correct rapidly due to free water excretion and
suppression of ADH so be careful for overly rapid Na correction and
Osmotic demyelination syndrome
Prevention of adrenal Crisis
1 Appropriate management of patient with adrenal insufficiency
includes extensive management of stress dosing of steroids for
febrile illness emotional stress increased physical stress etc
1 All patients should be instructed on stress dosing and parenteral
glucocorticoid administration
1 carry a steroid dependency card
1 wear a MedicAlert bracelet or similar identification
Thyroid Storm
Thyroid storm is an endocrine emergency that is characterized by
rapid deterioration of a patient with thyrotoxicosis within days or hours
of presentation and is associated with high mortality
Thyroid Storma rare life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis
Epidemiology of Thyroid Storm
Incidence of thyroid storm 057-076 100000 persons per year in
the US
Incidence among hospitalized patients 48-56 cases100000
persons per year
142-184 of patients hospitalized for thyrotoxicosis
Hospital mortality was 12-36 (higher in japanese series)
Galindo RJ et al Thyroid 2019 29 36-43
Akamizu et al Thyroid 2018 Jan28(1)32-40
Precipitants of Thyroid Storm
Akamizu et al Thyroid 2018 Jan28(1)32-40
Galindo RJ et al Thyroid 2019 29 36-43
Why does storm develop Is this a reasonable
question
Clinical manifestations of Thyroid Storm
Fever 42 in
japanese survey
56 reported in
literature
Tachycardia (76
gt130)
CHF (70)
CNS manifestations
(84)
agitation restlessness
delirium mental
aberrationpsychosis
somnolencelethargy
convulsion or coma
GI symptoms (70)
abdominal pain
Diarrhea
nauseavomiting
jaundice with liver
dysfunction
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Work Up of Possible Adrenal Crises
1 In patient with known AI presenting with symptoms cw AC therapy
should be instituted immediately
2 In those wo a prior dx of AI
a Serum Cortisol gt 20 ugdl usually excludes AI while an AM
cortisolstressed state cortisol lt 5 ugdl is supportive
b Draw a cortisol ACTH Renin Aldosterone and DHEA-S and
then give 100 mg of hydrocortisone
Puar et al The American Journal of
Medicine Vol 129 No 3 March
2016
Treatment of Adrenal Crisis
1 100 mg of parenteral (IV or IM) hydrocortisone or 4 mg
dexamethasone IV in patients without a known diagnosis
2 This to be follow by 200 mg of parenteral hydrocortisone over the
next 24 hours or 4 mg of dexamethasone every 12 hours
a Can be 50 mg q 6 hours or as a continuous infusion
3 Fluid administrations as clinically indicated
Neiman Treatment of adrenal
insufficiency in adults UpToDate
Hyponatremia
1 Due to AI can correct rapidly due to free water excretion and
suppression of ADH so be careful for overly rapid Na correction and
Osmotic demyelination syndrome
Prevention of adrenal Crisis
1 Appropriate management of patient with adrenal insufficiency
includes extensive management of stress dosing of steroids for
febrile illness emotional stress increased physical stress etc
1 All patients should be instructed on stress dosing and parenteral
glucocorticoid administration
1 carry a steroid dependency card
1 wear a MedicAlert bracelet or similar identification
Thyroid Storm
Thyroid storm is an endocrine emergency that is characterized by
rapid deterioration of a patient with thyrotoxicosis within days or hours
of presentation and is associated with high mortality
Thyroid Storma rare life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis
Epidemiology of Thyroid Storm
Incidence of thyroid storm 057-076 100000 persons per year in
the US
Incidence among hospitalized patients 48-56 cases100000
persons per year
142-184 of patients hospitalized for thyrotoxicosis
Hospital mortality was 12-36 (higher in japanese series)
Galindo RJ et al Thyroid 2019 29 36-43
Akamizu et al Thyroid 2018 Jan28(1)32-40
Precipitants of Thyroid Storm
Akamizu et al Thyroid 2018 Jan28(1)32-40
Galindo RJ et al Thyroid 2019 29 36-43
Why does storm develop Is this a reasonable
question
Clinical manifestations of Thyroid Storm
Fever 42 in
japanese survey
56 reported in
literature
Tachycardia (76
gt130)
CHF (70)
CNS manifestations
(84)
agitation restlessness
delirium mental
aberrationpsychosis
somnolencelethargy
convulsion or coma
GI symptoms (70)
abdominal pain
Diarrhea
nauseavomiting
jaundice with liver
dysfunction
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Treatment of Adrenal Crisis
1 100 mg of parenteral (IV or IM) hydrocortisone or 4 mg
dexamethasone IV in patients without a known diagnosis
2 This to be follow by 200 mg of parenteral hydrocortisone over the
