Thyroid Disorders

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Thyroid Disorders

  1. 1. Thyroid Disorders William Harper, MD, FRCPC Endocrinology & Metabolism Assistant Professor of Medicine, McMaster University
  2. 2. Case 1 <ul><li>31 year old female </li></ul><ul><li>Somalia  Canada 3 years ago </li></ul><ul><li>G2P1A0, 11 weeks pregnant </li></ul><ul><li>Well except fatigue </li></ul><ul><li>Hb 108 , ferritin 7 (Fe and LT4 interaction?) </li></ul><ul><li>TSH 0.2 mU/L, FT4 7 pM </li></ul><ul><li>Started on LT4 0.05  TSH < 0.01 mU/L </li></ul><ul><li> FT4 12 pM, FT3 2.1 pM </li></ul>
  3. 3. Case 1 <ul><li>How would you characterize her hypothyroidism? </li></ul><ul><li>What are the ramifications of pregnancy to thyroid function/dysfunction? </li></ul>
  4. 4. TSH Low High FT4 FT4 & FT3 Low 1 ° Hypothyroid Low Central Hypothyroid TRH Stim. If equivocal MRI, etc. High 1 ° Thyrotoxicosis High 2 ° thyrotoxicosis <ul><li>Endo consult </li></ul><ul><li>FT3, rT3 </li></ul><ul><li>MRI, α -SU </li></ul>RAIU
  5. 5. TRH Stimulation test A) 1 ° Hypothyroidism B) Central Hypothyroidism C) Euthyroid D) 1 ° Thyrotoxicosis
  6. 6. Case 1 <ul><li>GH, IGF-1 normal </li></ul><ul><li>LH, FSH, E2, progesterone, PRL normal for pregnancy </li></ul><ul><li>8 AM cortisol 345, short ACTH test normal </li></ul><ul><li>MRI: normal pituitary </li></ul><ul><li>TGAB, TPOAB negative </li></ul><ul><li>LT4 increased until FT4 in hi-normal range </li></ul><ul><li>Normal pregnancy, delivery, baby, lactation </li></ul><ul><li>Considering TRH stim once done breast-feeding </li></ul>
  7. 7. Thyroid Tests <ul><li>Thyroid Function </li></ul><ul><li>Iodine Kinetics </li></ul><ul><li>Thyroid Structure </li></ul><ul><li>FNA </li></ul><ul><li>Thyroid Antibodies </li></ul><ul><li>Thyroglobulin </li></ul>
  8. 8. T4 T3 80% (peripheral) 20% Protein* binding + 0.03% free T4 Protein* binding + 0.3% free T3 (10-20x less than T4) Total T4 60-155 nM Total T3 0.7-2.1 nM T 3 RU/THBI 0.77-1.23 TBG 75% TBPA 15% Albumin 10% *
  9. 9. Thyroid Function Tests <ul><li>TSH 0.4 –5.0 mU/L </li></ul><ul><li>Free T4 (thyroxine) 9.1 – 23.8 pM </li></ul><ul><li>Free T3 (triiodothyronine) 2.23-5.3 pM </li></ul>
  10. 10. TSH Assay (0.4-5 mU/L) <ul><li>Early RIA < 1.0 mU/L </li></ul><ul><ul><ul><li>Thyrotoxicosis / 2 º hypothyroidism </li></ul></ul></ul><ul><ul><ul><ul><li>Unable to detect lower range of normal </li></ul></ul></ul></ul><ul><li>Monoclonal SEN < 0.1 mU/L </li></ul><ul><li>Super SEN < 0.01 mU/L </li></ul>
  11. 11. Case 1 <ul><li>How would you characterize her hypothyroidism? </li></ul><ul><li>What are the ramifications of pregnancy to thyroid function/dysfunction? </li></ul>
  12. 12. Thyroid & Pregnancy: Normal Physiology <ul><li>Increased estrogen  increased TBG </li></ul><ul><li>Higher total T4, T3 (normal FT4, FT3 if thyroid gland working properly) </li></ul><ul><li>hCG peak end of 1 st trimester, weak TSH agonist so may cause slight goitre </li></ul><ul><li>Fetal thyroid starts working at 11 wks </li></ul><ul><li>T4 & T3 do NOT cross placenta (or do so minimally) </li></ul><ul><li>Do cross placenta: PTU, MTZ, TSH-R Ab (stim or block) </li></ul><ul><li>MTZ  aplasia cutis scalp defects </li></ul>
  13. 14. Thyroid & Pregnancy: Hypothyroidism <ul><li>Will need ~ 25% increase in LT4 during pregnancy due to increased TBG levels </li></ul><ul><li>Risks: increased spont abort, HTN, preterm pregnancy, 7 IQ points for fetus (NEJM, 341(8):549-555, Aug 31, 2001) </li></ul>
  14. 15. LT4 dose adjustment in Pregnancy: Need TSH at baseline & q2mos while pregnant Starting LT4: 2 ug/kg/d and check TSH q4wk until euthythyroid Increase dose by 100 ug/d TSH > 20 Increase dose by 50-75 ug/d TSH 10-20 Increase dose by 50 ug/d TSH increased but < 10 Dose Adjustment TSH
