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Hypothyroidism --a clinical perspective

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Hypothyroidism --a clinical perspective

  1. 1. Clinician’s Perspective to Hypothyroidism Module 2 Copyright © 2011 Abbott India Limited. All rights reserved
  2. 2. <ul><li>&quot;The thyroid gland regulates the metabolic functions of the body in virtually every cell,“ . &quot;Everything from the brain to the skin is affected by the hormone made by the thyroid gland.“ </li></ul><ul><li>Hypothyroidism &quot;It slows you down,It makes you lethargic and fatigued Your hair becomes brittle, and your skin becomes dry. You become cold much easier than the average person. </li></ul>
  3. 3. Case Presentation 1 <ul><li>During her routine visit to doctor, Ayesha, an apparently healthy 70-year-old woman complained of mild fatigue, dry skin, and difficulty in losing weight since last 2 years. </li></ul><ul><li>The past medical and surgical history were uneventful. </li></ul><ul><li>There was no reported family history of DM/HTN/IHD. </li></ul><ul><li>Physical examination results were normal including a non- palpable thyroid gland. </li></ul><ul><li>ECG was normal. Fasting and postprandial blood sugar and CBC were within normal limits. </li></ul><ul><li>Serum TSH and FT4 tests were repeated 2 weeks after the first visit and were found to be 8.1 mIU/L and 1.4 ng/dL, respectively. </li></ul><ul><li>Diagnosis: Subclinical hypothyroidism (Hashimoto’s thyroiditis) </li></ul>Serum TSH 8.0 mlU/L(0.3-5.5) Serum free T4 1.3 ng/dL(0.7-2) Serum total cholesterol 220 mg/dL(150-200) Serum HDL cholesterol 46 mg/dL(30-60) Serum LDL cholesterol 150 mg/dl(80-150) Serum triglycerides 80 mg/dL(75-150) Thyroperoxidase antibodies Positive
  4. 4. Hypothyroidism: Overview, Manifestations and Treatment
  5. 5. Hypothyroidism <ul><li>Condition where there is a reduced production of thyroid hormone 1 </li></ul><ul><li>Categorized as primary and secondary on the basis of its cause </li></ul><ul><li>Primary hypothyroidism occurs due to improper functioning of the thyroid gland </li></ul><ul><ul><li>May be further classified as overt and subclinical hypothyroidism 2,3 </li></ul></ul><ul><ul><li>Affects approximately 5% of individuals with elderly women being most commonly affected 3 </li></ul></ul><ul><li>Secondary hypothyroidism occurs due to inadequate stimulation of thyroid gland by thyroid stimulating hormone (TSH) </li></ul><ul><li>May be due to congenital or acquired defects in the pituitary or hypothalamus </li></ul><ul><li>Rare and occurs in less than 1% of individuals 3 </li></ul>Thyroid gland <ul><li>Hypothyroidism, Medline Plus. Available at: http://www.nlm.nih.gov/medlineplus/ency/article/000353.htm ; 2011:1-7. </li></ul><ul><li>Roberts CGP. Lancet . 2004;363: 793-803. </li></ul><ul><li>Ladenson P. Cecil Medicine. 2008:1698-1713. </li></ul><ul><li>AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13 http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf . </li></ul>
  6. 6. Primary Hypothyroidism: Etiology <ul><li>Thyroid dysfunction </li></ul><ul><ul><li>Autoimmune thyroiditis (Hashimoto’s thyroiditis) </li></ul></ul><ul><ul><li>Congenital absence or defect in the thyroid tissue </li></ul></ul><ul><ul><li>Thyroid removal by surgery </li></ul></ul><ul><ul><li>Radio ablation by radio active iodine or irradiation </li></ul></ul><ul><ul><li>Destruction of thyroid tissue caused by infiltrative disorders(amyloidosis,sarcoidosis) </li></ul></ul><ul><li>Impaired synthesis of thyroid hormone </li></ul><ul><ul><li>Iodine deficiency----MOST COMMON CAUSE </li></ul></ul><ul><ul><li>Congenital enzymatic defects </li></ul></ul><ul><ul><li>Drug-mediated: thionamides, amiodarone, lithium, aminoglutethimide,carbemazole </li></ul></ul>Ladenson P, Kim M. Cecil Medicine. 2008:1698-1713.
