Hypothyroidism - A comprehensive approach

Hypothyroidism - A comprehensive approach - hashimoto autoimmune graves thyroiditis surgery radioiodine

1. HYPOTHYROIDISM CHAIR PERSON- Dr KIRAN HAVANUR STUDENT – Dr GAVISIDDESH

2. THYROID GLAND The thyroid (Greek thyreos , shield, plus eidos , form) consists of two lobes connected by an isthmus. It is located anterior to the trachea between the cricoid cartilage and the suprasternal notch . The thyroid gland produces two related hormones, thyroxine (T4 ) and triiodothyronine (T3 ) .

3. DEVELOPMENT Median anlage-midline thickening of ventral surface between 1 and 2 Branchial arches Diverticulum at 16 or 17 day-Foramen caecum Lateral anlage- ultimobranchial bodies from 4 or 5 pouches Fuse with median by 6 th week Thyroid hormone synthesis normally begins by 11 weeks of gestation

4. ANATOMY The normal thyroid is 12–20 g in size highly vascular soft in consistency Four parathyroid glands, which produce parathyroid hormone are located posterior to each pole of the thyroid. Right lobe is larger than the left lobe and is more vascular

5. ARTERIAL SUPPLY

6. VENOUS DRAINAGE

7. HISTOLOGY Thyroid follicular cells that surround secreted colloid, a proteinaceous fluid containing large amounts of thyroglobulin, the protein precursor of thyroid hormones . The thyroid follicular cells are polarized—the basolateral surface is apposed to the bloodstream and an apical surface faces the follicular lumen.

8. Bio-synthesis and Secretion of Thyroid Hormone Iodide Transport Thyroglobulin Synthesis Oxidation o f Iodide Organification ( lodination ) Coupling Storage Secretion

9. Iodification of thyroglobulin Pituitary produces TSH, which binds to follicle cell receptors . The follicle cells of the thyroid produce thyroglobulin. Thyroglobulin incorporated in apical vesicles At apical membrane thyroid peroxidase use H2O2 and iodide to oxidize and organify thyrogloulin protein into MIT and DIT as well as some T4&T3.

10. Iodine metabolism Available through certain foods ( eg , seafood, bread, dairy products, eggs), iodized salt, or dietary supplements, drinking water as a trace mineral Dietary iodine is absorbed in the GI tract and 90% excreted in kidney The transport of iodide into follicular cells is dependent upon a Na + /I - cotransport system. Iodide taken up by the thyroid gland is oxidized by peroxide in the lumen of the follicle Oxidized iodine can then be used in production of thyroid hormones.

11. Daily iodine requirement(RDA) – US Institute of Medicine 150 microgram/d – Adults and Adolescents 220 microgram/d – Pregnant women (WHO=200 microgram/d ) 290 microgram/d – Lactating women 90-120 microgram/d – Children aged 1-11 yrs 110-130 microgram/d – Infants (WHO=50-90 microgram/d ) Selenium – Needed for synthesis and activity of iodothyronine deiodinase . Iodine excess- inhibits iodide oxidation organification and thyroglobulin proteolysis

12. Transport of thyroid hormones 13 TBG (T ½ = 5d) T4,T3,rT3 80% ALBUMIN (T ½ = 13d) T4,T3 10% TRANSTHYRETIN (T ½ = 2d) T4,T3 10%

13. T4 T3 Total conc. in plasma 8 µg/dl 0.14 µg/dl % of bound form 99.98% 99.7% Free form 2 ng /dl 0.3 ng /dl % of free form 0.02% 0.3% Biological half-life Long (6-7days) Shorter average 2 days Daily rate of secretion 90µg 32µg

14. Thyroxine (T 4 ) D2 ( deiodinate outer ring 5’C): brain, pituitary, heart, skeletal muscles and brown fat D3 ( deiodinate inner ring 5C): brain except pituitary, placenta, fetal and reproductive tissues T3 rT3 Deiodinase Deiodinase Deiodinase DIT MIT Thyronine

15. Significance of rT 3 RT 3 is inert. In cardiomyopathy, D3 in heart increases to decrease energy turnover and oxygen consumption Selenium deficiency, starvation, burns, major trauma, advanced cancer, cirrhosis, renal failure, MI and febrile states  suppresses deiodinases (D2) decreased T3, Normal T4, increased RT3 :: LOW T3 SYNDROME

16. 1.EFFECT OF THYROID HARMONES ON BMR Extreme excess of thyroid secretion increases BMR to 60-100% above normal Complete lack of thyroid secretion causes BMR to fall 40-50% below normal Mechanism of increasing metabolic rate and temperature By increasing number, size and activity of mitochondria By increasing plasma membrane Na + -K + ATPase Activity By stimulating both catabolic and anabolic reactions in pathways affecting fats ,carbohydrates, and proteins .