  15. 16. Thyrotoxicosis & Pregnancy <ul><li>Risks: fetal anomalies, spont abort, preterm labor, fetal hyperthyoridism, thyroid storm in labor </li></ul><ul><li>No RAI ever </li></ul><ul><li>Rx options: ATD or 2 nd trimester thyroidectomy </li></ul><ul><li>PTU drug of choice (avoid MTZ due to scalp defects) </li></ul><ul><li>Aim to keep FT4 levels in hi normal range </li></ul><ul><li>OK to breast feed on PTU as does not go into breast milk </li></ul>
  16. 17. Neonatal Grave’s <ul><li>Rare < 2% infants born to Graves” moms </li></ul><ul><li>2 types: </li></ul><ul><li>Transplacental trnsfr of TSH-R ab (IgG) </li></ul><ul><ul><ul><li>Present at birth, self-limited </li></ul></ul></ul><ul><ul><ul><li>Rx PTU, Lugol’s, propanolol, prednisone </li></ul></ul></ul><ul><ul><ul><li>Prevention: TSI in mom 2 nd trimester, if 5X normal then Rx mom with PTU (crosses placenta to protect fetus) even if mom is euthyroid (can give mom LT4 which won’t cross placenta) </li></ul></ul></ul><ul><li>Child develops own TSH-R ab </li></ul><ul><ul><ul><li>Strong family hx of Grave’s </li></ul></ul></ul><ul><ul><ul><li>Present @ 3-6 mos </li></ul></ul></ul><ul><ul><ul><li>20% mortality, persistant brain dysfunction </li></ul></ul></ul>
  17. 18. Postpartum & Thyroid <ul><li>5% (3-16%) postpartum women (25% T1DM) </li></ul><ul><li>Up to 1 year postpartum (most 1-4 months) </li></ul><ul><li>Lymphocytic infiltration (Hashimoto’s) </li></ul><ul><li>Postpartum  Exacerbation of all autoimmune dx </li></ul><ul><li>25-50% persistant hypothyroidism </li></ul><ul><li>Small, diffuse, nontender goitre </li></ul><ul><li>Transiently thyrotoxic  Hypothyroid </li></ul>
  18. 20. Postpartum & Thyroid <ul><li>Distinguish Thyrotoxic phase from Grave’s: </li></ul><ul><ul><ul><li>No Eye disease </li></ul></ul></ul><ul><ul><ul><li>Less severe thyrotoxic, transient (repeat thyroid fn 2-3 mos) </li></ul></ul></ul><ul><ul><ul><li>RAI (if not breast-feeding) </li></ul></ul></ul><ul><li>Rx: </li></ul><ul><ul><ul><li>Hyperthyroid symptoms: atenolol 25-50 mg od </li></ul></ul></ul><ul><ul><ul><li>Hypothyroid symptoms: LT4 50-100 ug/d to start </li></ul></ul></ul><ul><ul><ul><ul><ul><li>Adjust LT4 dose for symtoms and normalization TSH </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Consider withdrawal at 6-9 months </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>(25-50% persistent hypothyroid, hi-risk recur future preg) </li></ul></ul></ul></ul></ul>
  19. 21. Postpartum & Thyroid <ul><li>Postpartum depression </li></ul><ul><ul><ul><li>When studied, no association between postpartum depression/thyroiditis </li></ul></ul></ul><ul><ul><ul><li>Overlapping symtoms, R/O thyroid before start antidepressents </li></ul></ul></ul><ul><li>Screening for Postpartum Thyroiditis </li></ul><ul><ul><ul><li>HOW: TSH q3mos from 1 mos to 1 year postpartum? </li></ul></ul></ul><ul><ul><ul><li>WHO: </li></ul></ul></ul><ul><ul><ul><ul><li>Symptoms of thyroid dysfn. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Goitre </li></ul></ul></ul></ul><ul><ul><ul><ul><li>T1DM </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Postpartum thyroiditis with prior pregnancy </li></ul></ul></ul></ul>
  20. 22. Case 2 <ul><li>47 year old female </li></ul><ul><li>Concerned about weight gain over past 15 years (15 lbs). Otherwise asymptomatic </li></ul><ul><li>BMI 25, Thyroid: 40 gm, rubbery firm. </li></ul><ul><li>TSH 6.7 mU/L, FT4 13 pM, FT3 2.5 pM </li></ul><ul><li>FHx: mother, sister – both on LT4 </li></ul><ul><li>Medications: “Thyrosol” (health store) </li></ul><ul><li>Wondering about hypothyroidism causing her weight gain </li></ul><ul><li>Read on internet about “Wilson’s Disease” </li></ul>