  7. 7. Secondary Hypothyroidism: Etiology <ul><li>Reduced secretion of TRH or TSH </li></ul><ul><ul><li>Hypothalamic disorders </li></ul></ul><ul><ul><ul><li>Tumor (lymphoma, germinoma, glioma) </li></ul></ul></ul><ul><ul><ul><li>Infiltrative disorders (sarcoidosis, hemochromatosis, and histiocytosis) </li></ul></ul></ul><ul><ul><li>Hypopituitarism </li></ul></ul><ul><ul><ul><li>Mass lesions </li></ul></ul></ul><ul><ul><ul><li>Pituitary surgery </li></ul></ul></ul><ul><ul><ul><li>Pituitary irradiation </li></ul></ul></ul><ul><ul><ul><li>Hemorrhagic apoplexy (Sheehan’s syndrome) </li></ul></ul></ul><ul><ul><ul><li>Lymphocytic hypophysitis </li></ul></ul></ul>Ladenson P, Kim M. Cecil Medicine. 2008:1698-1713.
  8. 8. Clinical Manifestations: Symptoms <ul><li>Symptoms 1,2 </li></ul><ul><ul><li>Tiredness/ weakness </li></ul></ul><ul><ul><li>Weight gain with poor appetite </li></ul></ul><ul><ul><li>Dry skin </li></ul></ul><ul><ul><li>Cold sensation </li></ul></ul><ul><ul><li>Hair loss(diffuse alopecia) </li></ul></ul><ul><ul><li>Nail growth is retarded </li></ul></ul><ul><ul><li>Poor concentration/memory loss </li></ul></ul><ul><ul><li>Constipation </li></ul></ul><ul><ul><li>Dyspnea </li></ul></ul><ul><ul><li>Hoarseness of voice </li></ul></ul><ul><ul><li>Hearing Impairment </li></ul></ul><ul><ul><li>Carpal tunnel syndrome </li></ul></ul><ul><ul><li>Menorrhagia(miscarriage) </li></ul></ul><ul><ul><li>Paresthesia </li></ul></ul><ul><li>Ladenson P and Kim M. Cecil Medicine. 2008:1698-1713. </li></ul><ul><li>Jameson JL, et al. Harrison's Principles of Internal Medicine . 2008: 2224-2247. </li></ul>
  9. 9. Clinical Manifestations: Signs <ul><li>Signs 1,2 </li></ul><ul><ul><li>Cold peripheral extremities </li></ul></ul><ul><ul><li>Dry, coarse and yellow skin </li></ul></ul><ul><ul><li>Puffiness of face, hands and feet </li></ul></ul><ul><ul><li>Pre tibial non pitting edema </li></ul></ul><ul><ul><li>Hair loss and brittle nails </li></ul></ul><ul><ul><li>Bradycardia/ diastolic hypertension </li></ul></ul><ul><ul><li>Slow relaxation of tendon reflex (woltmans sign) </li></ul></ul><ul><ul><li>Serous cavity effusions </li></ul></ul><ul><ul><li>Normal/enlarged/atrophied thyroid gland </li></ul></ul><ul><li>Hypothyroidism in children </li></ul><ul><ul><li>Delayed growth in children and delayed appearance of permanent teeth </li></ul></ul><ul><ul><li>Delayed or precocious puberty </li></ul></ul><ul><ul><li>Pseudohypertrophy of muscles </li></ul></ul><ul><li>Ladenson P and Kim M. Cecil Medicine. 2008:1698-1713. </li></ul><ul><li>Jameson JL et al. Harrison's Principles of Internal Medicine . 2008: 2224-2247. </li></ul>
  10. 10. Laboratory Diagnosis <ul><li>TSH assay: Primary test to establish the diagnosis </li></ul><ul><li>Additional tests: </li></ul><ul><ul><li>Estimation of free T 3 and T 4 </li></ul></ul><ul><ul><li>Test for thyroid autoantibodies </li></ul></ul><ul><ul><li>Thyroid scan/ultrasonography </li></ul></ul><ul><ul><li>Serum cholesterol-  in hypothyroidism </li></ul></ul>T 3 /T 4 Subclinical hypothyroidism Overt hypothyroidism TSH TSH AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13 http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf . T 3 /T 4
  11. 11. Treatment Overview <ul><li>Goal: To mimic normal, physiological levels and alleviate signs, symptoms, and biochemical abnormalities </li></ul><ul><li>Treatment should be tailored to individual needs </li></ul><ul><li>Treatment of choice: Levothyroxine (LT4) replacement therapy </li></ul><ul><li>Desiccated thyroid hormone and T 3 +T 4 mixture: Insufficient evidence and not recommended for replacement therapy by the AACE guidelines </li></ul>AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13 http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf .
