Hypothyroidism clinical features and management.pptx

Hypothyroidism clinical features and management

1. HYPOTHYROIDISM MODERATOR: DR PRABHU ASSOC.PROFFESSOR ,DEPT OF MEDCINE PRESENTER: DR BHARATH POST GRADUATE ,DEPT OF MEDICINE

2. THYROID GLAND ANATOMY Consists of two lobes connected by an isthmus Located anterior to trachea between cricoid cartilage and supra sternal notch 12-20 g, highly vascular, soft 4 parathyroid glands are located posterior at each pole of thyroid

3. Thyroid produces …. T3 T4 CALCITONIN-REGULATION OF CALCIUM LEVELS

4. Physiology

5. SYNTHESIS OF THYROID HARMONE

6. CHARACTERISTICS OF CIRCULATING T3 AND T4 Hormone property t4 t3 Serum concentration total hormone 8 μ g/dL 0.14 μ g/dL Fraction bound 99.98 % 99.86 % Unbound free harmone 0.8-1.8ng/ml ( fun:1.0-1.8ng/ml) 2.3-4.2pg/ml (fun:3.0-4.0pg/ml) Half life 7DAYS 14 HOURS Metabolic potency 1 3 TSH- .5-5mIU/L

7. T4 to T3 conversion By deiodinases(I and II) Inhibited in a. Systemic illness b.Acute infection and trauma Drugs 1.B- Blocker- Propranol 2.PTU 3.Amiodarone 4. Steroids Thus,Don’t measure T3 and T4 levels in systemic illness,acute infection because they show false values.

8. Thyroid Hormone receptor: TSH receptor- (a cell membrane receptor ) acts via CAMP T3/T4 acts on Intranuclear receptors -TR T3 and T4 are bound to 3 proteins TBG(70%). Albumin(20-10%). Transthyretin (10%).

9. Maintains Basal metabolic rate 1.Carbohydrate metabolism: Increase glucose uptake in tissues gluconeogenesis and glycogenolysis Hypothyroidism(myxedema coma) - hypoglycemia fatigue 2.Protein metabolism Catabolic action proteolysis Hyperthyroidism- osteopenia myopathy fat metabolism Increases lipolysis Increase clearance of cholesterol hypothyroid - Hypercholesterolemia (SUS) 6.GROWTH Causes bone growth CNS myelination Hypothyroidism- Short stature and mental retardation(children). 8.Liver It converts B-carotene to Vit A Also stimulates erythropoiesis Hypothyroidism- Anaemia fatigue NOTE-ETC 7.HEART Increases sensitivity to catecholamines and myocardial contractibility. Hypothyroidism- bradycardia Fatigue

10. Wolf chaikoff effect Excessive Iodine inhibits iodine organification and synthesis of T4 and T3.(Hypothyroidism) Most patients quickly recover from this effect. However Patients with abnormal thyroid gland can develop hypothyroid if Iodine is given more than a few days. Risk factors are Autoimmune Thyroiditis Partial thyroidectomy Previous history of radioiodine therapy Subacute thyroiditis

11. Classification of Hypothyroidism Primary hypothyroidism : (90%) high serum TSH (symptoms present) low serum free thyroxine(T4) Subclinical Hypothyroidism : high TSH concentration. normal free T4 (symptoms absent) Secondary hypothyroidism : serum TSH concentration( normal low high) low serum T4

12. CAUSES OF HYPOTHYROIDISM

13. AUTOIMMUNE HYPOTHYROIDISM May be associated with goitre PREVALANCE : 4/ 1000 women, 1/ 1000 men, Mean age of diagnosis is 60 years, subclinical hypothyroidism is 6-8%. Risk of developing clinical hypothyroidism is 4% when subclinical hypothyroidism ,

14. PATHOGENESIS In Hashimoto's thyroiditis, marked lymphocytic infiltration of thyroid with germinal centre formation, atrophy of thyroid follicles abscence of colliod and mild to moderate fibrosis In atrophic thyroiditis- extensive fibrosis, less lymphocytic infiltration and absent thyroid follicles HLA-DR polymorphisms are the best documented risk factors, especially HLA-DR3,4,5 in Caucasians The female preponderance sex steroid effects on the immune response. Useful markers of thyroid autoimmunity- Antibodies to TPO and Tg 20% have antibodies against TSH-R which prevent binding of TSH to receptor

15. Associated conditions Other Autoimmune disorders: Type 1 diabetes mellitus Addison's disease Pernicious anemia Vitiligo

