hypo- and hyperthyroidism -...

HYPO- AND

HYPERTHYROIDISM

Esztella Mikolás MD

Semmelweis University

2nd Department of Medicine

Anatomy

https://healthjade.com

Histology

http://www.proteinatlas.org

Thyroxin synthesis and excretion

Production is regulated by TSH (thyroid-stimulating hormone) level and iodine supply

Häggström, Mikael (2014).

"Medical gallery of Mikael

Häggström 2014". WikiJournal of

Medicine 1 (2). DOI:10.15347/wj

m/2014.008. ISSN 2002-4436

Regulation of thyroid hormone secretion

Hypothalamic-pituitary-thyroid axis

From the collection of Dr Sheikh-Ali

Physiological effects

thyroid hormone receptors (nuclear):

TR-alpha 1: widely expressed (heart, skeletal muscles, bone)

TR-alpha 2: antagonistic

TR-beta 1: brain, liver, kidney

TR-beta 2: pituitary gland, hypothalamus

increase basal metabolic rate and thermogenesis

stimulate water- and electrolyte transport

accelerate the substrate-turnover, the amino acid and lipidmetabolism

potentiate the effect of catecholamine compounds

regulate growth and neurological development

TSH - thyroid

stimulating

hormone

normal range: 0.45-4.12 mU/l

depends on age, iodine supply, BMI, pregnancy, ethnicity, test method, etc.

www.synthroidpro.com

T3 and T4

Biologically active portion:

FT4 (free T4) ~0,015%

FT3 (free T3)~0,33%

normal range:

FT4: 12-22 pmol/l

FT3: 2.5-6.5 pmol/l

T3 is 2-10-fold more potent

Binding proteins: thyroxine binding protein,

transthyretin, albumin

http://www.anaesthetist.com

Conversion

Deiodinase 1:

expressed mainly in liver and kidney, with lesser expression in the thyroid

Produces small amount of circulating T3 (approx. 24%)

Preserves iodide by removing iodine from inactive metabolites of T3 and T4 in the liver and

kidney

Deiodinase 2:

central nervous system, pituitary gland, thyroid, heart,

brown adipose tissue, and skeletal muscle

T4=>T3 conversion (approx 60%)

Deiodinase 3:

brain and skin

T4=>T2

T4=>rT3

Pol et al, DOI: 10.1007/s10741-008-9133-7

HYPOTHYROIDISM

Definition and frequency

subclinical hypothyroidism: elevated TSH, normal FT4

prevalence: 4-10%

manifest hypothyroidism: elevated TSH, low FT4

prevalence: 0,2-1%

secondary hypothyroidism: elevated/normal/low TSH,low/normal FT4

Clinical symptoms

general: fatigue, headache, cold intolerance, weight gain, anemia

cardiac: pericardial fluid, heart contractility and pulse rate decrease,

but hypertension (peripheral resistance increases)

metabolic: dyslipidemia, hyponatremia

GI tract: constipation, dysphagia

skin: pale, cold, atrophic, myxedema, hair loss, weak, fragile nails

neurological: ataxia, dementia, cognitive dysfunction, hypo-areflexia

respiratory system: hypoventilation, sleep apnea

reproductive system: amenorrhea, decrease of sex drive, infertility,

hyperprolactinemia

musculoskeletal: elevation of creatin-kinase, myopathy, myalgia,

rhabdomyolysis

Etiology

primary hypothyroidism (99%):

autoimmune thyroiditis

iatrogenic (radioiodine

treatment, surgery,

amiodarone)

congenital

iodine insufficiency

malignancy

transient (Wolff-Chaikoff effect,

thyroiditis, thyreostatic

treatment, Li-carbonate, IF-

alpha, IL-2)

secondary hypothyroidism:

pituitary

tertiary hypothyroidism:

hypothalamic origin

thyroid hormone

resistance

http://wikiwel.com/wikihealing//images/d/df/Hypothyroidism.jpg

Diagnostic protocol

aspecific symptoms (elderly!)

history: previous irradiation, thyreostatic treatment,

amiodarone, surgery

TSH, if out of normal range FT4

thyroid specific antibodies

neck ultrasonography

www.med-ed.virginia.edu

Treatment I.

Main goals (ATA 2014):

to provide resolution of the patients' symptoms and

hypothyroid signs, including biological and physiologic

markers of hypothyroidism

to achieve normalization of serum thyrotropin with

improvement in thyroid hormone concentrations

to avoid overtreatment (iatrogenic thyrotoxicosis), especially

in the elderly.

Treatment II.