next 24 hours or 4 mg of dexamethasone every 12 hours
a Can be 50 mg q 6 hours or as a continuous infusion
3 Fluid administrations as clinically indicated
Neiman Treatment of adrenal
insufficiency in adults UpToDate
Hyponatremia
1 Due to AI can correct rapidly due to free water excretion and
suppression of ADH so be careful for overly rapid Na correction and
Osmotic demyelination syndrome
Prevention of adrenal Crisis
1 Appropriate management of patient with adrenal insufficiency
includes extensive management of stress dosing of steroids for
febrile illness emotional stress increased physical stress etc
1 All patients should be instructed on stress dosing and parenteral
glucocorticoid administration
1 carry a steroid dependency card
1 wear a MedicAlert bracelet or similar identification
Thyroid Storm
Thyroid storm is an endocrine emergency that is characterized by
rapid deterioration of a patient with thyrotoxicosis within days or hours
of presentation and is associated with high mortality
Thyroid Storma rare life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis
Epidemiology of Thyroid Storm
Incidence of thyroid storm 057-076 100000 persons per year in
the US
Incidence among hospitalized patients 48-56 cases100000
persons per year
142-184 of patients hospitalized for thyrotoxicosis
Hospital mortality was 12-36 (higher in japanese series)
Galindo RJ et al Thyroid 2019 29 36-43
Akamizu et al Thyroid 2018 Jan28(1)32-40
Precipitants of Thyroid Storm
Akamizu et al Thyroid 2018 Jan28(1)32-40
Galindo RJ et al Thyroid 2019 29 36-43
Why does storm develop Is this a reasonable
question
Clinical manifestations of Thyroid Storm
Fever 42 in
japanese survey
56 reported in
literature
Tachycardia (76
gt130)
CHF (70)
CNS manifestations
(84)
agitation restlessness
delirium mental
aberrationpsychosis
somnolencelethargy
convulsion or coma
GI symptoms (70)
abdominal pain
Diarrhea
nauseavomiting
jaundice with liver
dysfunction
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Hyponatremia
1 Due to AI can correct rapidly due to free water excretion and
suppression of ADH so be careful for overly rapid Na correction and
Osmotic demyelination syndrome
Prevention of adrenal Crisis
1 Appropriate management of patient with adrenal insufficiency
includes extensive management of stress dosing of steroids for
febrile illness emotional stress increased physical stress etc
1 All patients should be instructed on stress dosing and parenteral
glucocorticoid administration
1 carry a steroid dependency card
1 wear a MedicAlert bracelet or similar identification
Thyroid Storm
Thyroid storm is an endocrine emergency that is characterized by
rapid deterioration of a patient with thyrotoxicosis within days or hours
of presentation and is associated with high mortality
Thyroid Storma rare life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis
Epidemiology of Thyroid Storm
Incidence of thyroid storm 057-076 100000 persons per year in
the US
Incidence among hospitalized patients 48-56 cases100000
persons per year
142-184 of patients hospitalized for thyrotoxicosis
Hospital mortality was 12-36 (higher in japanese series)
Galindo RJ et al Thyroid 2019 29 36-43
Akamizu et al Thyroid 2018 Jan28(1)32-40
Precipitants of Thyroid Storm
Akamizu et al Thyroid 2018 Jan28(1)32-40
Galindo RJ et al Thyroid 2019 29 36-43
Why does storm develop Is this a reasonable
question
Clinical manifestations of Thyroid Storm
Fever 42 in
japanese survey
56 reported in
literature
Tachycardia (76
gt130)
CHF (70)
CNS manifestations
(84)
agitation restlessness
delirium mental
aberrationpsychosis
somnolencelethargy
convulsion or coma
GI symptoms (70)
abdominal pain
Diarrhea
nauseavomiting
jaundice with liver
dysfunction
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Prevention of adrenal Crisis
1 Appropriate management of patient with adrenal insufficiency
includes extensive management of stress dosing of steroids for
febrile illness emotional stress increased physical stress etc
1 All patients should be instructed on stress dosing and parenteral
glucocorticoid administration
1 carry a steroid dependency card
1 wear a MedicAlert bracelet or similar identification
Thyroid Storm
Thyroid storm is an endocrine emergency that is characterized by
rapid deterioration of a patient with thyrotoxicosis within days or hours
of presentation and is associated with high mortality
Thyroid Storma rare life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis
Epidemiology of Thyroid Storm
Incidence of thyroid storm 057-076 100000 persons per year in