  21. 23. Case 2 <ul><li>When to treat “Subclinical” thyroid dysfunction? </li></ul><ul><li>Naturopathic thyroid remedies </li></ul><ul><li>Hypothryoidism Rx other than Levothyroxine </li></ul><ul><li>What is Wilson’s Thyroid Disease? </li></ul>
  22. 24. Subclincal Hypothyroidism <ul><li> TSH, normal FT4 </li></ul><ul><li>Most asymptomatic & don’t need Rx (monitor TSH q2-5y) </li></ul><ul><li>Rx Indications: </li></ul><ul><ul><li>Increased risk of progression </li></ul></ul><ul><ul><ul><li>TSH > 10, Female > 50 y.o. </li></ul></ul></ul><ul><ul><ul><li>Anti-TPO Ab titre > 1:100,000 ? </li></ul></ul></ul><ul><ul><ul><li>Goitre present ? </li></ul></ul></ul><ul><ul><li>Dyslipidemia? </li></ul></ul><ul><ul><ul><li>Total cholesterol (TC)  6-8% if TSH > 10 and TC > 6.2 nM </li></ul></ul></ul><ul><ul><li>Symptoms? </li></ul></ul><ul><ul><li>Pregnancy, Infertility, Ovulatory Dysfn. </li></ul></ul>
  23. 25. Case 2 <ul><li>When to treat “Subclinical” thyroid dysfunction? </li></ul><ul><li>Naturopathic thyroid remedies (Thyrosol) </li></ul><ul><li>Hypothryoidism Rx other than Levothyroxine </li></ul><ul><li>What is Wilson’s Thyroid Disease? </li></ul>
  24. 27. Hashimoto’s Disease <ul><li>Most common cause of hypothyroidism in North America (not idodine defeciency!) </li></ul><ul><li>Autoimmune </li></ul><ul><li>lymphocytic thyroiditis </li></ul><ul><li>Females > Males, Runs in Families </li></ul><ul><li>Antithyroid antibodies: </li></ul><ul><ul><ul><li>Thyroglobulin Ab </li></ul></ul></ul><ul><ul><ul><li>Microsomal Ab </li></ul></ul></ul><ul><ul><ul><li>TSH-R Ab (block) </li></ul></ul></ul>
  25. 28. Hashimoto’s Disease <ul><li>Treatment: </li></ul><ul><ul><ul><li>Thyroid Hormone Replacement </li></ul></ul></ul><ul><ul><ul><li>Levothyroxine (T4) </li></ul></ul></ul><ul><ul><ul><li>T3?, T4/T3 combo?, dessicated thyroid? </li></ul></ul></ul><ul><li>No benefit to giving iodine! </li></ul><ul><ul><ul><li>In fact, iodine may decrease hormone production </li></ul></ul></ul><ul><ul><ul><li>Wolff-Chaikoff effect (lack of escape) </li></ul></ul></ul>
  26. 29. Case 2 <ul><li>When to treat “Subclinical” thyroid dysfunction? </li></ul><ul><li>Naturopathic thyroid remedies </li></ul><ul><li>Hypothryoidism Rx other than Levothyroxine </li></ul><ul><li>What is Wilson’s Thyroid Disease? </li></ul>
  27. 30. Treatment of Hypothyroidism <ul><li>Iodine only if iodine deficiency is the cause </li></ul><ul><ul><ul><li>Rare in North America! </li></ul></ul></ul><ul><li>Replacement thyroid hormone medication: </li></ul><ul><ul><ul><li>T4? </li></ul></ul></ul><ul><ul><ul><li>T3? </li></ul></ul></ul><ul><ul><ul><li>T4 + T3 Mixture? </li></ul></ul></ul><ul><ul><ul><li>Thyroid Hormone from “natural sources” ? </li></ul></ul></ul>
  28. 31. T4 T3 85% (peripheral conversion) 15% Protein* binding + 0.03% free T4 Protein* binding + 0.3% free T3 (10-20x less than T4) Normal Daily Thyroid Secretion Rate: T4 = 100 ug/day T3 = 6 ug/day ( ratio T4:T3 = 14:1 )
  29. 32. < 24h 5-7d Half-Life 6 ug/d 100 ug/d Secreted by thyroid 1 10-20 Protein Bound 10 1 Potency T3 T4
  30. 33. Levothyroxine (T4) <ul><li>Synthroid (Abbott), Eltroxin (GSK) </li></ul><ul><li>Synthetically made </li></ul><ul><li>50 ug white pill  no dye (hypoallergenic) </li></ul><ul><li>Most commonly prescribed treatment for hypothyroidism </li></ul><ul><li>No T3 (but 85% of T3 comes from T4 conversion) </li></ul><ul><li>All patients made euthyroid biochemically </li></ul><ul><li>Most (but not all) patients feel normal </li></ul>
  31. 34. Levothyroxine (T4) <ul><li>Average dose 1.6 ug/kg </li></ul><ul><li>Age > 50-60 or cardiac disease: must start at a low dose (25 ug/d) </li></ul><ul><li>Recheck thyroid hormone levels every 4-6 weeks after a dose change </li></ul><ul><li>Aim for a normal TSH level </li></ul>