  12. 12. Subclinical Hypothyroidism
  13. 13. Subclinical Hypothyroidism: Ayesha’s Case <ul><li>Criteria defining subclinical hyperthyroidism: </li></ul><ul><ul><li>Slightly elevated serum TSH levels </li></ul></ul><ul><ul><li>FT4 and T 3 levels within the reference range </li></ul></ul><ul><li>Affects 1-10% of adults, with greater prevalence in women </li></ul><ul><li>Most common cause: autoimmune thyroiditis (Hashimoto’s disease) </li></ul><ul><li>Predisposing factors </li></ul><ul><ul><li>Advancing age </li></ul></ul><ul><ul><li>Greater iodine consumption </li></ul></ul><ul><li>Often asymptomatic </li></ul><ul><li>May represent early thyroid failure </li></ul>AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13 http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf .
  14. 14. Subclinical Hypothyroidism: Management Algorithm <ul><li>Col NF, et al. JAMA 2004; 291:239-243. </li></ul><ul><li>Surks MI, et al. JAMA 2004;291:228-238. </li></ul>Algorithm for the management of subclinical hypothyroidism (T 4 = thyroxine: TSH = thyrotropin-stimulating hormone) Serum TSH >4.5 mU/L Repeat Serum TSH Measurement with FT 4 Measurement 2 to 12 Weeks Later Serum TSH Level within Reference Range (0.45 to 4.5 mlU/L)? Serum TSH Level 4.5 to 10mlU/L Monitor Every 6 to 12 mo for Several Years Serum TSH Level > 10mlU/L Signs or Symptoms Consistent with Hypothyroidism? FT 4 Level Decreased (<0.8 ng/dL)? Treat with Levothyroxine* Pregnant or Contemplating Pregnancy? Consider Levothyroxine Treatment with Periodic Monitoring Monitor Serum TSH Every 6 to 12 mo FT 4 Level Decreased (<0.8 ng/dL)? Treat with Levothyroxine* Pregnant or Contemplating Pregnancy? Consider Levothyroxine Treatment in Appropriate Clinical Settings Yes No Yes No Yes No No Yes Yes No No Yes <ul><li>TSH: Thyroid stimulating hormone </li></ul><ul><li>FT4: Free Thyroxine </li></ul><ul><li>Mo: Months </li></ul>Rule out hypopituitarism
  15. 15. Subclinical Hypothyroidism <ul><li>Dosing and Monitoring 1,2 </li></ul><ul><ul><li>Always start with a small dose to prevent risk of Atrial Fibrillation </li></ul></ul><ul><ul><li>Dose of LT4: 25-50 mcg/day (reduced dose in elderly and in patients with heart disease) </li></ul></ul><ul><ul><li>Adjustment in dosage is made in 12.5-25µg inc or dec </li></ul></ul><ul><ul><li>Serum TSH levels to be measured 6-8 weeks after starting treatment or after a change in the dosage </li></ul></ul><ul><ul><li>Target TSH levels: 0.3-3.0 µIU/mL </li></ul></ul><ul><ul><li>Annual examination after achieving stable TSH levels </li></ul></ul><ul><li>Progression to overt hypothyroidism 1 </li></ul><ul><ul><li>Occurs in 3-20% patients </li></ul></ul><ul><ul><li>Patients with goiter and thyroid antibodies at higher risk for progression </li></ul></ul><ul><li>Associated risks 1 </li></ul><ul><ul><li>Progression to overt hypothyroidism </li></ul></ul><ul><ul><li>Cardiovascular effects </li></ul></ul><ul><ul><li>Hyperlipidemia </li></ul></ul><ul><ul><li>Neuropsychiatric effects </li></ul></ul><ul><li>AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13. </li></ul><ul><li>http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf . </li></ul><ul><li>2. Shah SN, Joshi SR. Journal of the Association of Physicians of India. 2011;59(Supplement):1-68. </li></ul>
  16. 16. Learning Activity
  17. 17. Learning Activity <ul><li>All of the following statements related to subclinical hypothyroidism are true, EXCEPT: </li></ul><ul><ul><li>The most common cause of subclinical hypothyroidism is Hashimoto’s disease. </li></ul></ul><ul><ul><li>Subclinical hypothyroidism is more common in women. </li></ul></ul><ul><ul><li>Subclinical hypothyroidism is characterized by elevated levels of TSH and free T4. </li></ul></ul><ul><ul><li>Subclinical hypothyroidism may represent early thyroid failure. </li></ul></ul>
  18. 18. Case Study
  19. 19. Ayesha's Case: Management <ul><li>Ayesha was put on LT4 therapy based on the following findings: </li></ul><ul><ul><li>Increased TSH </li></ul></ul><ul><ul><li>Positive antithyroid antibodies </li></ul></ul><ul><ul><li>Dyslipidemia </li></ul></ul><ul><li>Dosage administered was 30 mcg/day. </li></ul><ul><li>She was asked to visit again for follow-up after 8 weeks </li></ul>
  20. 20. Levothyroxine
  21. 21. Levothyroxine <ul><li>Synthetic T4 identical to that produced in the human thyroid gland </li></ul><ul><li>Indications: </li></ul><ul><ul><li>Hypothyroidism: All types </li></ul></ul><ul><ul><li>Pituitary TSH suppression </li></ul></ul><ul><ul><ul><li>Euthyroid goiters </li></ul></ul></ul><ul><ul><ul><ul><li>Thyroid nodules </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Subacute or chronic lymphocytic thyroiditis (Hashimoto’s thyroiditis) </li></ul></ul></ul></ul><ul><ul><ul><li>Adjunct to surgery and radioiodine therapy in the management of thyroid cancer </li></ul></ul></ul>Synthroid PI,Abbott. 2008
  22. 22. Levothyroxine: Important Facts <ul><li>Levothyroxine sodium has a narrow therapeutic range </li></ul><ul><ul><li>Regardless of indication of use, careful dose titration is necessary to avoid consequences of over- or under- treatment </li></ul></ul><ul><ul><li>Even small changes in the dose of LT4 can shift a patient from a euthyroid to a hyperthyroid or hypothyroid state. </li></ul></ul><ul><li>The AACE recommends the use of a high-quality brand preparation of levothyroxine </li></ul><ul><li>Same brand of LT4 should be received throughout treatment </li></ul>AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13 http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf .
