JANUARY, 2010DEEPIKA REDDY, MD

Adrenal and Thyroid Diseases

( seen in acutely ill patients)

Case 1

The patient is a 22 year with no prior medical history. About 6 weeks prior to coming to the ER she started to have palpitations, tremors and diarrhea. She also reports 25 lb weight loss over the past 2 months. She presented to the emergency room with, nausea/vomiting and abdominal pain.

She also complained of an inability to catch her breath

She vomited 10 times in 24 hours

Case 1

On physical exam, her temp was 101.5 F. Her HR was 120. BP 130/90

She was thin, skin was warm to touch. Mild bilateral proptosis

Thyroid was diffusely enlarged, soft, no nodules

Heart: tachycardic but regular, no murmurs.Lungs CTA, no crackles, no wheezesAbdomen: minimal discomfort on abdomen

palpation, not localizedExt: mild edema, tremors of hands

Case 1

Labs’: TSH was undetectableFT4 : 7.72 (.76-1.46)WBC 3.2, Hgb 11.4LFTs normal

Signs and symptoms of Thyrotoxicosis

Neuropsychiatric/Neuromuscular Emotional lability Anxiety Confusion Coma Muscle wasting Hyperreflexia Fine tremor Periodic paralysis

Gastrointestinal Diarrhea

Reproductive Oligomenorrhea Decreased libido Gynecomastia Spider angiomas

Thyroid gland Neck fullness Tenderness Diffuse enlargement Bruit

Signs and symptoms of Thyrotoxicosis

Cardiorespiratory Palpitations Dyspnea Chest pain Atrial fibrillation Sinus tachycardia Hyperdynamic precordium Congestive heart failure

Dermatologic Hair loss Pretibial myxedema Warm, moist skin Palmar erythema

Ophthalmologic Diplopia Eye irritation Exophthalmos Ophthalmoplegia Conjunctival injection

NOTE: Elderly patients may not have the classic symptoms: Apathetic hyperthyroidism

Lab Findings in Thyrotoxicosis

Hyperglycemia (catecholamines reduce insulin secretion)

Hypercalcemia ( due to dehydration, increased bone resorption)

Increased LFTsIncreased alkaline phosphatase

Diagnostic Criteria for Thyroid Storm

Thermoregulatory dysfunction Temperature 99–99.9 5 100–100.9 10 101–101.9 15 102–102.9 20 103–103.9 25 R104.0 30

Central nervous system effects Absent 0 Mild (agitation) 10 Moderate (delirium, psychosis, extreme lethargy 20 Severe (seizures, coma) 30

Gastrointestinal-hepatic dysfunction Absent 0 Moderate (diarrhea, nausea/vomiting, abdominal pain) 10 Severe (unexplained jaundice) 20

Diagnostic Criteria for Thyroid Storm

Cardiovascular dysfunction Tachycardia (beats/minute) 90–109 5 110–119 10 120–129 15 R140 25

Congestive heart failure Absent 0 Mild (pedal edema) 5 Moderate (bibasilar rales) 10 Severe (pulmonary edema) 15

Atrial fibrillation Absent 0 Present 10

Precipitating event Absent 0 Present 10

Diagnostic Criteria for Thyroid Storm

Scoring system: A score of 45 or greater is highly suggestive of thyroid storm; a score of 25–44 is suggestive of impending storm, and a score below 25 is unlikely to represent thyroid storm.

Endocrinol Metab Clin N Am 35 (2006) 663–686

Management: General Plan

Stop synthesis of new hormone within the thyroid

gland (anti thyroid drug ATD)Halt the release of stored thyroid hormone

from the thyroid gland ( iodide such as SSKI)Prevent conversion of T4 to T3 (ATD, beta

blocker, steroids)Control the adrenergic symptoms associated

with thyrotoxicosis (beta blocker) Control systemic decompensation with supportive therapy (steroids, acetominophen)

Decreased Synthesis of Thyroid hormone: Anti thyroid Medication

WHICH ONE IS BETTER? PTU

It is a Thiouracil: reduces synthesis of hormone and reduces T4 to T3 conversion

Short half life Associated with hepatitis and increased risk of hepatic

failure compared to methimazole . Onset of hepatic dysfunction variable and unpredictable

Also associated with agranulocytosis (0.37%) It is idiosyncratic and not dose related.

Can dose PO or rectally In storm, start at 200-300mg q6 hrs. The drug of choice in pregnancy.

Decreased Synthesis of Thyroid hormone: Anti thyroid Medication

Methimazole Is an imidazole: decreases synthesis of thyroid

hormone Longer half life Associated with hepatic dysfunction which is usually

cholestatic. Onset is variable and unpredictable Also see agranulocytosis (0.35%). It is dose dependent

and rarely seen in doses less than 40 mg a day. Can dose PO, rectally or IV In storm can give 80 – 100 mg a day in divided doses.