the US
Incidence among hospitalized patients 48-56 cases100000
persons per year
142-184 of patients hospitalized for thyrotoxicosis
Hospital mortality was 12-36 (higher in japanese series)
Galindo RJ et al Thyroid 2019 29 36-43
Akamizu et al Thyroid 2018 Jan28(1)32-40
Precipitants of Thyroid Storm
Akamizu et al Thyroid 2018 Jan28(1)32-40
Galindo RJ et al Thyroid 2019 29 36-43
Why does storm develop Is this a reasonable
question
Clinical manifestations of Thyroid Storm
Fever 42 in
japanese survey
56 reported in
literature
Tachycardia (76
gt130)
CHF (70)
CNS manifestations
(84)
agitation restlessness
delirium mental
aberrationpsychosis
somnolencelethargy
convulsion or coma
GI symptoms (70)
abdominal pain
Diarrhea
nauseavomiting
jaundice with liver
dysfunction
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Thyroid Storm
Thyroid storm is an endocrine emergency that is characterized by
rapid deterioration of a patient with thyrotoxicosis within days or hours
of presentation and is associated with high mortality
Thyroid Storma rare life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis
Epidemiology of Thyroid Storm
Incidence of thyroid storm 057-076 100000 persons per year in
the US
Incidence among hospitalized patients 48-56 cases100000
persons per year
142-184 of patients hospitalized for thyrotoxicosis
Hospital mortality was 12-36 (higher in japanese series)
Galindo RJ et al Thyroid 2019 29 36-43
Akamizu et al Thyroid 2018 Jan28(1)32-40
Precipitants of Thyroid Storm
Akamizu et al Thyroid 2018 Jan28(1)32-40
Galindo RJ et al Thyroid 2019 29 36-43
Why does storm develop Is this a reasonable
question
Clinical manifestations of Thyroid Storm
Fever 42 in
japanese survey
56 reported in
literature
Tachycardia (76
gt130)
CHF (70)
CNS manifestations
(84)
agitation restlessness
delirium mental
aberrationpsychosis
somnolencelethargy
convulsion or coma
GI symptoms (70)
abdominal pain
Diarrhea
nauseavomiting
jaundice with liver
dysfunction
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Epidemiology of Thyroid Storm
Incidence of thyroid storm 057-076 100000 persons per year in
the US
Incidence among hospitalized patients 48-56 cases100000
persons per year
142-184 of patients hospitalized for thyrotoxicosis
Hospital mortality was 12-36 (higher in japanese series)
Galindo RJ et al Thyroid 2019 29 36-43
Akamizu et al Thyroid 2018 Jan28(1)32-40
Precipitants of Thyroid Storm
Akamizu et al Thyroid 2018 Jan28(1)32-40
Galindo RJ et al Thyroid 2019 29 36-43
Why does storm develop Is this a reasonable
question
Clinical manifestations of Thyroid Storm
Fever 42 in
japanese survey
56 reported in
literature
Tachycardia (76
gt130)
CHF (70)
CNS manifestations
(84)
agitation restlessness
delirium mental
aberrationpsychosis
somnolencelethargy
convulsion or coma
GI symptoms (70)
abdominal pain
Diarrhea
nauseavomiting
jaundice with liver
dysfunction
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Akamizu et al Thyroid 2018 Jan28(1)32-40
Precipitants of Thyroid Storm
Akamizu et al Thyroid 2018 Jan28(1)32-40
Galindo RJ et al Thyroid 2019 29 36-43
Why does storm develop Is this a reasonable
question
Clinical manifestations of Thyroid Storm
Fever 42 in
japanese survey
56 reported in
literature
Tachycardia (76
gt130)
CHF (70)
CNS manifestations
(84)
agitation restlessness
delirium mental
aberrationpsychosis
somnolencelethargy
convulsion or coma
GI symptoms (70)
abdominal pain
Diarrhea
nauseavomiting
jaundice with liver
dysfunction
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Precipitants of Thyroid Storm
Akamizu et al Thyroid 2018 Jan28(1)32-40
Galindo RJ et al Thyroid 2019 29 36-43
Why does storm develop Is this a reasonable
question
Clinical manifestations of Thyroid Storm
Fever 42 in
japanese survey
56 reported in
literature
Tachycardia (76
gt130)
CHF (70)
CNS manifestations
(84)
agitation restlessness
delirium mental
aberrationpsychosis
somnolencelethargy
convulsion or coma
GI symptoms (70)
abdominal pain
Diarrhea
nauseavomiting
jaundice with liver
dysfunction
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Why does storm develop Is this a reasonable
question
Clinical manifestations of Thyroid Storm
Fever 42 in
japanese survey
56 reported in
literature
Tachycardia (76
gt130)
CHF (70)
CNS manifestations
(84)
agitation restlessness
delirium mental
aberrationpsychosis
somnolencelethargy
convulsion or coma
GI symptoms (70)
abdominal pain
Diarrhea
nauseavomiting
jaundice with liver
dysfunction
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Clinical manifestations of Thyroid Storm
Fever 42 in
