Thyroid Disease Facts

1. Thyroid Disease Facts Jeffrey Medland Lt Col, USAF, MC, SFS Chief, Endocrinology MGMC, Andrews AFB, MD Capital Conference-June 2007

2. Outline Thyroid Testing Hypothyroidism Causes Signs/symptoms Treatment Hyperthyroidism Causes Signs/symptoms Treatment Thyroid Nodules/ Cancer Thyroid Disease and Pregnancy Hypothyroidism Hyperthyroidism (Hyperemesis Gravidarum, Graves’) Thyroiditis Factors affecting Thyroid function, LT4

3. Thyroid

4. Thyroid Peroxidase (TPO)

5. Thyroid Testing TSH Best test for screening for thyroid dysfunction! Log/linear response w/ FT4 A 2-fold change in FT4 produces a 100-fold change in TSH Not specific for a particular thyroid disease. Don’t use TSH alone for diagnosis! Also useful in Assessing LT4 tx in 1° hypothyroidism Monitoring TSH-suppressive tx in thyroid Ca

6. Thyroid Testing FT4 Testing methods: Equilibrium dialysis Analog assays Abnormal TSH check this next Indications: In conjunction w/ TSH for diagnosing hyperthyroidism or hypothyroidism. Monitoring LT4 replacement in central hypothyroidism (TSH not helpful) Assessing response to tx following 131-RAIA (Graves, toxic nodules) Monitoring ATD tx in pregnant females FT3 Abnormal TSH + normal FT4, then check this (T3 Thyrotoxicosis)

8. Thyroid Testing Thyroid Antibodies (TPO, Tg, TSI, TRAb) TPO TPO + Tg Ab’s assoc w/ Hashimoto’s. TPO more sensitive. Helpful in predicting those w/ subclinical hypothyroidism who are at ? risk for progression to overt hypothyroidism. TSI When dx of Graves’ in question Note: a negative test does not r/o Graves’ Pregnant women w/ Graves’ to determine fetal risk of thyroid dysfunction (due to transplacental passage of stimulating or blocking Ab’s). Suspected euthyroid ophthalmopathy. In pt’s w/ alternating hyper- and hypothyroidism (due to fluctuations in TSH receptor stimulating and blocking and stimulating Ab’s) Thyroglobulin (Tg) Indications Thyroid cancer recurrence Factitious (exogenous) vs. endogenous hyperthyroidism Note: Most assays are not reliable in pt’s (+) for anti-Tg Ab Interferes w/ method of Tg measurement (causing factitious low Tg)

9. Thyroid Testing Radioactive Iodine Uptake and Scan (RAIU/Scan) 123-RAIU/Scan or 131-RAIU/Scan Indications: biochemically hyperthyroid pt No role in euthyroid or hypothyroid pt’s RAIU produces a number. 4-hr (normal 10-15%) 24-hr (normal 20-30%) The scan produces a picture Tc99m-Pertechnetate Scan Picture only, no number

10. Thyroid Testing Fine Needle Aspiration (FNA) provides the most direct information about a thyroid nodule 95% sensitivity Ultrasound to assess thyroid nodule size and characteristics (cystic vs. solid) often used to guide FNA’s Calcitonin h/o MTC Thyroid nodule and (+) FHx of MTC (Familial, MEN2A, MEN2B) MEN2A: MTC, HyperPTH, Pheo MEN2B: MTC, Pheo, Mucosal neuromas

12. Hypothyroidism More common than hyperthyroidism 99% is primary (< 1% due to TSH deficiency) Hashimoto’s most common thyroid problem (4% of population) most common cause in iodine-replete areas aka chronic lymphocytic thyroiditis Assoc w/ TPO Ab’s (90%), less commonly Tg Ab’s. Iatrogenic Hypothyroidism from 131-RAIA (following tx for Graves’) Postpartum (silent) thyroiditis Silent/painless Occurs within 6 weeks?6 months postpartum Incidence: 10-15% of all women, ˜ 25% women w/ Type 1 DM Up to 50% are TPO Ab (+) 70% chance of recurrence w/ subsequent pregnancies

13. Hypothyroidism Subacute thyroiditis aka de Quervain’s, Granulomatous Painful, often radiates to the ear c/o malaise, pharyngitis, fatigue, fever, neck pain/swelling Viral etiology (URI/ pharyngitis) self-limited. Can tx inflammation w/ ASA, NSAID’s or steroids Suppurative/ Acute Infectious Thyroiditis Infections of the thyroid are rare normally protected from infection by its thick capsule Bacterial >> fungal, mycobacterial or parasitic Pt’s are acutely ill w/ a painful thyroid gland assoc w/ fever/chills, anterior neck pain/swelling, dysphagia and dysphonia