  23. 23. Levothyroxine: Dosing <ul><li>Recommended mean daily dose of LT4 therapy: 1.6 mcg/kg of body weight </li></ul><ul><li>Initiate with 12.5 mcg daily to a full replacement dose of LT4 depending on age, weight, and cardiac status </li></ul><ul><li>Reassess TSH and/or free T4 after 6 weeks </li></ul><ul><li>Follow up after 6 months and thereafter annually, once TSH is in normal range </li></ul><ul><li>Adjust doses as appropriate in case of absorption variability and drug interactions </li></ul><ul><li>Keep in mind that inappropriate dose adjustments can lead to increased costs due to additional patient visits and laboratory tests </li></ul>AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13 http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf .
  24. 24. Levothyroxine: Drug Interactions <ul><li>Increase LT4 dose with </li></ul><ul><ul><li>Drugs that reduce thyroxine production: lithium, iodine-containing drugs, and amiodarone </li></ul></ul><ul><ul><li>Drugs that reduce thyroxine absorption: sucralfate, ferrous sulfate, cholestyramine, colestipol, aluminum-containing antacids, and calcium supplements </li></ul></ul><ul><ul><li>Drugs that increase thyroxine metabolism: rifampin, phenobarbital, carbamazepine, warfarin, and oral hypoglycemic agents </li></ul></ul><ul><li>Decrease LT4 dose with </li></ul><ul><ul><li>Drugs that displace thyroxine from binding proteins: furosemide, mefenamic acid, salicylates, vitamin C </li></ul></ul><ul><li>Hueston WJ. Treatment of Hypothyroidism. American family physician. 64(10): 1717-1724. </li></ul><ul><li>AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13 </li></ul><ul><li>http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf . </li></ul>
  25. 25. Learning Activity
  26. 26. Learning Activity <ul><li>Which of the following agents increase the absorption of LT4? </li></ul><ul><ul><li>Calcium </li></ul></ul><ul><ul><li>Furosemide </li></ul></ul><ul><ul><li>Ferrous sulfate </li></ul></ul><ul><ul><li>Rifampin </li></ul></ul>
  27. 27. Case Study 1
  28. 28. Ayesha's Case: Therapy and Follow-up <ul><li>Follow-up </li></ul><ul><ul><li>Serum TSH measurement was repeated after 8 weeks of commencing the treatment. They had fallen to 1.2 mIU/mL and remained within the range of 1 to 1.5 mIU/mL on consecutive visits. </li></ul></ul><ul><ul><li>She was asked to stay on the treatment and follow up after 1 year. </li></ul></ul><ul><ul><li>After 1 year of treatment, she had lost weight and was asymptomatic. On investigation, her serum cholesterol and low-density lipoprotein (LDL) cholesterol levels were 190 and 100 mg/dL, respectively. </li></ul></ul>
  29. 29. Case Study 2
  30. 30. Case Presentation: 2 <ul><li>Patient </li></ul><ul><ul><li>Shobha, a 32-week pregnant 30-year-old woman presents premature labor </li></ul></ul><ul><ul><li>Inappropriate weight gain for gestational age </li></ul></ul><ul><ul><li>Cold intolerance during past few months </li></ul></ul><ul><li>Past medical history </li></ul><ul><ul><li>She was diagnosed with hypothyroidism at the age of 20 </li></ul></ul><ul><ul><li>She was on LT4 therapy </li></ul></ul><ul><ul><li>Last dose modification was 2 years back after which she continued on same dose. </li></ul></ul>