Halt Release of Stored Hormone from the Thyroid: IODIDE

Can be given in the form of Super Saturated Potassium Iodide (SSKI) or Lugols Solution

Lugols 4-8 drops q6-8 hrsSSKI 5 drops q6 hrsHAS TO BE GIVEN AFTER THE ATDWait at least 1 hourMax effect 7-14 days, if no other Rx given

patients will get toxic again in this time frame.

Block Conversion from T4 to T3

ATD (PTU)Beta BlockersGlucocorticoids

Glucocorticoids also treat relative adrenal insufficiency

Typically hydrocortisone 100 mg q8hrs If patient is elderly and worried about fluid retension

may try Decadron 2 mg IV q6 hrs

Control Adrenergic Symptoms

Beta Blockers Traditionally propranalol used. Large doses may be required. Start at 40mg

q8 hours titrate up to keep HR in 80’sCan use Esmolol, atenolol, metoprolol as well

Other agents

LITHIUM can be used if ATD allergy is encountered and surgery not an option

It reduces formation and release of thyroid hormone

Dose in thyroid storm 300 mg q8 hrsNeed to check Lithium levels and keep level

between 0.6 – 1.0CHOLESTYRAMINE : Reduces Thyroid

hormone absorption from gut.It can affect absorption of other medications

Supportive Care

Avoid salicylates: they cause decreased binding of thyroid hormones to proteins.

In atrial fibrillation, may need warfarin. If already on warfarin, may need to reduce dose due to increased clearance of Vit k dependent clotting factors.

Case 1 continued

The patient was started on ATD, SSKI, beta blockers, steroids

On day 3, she was noted to have a significant drop in WBC count specifically a drop in granulocyte percentage.

Surgery was consulted since she was still symptomatic. She was taken to the OR and had a sub total thyroidectomy

Surgical Option

When rapid control of thyrotoxicosis is required

When patients have allergies/side effects to ATD and need surgical intervention for thyrotoxicosis

Patients should be prepared with ATD ( if tolerated, iodide, steroids and beta blockers)

Case 2

The patient is a 33 year old African American patient with a past history of hypothyroidism presented with increasing lethargy and confusion reported by family. She had missed a clinic visit and did not get her thyroid medication refilled. She had been off levothyroxine for 4 months. She was seen about 5 months ago, at which point her TSH was 42, F T4 was .2

Now her TSH is 55 and FT4 is .23She has had weight gain 37 lbs in six months,

constipation, cold intolerance, amenorrhea for over a year. She recently had a URI. She has sleep apnea and was using her CPAP machine

Case 2

PhysicalBP 112/70, HR 64, Temp 96.5 Gen: Lethargic but arousableHEENT: skin / hair dry, Periorbital edema, facial

swelling. Significant swelling of the tongue, she did not completely close her mouth because of macroglossia

Lung: Good air movement in all lung fieldsHeart: Slow normal in rate, regularAbd: Obese, few BS, non tenderExt: swelling of lower extremitiesNeuro: drowsy but arousable, answering

questions appropriately.

Labs

ABG showed hypoxia and hypercapneaChemistry panel showed low glucose of 67

and Sodium was 129

Clinical Features of Myxedema

Lethargy and confusionHypothermiaBradycardiaReduced cardiac contractilityHypotensionHypoxia/ hypercapnia due to reduced

respiratory driveNausea/abdominal pain/reduced gastric

motilityElectrolyte abnormalities : hyponatremia,

Hyperkalemia

Management

Mortality rates highShould be in ICU settingAssess airway , May need mechanical ventilation.Dextrose and fluid resuscitation since may be

hypovolemicSteroids should be considered especially if

hypotensiveMay need hypertonic saline and lasix if

hyponatremia severeHypothermia should be corrected carefully since

it may result in hypotension.Also evaluate carefully for precipitating event

such as infection/ischemia

Management

Thyroid hormone replacement critical.Some controversy over the way in which to

replace the thyroid hormoneSome recommend large loading dose of T4 300-

500 mcg IV followed by 50-100mcg daily IVUse lower doses in the elderly with

cardiovascular diseaseSome suggest that the T4 to T3 conversion is

impaired in the severely ill. They suggest T3 IV upto 20 mcg, the 2.5 -5 q6 hrs

Management

Can switch to PO levothyroxine after the patient has a bowel movement.

Extubate only when patient has shown significant improvement. Wait till patient regains conciousness.

Monitor closely till vitals, cardio-respiratory status, neurologic and GI symptoms improve.