  32. 35. Levothyroxine (T4) <ul><li>Medical situations where T4 medication may be affected. </li></ul><ul><li>Estrogen: Pregnancy, OCP, HRT </li></ul><ul><ul><ul><li>Need to increase T4 dose! </li></ul></ul></ul><ul><li>Drugs that interfere with T4 absorption </li></ul><ul><ul><ul><li>Iron, Calcium </li></ul></ul></ul><ul><ul><ul><li>Cholestyramine (cholesterol resin Rx) </li></ul></ul></ul><ul><ul><ul><li>At least 4h between T4 and these drugs! </li></ul></ul></ul>
  33. 36. “ I still don’t feel normal on Synthroid even though my blood tests are normal.” <ul><li>Free T4, Free T3 </li></ul><ul><ul><ul><li>wide range of normal </li></ul></ul></ul><ul><li>TSH ( 0.4 –5.0 mU/L) </li></ul><ul><ul><ul><li>Narrow range of normal, but still a range! </li></ul></ul></ul><ul><ul><ul><li>Adjust dose for a lower TSH still in the normal range? </li></ul></ul></ul><ul><li>Tissue levels versus circulating levels? </li></ul><ul><ul><ul><li>No human studies </li></ul></ul></ul><ul><ul><ul><li>Rodents: High T4 and normal T3 tissue levels </li></ul></ul></ul>
  34. 37. Liothyronine (T3) <ul><li>Cytomel (Theramed) </li></ul><ul><li>Shorter half-life </li></ul><ul><ul><ul><li>Fluctuating levels (i.e. need a slow-release pill) </li></ul></ul></ul><ul><ul><ul><li>Twice daily dosing often needed </li></ul></ul></ul><ul><li>10x more potent: palpitations & other cardiac side effects </li></ul><ul><li>High T3 levels, low T4 levels (not physiologic either!) </li></ul>
  35. 38. T3/T4 Liotrix <ul><li>Thyrolar </li></ul><ul><li>Combo pill of T3 and T4 </li></ul><ul><li>Ratio of T4:T3 = 4:1 (not 14:1) </li></ul><ul><li>T3 still not slow release </li></ul><ul><li>Few small studies showing benefit </li></ul><ul><ul><ul><li>1999 NEJM study 33 patients </li></ul></ul></ul><ul><ul><ul><li>Benefit: mood & cognitive function </li></ul></ul></ul><ul><li>Not available in Canada </li></ul>
  36. 39. Desiccated Thyroid (Armour) <ul><li>Desiccated powder derived from thyroids of slaughtered pigs or cows </li></ul><ul><ul><ul><li>Vegetarian? </li></ul></ul></ul><ul><ul><ul><li>Mad Cow Disease? </li></ul></ul></ul><ul><li>Contains T4 and T3 </li></ul><ul><li>Still no slow-release of T3 </li></ul><ul><li>Ratio of T4:T3 </li></ul><ul><ul><ul><li>Variable </li></ul></ul></ul><ul><ul><ul><li>Still not physiologic, often too high in T3 (T4:T3 = 3:1) </li></ul></ul></ul>
  37. 40. “ In an ideal world…” <ul><li>Mixed compound with T4:T3 = 14:1 </li></ul><ul><li>T3 component slow release formulation </li></ul><ul><li>Resultant: </li></ul><ul><ul><ul><li>Normal circulating TSH, FT4, FT3 </li></ul></ul></ul><ul><ul><ul><li>Normal tissue levels of T4 and T3 </li></ul></ul></ul><ul><li>Good, large studies (RCTs) demonstrating clear benefit over T4 alone </li></ul>
  38. 41. Case 2 <ul><li>When to treat “Subclinical” thyroid dysfunction? </li></ul><ul><li>Naturopathic thyroid remedies </li></ul><ul><li>Hypothryoidism Rx other than Levothyroxine </li></ul><ul><li>What is Wilson’s Thyroid Disease? </li></ul>
  39. 42. “Wilson’s Syndrome” <ul><li>Wilson’s disease: copper toxicity  liver failure </li></ul><ul><li>“ Wilson’s Syndrome” </li></ul><ul><ul><ul><li>Dr. E. D. Wilson “discovered” this condition and named it after himself in late 1980’s </li></ul></ul></ul><ul><ul><ul><li>Decreased body temperature (low normal range) </li></ul></ul></ul><ul><ul><ul><li>Hypothyroid symptoms (nonspecific) </li></ul></ul></ul><ul><ul><ul><li>Normal thyroid function tests </li></ul></ul></ul><ul><ul><ul><li>“ Impaired T4  T3 conversion” </li></ul></ul></ul><ul><ul><ul><li>“ Build up of reverse T3” </li></ul></ul></ul><ul><ul><ul><li>Treat with “Wilson’s T3-therapy” (presumably T3) </li></ul></ul></ul>
  40. 43. Sick Euthyroid Syndrome, not Wilson’s syndrome!