  31. 31. Case Presentation: 2 (Continued) <ul><li>Physical Examination </li></ul><ul><ul><li>Weight : 100 kg </li></ul></ul><ul><ul><li>Pulse Rate: 68 per minute </li></ul></ul><ul><ul><li>BP: 140/90 mm Hg </li></ul></ul><ul><ul><li>Facial puffiness </li></ul></ul><ul><ul><li>Skin: Cold, Dry </li></ul></ul><ul><ul><li>Deep tendon reflexes,: Slow relaxation </li></ul></ul><ul><li>Thyroid Function Tests </li></ul><ul><ul><li>Serum TSH: 11 mIU/L </li></ul></ul><ul><ul><li>Free T4: 1.2 pmol/L </li></ul></ul><ul><li>Fetal Examination </li></ul><ul><ul><li>Fetal distress in labour </li></ul></ul><ul><li>Outcome of Pregnancy </li></ul><ul><ul><li>She delivered a preterm low birth weight male. </li></ul></ul>
  32. 32. Maternal Hypothyroidism
  33. 33. Maternal Hypothyroidism <ul><li>One of the most common endocrine disorders in pregnancy 1 </li></ul><ul><li>Overt hypothyroidism found in 1.3 per 1000 pregnant women and subclinical hypothyroidism in 23 per 1000 pregnant women 1 </li></ul><ul><li>Most common cause: endemic iodine deficiency 2 </li></ul><ul><li>Women with hypothyroidism carry an increased risk of infertility, miscarriage, and obstetric complications 1 </li></ul><ul><li>Foetal complications: p remature birth, low-birth weight (LBW), fetal distress in labor, fetal death, perinatal death, and c ongenital hypothyroidism 1 </li></ul><ul><li>Even an untreated subclinical hypothyroidism during pregnancy can lead to cognitive impairment in the offspring. 3 </li></ul><ul><li>Sahu MT, et al. Arch.Gynaecol. Obstet . 2010;218:215-220. </li></ul><ul><li>Lazaras JH. British Medical Bulletin . 2010;1-12. </li></ul><ul><li>AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13 http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf . </li></ul>
  34. 34. Thyroid Physiology in Pregnancy Decreased TSH Placenta hCG Increased TH degradation Thyroid stimulation for increased TH Production Estrogen Increased serum TBG Increased hepatic production of TBG Increased half life of TBG Type 3 deiodinase Stimulates TSH receptor Decreased free TH Stimulation of hypothalamic pituitary axis Increased serum TH hCG: Human chorionic gonadotropin TSH: Thyroid stimulating hormone TH: Thyroid hormone TBG: Thyroxine-binding globulin
  35. 35. Thyroid Physiology in Pregnancy Increased oestrogen in pregnancy Two- to threefold increase in TBG Decrease Free T 3 and T 4 Similar structure of hCG and TSH hCG stimulates release of T 3 and T 4 Transient TSH decrease in weeks 8 to 14 Increased peripheral metabolism of T 3 and T 4 Decrease Free T 3 and T 4 <ul><li>Jameson JL. Harrison's Principles of Internal Medicine . 2008:2224-2247. </li></ul><ul><li>Lazarus JH. Br Med Bull. 2010;1-12. </li></ul><ul><li>Galofre JC, Davies TF. J Womens Health (Larchmt). 2009;18(11):1847-1856. . </li></ul>0 50 75 100 125 150 0 0.5 1.5 2.5 3.5 4.5 4 0 8 12 16 20 24 28 32 36 40 TSH (mU/L) hCG (IU/mL Weeks of gestation 0.2 0.6 1.0 1.4 1.8 160 220 280 340 400 4 0 8 12 16 20 24 28 32 36 40 FT3 (pg/dL) FT4 (ng/dL) Weeks of gestation A B C TBG: Thyroxine- binding globulin TSH: Thyroid stimulating hormone HCG: Human chorionic gonadotropin TT4: Total thyroxine FT3: Free triiodothyronine FT4: Free thyroxine hCG TSH 0 1.5 2.0 2.5 3.0 3.5 0 5 10 15 20 25 4 0 8 12 16 20 24 28 32 36 40 TT4 (mcg/dL) TBG (mg/dL) TBG Total T4 Weeks of gestation Free T4 Free T3
  36. 36. Thyroid Function Tests in Pregnancy FT4, Free thyroxine; FT3, Free triiodothyronine; TSH, Thyroid stimulating hormone 1. Marwaha RK. BJOG. 2008;115(5):602-606. 2. SI Units for Clinical Data. University of North Carolina. Referral Values for TFT in Pregnant Indian Women 1,2 Thyroid Hormone Normal Values in Nonpregnant Trimester Range (5 th -95 th Percentile) FT 3 3.7-7.2 pM/L(240.26-467.53 pg/dL) I 1.92-5.86 pM/L (124.68-380.51 pg/dL) II 3.2-5.73 pM/L (207.8-372 pg/dL) III 3.3-5.18 pM/L (214.3-336.36 pg/dL) FT 4 12-23 pM/L (0.93-1.79 ng/dL) I 12-19.45 pM/L (0.93-1.51 ng/dL) II 9.48-19.58 pM/L (0.74-1.521 ng/dL) III 11.32-17.7 pM/L (0.88-1.38 ng/dL) TSH 0.27-4.2 µIU/mL I 0.6-5.0 µIU/mL II 0.44-5.78 µIU/mL III 0.74-5.7 µIU/mL