14. Thyroiditis

15. Hypothyroidism Reidel’s Struma/Thyroiditis (rare) Pt’s present w/ a painless, hard, fixed goiter hypothyroidism occurs when entire gland becomes fibrosed can see fibrosis of other tissues (fibrosing retroperitonitis, orbital fibrosis, or sclerosing cholangitis) Drug-induced Amiodarone Lithium Interferon-alpha Interleukin-2 Iodine deficiency Most common cause of hypothyroidism worldwide!!

16. Hypothyroidism Symptoms General Slowing Down Lethargy/somnolence Depression Modest Weight Gain Cold Intolerance Hoarseness Dry skin Constipation (? peristaltic activity) General Aches/Pains Arthralgias or myalgias (worsened by cold temps) Brittle Hair Menstrual irregularities Excessive bleeding Failure of ovulation ? Libido

17. Hypothyroidism Exam: Dry, pale, course skin w/ yellowish tinge Periorbital edema Puffy face and extremities Sinus Bradycardia Diastolic HTN ? Body Temperature Delayed relaxation of DTRs Megacolon (? peristaltic activity) Pericardial/ pleural effusions CHF Myxedema (nonpitting edema) Bradycardia and hypothermia- think hypothyroidism!

18. Hypothyroidism Laboratory Findings Elevated TSH Low FT4 TPO Ab (+) Pregnant women w/ TPO Ab (+) Miscarriage rate doubles ? risk post partum thyroiditis (35%) mild anemia ? CPK-MB ? LDL,? Chol (? lipid clearance) Hyponatremia

19. Hypothyroidism (Treatment) Synthroid (LT4) Initial starting dosage 1.6 mg/kg/day. Dose correlates better w/ lean body wt ˜ 80% of PO dose of LT4 is absorbed vs. Cytomel which is 95% absorbed The main absorptive sites proximal and mid-jejunum. Food can ? LT4 absorption up to 40-50%. Serum LT4 levels rise 10-15% after ingestion, peaking at 2-4 hrs. Serum LT3 levels don’t change due to the slow peripheral conversion of T4 ? T3. T-1/2 LT4 is 7 days can be given weekly in non compliant pt’s. Goal LT4 replacement: TSH 1.0-2.5 mU/L

20. Hypothyroidism (treatment in general) Indications for LT4 replacement Asymptomatic: TSH > 10 Asymptomatic and TPO Ab (+): TSH > 5 Symptomatic: TSH > 5 Pregnant female: TSH > 5 Goitrous: TSH > 5

21. Hypothyroidism (treatment in general) Hypothyroidism + surgery Postpone elective surgery in any hypothyroid pt until the euthyroid state is restored, however Urgent surgery should not be postponed in hypothyroid pt’s, though potential complications should be watched for. Hypothyroidism + elderly It is prudent to begin treatment with low dose LT4, starting at 12.5 or 25 mcg/day Titrate to goal or less than goal if cardiac symptoms develop despite max anti-anginal tx.

22. Hypothyroidism (treatment in general) Combined LT4/LT3 tx Bottom Line: most studies show combination T4/T3 therapy does not appear to be superior to LT4 alone, for the management of hypothyroid symptoms. If you decide to try combined T4/T3 therapy ? LT4 by 50 mcg and add 12.5 mcg LT3 (cytomel) in the a.m. ? LT4 by 12.5-25 mcg, and add 5 mcg LT3 in the a.m. Check TSH before LT3 dose T-1/2 Cytomel is 1 day

24. Hyperthyroidism Thyrotoxicosis = “any condition that results in thyroid hormone excess” Includes: Graves Disease, Toxic Goiter, Thyroiditis, and Excessive Thyroxine Ingestion Hyperthyroidism = “Specifically hyperfunctioning of the thyroid gland” Most Commonly caused by Graves Disease in the young Toxic Nodular Goiter in the elderly