japanese survey
56 reported in
literature
Tachycardia (76
gt130)
CHF (70)
CNS manifestations
(84)
agitation restlessness
delirium mental
aberrationpsychosis
somnolencelethargy
convulsion or coma
GI symptoms (70)
abdominal pain
Diarrhea
nauseavomiting
jaundice with liver
dysfunction
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Making The diagnosis of thyroid storm
From the american thyroid association guideline on the Dx and mgmt of hyperthyroidism
ldquoThe diagnosis of thyroid storm should be made
clinically in a severely thyrotoxic patient with
evidence of systemic decompensationrdquo
ldquoAdjunctive use of a sensitive diagnostic system
should be consideredrdquo
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Burch-Wartofsky Point Scale
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Japanese Thyroid Association
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Treatment of Thyroid Storm
Aggressive treatment designed to maximally target areas of
interventions
block thyroid hormone secretion and synthesis
Block the peripheral action of thyroid hormone at the tissue level
Provide the patient with systemic support
Treat precipitatingintercurrent illness
Possibly to provide definitive therapy
Ross et al Thyroid 2016 Oct26(10)1343-1421
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Ross et al Thyroid 2016 Oct26(10)1343-1421
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Inhibiting Thyroid Hormone
production and release
1 Methimazole or Propylthiouracil
2 Iodine
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Which to use Methimazole or PTU
1 ATA guideline for hyperthyroidism recommends everyone be on
methimazole except during the 1st trimester of pregnancy and
thyroid storm
a JTA recommends methimazole over PTU in storm
2 Dosing of Propylthiouracil in thyroid Storm
a 500-1000 mg load followed by 250 mg every 4 hours
3 Dosing of Methimazole in Thyroid Storm
a 60-80 mgday or 20 mg po every 6-8 hours
Ross et al Thyroid 2016Oct26(10)1343-1421
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Provide Data on reduction of T 3 with PTU
over MMI
Abuid et al The Journal of Clinical
Investigation Volume 54 July 1974 201-
208
13
45
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Parenteral use of Anti-thyroid Drugs none are FDA approved
Water-suspension enema preparation
1 grinding eight 50-mg tablets of PTU and suspend it in 90 mL of sterile water
1 The suspension was administered by a disposable urinary catheter via rectum
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Inorganic Iodine (SSKI or Lugolrsquos)
Acutely Inhibits release of thyroid hormone
Blocks production of new hormone wolff-Chaikoff effect
SSKI 5 drops (250 mg) mixed with water or juice every 6 hours
dosed 1 hr after dose of ATD Case reports of this give per rectum as well
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Inhibiting T4rarrT3 conversion
PTU
glucocorticoid therapy
use of b-adrenergic blocking agents such as propranolol with
selective ability to inhibit type 1 deiodinase
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Blocking End Organ Effects of thyroid hormone
1 Beta Blockers
1 Corticosteroids
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Which Beta Blocker
Propranolol
1 Most recommended and blocks T4--gtT3 conversion at high doses
2 Typically given 60-80 mg every 6 hours orally but can be give IV 05-
1 mg IV every 3 hours
Problems with propranolol
1 Half life of 3-4 hours
2 Has been associated with cardiovascular collapse(12)
3 Non-selective so is Contraindicated in severe asthma
1 Dalan et al Cardiovascular collapse associated with beta
blockade in thyroid storm Exp Clin Endocrinol Diabetes
115 392-396
2 Abubakar et al J Investig Med High Impact Case Rep
2017 Oct-Dec 5(4)
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Esmolol
1 Ultrashort acting so facilitates titration
a Beta 1 selective with a half-life of 8 minutes
2 Lower risk of cardiovascular collapse
3 Dosing 250-500 mcgkg load then 50-100 mcgkgmin infusion
4 Recommended as first line by the Japanese Thyroid association due
to concern over possible increased risk of circulatory collapse with
propranolol
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Plasmapheresis
Simsir et al Endocrine (2018)
62144ndash148
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Goals after storm
1 Definitive therapy
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Myxedema coma
httpfamilymedicinehelpcomwp-contentuploads201007myxedemajpghttpwwwhxbenefitcomwp-contentuploads201201Myxedema-pictures-before-and-afterjpg