  37. 37. Maternal Hypothyroidism <ul><li>AACE recommendations </li></ul><ul><ul><li>Carry out TSH assay routinely before pregnancy or during the first trimester to rule out thyroid disorder </li></ul></ul><ul><ul><li>Avoid complications by administering thyroid hormone replacement therapy </li></ul></ul><ul><ul><li>Both mild as well as overt hypothyroidism are managed by administering levothyroxine therapy which can be safely administered during pregnancy </li></ul></ul><ul><ul><li>Assess TSH levels every 6 weeks during pregnancy for appropriate dose adjustments </li></ul></ul><ul><ul><li>Increase the dose of thyroid hormone in pregnant women with moderate to severe hypothyroidism </li></ul></ul>AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13 http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf .
  38. 38. Maternal Hypothyroidism <ul><li>Preconception: Optimize therapy in patients with preexisting disease </li></ul><ul><li>Pregnancy confirmed: Increase dose by 30-50% of preconception dose </li></ul><ul><li>Target levels </li></ul><ul><ul><li>TSH<2.5 mIU/L in the first trimester </li></ul></ul><ul><ul><li>TSH<3 mIU/L in later pregnancy </li></ul></ul><ul><li>After delivery, reduce dose to preconception dose </li></ul><ul><li>Assess thyroid function at 6 weeks postpartum </li></ul><ul><li>Post-ablative and post-surgical hypothyroidism require higher dose </li></ul>Lazaras JH. British Medical Bulletin . 2010;1-12.
  39. 39. Learning Activity <ul><li>Women with hypothyroidism carry an increased risk of ______. </li></ul><ul><ul><li>Infertility </li></ul></ul><ul><ul><li>Miscarriage/spontaneous abortion </li></ul></ul><ul><ul><li>Maternal hypertension </li></ul></ul><ul><ul><li>All of the above </li></ul></ul>
  40. 40. Case Presentation II: Congenital Hypothyroidism <ul><li>The baby delivered by Shobha was apparently normal. </li></ul><ul><li>Findings on neonatal examination are within normal limits </li></ul><ul><li>Neonatal screening for congenital hypothyroidism on the 3rd day by cord blood </li></ul><ul><ul><li>TSH: 38 mIU/L </li></ul></ul><ul><ul><li>Serum free T4: 0.5 ng/dL </li></ul></ul><ul><li>Diagnosis: Congenital Hypothyroidism </li></ul>
  41. 41. Congenital Hypothyroidism
  42. 42. Congenital Hypothyroidism <ul><li>Abnormality in the development of thyroid gland (dysgenesis or agenesis) and defect in the biosynthesis of thyroid hormones </li></ul><ul><li>Prevalence rate 1 in 4000 newborn infants in regions of sufficient daily iodine intake </li></ul><ul><li>2:1 incidence in females compared with males </li></ul><ul><li>Causes: Endemic iodine deficiency, genetic mutation, and hemangiomas </li></ul><ul><li>Routine thyroid function screening in neonates is recommended since no apparent clinical manifestation </li></ul><ul><li>Untreated congenital hypothyroidism results in development of cretinism </li></ul><ul><li>Do not delay diagnosis of congenital hypothyroidism until physical manifestations are seen </li></ul><ul><ul><li>Mental retardation </li></ul></ul><ul><ul><li>Deafness </li></ul></ul><ul><ul><li>Short stature </li></ul></ul><ul><ul><li>Characteristic facial deformities </li></ul></ul>Roberts CGP et al. Lancet. 2004;363: 793-803.