When to treat:

manifest hypothyroidism

subclinical hypothyroidism:

TSH>10 mU/l

goiter

ischemic heart disease

pregnancy

aTPO positivity

older than 70, TSH>8 mU/l + any of above

symptomatic disease

Treatment III.

levothyroxine (L-T4): 1.6-1.8 µg/kg (75-150 µg)

T1/2 : 7-8 days => orally once daily

absorbed only at low pH value => 30 min before meal

start with lower dose, especially in elderly and/or in case of

cardiac disease (25-50 µg)

first TSH control after 4 weeks

TSH control 6 weeks after every dose adjustments

if stable - yearly

Pregnancy

placental deiodinase => ~45% higher L-T4 dose needed

trimester specific target values:

1st: 0.1-2.5 mU/l

2nd: 0.2-3.0 mU/l

3rd: 0.3-3.0 mU/l

subclinical cases have to be treated

closer TSH control

screening in case of aTPO or aTG positivity, autoimmune history,

goiter, any relevant symptoms present, positive family history,

radioiodine therapy, surgery, miscarriage

routine screening?

Elderly I.

Age-Specific Distribution of Serum Thyrotropin and Antithyroid Antibodies in the U.S. Population: Implications for the Prevalence of Subclinical Hypothyroidism Martin I. Surks, and Joseph G. Hollowell J Clin Endocrinol Metab DOI:

http://dx.doi.org/10.1210/jc.2007-1499

Elderly II.

sensitivity of feedback mechanism decrease with age

alteration of biological activity of TSH

decrease of thyroidal sensitivity to TSH

apathetic hyperthyroidism

Thyroiditis

acute

infective thyroiditis

radiation-induced thyroiditis

palpation-induced thyroiditis

subacute

de Quervain thyroiditis

painless thyroiditis

drug induced (amiodarone, alpha-interferon, IL-2)

chronic

Hashimoto-thyroiditis

infective thyroiditis (immunodeficiency)

De Quervain thyroiditis

(subacute granulomatosis thyroiditis)

etiology: viral infection (?)

female:male=5:1

clinical signs: myalgia, fatigue, thyroid is painful, swollen

laboratory markers: high sedimentation rate, elevated CRP,elevated TG level, moderate leucocytosis

low 24 hour radioiodine uptake

hyper-, eu-, hypothyroidism, euthyroidism

therapy: NSAID, corticosteroids, propranolol

recovery in 3-6 months

short term relapse ~20%, long term relapse ~4%

Hashimoto thyroiditis

organ-specific autoimmune disease => 90% follicular destruction => chronichypothyroidism

female: male=10:1

prevalence: 2-7% (female)

histology: infiltration of lymphocytes, Hürtle-Askanazy cells, follicular destruction, fibrosis(FGF-23)

aTPO and aTG positivity >95%

laboratory markers: sedimentation, CRP mildly elevated

radioiodine uptake: „salt and pepper” pattern

clinical signs: mild thyroid enlargement, sensitivity, transitional hyperthyroidism,permanent hypothyroidism, rare endocrine orbitopathy

therapy: levothyroxine substitution (50-200 µg)

TSH target: 2.5 mU/l

prednisolon in acute phase if necessary

Normal

Hashimoto-thyroiditis De-Quervain-thyroiditishttp://www.ultrasoundcases.info

Congenital hypothyroidism

hypothyroidism is present at birth

incidence:

primary form: 1:3000-5000

secondary form: 1: 10 000

more frequent in girls and twins

in Hungary screened since 1984

only 1/3 of the world is screened!

Orphanet Journal of Rare Diseases20105:17

https://doi.org/10.1186/1750-1172-5-17

HYPERTHYROIDISM

Definition

subclinical hyperthyroidism: low TSH (0.1 mU/l>), normal FT4

manifest hyperthyroidism: low TSH (0.1 mU/l>), high FT4

prevalence: ~0.75%

secondary hyperthyroidism: elevated/normal TSH, elevated

FT4

Clinical symptoms general: weakness, fatigue, high body temperature, hot

intolerance, weight loss with good appetite, resting tremor

skin: warm, wet skin, intense sweating

cardiac: tachycardia, systolic blood pressure elevation, lower

diastolic pressure, positive inotropic effect

metabolic: high metabolic rate

GI tract: diarrhea

neurological: tremor, hyperactivity

respiratory system: hyperventilation

reproductive system: irregular period, amenorrhea,

sex hormone binding protein

musculoskeletal: muscle weakness

Etiology

Thyroid hormone overproduction

TSH-receptor stimulation

Graves-Basedow-disease

mola hydatiosa

choriocarcinoma

TSH overproduction

TSH-producing pituitary adenoma

thyroid hormone resistance

Thyroid autonomy

toxic adenoma

toxic multinodular struma

Unregulated hormone excretion

subacute

Hashimoto

silent (painless) thyroiditis

postpartum

iodine induced

Extra thyroidal hormone production

DTC

struma ovarii

Factitious hyperthyroidism

Diagnosis I.