17. 2.Cardiovascular effects Positive chronotropic , inotropic and lusitropic effect. Increases systolic BP and decreased Diastolic BP – Increased Pulse pressure and mean arterial pressure remains somewhat constant

18. Thyroid hormones stimulate oxygen utilization Increases resting respiratory rate, minute ventilation and the ventilatory respose to hypercapnia and hypoxia Increase hematocrit secondary to EPO secretion Increase dissociation of O 2 from hemoglobin by increasing red cell 2,3-diphosphoglycerate (DPG). 3.Respiratory Effects

19. 4. Autonomic Nervous system Thyroid hormones are synergistic with catecholamines in increasing the metabolic rate, heat production, heart rate ,motor activity and excitation of central nervous system Increases the no. of β adrenergic receptors(Permissive action)

20. 5. Effects on Nervous System Growth of cerebral and cerebellar cortices. Proliferation of axons and branching of dendrites, synaptogenesis, myelination and cell migration during brain development. Enhances wakefulness, alertness, responsiveness to various stimuli. The speed and amplitude of peripheral nerve reflexes are increased. Memory, learning and intellectual capacities.

21. 6.Effects on growth and development Promote expression of gene for growth hormone in somatotrophs . T3 is required for production of both growth hormone and insulin like growth factors. It is also required for action of insulin like growth factors on epiphyseal cartilage. They stimulate linear growth of bones and endochondral ossification and maturation of epiphyseal bone centers.

22. 7.Effects on reproductive system Required for normal ovarian cycle of follicular development, maturation,and ovulation, maintenance of the healthy pregnant state ,and the homologous testicular process of spermatogenesis. Deleterious effects may be caused by alterations in the metabolism or availability of steroid hormones – thyroid hormones stimulates hepatic synthesis and release of sex steroid-binding globulin.

23. HYPOTHYROIDISM It refers to state when thyroid gland doesnot produce sufficent amount of thyroid hormones.

24. US population Clinical hypothyroidism – 0.33% Subclinical – 4.3% India Clinical hypothyroidism – 10.95% Subclinical – 8.02% Pregnancy- USA-15.5% INDIA-13.13% 25 Prevalence of hypothyroidism in adults: An epidemiological study in eight cities of India Indian J Endocrinol Metabolism

25. Primary (1ry): due to failure of the thyroid gland itself (99%) Secondary (2ry): due to hypopituitarism Tertiary (3ry): due to failure of hypothalamus Quaternary (4ry): due to tissue insensitivity to action of thyroid hormone 26 Causes of hypothyroidism (2ry ): (1ry): (3ry ): (4ry ):

26. PRIMARY HYPOTHYROIDISM ACQUIRED IODINE DEFICIENCY (mc) AI HYPOTHYROIDISM(HASHIMOTO’S/ATROPHIC)- (2 ND MC) IATROGENIC,SUBTOTAL OR TOTAL THYROIDECTOMY,RADIATION. DRUGS-IODINE EXCESS(AMIODARONE,CONTRAST MEDIA),LITHIUM,ANTITHYROIDS,P-AS ACID,INF ALPHA,AMINOGLUTHETIDE,TKI(SUNITINIB) INFILTRATIVE DISORDERS-AMLOIDOSIS,SARCOIDOSIS,HEAMOCHROMATOSIS,SCLERODERMA,CYSTINOSIS,REIDEL’S THYROIDITIS. CONGENITAL ABSENT OR ECTOPIC THYROID GLAND,TSH-RECEPTOR MUTATION,DYSHORMONOGENSIS.

27. CLINICAL PRESENTATION SKIN AND APPENDAGES SKIN - Pale,cool,dry,coarse skin Myxedematous tissue -boggy non pitting due to accumulation of hyaluronic acid present around eyes,dorsa of hands and feet and supraclavicular fossae. Wounds of the skin tend to heal slowly. Easy bruising is due to an increase in capillary fragility. HAIR - Head and body hair is dry and brittle, lacks luster, and tends to fall out. NAILS -The nails are brittle and grow slowly Patients with hypothyroidism due to Hashimoto thyroiditis may also have skin lesions with loss of pigmentation characteristic of the autoimmune skin condition vitiligo .