  41. 44. “Wilson’s Syndrome” <ul><li>No scientific evidence that this condition exists </li></ul><ul><li>No randomized trials proving safety or any benefit of giving people T3 when their thyroid hormone levels are normal </li></ul><ul><li>This condition not endorsed by: </li></ul><ul><ul><ul><li>Canadain Society of Endocrinology and Metabolism (CSEM) </li></ul></ul></ul><ul><ul><ul><li>American Thyroid Association (ATA) </li></ul></ul></ul><ul><ul><ul><li>Endocrine Society </li></ul></ul></ul>
  42. 45. Case 3 <ul><li>62 y male </li></ul><ul><li>Afib: amiodarone, warfarin x 11 months </li></ul><ul><li>2 months: fatigue, muscle weakness, increasing dyspnea/edema, weight gain </li></ul><ul><li>O/E: HR 110 irreg-irreg, appears malnourished,  JVP, SOA, lung crackles </li></ul>
  43. 46. Case 3 <ul><li>TSH < 0.05 mU/L, FT4 60 pM, FT3 24 pM </li></ul><ul><li>INR 4.2, Echo: LVH, normal LV syst fn. </li></ul><ul><li>RAIU 2%, Thyroid scan: no gland seen </li></ul><ul><li>Rx: Methimazole 40 mg/d, lasix, aldactone, ramipril, reduced warfarin </li></ul><ul><li>Cardiolgist: d/c amiodarone  bisoprolol </li></ul>
  44. 47. Case 3 <ul><li>F/up @ 2 mos: </li></ul><ul><li>weight loss (more muscle, less fluid) </li></ul><ul><li>Resolved: Fatigue, SOB, SOA </li></ul><ul><li>HR 76 irreg-irreg </li></ul><ul><li>TSH < 0.05, FT4 8 pM, FT3 2.1 pM </li></ul><ul><li>INR 1.5 </li></ul>
  45. 48. Case 3 <ul><li>What is difference between thyrotoxicosis and hyperthyroidism? </li></ul><ul><li>What is “apathetic” hyperthyroidism? </li></ul><ul><li>Amiodarone induced thyrotoxicosis? </li></ul><ul><li>Thyroid & drug-interactions (warfarin)? </li></ul><ul><li>Subclinical Thyrotoxicosis? </li></ul>
  46. 49. RAIU <ul><li>Oral dose of I 131 5 uCi (or I 123 200 uCi but more $) </li></ul><ul><li>Measure neck counts @ 24h (+/- 4h if suspect high turnover) </li></ul><ul><li>RAIU = neck counts – bkgd (thigh counts) x 100 </li></ul><ul><li>pill counts - bkgd </li></ul>
  47. 50. RAIU <ul><li>Normal 4h RAIU = 5-15 % </li></ul><ul><li>24h RAIU : </li></ul><ul><ul><ul><li>>25% Hyperthyroid </li></ul></ul></ul><ul><ul><ul><li>20-25% Equivocal (check TSH) </li></ul></ul></ul><ul><ul><ul><li>9-20% Normal </li></ul></ul></ul><ul><ul><ul><li>5-9% Equivocal (check TSH) </li></ul></ul></ul><ul><ul><ul><li><5% Hypothyroid </li></ul></ul></ul><ul><li>Dependent on dietary iodine intake! </li></ul><ul><li>Must be: not pregnant! ( ß-hCG), no ATD x 7d, no LT4 x 4d, no large doses of iodine or radiocontrast for 2 wk (prefer 4-6 wk) </li></ul>
  48. 52. Thyrotoxicosis Treatment <ul><li>Beta-blockers (hyperadrenergic symptoms) </li></ul><ul><li>Hyperthyroidism: </li></ul><ul><ul><ul><li>Anti-thyroid Drugs </li></ul></ul></ul><ul><ul><ul><ul><li>Propylthiouracil (PTU), Methimazole </li></ul></ul></ul></ul><ul><ul><ul><li>Radioiodine Ablation </li></ul></ul></ul><ul><ul><ul><li>Surgical Thyroidectomy </li></ul></ul></ul><ul><li>Thyroiditis: </li></ul><ul><ul><ul><li>ASA, NSAIDS, +/- corticosteroids </li></ul></ul></ul><ul><li>Iodine (high doses  Wolff Chaikoff effect) </li></ul>
  49. 53. “ Apathetic Hyperthyroidism” <ul><li>Elderly population </li></ul><ul><li>Lack of tremor, diaphoresis, heat-intolerance, hyperdefecation and other classic symptoms from sympathetic over-activity </li></ul><ul><li>TMNG more likely than in young (but Grave’s still most common) </li></ul><ul><li>Less likely to have a goitre </li></ul><ul><li>Common symptoms: </li></ul><ul><ul><ul><li>Weight loss, anorexia </li></ul></ul></ul><ul><ul><ul><li>Constipation despite thyrotoxic </li></ul></ul></ul><ul><ul><ul><li>Tachycardia, Afib, CHF, angina </li></ul></ul></ul><ul><ul><ul><li>Cognitive Dysfunction </li></ul></ul></ul>
