hypothyroidism by: elias s.. hypothyroidism a common disorder associated with thyroid hormone...
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HypothyroidismHypothyroidismBy: Elias S.By: Elias S.
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HypothyroidismHypothyroidism• 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
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Prevalence cont…….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%)
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causescauses• 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)
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Autoimmune hypothyroidismAutoimmune 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
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• 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
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Risk factorsRisk 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
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Iatrogenic causesIatrogenic 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.)
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Other causesOther 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 T4T3
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Other causes cont…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
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Secondary/tertiary Secondary/tertiary Hypothyroidism(Central)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
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Congenital hypothyroidismCongenital hypothyroidism• 1:4000 newborns
• Thyroid g. agenesis 80-85%• Inborn errors of thyroid H. synthesis 10-15%• TSH-R Ab mediated(Moinfant) 5%• Anti-thyroid (Moinfant)
• 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
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Mechanisms Symptoms Signs
Slowing ofMetabolic process
Fatigue, weaknessCold intoleranceDyspnea on exertionW’t gainSleepinessCognitive dysfunctionMental retardationConstipationGrowth failure
Slow mov’t, slow speechDelayed relaxation of tendon reflexesBradycardiaCarotenemia
Accumulation of Matrix
Dry skinHoarsness of voiceEdema
Rough thick skinPuffy face with loss of eye browPeriorbital edemaEnlargement of the tongue
others Decreased hearingMyalgia/ paresthesiaProximal M. weaknessDepressionMenst. IrregularityInfertility, LibidoArthralgiaPubertal delay
HTNPericardial/pleural effusionAscitisGalactorrhea
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Neurologic manifestationsNeurologic 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
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Metabolic AbnormalitiesMetabolic Abnormalities• Hyponatremia• Hyperlipidemia (LDL, cholesterol)• Hyperuricemia (Gout) serum creatinin• carotenemia drug clearance drug toxicity
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TSH
Elevated Normall
FT4
Normal Low
Pituitary D.Supected?
no yes
Mildhypothyroidism
Primaryhypothyroidism
No further test
FT4
TPOAb+ or SX
TPOAb-,noSx TPOAb+ TPOAb- low Normal
T4 RxAnnual
followup
AutoimmuneHypo.
T4 Rx
Rule outOther causes
Rule out drug effects,Sick euthyroid s.,
Then evaluate ant.pituit.f.
No further test
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disorders that affect TSHdisorders that affect TSH• 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
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Other investigationsOther investigations• CBC, ESR• OFT, Electrolytes• Lipid profile• Uric acid• FNACentral hypothyroidism
– Imaging studies(sellar/supracellar)– Other hormonal profiles (pituitary)
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TreatmentTreatment• 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
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Replacement doseReplacement dose• Adults <60 with out evidence of Heart D.
1.6 mcg/kg/day (50-150)
• Older p’ts , p’ts with CHD1/2-1/4 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
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AdditionalAdditional adjustmentadjustment dose: Pregnancy
Estrogen Rx Nephrotic syndrom coadministration of drugs that clearance orabsorbtion dose: elderly
marked w’t loss androgen therapy
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?T3 ?T3+T4?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
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Central HypothyroidismCentral 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)