  43. 43. Congenital Hypothyroidism: Clinical Features Roberts CGP et al. Lancet. 2004;363: 793-803. <ul><ul><li>Infants </li></ul></ul>Children and Adolescents Hypothermia <ul><ul><li>Growth failure </li></ul></ul>Poor feeding <ul><ul><li>Markedly delayed bone maturation </li></ul></ul>Bradycardia <ul><ul><li>Delayed eruption of permanent teeth </li></ul></ul>Jaundice <ul><ul><li>Muscle pseudohypertrophy </li></ul></ul>Enlarged posterior fontanel Delayed or precocious puberty Umbilical hernia Pituitary enlargement <ul><ul><li>Galactorrhoea </li></ul></ul>
  44. 44. Diagnosis Of Congenital Hypothyroidism Rastogi and LaFranchi. Orphanet Journal of Rare Diseases 2010,5:17;1-22. DIAGNOSTIC ALGORITHM Screen the newborn for hypothyroidism: Initial T4 <10%, TSH ↑ Or Initial TSH ↑ Clinical suspicion of hypothyroidism Measure serum TSH and free T4 (or T 4 and T 3 resin uptake) TSH ↑(>9 mU/L) Free T 4 ↓ (<0.6 ng/dL) Diagnosis primary CH confirmed TSH ↓ or normal (<9 mU/L) Free T 4 ↓ (<0.6 ng/dL) Diagnosis likely secondary (central) hypothyroidism <ul><li>Other diagnostic tests to </li></ul><ul><li>determine etiology (optional): </li></ul><ul><li>Radionuclide uptake and scan </li></ul><ul><li>Ultrasonography </li></ul><ul><li>Serum thyroglobulin </li></ul><ul><li>Maternal antithyroid antibodies </li></ul><ul><li>Urinary iodine </li></ul><ul><li>Isolated: TSH β gene analysis </li></ul><ul><li>Evaluate for other pituitary hormone deficiencies </li></ul><ul><li>MRI of brain </li></ul><ul><li>Eye exam to check for optic nerve hypoplasia </li></ul>TSH: Thyroid stimulating hormone T4: Thyroxine T3: Triiodothyronine Free T4: Free thyroxine TSH β : Thyroid stimulating hormone beta
  45. 45. Congenital Hypothyroidism Case: Follow Up <ul><li>Initial work-up for Shobha’s child </li></ul><ul><ul><li>The baby was referred to pediatric endocrinologist </li></ul></ul><ul><ul><li>Thyroid ultrasonography showed a normal thyroid gland. </li></ul></ul><ul><li>Management </li></ul><ul><ul><li>The baby was started on LT4 at an initial daily dose of 50 mcg </li></ul></ul><ul><ul><li>The serum T4 normalized in 3 days </li></ul></ul><ul><ul><li>TSH normalized by end of 2 weeks </li></ul></ul><ul><ul><li>The mother was asked to follow-up with the baby on monthly basis. </li></ul></ul>
  46. 46. Management of Congenital Hypothyroidism <ul><li>Goal: To normalize T4 within 2 weeks and TSH within 1 month </li></ul><ul><li>Assess permanence of congenital hypothyroidism </li></ul><ul><ul><li>If initial thyroid scan shows ectopic/absent gland, congenital hypothyroidism is permanent </li></ul></ul><ul><ul><li>If initial TSH is <50 mIU/L and there is no increase in TSH after newborn period, off- therapy period is recommended at 3 years of age </li></ul></ul><ul><ul><li>If TSH increases during the off-therapy period, consider the condition as permanent congenital hypothyroidism </li></ul></ul><ul><li>Medications: LT4: 10-15  g/kg by mouth once-daily </li></ul><ul><li>Monitoring: Recheck T4 and TSH </li></ul><ul><ul><li>At 2-4 weeks after initiation of LT4 treatment </li></ul></ul><ul><ul><li>Every 1-2 months in the first 6 months </li></ul></ul><ul><ul><li>Every 3-4 months between 6 months and 3 years of age </li></ul></ul><ul><ul><li>Every 6-12 months from 3 years of age to end of growth </li></ul></ul>Rose SR and Brown RS. Pediatric s. 2006;117(6):2290-2303.
  47. 47. Learning Activity <ul><li>All of the following signs represent congenital hypothyroidism, EXCEPT </li></ul><ul><li>Tachycardia </li></ul><ul><li>Jaundice </li></ul><ul><li>Enlarged posterior fontanel </li></ul><ul><li>Umbilical hernia </li></ul>
  48. 48. Comorbid Conditions
  49. 49. Comorbid Conditions 1. AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13 http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf . 2. Duntas LH, Biondi B. Semin Thromb Hemost . 2011;37(1):27-34.