25. Hyperthyroidism Graves’ Disease Due to autoAb’s directed against the TSH receptor, resulting in continuous stimulation of the thyroid gland to secrete hormone. Ab’s to TSH receptor (+) in ˜ 80% of Graves’ pt’s Ab’s to TPO or Tg are (+) in ˜ 80% of Graves’ pt’s Female:Male (5-10:1) Caucasian = Asian > Black Toxic MNG Generally arises in the setting of a long-standing MNG More common in the elderly, areas of iodine deficiency Toxic Adenoma (Plummer’s Disease) More common in women, areas of iodine deficiency adenomas > 3 cm are more prone to overt hyperthyroidism

26. Hyperthyroidism Iodine-induced Hyperthyroidism (jod-basedow phenomenom) Amiodarone-induced (AIT Type 1) IV Contrast Diets high in iodine Thyroiditis Subacute (de Quervains) painful Postpartum painless Suppurative painful Amiodarone-induced (AIT Type 2)

27. Hyperthyroidism Symptoms Jittery, shaky, nervous Difficulty concentrating Emotional lability Insomnia Rapid HR, palpitations, DOE Feeling Hot Weight Loss (can see weight gain) Freq BMs (hyperdefecation, not diarrhea) Fatigue Menses w/ lighter flow, shorter duration

28. Hyperthyroidism Exam Eye findings (20%) Goiter Thyroid bruit or thrill Tachycardia: Sinus Tach, A-Fib Flow murmur Systolic Hypertension Hyperreflexia Tremors UE, tongue Proximal muscle weakness Thenar/ hypothenar atrophy Acropachy Onycholysis (<1%) separation of nail from the nailbed Dermopathy (1%)

29. Hyperthyroid Eye Disease Hyperthyroidism (any cause) Lid lag, lid retraction and stare Due to increased adrenergic tone stimulating the levator palpebral muscles. True Graves’ Ophthalmopathy Proptosis Diplopia Inflammatory changes Conjunctival injection Periorbital edema Chemosis Due to thyroid autoAb’s that cross-react w/ Ag’s in fibroblasts, adipo-cytes, + myocytes behind the eyes.

30. Hyperthyroid Eye Disease Causes of Worsening Ophthalmopathy Pre-existing eye disease Smoking marked ? T3 marked ? TSI titers Not letting pt get to hypothyroid state following 131-RAIA. Does131-RAIA worse ophthalmopathy? Majority of cases arise in the 18 mos before to 18 mos after the onset of thyrotoxicosis. Thus a fair number of cases can be ex-pected to coincide w/ timing of 131-RAIA. Two prospective randomized trials have shown that 131-RAIA more likely (vs. other tx modalities) to worsen ophthalmopathy.

31. Graves’ Dermopathy Thyroid Dermopathy Thickening and redness of the dermis Due to lymphocytic infiltration Distribution Pretibial (93.3%), Pretibial+ feet (4.3%), Pretibial + UE (1.1%).

32. Graves’ Dermopathy

33. Thyroid Acropachy Thyroid acropachy. This is most marked in the index fingers and thumbs.

34. Hyperthyroidism Laboratory Findings TSH nearly undetectable Elevated FT4 or FT3 mild leukopenia, N/N anemia, ? LFT’s and alk phos, mild ? Ca++, ? albumin ? chol

35. RAIU/Scan Increased RAIU Graves’ Disease Toxic Nodules MNG Adenoma hCG secreting tumors Hydatidiform mole Choriocarcinoma TSH mediated thyrotoxicosis Pituitary tumor Pituitary resistance to thyroid hormone Iodine Deficiency

36. RAIU/Scan Decreased RAIU Thyroiditis Chronic painless Postpartum Subacute Amiodarone-induced Thyroiditis Factitia Iodine Excess Contrast dye Diet Amiodarone Struma ovarii: (ectopic thyroid hormone production from thyroid tissue in an ovarian teratoma)

38. Hyperthyroidism (Treatment) 1) ß-blockers (symptom control) Propranolol (Inderal ®) LA: 60-320 mg daily Atenolol (Tenormin ®): 50-100 mg daily Metoprolol (Lopressor ®): 50-100 mg bid If ß-blocker contraindicated then Verapamil (Calan ®) 40-80 mg tid 2) 131-RAIA (70% thyroidologists prefer) Dosing Graves: 10-15 mCi Toxic MNG/Adenoma: 20-30 mCi Absolute contraindications Pregnancy and nursing moms (excreted in breast milk)! Pregnancy should be deferred for at least 6 months following tx w/ 131-RAIA. Prudent to avoid 131-RAIA in pt’s w/ active moderate? severe Graves’ ophthalmopathy.

