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Hypothyroidism

Hypothyroidism. By: Elias S. Hypothyroidism. A common disorder associated with thyroid hormone deficiency resulting from a defect anywhere in the hypothalamic-pituitary-thyroid axis Majority  primary thyroid D. Less common TSH , TRH Prevalence U.S. NHANES III on 17353 persons

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Hypothyroidism

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  1. Hypothyroidism By: Elias S.

  2. Hypothyroidism • A common disorder associated with thyroid hormone deficiency resulting from a defect anywhere in the hypothalamic-pituitary-thyroid axis • Majority  primary thyroid D. • Less common TSH , TRH • Prevalence • U.S. NHANES III on 17353 persons hypothyroidism… 4.6% (subclinical 4.3%, overt 0.3%) • international 2-5% ( to 15% by the age of 75) • Autoimmune Hypothyroidism annual incidence: 4/1000 women, 1/1000 men

  3. Prevalence cont……. • Age: … with age • More prevalent in elderly • Autoimmune hypoth.- Mean age at Dx- 60. • sex: women >(5-8x) Men Framingham study in adults>60yrs 5.9%-women 2.4%- men Race: more common-Japanese NHASESIII, U.S whites(5.1%)>Hispanic A.(4.1%)>African A(1.7%)

  4. causes • Worldwide: • iodine deficiency most common cause • In areas of iodine sufficiency • Autoimmune thyroiditis (Hashimoto’s) • Iatrogenic causes • Hypothyroidism - Primary H. - Central (secondary/tertiary) • Primary hypothyroidism – 2 forms Subclinical  Overt( clinical) (TSH, N FT4,N FT3) (TSH, FT4,FT3)

  5. Autoimmune hypothyroidism • Ch. Autoimmune thyroiditis (Hashimoto’s thyroiditis) • Caused by cell-and Ab mediatd destruction of thyroid tissue • Both humoral and cellular factors contribute • Cytotxic T cells • Auto Abs.. TPO 95%, Tg 60%, TSH-R bloking Ab 20%, TBII 10-20% • Two formsHashimoto’s(goitrous)thyroiditis Atrophic thyroiditis

  6. Hashimotos (goitruos)thyroiditis Marked lymph.infiltration Atrophy of thyroid follicles with absence of colloid Mild to moderate fibrosis Present with goiter Minimal or no Sx Atrophic thyroiditis  fibrosis Less lymph. infiltration Thyroid follicles completely absent Late stage of Hashimotos thyroiditis Minimal residual thyroid tissue Overt symptoms

  7. Risk factors • Genetic suseptibility • Polymorphism in: HLA DR3,-DR4,-DR5 • CTLA-4(a T-cell regulating gene) •  in down’s S., Turners S. • Env. Factors • High iodine intake • infection: congenital rubella s. - autoimmune H. • Cigarette smoking

  8. Iatrogenic causes • Thyroidectomy • 1-4wks after total thyroidectomy • In the 1st yr in the majority of subtotal t.  If euthyroid at one year, 0.5-1% chance of hypothyroidism each year • Radioiodine(I-131)therapy • Months to yrs later • Dose dependant • External neck/Total body irradiations • Anti-thyroid drugs (over Rx of Hyperth.)

  9. Other causes • Iodine deficiency • Iodine excess (the wolf-chaikoff effect) • Drugs – Ethanolamine, Lithium, Amiodarone, INF-alpha, IL2 • In Hypothyroid P’ts taking T4: Chlestyramine,Iron salts - T4 absorption Rifampin, Phenytoin,Carbamazepin- clearance Amiodarone, glucocotricoids - conversion of T4T3

  10. Other causes cont… • Infiltrative diseases – rare • Fibrous thyroiditis(reidel’s th.),hemochromatosis,scleroderma, leukemia,amyloidosis • Infections: Tbc., P.carini • Subacut thyroiditis (De-quervain’s,granulomatous) • Silent(painless)thyroiditis –postpartum th. ESR -ve TPOAB Normal ESR, +TPOAb