  50. 50. Comorbid Conditions (Contd.) <ul><li>Diabetes mellitus </li></ul><ul><li>Hashimoto’s thyroiditis may be associated with 10% patients of type 1 diabetes mellitus </li></ul><ul><li>Approximately one-fourth of female patients with type 1 diabetes mellitus develop postpartum thyroiditis </li></ul><ul><li>AACE recommendations for patients with diabetes mellitus </li></ul><ul><ul><li>Examine for goiter </li></ul></ul><ul><ul><li>Assess TSH levels regularly especially in the presence of a goiter or other autoimmune disorders </li></ul></ul><ul><li>Infertility </li></ul><ul><li>Hypothyroidism due to chronic thyroiditis may cause infertility, miscarriage, and menstrual irregularities </li></ul><ul><ul><li>Treatment with LT4 replacement therapy restores normal menstrual cycle and fertility </li></ul></ul>AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13 http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf .
  51. 51. Comorbid Conditions (Contd.) <ul><li>Depression </li></ul><ul><li>In every patient with depression, diagnosis of overt or subclinical hypothyroidism should be considered </li></ul><ul><li>Periodic evaluation for thyroid function should be performed in patients receiving lithium therapy </li></ul><ul><ul><li>Treatment is with LT4 replacement therapy </li></ul></ul><ul><ul><li>LT4 is indicated occasionally in combination with antidepressants in euthyroid patients with depression </li></ul></ul>AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13 http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf .
  52. 52. Comorbid Conditions (Contd.) <ul><li>Dyslipidemia and cardiovascular sequelae comorbid with overt hypothyroidism </li></ul><ul><li>Overt hypothyroidism with dyslipidemia is characterized by </li></ul><ul><ul><li>Increased levels of total cholesterol </li></ul></ul><ul><ul><li>Increased LDL cholesterol </li></ul></ul><ul><li>Mechanisms for dyslipidemia </li></ul><ul><ul><li>Impaired production of TC and </li></ul></ul><ul><ul><li>Decreased expression of the LDL receptors </li></ul></ul><ul><li>Severe cardiovascular disease and premature atherosclerosis, if untreated, lead to </li></ul><ul><ul><li>Pericardial effusion </li></ul></ul><ul><ul><li>Congestive heart failure </li></ul></ul><ul><ul><li>Coronary artery disease </li></ul></ul>Duntas LH, Biondi B. Semin Thromb Hemost. 2011;37(1):27-34
  53. 53. Comorbid Conditions (Contd.) <ul><li>Cardiovascular sequelae comorbid with subclinical hypothyroidism </li></ul><ul><li>Subclinical hypothyroidism is associated with </li></ul><ul><ul><ul><li>Impaired diastolic function and depressed left ventricular systolic function in middle-aged patients </li></ul></ul></ul><ul><ul><ul><li>Increased risks of atherosclerosis and myocardial infarction </li></ul></ul></ul><ul><ul><ul><li>Mortality in patients less than 65 years of age due to cardiovascular events </li></ul></ul></ul><ul><ul><ul><li>Proatherogenic mechanisms that leads to low-grade inflammation and may suggest CVD </li></ul></ul></ul><ul><ul><ul><li>Hypercoagulable state </li></ul></ul></ul><ul><li>LT4 therapy for subclinical hypothyroidism </li></ul><ul><ul><ul><li>Reverses cardiovascular alterations </li></ul></ul></ul><ul><ul><ul><li>Reduces cardiovascular risk factors </li></ul></ul></ul><ul><ul><ul><li>Improves dyslipidaemia </li></ul></ul></ul><ul><ul><ul><li>Minimizes neurobehavioral changes </li></ul></ul></ul>Duntas LH, Biondi B. Semin Thromb Hemost. 2011;37(1):27-34 CVD: Cardiovascular disease The Cycle of Disease Subclinical Hypothyroidism Emerging Risk Factors CVD Endothelial Dysfunction Cardiac Alterations Blood Pressure Hyperlipidemia Hemostatic Balance Obesity
  54. 54. Learning Activity
  55. 55. Learning Activity <ul><li>Which of the following statements are TRUE regarding LT4 therapy in hypothyroidism? (Select all that apply.) </li></ul><ul><li>Congenital hypothyroidism is treated with LT4 at a dose of 50-100 mcg/kg orally once-daily. </li></ul><ul><li>LT4 therapy for subclinical hypothyroidism reverses cardiovascular alterations. </li></ul><ul><li>LT4 is contraindicated in combination with antidepressants in euthyroid patients with depression. </li></ul><ul><li>Both mild as well as overt hypothyroidism are managed by administering levothyroxine therapy. </li></ul>
  56. 56. Thank You Copyright © 2011 Abbott India Limited. All rights reserved

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