  50. 54. Amiodarone and Thyroid <ul><li>PHYSIOLOGIC EFFECTS </li></ul><ul><li>1) Increase iodine pool in body and therefore decrease RAIU. </li></ul><ul><li>2) Decrease peripheral deiodination of T4 to T3. </li></ul><ul><li>3) Decrease pituitary deiodination and therefore transient rise in TSH for 1st 3 mos of Rx. </li></ul><ul><li>Amiodarone Induced Thyroid Dysfunction: </li></ul><ul><li>3 months to 4 years after starting amiodarone </li></ul><ul><li>Hypothyroidism 8% (subclinical hypothyroidism 20%) </li></ul><ul><li>Thyrotoxicosis 3% (10% iodine deficiency areas) </li></ul>
  51. 55. Amiodarone induced Hypothyroidism <ul><li>1) Increased TSH (not useful 1st 3 mos). </li></ul><ul><li>2) Decreased FT4 </li></ul><ul><li>3) Decreased FT3 (not neccesary to measure) </li></ul><ul><li>4) More common in areas of hi iodine intake (North America) d/t Wolff Chaikoff effect. </li></ul><ul><li>5) Rx: </li></ul><ul><ul><ul><li>Stop amiodarone if possible. </li></ul></ul></ul><ul><ul><ul><li>LT4 aim dose to keep FT4 level at high normal to slightly above normal. </li></ul></ul></ul><ul><ul><ul><li>Unlike other types of hypothyroidism do NOT try to normalize TSH as this requires dose ~ 250 ug/d and clearly causes hyperthyroidism. </li></ul></ul></ul>
  52. 56. Amiodarone induced Thyrotoxicosis (AIT) <ul><li>1) Decreased TSH </li></ul><ul><li>2) Increased FT4 </li></ul><ul><li>3) Increased FT3 in some patients (inhibition of deiodinase) </li></ul><ul><li>4) More common in areas of low iodine intake (Europe) d/t Jodbasedow effect or iodine/amiodarone induced thyroid damage. </li></ul><ul><li>5) Two types of AIT: </li></ul><ul><ul><ul><li>Hyperthyroidism (RAIU low but measurable) – Jodbasedow, often goitre/nodule(s) </li></ul></ul></ul><ul><ul><ul><li>Thyroiditis (RAIU 0%) </li></ul></ul></ul><ul><li>6) May present without hyperthyroid symptoms and simply worsening of cardiac disorder (arrythmia, angina, CHF, etc). </li></ul>
  53. 57. Amiodarone induced Thyrotoxicosis (AIT) <ul><li>Rx: </li></ul><ul><li>Stopping amiodarone may not help as amiodarone still present in body tissue stores for months </li></ul><ul><li>May need amiodarone to still treat arrythmias made worse by thyrotoxicosis </li></ul><ul><li>Radioactive I-131 useless d/t decreased RAIU. </li></ul><ul><li>Thionamide ATDs (PTU, methimazole): Rx of choice </li></ul><ul><li>Glucocorticoids if RAIU indicates thyroiditis & no response to ATD </li></ul><ul><ul><ul><li>Prednisone 40 mg/d </li></ul></ul></ul><ul><li>Surgery? Somewhat risky d/t unknown safety wrt thyroid storm & underlying heart condition that required amiodarone in the first place! </li></ul><ul><li>KClO4 (potassium perchlorate)? </li></ul>
  54. 59. Thyroid & Drug Interactions <ul><li>1) Warfarin </li></ul><ul><li>T4 increases catabolism of vitamin K dependent clotting factors. </li></ul><ul><li>Increase LT4/hyperthyroidism will increase sensitivity to warfarin (decrease dose). </li></ul><ul><li>Decrease LT4/hypothyroidism will decrease sensitivity to warfarin (increase dose). </li></ul><ul><li>2) Cholestyramine </li></ul><ul><li>Binds T4 & T3 </li></ul><ul><li>4-5h between resin & LT4 or T3. </li></ul><ul><li>3) Iron or Calcium </li></ul><ul><li>Also binds T4 & T3 </li></ul>