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Epidemiology
- Incidence rate of 0221000000 per year
Rodriguez et al J Endocrinol 2004
Feb180(2)347-50
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Clinical Presentation
Classic presentation is an elderly woman with a hx of hypothyroidism
found in winter with altered mental status and hypothermia
1 80 of cases seen in women gt 60 years old
2 Generally occurs in winter months
Cardinal Manifestation
- Hypothermia (often profound to 80 F)
- Impairment of consciousness
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Precipitating Factor of myxedema Coma
1 LT4 withdrawal
2 Amiodarone
3 Lithium
4 Anesthetic
5 Tranquilizers
6 sunitinib
Infection
1 CVA
2 TraumaLow Temperature
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
CNS manifestations of Myxedema Coma
Gish et al BMJ Case Rep 2016
Jun 28201
disorientation
depression
Paranoia
hallucinations =
myxedema madness
cerebellar
signs
- abnormal findings on
electroencephalography
- Status epilepticus
Coma
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Cardiovascular Manifestations
Ueda et al Endocrine Journal 2019 66 (5) 469-474
Typical ECG changes
bradycardia varying degrees of
block low voltage
flattenedinverte T waves Pericardial effusion
Impaired cardiac
contractility with
reduced stroke
volume and CO
prolonged Q-T
interval
torsades VT
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Respiratory manifestations
Depressed hypoxic
resp Drive
Depressed
ventilatory
response to
hypercapnia
Upper airway
obstruction
Evidence-Based Critical Care pp 447-450
Med Clin North Am 2012 Mar96(2)385-403
Reduced tital volume
due to pleural effusion
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Hematologic manifestations
Increased risk of
bleeding due to1 Acquired VW
syndrome type 1
2 Deficiency in factors V
VII VIII
IX and X
DIC associated with
sepsis (increased risk
due to immune defects) Anemia is a common
Med Clin North Am 2012 Mar96(2)385-403
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Diagnosis
1 It is a clinical Diagnosis using the features described previously plus
assessment of hormone values
1 Thyroid hormone values a T4 is typically very low to undetectable
b TSH might not be as high due to HPT axis suppression (critical illness) or pituitary
disease causing hypothyroidism
i Ie central hypothroidism will have very low to undetectable TSH
Med Clin North Am 2012 Mar96(2)385-403
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Prospective case series of 11 patients
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Treatment questions
LT4 T3 LT4 + T3
What is optimal Dose
IV or PO
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Monotherapy
with T3 alone
at levels gt 75
mcg
Monotherapy
with LT4 gt
500 mcgday
associated
with
increased
mortality
Yamamoto et al
thyroid 1999
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Treatment of myxedema coma
Per the American Thyroid Association Guidelines
1 200-400 mcg of LT4 given IV as a loading dose with lower doses for
smaller or older patients
a A daily dose of 16 mcgkg x 075 IV
2 Use of T3 (liothyronine)
a Loading dose of 5-20 mcg follow by 25-10 mcg every 8 hours
3 Stress dose steroids should be given in the treatment of myxedema
(200 mg of IV hydrocortisone per day or 50 mg IV q 6 hours)
Jonklaas Bianco et al Thyroid 24(12) 1670-1751
2014
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Supportive care in the ICU
Ventilatory support
Is most important supportive measure in this illness
Careful warming to correct hypothermia
Management of bradycardia and hypotension
Hyponatremia
Glucocorticoid therapy
Routine use of antibiotics is controversial but suggested
by some and should be strongly considered
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Therapeutic Endpoints
- improved mental status
- improved cardiac function
- improved pulmonary function
- Measurement of thyroid hormones every 1ndash2 days
- While optimal levels for serum TSH and thyroid hormones are not well
defined failure of TSH to trend down or for thyroid hormone levels to improve
could be considered indications to increase levothyroxine therapy andor add
liothyronine therapy
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012
Prognosis
Factors associated with death in myxedema coma
1 Older age
2 Persistent bradycardia
3 Symptomatic hyponatremia
4 Lower degree of consciousness
5 Multi-organ impairment
Most common causes of death are respiratory failure sepsis and GI bleeding
Klubo-Gwiezdzinska et al Med Clin
North America 2012