28. Cardiovascular System HR REDUCES CARDIAC OUTPUT REDUCES STROKE VOLUME REDUCES Peripheral resistance increases-diastolic BP Increases The reduction in cutaneous circulation is responsible for the coolness and pallor of the skin and the sensitivity to cold Pericrdial effusion + in 30% The combination of large heart, hemodynamic and electrocardiographic alterations, and the serum enzyme changes has been termed MYXEDEMA HEART.

29. Respiratory System Pleural effusions usually are evident only on radiologic examination but in rare instances may cause dyspnea. In severe Hypothyroidism i.myxedematous involvement of respiratory muscles ii.depression of both the hypoxic and the hypercapnic ventilatory drives alveolar hypoventilation and carbon dioxide retention contribute to the development of myxedema coma. An increased prevalence of obstructive sleep apnea is seen in hypothyroid patients.

30. Alimentary System Appetite is reduced Weight gain + not more than 10% - due to retention of fluid Peristaltic activity is decreased decreased food intake Overt pernicious anemia is reported in about 12% of patients with primary hypothyroidism. Atrophy of the gastric and intestinal mucosa and myxedematous infiltration of the bowel wall may be demonstrated on histologic examination. constipation

31. Central and Peripheral Nervous Systems Deficiency in fetal life or at birth impairs neurologic development, including hypoplasia of cortical neurons with poor development of cellular processes, retarded myelination, and reduced vascularity. All intellectual functions, including speech, are slowed in thyroid hormone deficiency Loss of initiative is present lethargy and somnolence are prominent dementia in elderly patients may be mistaken for senile dementia

32. Epileptic seizures have been reported and tend to occur in myxedema coma. Body movements are slow and clumsy, and cerebellar ataxia may occur. Numbness and tingling of the extremities are frequent; in the fingers these symptoms may be due to compression by glycosaminoglycan deposits in and around the median nerve in the carpal tunnel ( carpal tunnel syndrome ). The tendon reflexes are slow, especially during the relaxation phase, producing the characteristic “hung-up reflexes”.

33. Muscular System Stiffness and aching of muscles are common in hypothyroidism and are worsened by cold temperatures. Rarely, a profound increase in muscle mass with slowness of muscular activity may be the predominant- Hoffmann syndrome .

34. RENAL SYSTEM RENAL BLOOD FLOW REDUCED GFR REDUCED The impaired renal excretion of water and the retention of water Lead to increase in total body water This increase accounts for the hyponatremia occasionally noted because the level of exchangeable sodium is increased.

35. HEMATOLOGIC MANIFESTATIONS Decrease in red blood cell mass Normochromic, normocytic hypoproliferative anemia Pernicious anemia occurs in 10 percent of patients with hypothyroidism caused by chronic autoimmune thyroiditis : macrocytic anemia with marrow megaloblastosis Women in the childbearing years may develop iron deficiency anemia, secondary to menorrhagia. In patients with IDA and hypothyroidism, combined therapy with levothyroxine and oral iron supplements results in correction of the anemia, which may be refractory to treatment with iron alone

36. REPRODUCTIVE MANIFESTATIONS Decreased fertility Early abortion Hypermenorrhea -menorrhagia (More common) Or oligo - or amenorrhea (later stage) Low serum sex hormone-binding globulin concentration Hyperprolactinemia may occur, and is occasionally sufficiently severe to cause amenorrhea or galactorrhea Decreased libido, erectile dysfunction

37. Energy Metabolism: Protein, Carbohydrate, and Lipid Metabolism The decrease in energy metabolism and heat production is reflected in a low basal metabolic rate, decreased appetite, and cold intolerance. Protein i.Both the synthesis and the degradation of protein are decreased. ii.Permeability of capillaries to protein is increased, accounting for the high levels of protein in effusions and in cerebrospinal fluid

38. Carbohydrate - Degradation of insulin is slowed . -sensitivity to exogenous insulin may be increased. -In a patient with preexisting diabetes mellitus who develops hypothyroidism, insulin requirements may be reduced. -reduced gluconeogenesis Lipids -Both the synthesis and the degradation of lipid are depressed in hypothyroidism. - Degradation, however, is reduced to a greater extent, with a net effect of accumulation of LDL and triglycerides