  55. 60. Thyroid & Drug Interactions <ul><li>4) Estrogens </li></ul><ul><li>Increase TBG, decrease FT4 level </li></ul><ul><li>Need to increase LT4 in some patients </li></ul><ul><li>5) Androgens/corticosteroids </li></ul><ul><li>Decrease TBG, increase FT4 level </li></ul><ul><li>Need to decrease LT4 in some patients </li></ul><ul><li>5) Diabetes </li></ul><ul><li>Increase LT4/hyperthyroidism will increase insulin/OHA requirements. </li></ul><ul><li>Decrease LT4/hypothyroidism will decrease insulin/OHA requirements. </li></ul>
  56. 61. Subclinical Hyperthyroidism <ul><li> TSH, Normal FT4 and FT3 </li></ul><ul><li>Progression to overt hyperthyroidism low: </li></ul><ul><ul><ul><li>Men 0% per year </li></ul></ul></ul><ul><ul><ul><li>Women 1.5% per year </li></ul></ul></ul><ul><ul><ul><li>TMNG or toxic adenoma present 5% per year </li></ul></ul></ul><ul><li>Indications to Rx: </li></ul><ul><ul><ul><li>Any cardiac disease (CAD, AFIB, etc.) </li></ul></ul></ul><ul><ul><ul><li>Age > 60 (10 year risk AFIB 32%, 10% if normal TSH) </li></ul></ul></ul><ul><ul><ul><li>TMNG or toxic adenoma </li></ul></ul></ul><ul><ul><ul><li>Osteoporosis </li></ul></ul></ul>
  57. 62. Case 4 <ul><li>29 year old female, engaged to be married </li></ul><ul><li>T1DM </li></ul><ul><li>Thyroid U/S: </li></ul><ul><ul><ul><li>2.9 cm R lower pole </li></ul></ul></ul><ul><ul><ul><li>2.0 cm L lower pole, </li></ul></ul></ul><ul><ul><ul><li>Many others ranging from 0.5-1.5 cm </li></ul></ul></ul><ul><li>TSH < 0.05 mU/L, FT4 19 pM, FT3 6.9 pM </li></ul><ul><li>RAIU/Scan: 45% RAIU, hot nodule on Left </li></ul>
  58. 63. Case 4 <ul><li>FNA of 3cm nodule on Right: benign </li></ul><ul><li>Rx’s offered: </li></ul><ul><ul><ul><li>RAI ablation versus thyroidectomy </li></ul></ul></ul><ul><li>Patient chose Thyroidectomy </li></ul>
  59. 64. Thyroid Structure <ul><li>Physical Exam </li></ul><ul><li>Thyroid Ultrasound </li></ul><ul><li>Thyroid Scan </li></ul>
  60. 65. Thyroid nodules <ul><li>U/S more sensitive than P.E., particularly for nodules that are < 1 cm or located posteriorly in the gland. </li></ul><ul><li>U/S also more SEN than thyroid scan </li></ul><ul><li>U/S too Sensitive? </li></ul><ul><ul><ul><li>Thyroid Incidentaloma (Carotid duplex, etc.) </li></ul></ul></ul>
  61. 66. Thyroid U/S Microcalcification Egg shell calcification Intranodular vascular spots (color doppler) N/A Hypoechoic (more vascular) Hyperechoic Irregular border No Halo Regular border Halo (sonolucent rim) Malignant Characteristics Benign Characteristics
  62. 67. Thyroid Scan Thyroid nodule: risk of malignancy 6.5% Cold nodule 16-20% malignant “Warm” Nodule (indeterminant) 5% malignant Hot Nodule Tc-99m < 5% malignant I 123 < 1% malignant only 5-10% of nodules
  63. 68. Fine Needle Aspiration (FNA) <ul><li>25G Needle, 10cc syringe </li></ul><ul><li>Done in Office </li></ul><ul><li>+/- Local </li></ul><ul><li>3-5 passes </li></ul><ul><li>SEN 95-99% (False Negative rate 1-5%) </li></ul><ul><li>SPEC > 95% </li></ul>
  64. 69. FNA Results <ul><li>Nondiagnostic: repeat FNA </li></ul><ul><li>Benign: macrofollicular or &quot;colloid&quot; adenomas, chronic autoimmune (Hashimoto's) thyroiditis </li></ul><ul><li>Suspicious or Indeterminant: microfollicular or cellular adenomas (follicular neoplasm) </li></ul><ul><li>Malignant </li></ul>
  65. 70. Benign Lesions
  66. 71. Papillary Carcinoma FNA Surgical Specimen
  67. 72. Follicular Lesions on FNA: Can’t Distinguish!