Case 2

Our patient was watched in the progressive care unit

On Bipap for her respiratory difficultiesGiven ‘loading dose’ of 200 mcg of

Levothyroxine IV. Then 100 mcg a day IV till she had a bowel movement then switched to a weight based dose ( 1.5 x weight in KG) Received dextrose, IVF.

Clinically improved over the next 3-4 days

Case 3

A 78 year old gentleman presented to the ER with N/V , loose stool, confusion over 24 hrs. In ER noted to have hypotension 70/50.

Relevant past history: Has had a GH secreting pituitary macroadenoma resected 30 years earlier. He was on Pred 5 mg a day. He had recent ( 2 weeks ago ) been to the dentist who noted he had an oral infection and given him and antibiotic. About 2 days prior to admission he started to have loose stool and over 24 hr had the rest of symptoms develop. He had not changed his does of steroid during this time

Labs: mild hypoglycemia, hyponatremia and elevated WBC count.

Case 3

PE: BP 78/60, HR 115 Temp 101.3 sats OKGen : Confused, not oriented. Unable to get any

history.HEENT: pupils were reactive to lightLungs: good air movement and clear to

ausculatationCardiac : tachycardic no murmursAbd : distended, tender, mostly lower quadrantsSkin: dry, no hyperpigmentationRest of exam unremarkable.

Who presents in adrenal crisis?

Patients with undiagnosed chronic adrenal insufficiency who have a ‘stressful event’ such as an infection. Or recent event such as bilateral adrenal hemorrhage

Patients with known primary adrenal insuffieciency who did not received adequate glucocorticoid replacement. Like this patient.

There are instances where patients with secondary adrenal insufficiency present in crisis such and pituitary infarction.

Presenting features of adrenal crisis

ShockAbdominal tenderness, N/VPsychiatric manifestations: confusion, delirium,

stuporFeverHyperpigmentation, vitiligo, Evidence of androgen deficiency in women with

primary Adrenal insufficiencyHypoglycemia ( more common in secondary

adrenal insufficiency)Electrolyte abnormalities

Primary low NA and high K Secondary may have low Na due to vasopressin excess but K

is usually normal

Evaluation of adrenal function in a patient with hypotension

Evaluation of adrenal function (which test to use)

Does the patient have primary or secondary adrenal insufficiency?

Evaluation of etiology if diagnosis has been confirmed

Are there other medical issues that need to be treated

Long term management of adrenal insufficiencyInterpretation of the test (does the test work as

well in acutely ill patients?)

Evaluation

Before Evaluation, ensure patient is stableIf a patient is in shock treat with steroid

earlyUse Decadron since it does not interfere with

the testingHydrocortisone interacts with cortisol assay

and therefore should be avoided prior to testing

Evaluation: ACTH Stim Test( Make sure this is done right!!)

Draw baseline ACTH and cortisol. Note the ACTH should be in a EDTA tube and kept on ice!

Then give Cosyntropin 250 mcg IV over 1 minDraw cortisol 30 min and 60 min laterInterpretation: cortisol level of at least 18-20

at either 30-60 min indicates normal studyNote if the patient has been given ANY

steroid this will affect ACTH levels

Assess level of defect/Etiology

The ACTH level ( if done before any steroids are given) can help separate primary from secondary adrenal insufficiency.

In adrenal crises, treat first if testing non – diagnostic or equivocal. Can figure out level of defect once patient is stable

Look for clues : History of head trauma/radiation post partum : severe headache, hypotension: think

sheehans On anicoagulation: ? Bilateral adrenal hemorrageInfections: such as HIV may have primary adrenal

insufficiencyEvidence of other pituitary hormone deficiency can be

done when patient is stable.In our patient: insufficient steroid when ill

Management

1)Treat with IV glucocorticoid Decadrone 2-4 mg IV before the study, Hydrocortisone after the study 100 mg IV q8hrs

2) Continue with IVF3) Look for etiology and treat as needed

Case 3

Rapid improvement in mental status and cardiovascular complaints after steroids were given.

He was diagnosed with toxic megacolon due to clostriduim difficile.

Was advised on increasing steroid doses when ill

2-3 times normal daily dose. Decaron emergency Kit if he has N/V. ER if unable to control any other way.

Special considerations in acutely ill patients

(patients in septic shock)

A systemic review (Annane et al JAMA 2009, 301 (22) 2362-2375) demonstrated that glucocorticoids do not affect 28 day mortality in patient with sepsis (including those in shock)

A sub group analysis showed that low dose, longer duration of glucocorticoids may have mortality benefit

Special considerations in acutely ill patients

The ACTH stimulation test may not reflect adrenal function in acutely ill patients since hypoproteinemia can affect total cortisol levels.

Current recommendations suggest that low dose glucocortcoids may be considered in patients with hypotension, on fluids and vasopressors who do not respond to these measures