16. OTHER CAUSES OF HYPOTHYROIDISM IATROGENIC : radioiodine treatment, subtotal thyroidectomy, drugs like lithium IODINE DEFICIENCY : Endemic goitre, cretinism, associated with consumption of thiocyanates in cassava or selenium deficiency in adults CHRONIC IODINE EXCESS : Intracellular events are unclear, patients with autoimmune thyroiditis are susceptible, iodine excess causes hypothyroidism in upto 13% patients treated with amiodarone SECONDARY HYPOTHYROIDISM : Anterior pituitary hormone deficiencies, isolated TSH deficiency- rare

17. DRUGS CAUSING HYPOTHYROIDISM DECREASE THE CONVERTION OF T4 TO T3 STERIODS PROPRANOLOL IODINE AMIODARONE PROPYLTHIOURACIL ENZYME INDUCERS PHENYTOIN CARBAMAZEPINE RIFAMPICIN SERTRALINE RITONAVIR CAUSES HYPOTHYROIDISM LITHIUM D2 BLOCKER CLOMIPHENE CITRATE SPIRNOLACTONE DECREASE THE ABSORPTION AL(OH)3 CHOLESTYRAMINE CALICIUM CARBONATE FERROUS SULPHATE

18. CLINICAL PICTURE Goitre generalized slowing of BMR Accumulation of matrix glycosaminoglycans DECRESED BMR FATIGUE,SLOWING OF SPEECH, COLD INTOLERANCE, CONSTIPATION ,WEIGHT GAIN DEPISTE NOR APPETITE, BRDAYCARDIA, ACCUMULATION OF GAGS INCR TSH-STIMUATES FIBROBLAST-PRODUCTION OF GAGS FACIAL PUFFINESS MACROGLOSSIA PERIORBITAL EDEMA NON PITTING EDEMA Reproductive system (oligo- or amenorrhea – (rare)menorrhagia Hyperprolactinemia Decreased libido, erectile dysfunction Musculoskeletal Joint pains, Woltmans sign (Hung up ankle jerk) due to decresed myosin ATPase Hoffman’s syndrome Metabolic changes Hyponatremia reduction in free water clearance.(SIADH) Hypercholesterolemia and hypertriglyceridemia Neurological system Intellectual (<3 years) Carpal tunnel syndrome Slow relaxation of DTR Memory and concentration are impaired,psychosis , and myxedema coma. Hematologic Normochromic, normocytic anaemia Pernicious anemia iron deficiency anemia, secondary to menorrhagia . Cardiovascular system Reduced CO Diastolic Hypertension ECG : Low voltage, sinus bradycardia, Pericardial effusion Respiratory system Dyspnea due to Hypoventilation and decreased pulmonary responses to hypoxia and hypercapnia Sleep apnea due to macroglossia.

19. SREAT Hashimoto’s encephalopathy(Old term) Steroid responsive encephalopathy with autoimmune thyroid disease [new term] Autoimmune vasculitis unrelated to thyroid function. Hashimoto’s encephalopathy can occur with a normal TFT HLA-B-8 associated Elevated antibody titres . PRESENTATION Subacute onset of confusion/altered level of consciousness or seizure/myoclonus or small vessel stroke Good response to steroids Treatable condition

20. Other points of Hashimoto’s encephalopathy Anti Enolase antibody Can occur in Euthyroid state Background slowing of EEG Anybody presenting with subacute dementia and alt sensorium ,rule out thyroid illness, however don’t be foxed by normal tft , it is the antibody titre which is important,it is one treatable causes of alt sensorium .

21. TSH T4 FT4 T3 FT3 Condition Increased Normal Normal Normal Normal Subclinical hypothyroidism Recovery from acute illness Increased Decreased Decreased Decreased Decreased Primary hypothyroidism Increased Increased Increased Increased Increased Thyroid hormone resistance /thyroid adenoma Normal or low Decreased Decreased Decreased Decreased TSH appropriately normal;secondary hypothyroidism

22. Approach Signs slow DTRs, bradycardia, facial and periorbital edema , dry skin, and nonpitting edema . Mild weight gain (not marked obesity). hypoventilation, pericardial or pleural effusions, deafness, and signs carpal tunnel syndrome. Laboratory findings may include hyponatremia and elevated plasma levels of cholesterol, triglycerides, and creatine kinase.