39. AUTOIMMUNE HYPOTHYROIDISM Autoimmunity is responsible for over 90% of noniatrogenic hypothyroidism in countries with iodine sufficiency. The annual incidence of autoimmune hypothyroidism is around 80 per 100,000 men and 350 per 100,000 women. Average age-40-60 yrs AUTOIMMUNE HYPOTHYROIDISM a/w goiter-HASHIMOTO THYROIDITIS Later stages-minimal residual thyroid tissue + ATROPHIC THYROIDITIS

40. MC IN JAPANESE SUBCLINICAL HPOTHYROIDISM + IN - 6-8% OF WOMEN -3% OF MEN The annual risk of developing clinical hypothyroidism is about 4% when subclinical hypothyroidism is associated with positive TPO antibodies.

41. PATHOGENESIS IN HASHIMOTO’S Marked lymphocytic infiltration Atrophy of thyroid follicles Mild to moderate fibrosis In atrophic thyroiditis-extensive fibrosis & less pronounced lymphocyte infiltration & thyroid follicles are completely absent. End stage of hashimoto’s thyroiditis is atrophic thyroiditis.

42. GENETIC AND ENV FACTORS HLA-DR Polymorphism –Best Documented Genetic Risk Factor Especially HLA-DR3,DR4,DR5 CTLA-4 (Weak Association) A Gene On Chr 21-a/Btw Down’s And Ai Hypothyroidism High Iodine And Low Selenium Intake Smoking Cessation Transiently Increases Incidence. Alcohol Intake Is Protective.

43. Antibodies to TPO and Tg are clinically useful markers of thyroid autoimmunity. Up to 20% of patients with autoimmune hypothyroidism have antibodies against the TSH-R C/F-Patients with Hashimoto’s thyroiditis may present because of goiter rather than symptoms of hypothyroidism. it is usually irregular and firm in consistency Rarely is uncomplicated Hashimoto’s thyroiditis associated with pain

44. Hashimoto's encephalopathy A steroid-responsive syndrome associated with: TPO antibodies myoclonus & slow-wave activity on EEG An immune-mediated rather than effect of an altered thyroid state on the CNS 49

45. Associated conditions Type 1 DM Addison's disease Pernicious anemia Vitiligo Alopecia areata Celiac disease Dermatitis Herpatiformis Chronic Active Hepatitis RA, SLE, Sjogren syndrome Thyroid associated ophthalmopathy (in 5%) Turner syndrome, Down’s syndrome 50

46. CONGENITAL HYPOTHYROIDISM 1:4000 newborns (worldwide) 1:2640 newborns ( india ) More prone especially if mother has TSH-R blocking antibodies or has received antityhroid drugs. Permanent hypothyroidism occurs in majority.

47. 2 x more common in girls 80-85% due to thyroid dysgenesis 10-15% inborn errors of thyroid hormone synthesis. 5% TSH-R antibody mediated. Transient congenital hypothyroidism may occur following transplacental passage of TSH receptor blocking antibodies, iodine exposure and treatment with drugs like amiodarone . Most common preventable cause of mental retardation

48. Majority of infants appear normal at birth . Few cases are diagnosed based upon clinical features like:- prolonged jaundice,feeding problems,hypotonia,enlarged tongue,delayed bone maturation,umblical hernia. Permanent neurological damage results if treatment is delayed. Cardiac abnormality 4x more common.

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50. Goiter Enlargement of the thyroid gland. It occurs both in hypothyroidism and hyperthyroidism.

51. Goiter in Hypothyroidism – Non-toxic Goiter Enlargement of thyroid gland without increase in hormone secretion. It is also called hypothyroid goiter . Based on the cause, the non-toxic hypothyroid goiter is classified into two types. Endemic colloid goiter Idiopathic non-toxic goiter

52. Endemic Colloid Goiter It is the non-toxic goiter caused by iodine deficiency. It is also called iodine deficiency goiter. Prevalence = 4.6% {6.4%in women,1.5% in men}(Framingham Survey) India: Prevalence= 10%(ICMR) { Himalayas,Endemic belt- JK,HP,Pun,Har,UP,Bih,WB , Assam,Manipur,Arunachal : chotta Nagpur plateau,Sidhi Dist of MP,Aravali ranges in Rajasthan,Narmada valley in guj,Bombay,Pune,Vizag of AP} Karnataka – Chikmagalur,DK,Kodagu,UK Iodine deficiency occurs when intake is less than 50 μg /day.