39. Hyperthyroidism (Treatment) 3) Antithyroid Drugs (30% thyroidologists prefer) Propylthiouracil (PTU) 100 mg bid-tid to start Tapazole (Methimazole) 10X more potent the PTU 10 mg bid-tid to start Complications of ATD’s Dose dependent w/ Tapazole, Idiosyncratic w/ PTU. Agranulocytosis (1/200-500) usually presents w/ acute pharyngitis/ tonsilitis or pneumonia. Rash Hepatic necrosis w/ PTU, Cholestatic jaundice w/ Tapazole. Arthralgias

40. Hyperthyroidism (Treatment) 3) Antithyroid Drugs (30% thyroidologists prefer) Candidates for ATD’s Children and adolescents Pt’s w/ moderate? severe ophthalmopathy Thyroid Storm Pt’s w/ mild disease: small goiter, low titers of TSI (TSH-R Ab), low maintenance dose Pt’s w/ severe disease prior to 131-RAIA stop ATD’s 5-7 days prior to 131-RAIA Labs Follow TSH/FT4, CBC, LFT’s

41. Hyperthyroidism (Treatment) 4) Surgery (sub-total thyroidectomy) Indications Pt preference Pregnant women w/ failed ATD’s Large or symptomatic goiters When there is question of malignancy Need to be euthyroid prior to surgery To ? the risk of arrhythmias during induction of anesthesia To ? the risk of thyroid storm post operatively ATD’s + ß-blockers Risks Permanent hypoparathyroidism Recurrent laryngeal nerve problems Permanent hypothyroidism

42. Hyperthyroidism Apathetic Hyperthyroidism Elderly pt’s w/ Graves' disease may present w/ apathy, weight loss, muscular weakness, arrhythmias (esp A-fib), CHF, + constipation. A goiter may not be palpable in as many as 70% of pt’s There symptoms may suggest PMR or depression The usual hyperkinetic signs and symptoms seen in Graves’ are not typically present in the elderly. Check all elderly w/ new-onset atrial arrhythmias or CHF for hyperthyroidism

43. Hyperthyroidism Thyroid Storm A life-threatening condition characterized by an exaggeration of the manifestations of thyrotoxicosis Diagnostic Criteria (based on point system) Thermoregulatory Dysfunction: ? Temp (99°?>104°) CNS: +/-, mild (Agitation)/mod (delirium)/severe (seizures, coma) Tachycardia: (99?>140 bpm) CHF: +/-, mild (edema)/mod (rales)/severe (pulm edema) Atrial Fibrillation: +/- Precipitant History Treatment ATD’s (PTU, Tapazole) Iodide (Lugol’s solution) ß-blockers Corticosteroids Avoid ASA Definitive Tx when euthyroid: 131-RAIA or surgery

44. Subclinical Hyperthyroidism Refers to an elevation in T4 and/or T3 within the normal range, leading to suppression of the pituitary secretion of TSH in the subnormal range (i.e. normal T4 and T3, low TSH). Clinical symptoms and signs are frequently absent or nonspecific. Usually found in the elderly Often due to an autonomously functioning MNG or adenoma. Studies have linked subclinical thyrotoxicosis to Accelerated bone loss in postmenopausal women A higher incidence of atrial dysrhythmias (esp atrial fibrillation) Recent studies suggest an increase in cognitive impairment and all-cause mortality (esp CV disease). A TSH below the lower limit of normal, but above 0.1 mIU/mL are less likely to result in such complications. If pt’s are not treated, then careful f/u.

46. Thyroid Nodules Structural disorders of the thyroid (i.e. nodules- simple or multiple) are more common than functional disorders. Prevalence Palpable: 5% Non-Palpable: 40-50% Cancer in nodules: 5% Risks Women > Men Smoking h/o XRT to head/neck (esp children) Iodine deficiency Most are Euthyroid and Asymptomatic Less than 1% with thyrotoxicosis

47. Thyroid Nodules Red Flags concerning for Cancer Male Extremes of age (<20 or >60) Rapid Growth > 4 cm Symptoms of local invasion hoarseness, dysphagia h/o XRT to the head/neck (esp children) Family history of Thyroid Ca (PTC or MTC) Hard, fixed lesion (+) LN h/o familial adenomatous polyposis