  11. Secondary/tertiary Hypothyroidism(Central) • <1% • TSH or TRH • Dx – inappropriatly low(low or N. TSH) low T4 and T3 • Causes • Hypopituitarism(tumor,surgery irradiation,sheehan’s s.,hypophysitis) • Mutations in TSH/TSH-R gene • Hypothalamic Damage (tumor,trauma,radiation,inf. D.) • Mutations in TRH-R gene • Drugs – Dopamine, lithium • Dx - MRI

  12. Congenital hypothyroidism • 1:4000 newborns • Thyroid g. agenesis 80-85% • Inborn errors of thyroid H. synthesis 10-15% • TSH-R Ab mediated(Moinfant) 5% • Anti-thyroid (Moinfant) • Majority – appear normal at birth • <10% - prolonged jaundice,feeding problem,hypotonia,enlarged tongue,delayed bone maturation, unblical H., cong.Malf. • Permanent neurologeic D. – if Rx is delayed

  13. Neurologic manifestations • Mental state, poor concentration • Poor memory , emotional lability • Carpal tunnel S. (25-30%) • Cerebellar ataxia (10-30%) • Peripheral neuropathy • Proximal muscle weakness • Hashimoto’s encephalopathy • Myxedema coma

  14. Metabolic Abnormalities • Hyponatremia • Hyperlipidemia (LDL, cholesterol) • Hyperuricemia (Gout) • serum creatinin • carotenemia •  drug clearance drug toxicity

  15. High TSH 1° hypothyroidism Non-thyroidal illness(5%) Drugs: Dopamin antagonists, Amiodarone, cholecystographic dyes TSH-producing pit. Adenoma Adrenal insufficiency Thyroid homone resistance S. Low TSH 1° Hyperthyroidism Incomplete recovery from Hyperthyroidism Non-thyroidal illness (10%) High HCG (early pregnancy, molar P., choriocarcinoma) Central hypothyroidism Drugs: Dopamin, Glucocorticoids Somatostatin analogues Phenytoin disorders that affect TSH

  16. Other investigations • CBC, ESR • OFT, Electrolytes • Lipid profile • Uric acid • FNA • Central hypothyroidism • Imaging studies(sellar/supracellar) • Other hormonal profiles (pituitary)

  17. Treatment • Most P’ts …. Require lifelong Rx • The Goals Restoration of euthyroid State Reversion of Sx &Sns Reduction of gotre • Rx thyroid hormone replacement • Synthetic thyroxin(T4) • A pro-hormone, 80% absorbed • Active hormone production controlled by the patient’s own physiologic Mech. • Long half-life(7days) • Once daily when steady state is reached • Should be taken in an empty stomach

  18. Replacement dose • Adults <60 with out evidence of Heart D. • 1.6 mcg/kg/day (50-150) • Older p’ts , p’ts with CHD • 1/2-1/4 of the dose(25-50mcg) • P’t evaluation every 3-6wks • Measure T4(early phase), TSH • Dose adjustment by 12.5-25 ( or ) • Once steady state is reached • Maintenance dose, yearly evaluation with TSH

  19. Additionaladjustment • dose: Pregnancy Estrogen Rx Nephrotic syndrom coadministration of drugs that clearance orabsorbtion • dose: elderly marked w’t loss androgen therapy

  20. ?T3 ?T3+T4 • Not recommended • Wide fluctuations of serum T3 conc. • Multiple daily doses • Serum T4 remains low • T3+T4 therapy • For some hypothyroid p’ts who remain symptomatic despite Rx + normal TSH • Meta-analysis of 11 trials  No benefit

  21. Central Hypothyroidism • Think of other hormonal deficiencies • T4 Rx to p’ts with untreard 2° adrenal insuficiency acut adrenal crisis! • Glucocorticoid with T4 Rx if adr. Insuff. • Need less T4 than 1°hypothyroidism • Rx monitoring by- FT4 (TSH – no value)

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