Anamnesis and physical examination

Laboratory markers:

low TSH, elevated FT4 and FT3 levels

TSH can remain low for months after treatment

FT4 and FT3 indicate severity better

„grey zone TSH” 0.1-0.3 µU/l => repeat test 1-3 months later

Diagnosis II.

Radiology:

ultrasonography (hypervascularisation, nodules)

99mTc gamma scan

low uptake => thyroiditis

high uptake => Graves-Basedow disease

focal high uptake => toxic adenoma

Graves-Basedow disease

incidence: 5-10/100 000

20-40 year-old female patients

TSH-receptor stimulating IgG antibody (TSHR-Ab) in half of all cases

genetic predisposition: HLA-A1, -B8, DR3

physical signs: thyroid can be enlarged, look for signs of EOP or

pretibial myxedema

Graves-Basedow disease -> Thyroid inferno pattern

(increased vascularity and arteriovenous shunting)www.radiopaedia.org

Gamma scan

Treatment I.

Thyreostatic treatment – thionamides

thiamazol (methimazol)

20-60 mg/die => dose reduction

continue for at least one year in euthyreotic state

TSH in every 6-8 weeks

propylthiouracil (PTU)

150-400 mg/die => dose reduction

carbimazol

Side effects

agranulocytosis 1:1000 => radioiodine or surgery

ANCA positive vasculitis

fulminant hepatitis (PTU)

Treatment II.

Radioiodine (RI) treatment

131I-isotope orally – dose: 70 Gy

expected to be effective in 2-6 months

in case of severe, active EOP RI is contraindicated!

preventive corticosteroid for 6-12 weeks in risk groups (smokers, EOP in

history, 35-55-year-old females)

Subtotal thyroidectomy - indications

Basedow-Graves disease + cold thyroid nodule

RI not possible

size reduction needed

Endocrine orbitopathy I.

inflammation of the orbital tissue and ocular muscles

10-30% present in Basedow-Graves disease

TSH-R is expressed on orbital fibroblasts => lymphocyte and macrophage

activation => increase of glycosaminoglycan and sulphated

mucopolysaccharide formation

edema, thickening of orbital muscles, exophthalmos

smoking increases risk by 70%!

diagnosis: MRI T1 - muscle thickening

ATA classification

clinical activity score

Endocrine orbitopathy II.

treatment indications: loss of sight, subluxation of eyeball, change in color

sight, cornea blurriness, progressive exophthalmos, papillary edema,permanently visible cornea

treatment:

euthyreosis

avoidance of smoking

immunosuppression – corticosteroid (per os or iv)

pentoxyphyllin

selenium

retrobulbar irradiation (contraindicated in diabetes mellitus)

surgical decompression

antalgic treatment

Toxic adenoma (TA)

hot nodules on gamma camera

malignancy is extremely rare

compensated TA: normal thyroid tissue function decreases

decompensated TA: normal thyroid tissue is completely suppressed

subclinical cases have to be treated

therapy: RI 300 Gy

radio ablation

laser ablation

surgery

www.memorangapp.com

Toxic multinodular goiter

mainly in older age

can be contrast- or drug induced

therapy: RI 150 Gy (contraindication: significant trachea compr.)

surgery

Kamal A.S. Al-Shoumer, Hossein Gharibentokey.com

THYROID EMERGENCIES

Thyreotoxicosis (thyroid storm)

potentially life threatening condition

provoking factors: RI treatment, surgery, trauma, myocardial infarction, iodine

exposition

symptoms: fever, sweat, flush, tachycardy, cardiac failure, vomiting, diarrhea, loss

of conciousness, coma

FT3 and FT4 is increased but not extreme

Treatment

thyreostatic treatment (thiamazole 80 mg per day/ PTU 250 mg/6 hours)

iodine compounds (Lugol iodine or potassium iodine)

glucocorticoids

beta-blockers

sedatives

Myxedema coma

multi organ failure

more common in elderly

symptoms: severe myxedema, hypotension, bradycardia, low body temperature,

hypoventillation (CO2-retention), SIADH, convulsion, coma

treatment: iv 500 µg levothyroxine (or 25-50 µg T3 every 12 hours)

100 µg levothyroxine per day

5-10 mg/hour hydrocortisone

hyperosmolar fluids only

THANK YOU FOR YOUR ATTENTION!