53. Because of lack of iodine, there is no formation of hormones. By feedback mechanism, hypothalamus and anterior pituitary are stimulated. It increases the secretion of TRH and TSH. TSH then causes the thyroid cells to secrete tremendous amounts of thyroglobulin into the follicle As there are no hormones to be cleaved, the thyroglobulin remains as it is and gets accumulated in the follicles of the gland. This increases the size of gland 60

54. Reidel’s Thyroiditis Characterized by the fibrosis of the thyroid and adjacent structures Occurs in middle aged women Stony hard, immobile goitre resulting in pressure symptoms due to the compression of the trachea, oesophagus and the recurrent laryngeal nerve One third patients have hypothyroidism

55. SECONDARY HYPOTHYROIDISM D/T HYPOPITUITARISM TUMOURS,PITUITARY SURGERY,INFILTRATIVE DISORDERS,SHEEHANS SYNDROME,TRAUMA, GENETIC FORMS OF COMBINED PITUITARY HORMONE DEFICINCY. ISOLATED TSH DEFICIENCY,BEXAROTENE TREATMENT. HYPOTHALAMIC DEFICIENCY-TRAUMA,TUMOURS,INFILTRATIVE DISORDERS,IDIOPATHIC.

56. PRIMARY V/S SECONDARY HYPOTHYROIDISM PRIMARY SECONDARY SKIN Thick and without wrinkles Thin with fine wrinkles HAIR Coarse Fine MENSES Menorrhagia Amenorrhea SECONDARY SEXUAL CHARACTERS Normal Poor HEART SIZE May be enlarged Small GOITRE May be present Absent SOFT TISSUE EDEMA Marked Absent BLOOD PRESSURE Normal or High Low CHOLESTEROL Increased Normal TSH High Low

57. PRIMARY SECONDARY PLASMA CORTISOL Normal Low TRH STIMULATION TEST Exaggerated Response No response THYROID AUTO ANTIBODIES May be present Absent

58. TREATMENT STARTING TREATMENT- If no residual thyroid function then start levothyroxine 1.6mcg/kg/day ( approx 100-150mcg/day),ideally taken before 30min of breakfast . Adult under 60 yrs without any prevailing heart disease should be started on 50-100mcg/day with goal of treatment being a normal TSH ideally in the lower half of the reference range

59. Goal is to normalize TSH (lower half of the reference range) FOLLOW UP TSH responses are gradual and should be measured about 2 months after instituting treatment or after any subsequent change in levothyroxine dosage. Adjustment of levothyroxine dosage is made in 12.5- or 25-μg increments if the TSH is high ; decrements of the same magnitude should be made if the TSH is suppressed. The clinical effects of levothyroxine replacement are slow to appear. Patients may not experience full relief from symptoms until 3–6 months after normal TSH levels are restored

60. Patients with a suppressed TSH of any cause, including T4 overtreatment, have an increased risk of atrial fibrillation and reduced bone density. There is no place for liothyronine (T3) alone as long-term replacement, because the short half-life necessitates three or four daily doses and is associated with fluctuating T3 levels . Once full replacement is achieved and TSH levels are stable, follow-up measurement of TSH is recommended at annual intervals Because T4 has a long half-life (7 days), patients who miss a dose can be advised to take two doses of the skipped tablets at once.

61. High dose requirement of thyroxine Malabsorption (celiac disease, small bowel surgery) Compliance pregnancy Medications Estrogen Aluminium hydroxide Cholestyramine Ferrous sulfate Calcium Lovastatin Colsevelam 68 Lanthanum carbonate PPI Rifampicin Amiodarone Carbamazepine Phenytoin Magnesium containing laxatives Bulk laxatives with fiber

62. Subclinical Hypothyroidism Criteria defining subclinical hyothyroidim : Elevated serum TSH levels FT4 and T 3 levels within the reference range 3-8 % of individuals have subclinical thyroid disease with greater prevalence in women Most common cause: autoimmune thyroiditis (Hashimoto’s disease) Predisposing factors Advancing age Greater iodine consumption Often asymptomatic May represent early thyroid failure