23. What tests should I order ? TSH and free T4 for initial evalution For follow-up of treatment only TSH Don't order for Total T4 or Total T3 Never order RIU in pregnancy or lactation

24. TSH Shouldn’t be used alone……. Use of TSH as a screening test may be misleading… TSH FREE T4 T3 DISEASE INCREASED 1 HYPOTHYROIDISM INCREASED RTH NORMAL DECREASED INCREASED DECREASED 2 HYPOTHYROIDISM

25. Thyroid function test TSH-Better if done while fasting Free T3,T4-no relation to food A normal TSH excludes primary abnormality of thyroid function

26. TPO AB+ SYM(+) TPO AB- SYM (-) SUBCLINICAL 1* HYPOTHYROIDISM TPO AB+ TPO- AUTOIMMUNE HYPOTHYROIDISM (OTHER?) LOOK FOR OTHER CAUSES

27. Thyroid Antibodies Anti Thyroglobulin (TG) Antibodies Anti Thyroperoxidase (TPO) Ab Thyroid receptor (TRH-A) Antibodies

28. Treatment : Outline Goal : normalize TSH level,ideally in the lower half of the reference range. Single daily dose of levothyroxine as half life is 7 days. Empty stomach -30 mins before BF. Starting dose-healthy patients <60 years and no cardio issue 1.6 ug/kg/day.(50 to 100 ug/day) Starting dose for healthy patients > 60 OR cardio issue - <50 ug/day. TSH levels measured after 2 months.(after initiation and altering the dose) Dose should be increased or decresed by 12.5-25 ug/day(basis of TSH) Once stabilized TSH-annual follow up

29. For monitoring the patient on treatment , TSH is the best choice patients who miss a dose can take two doses of the skipped tablets at once. For TSH to normalize it will take 2-3months For symptoms to subside it will take 2 months after the normalization of TSH Most common treatment failure: Non compliance however, Increased t4 requirements must be excluded malabsorption ingestion with a meal drugs that interfere with T4 absorption or metabolism

30. TREATMENT SUBCLINICAL HYPOTHYROIDISM : Levothyroxine is considered in (high TSH levels should be there for 3months before rx ) Planning to conceive pregnant TSH levels >10 mU / L, Symptoms antibodies positive Low dose levothyroxine (25-50 micrograms/day). If T4 is not given , then annual follow up is recommended.

31. SPECIAL TREATMENT CONSIDERATIONS Every planning to conceive- thyroid profile has be checked if hypothyroid-maintain pre conceptional TSH-2.5mIU/L After pregnancy is confirmed – im mediately get thyroid profile done ,then once in 1month till 20weeks f/b 2 months thereafter. ( goal of TSH < 2.5 mIU /L ) Levothyroxine dose - increased by upto 45% during pregnancy Imp:separate ingestion of iron supplements from levothyroxine by at least 4 hours ELECTIVE surgery in a hypothyroid patient should be deferred until euthyroidism is achieved.

32. Over - and Under-Replacement Risks Over-replacement Risks : Reduced bone density/osteoporosis Tachycardia, arrhythmia : Atrial fibrillation In elderly or patients with heart disease- angina, arrhythmia, or myocardial infarction.(wise to start with less dose) Under-replacement Risks : Continued hypothyroid state Long-term end-organ effects of hypothyroidism Increased risk of hyperlipidemia

33. Before and After of L-Thyroxine

34. MYXEDEMA COMA Almost always occurs in elderly Seen in long standing hypothyroid History of treated hypothyroidism (very poor compliance) might be previo u sly undiagnosed also 20-40% mortality even with treatment doesn’t relate T4 and TSH levels Precipitated by factors that impair respiration- drugs ( sedatives, anesthetics and antidepressants), infection, CAD, GI bleed or CVA, exposure to cold CLINICAL MANIFESTATIONS- Reduced level of consciousness, seizures Bradycardia hyponatremia hypothermia can reach 23 ° C hypoglycemia and other features of hypothyroidism

35. TREATMENT:MYXEDEMA COMA Levothyroxine single IV bolus of 500 ug( loading dose) followed by a daily oral dose of 1.6 μg /kg/day IV preparation is not available - can be given by nasogastric tube (though absorption may be impaired in myxedema). Because T4 → T3 conversion is impaired (myxedema coma) adding liothyronine i.v or via nasogastric tube (excess arrhythmias). loading dose of 5–20 μg Maintaince dose: 2.5–10 μg 8 hourly(consider cardiovascular issues)

36. Supportive Treatment: Myxedema coma External warming (temperature is <30 °C) due to risk of cardiovascular collapse.( Space blankets to prevent) Parenteral hydrocortisone (50 mg every 6 h) decresed adrenal reserve in profound hypothyroidism. Any precipitating factors like infection to be treated with broad-spectrum antibiotics. Ventilatory support - regular blood gas analysis Hypertonic saline or IV glucose .hypotonic IV fluids should be avoided(RAAS) Sedatives should be avoided if possible or used in reduced doses and monitor blood levels of drugs.

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