  68. 73. Thyroid Nodule Palpable >15mm TSH Low Normal or High Scan Hot Not Hot FNA Malignant Suspicious (Follicular) Benign Insufficient Sample Repeat FNA +/- U/S guide Clin suspicion Low Clin suspicion High Total Thyroidectomy RAI Hemithyroidectomy with quick section + - Close <ul><li>Rx Plummer’s </li></ul><ul><li>Surgery </li></ul><ul><li>RAI </li></ul>Follow U/S q1y
  69. 74. Thyroid Nodule Palpable >15mm Incidentaloma (Size < 15mm) Hx of XRT exposure? FHx of thyroid cancer? Malign features on U/S? Age < 20 or > 60? Grave’s Disease? Familial Adenomatosis Polyposis No Follow U/S q1y ? Yes TSH Low Normal or High Scan Hot Not Hot FNA Malignant Suspicious (Follicular) Benign Insufficient Sample Repeat FNA +/- U/S guide Clin suspicion Low Clin suspicion High Total Thyroidectomy RAI Hemithyroidectomy with quick section + - Close <ul><li>Rx Plummer’s </li></ul><ul><li>Surgery </li></ul><ul><li>RAI </li></ul>Follow U/S q1y
  70. 75. Case 5 <ul><li>19 year old female </li></ul><ul><li>PMHx: Eating Disorder, Bulimia </li></ul><ul><li>Weight loss despite witnessed food intake </li></ul><ul><li>Tachycardia, palpitations </li></ul><ul><li>FHx: Hypothyroidism (mother) </li></ul><ul><li>No palpable goitre </li></ul><ul><li>TSH < 0.05 mU/L, FT4 23 pM, FT3 5.0 pM </li></ul><ul><li>24h RAIU 2%, Thyroid Scan: no gland seen </li></ul>
  71. 76. Case 5 <ul><li>TSH-R antibody negative </li></ul><ul><li>Thyroglobulin < 2 ng/mL (undetectable) </li></ul>
  72. 77. Autoimmune Thyroid Disease TSH-R ab stim Graves’ Dx (hyperthyroid) TSH-R ab block Thyroglobulin ab Microsomal ab Hashimoto’s (hypothyroid)
  73. 78. Thyroid Antibodies <ul><li>Hashimoto’s </li></ul><ul><ul><ul><li>Thyroglobulin AB (<40 KIU/L) </li></ul></ul></ul><ul><ul><ul><li>Thyroid peroxidase AB (< 35 KIU/L) </li></ul></ul></ul><ul><li>Grave’s </li></ul><ul><ul><ul><li>TSI or TSH Receptor Ab (Stim): IgG antibody </li></ul></ul></ul><ul><ul><ul><li>SEN 60% SPEC 90% </li></ul></ul></ul><ul><ul><ul><li>2-3 month turn-around time </li></ul></ul></ul><ul><ul><ul><li>Indications: </li></ul></ul></ul><ul><ul><ul><ul><ul><li>Pregnant & present or past hx Grave’s: check 2 nd trimester </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>(if hi-titre > 5X normal needs PTU as TSI crosses placenta) </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>? Euthyroid Grave’s ophthalmopathy </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Alternating hyper/hypo function due to alternating Stim/Block TSI </li></ul></ul></ul></ul></ul>
  74. 79. Thyroglobulin (Tg) <ul><li>Normal < 40 ng/mL </li></ul><ul><li>Increased in all thyroid disease </li></ul><ul><li>Thyrotoxicosis factitia : low or undetectable Tg </li></ul><ul><li>Useful for thyroid cancer surveillance post surgery & radioiodine ablation </li></ul><ul><li>Not useful for thyroid cancer diagnosis </li></ul><ul><li>Thyroglobulin antibodies in Hashimoto’s patients may falsely elevate or decrease thyroglobulin levels </li></ul>

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