63. 4.3 % progress to hypothyroidism is anti TPO antibody present Therapy indicated if patient is a woman who wishes to conceive or is pregnant OR 1. TSH > 10 mU /ml 2. Anti TPO positive 3. Goiter present 4. Menstrual irregularities/ infertility 5.Any evidence of heart disease

64. Dosing and Monitoring Always start with a small dose to prevent risk of Atrial Fibrillation Dose of LT4: 25-50 mcg/day (reduced dose in elderly and in patients with heart disease) Adjustment in dosage is made in 12.5-25µg inc or dec Serum TSH levels to be measured 6-8 weeks after starting treatment or after a change in the dosage Annual examination after achieving stable TSH levels Associated risks Progression to overt hypothyroidism Cardiovascular effects Hyperlipidemia Neuropsychiatric effects Subclinical Hypothyroidism management

65. Special consideration PREGNANCY- 1 st trimester TSH drops FT4 rise FT4 is helpful in evaluation Check TSH /4wk

66. Thyroid function test during pregnancy i.Every 4 th week till 20 th week of GA ii.Every 6-8 th week after 20 weeks of GA The levothyroxine dose may need to be increased by up to 50% during pregnancy. Goal TSH of less than 2.5 mIU /L during the first trimester and less than 3.0 mIU /L during the second and third trimesters The presence of thyroid autoantibodies alone , in a euthyroid patient, is also associated with miscarriage and preterm delivery Pregnant women should be counseled to separate ingestion of prenatal vitamins and iron supplements from levothyroxine by at least 4 h

67. Elderly Elderly(>65 yrs ) patients may require 20% less thyroxine than younger patients. In the elderly, especially patients with known coronary artery disease, the starting dose of levothyroxine is 12.5–25 μg /d with similar increments every 2–3 months until TSH is normalized. Emergency surgery is generally safe in patients with untreated hypothyroidism, although routine surgery in a hypothyroid patient should be deferred until euthyroidism is achieved.

68. MYXEDEMA COMA Myxedema coma is the ultimate stage of severe longstanding hypothyroidism. Risk factors Elderly Drugs that impair respiration-sedatives anti depressants Pneumonia CCF,MI Exposure to cold Hypoventilation Hypoglycemia and dilutional hyponatremia

69. 20-40% mortality rate Outcome depends on T4 &TSH levels. C/m- reduced level of conciousness a/w seizures features of hypothyroidism,hypothermia H/o treated hypothyroidism with poor compliance or previously undiagnosed.

70. MYXEDEMA COMA-TREATMENT APPROACH Levothyroxine i /v bolus 200-400mcg loading dose f/b daily oral dose of 1.6mcg/kg/day . Reduced oral dose to 25% if administered i /v If i /v not available then via RT but there will be decreased absorption in a case of myxedema . Because T4-T3 conversion is impaired,it is rationale to add Liothyronine to treatment. T3-initial loading dose of 5 -20mcg f/b 2.5-10mcg every 8 hrly,with lower doses for those at CVS risk.

71. External warming only if temp<30 C. I/v hydrocortisone 50mg every 6 hr. Ventilatory support with regular ABG in first 48 hours. Hypertonic saline or iv glucose as needed. Hypotonic i /v fluids should be avoided because they may exacerbate water retention secondary to reduced renal perfusion and inappropriate vasopressin secretion.

72. Adverse Effects of Levothyroxine Therapy excessive doses of levothyroxine causes accelerated bone loss in postmenopausal patients increases the risk of atrial fibrillation Rarely, levothyroxine replacement is associated with pseudotumor cerebri in children. Presentation appears to be idiosyncratic and occurs months after treatment has begun.

73. Messages TSH is the corner stone in approaching patients with hypothyroidism. Levothyroxine is the drug of choice to treat hypothyroidism. Dose changes in thyroxine according to TSH Thyroid hormone requirements increase during pregnancy. TPOab should be considered in approaching AITD. Most hypothyroidism patients require life long treatment. Some causes of primary hypothyroidism are reversible Treat patients only with abnormal thyroid functions

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75. REFERENCES Williams textbook of endocrinology,13th edition Harrison’s Principle of Internal Medicine,20 th edition Ghai Essential Pediatrics, 8 th edition Park’s textbookof preventive and social medicine Prevalence of hypothyroidism in adults: An epidemiological study in eight cities of India Indian J Endocrinol Metabolism