48. Thyroid Nodules FNA Results: Benign (69%) f/u 6-12 months Surgery if MNG w/ compressive Symptoms Growth of Nodule Recurrence of cystic nodule after aspiration Insufficient (17%) Repeat FNA 3-4 months Indeterminate/ Suspicious (10%) follicular neoplasm 85% benign adenomas 123-RAIU/Scan Surgery Malignant (5%) Surgery 131-RAIA if PTC or FTC

49. Thyroid Nodules “Mimickers” Thyroid Hemiagenesis Agenesis of one lobe of the thyroid, w/ hypertrophy of the other presenting as a mass in the neck mimicking a nodule. Occurs in 1/2500 people Usually the left lobe that fails to develop w/ hypertrophy in the right lobe. 95% of the time Parathyroid gland Thyroglossal duct remnants

50. Thyroid Cancer Papillary Thyroid Ca (PTC): 75% Follicular Thyroid Ca (FTC): 15-20% Medullary Thyroid Ca (MTC): < 5% Anaplastic: < 5 % Lymphoma: rare Hashimoto’s is a risk factor Metastatic to thyroid: rare Breast, Renal cell, melanoma and lung Ca MTC FMTC MEN2A MTC, HyperPTH, Pheo MEN2B MTC, Pheo, Mucosal neuromas

52. Thyroid Disease in Pregnancy Four factors alter thyroid function in pregnancy 1) Transient ? in hCG, during the 1st trimester can stimulate the TSH-R - Gestational Transient Thyrotoxicosis (GTT) - Hyperemesis gravidarum 2) E2-induced ? in TBG during the 1st trimester, which is sustained during pregnancy. 3) Alterations in immune function leading to onset, exacerbation, or amelioration of an underlying autoimmune thyroid disease. 4) ? urinary iodide excretion, which can cause impaired thyroid hormone production in areas of marginal iodine deficiency (<50 µg/d). - ? risk of goiter and hypothyroidism

53. Thyroid Disease in Pregnancy Women need more LT4 during pregnancy ? in TBG (2- to 3-fold) due to E2 resulting in a 30-100% increase in total T4 and total T3, but and ? in FT4 and FT3 ? renal LT4 clearance Transfer of LT4 to the fetus Known Hypothyroidism already on LT4 ? dose by 30% (25-50 µg) taking an extra pill 2 days a week as soon as pregnancy is confirmed. Make further dose changes based on serum FT4 + TSH levels measured every 4 weeks until it is normal, and then measure the TSH once per trimester.

54. Thyroid Disease in Pregnancy Frequency of various clinical presentations of postpartum thyroid dysfunction Hypothyroid (postpartum exacerbation of Hashimoto’s): 40% Hyper-/Hypothyroid (postpartum thyroiditis): 25% Hyperthyroid Thyroiditis (postpartum thyroiditis): 24% Hyperthyroid Graves’: 20%

55. Thyroid Disease in Pregnancy Glycoprotein hormones LH, FSH, TSH + hCG Share a similar alpha subunit (a-SU) Beta subunit (ß-SU) are immunologically + biologically unique. There is considerable homology between ß-SU’s of hCG and TSH. Distinct 1st trimester increase in hCG 10-20% of normal pregnant women have low TSH concentrations at peak hCG.

56. Thyroid Disease in Pregnancy Hyperemesis Gravidarum (HG) Hyperthyroidism is assoc w/ severe vomiting (“toxic vomiting”) + > 5% wt loss Hyperemesis is assoc w/ elevated T4 + low TSH in > 50% of affected woman. Usu transient w/ normal TFT’s by 2nd trimester In transient cases, no goiter, (-) Thyroid Ab’s, + few manifestations of hyperthyroidism Due to elevated hCG levels > 75,000-100,000 IU/L Treatment is controversial ATD’s do not reduce vomiting despite normalization of TFT’s Consider ATD’s if hyperthyroxinemia extends into the 2nd trimester.

57. Thyroid Disease in Pregnancy Hyperemesis Gravidarum vs. Graves’ Can be a difficult distinction if pt actively vomiting Clues pointing to Graves’ Disease Goiter Thyroid bruit Ophthalmopathy Onycholysis Pre-existing thyroid c/o prior to pregnancy (+) TSI Elevated FT3 levels See ? T4?T3 conversion w/ HG (assoc w/ ? in nutrition) Diagnostic123-RAI or 131-RAI scanning contraindicated!!! At 12 weeks gestation the fetal thyroid has 20-50x the avidity for iodine than does the maternal thyroid.

58. Thyroid Disease in Pregnancy Graves’ (Treatment) PTU, Tapazole and ß-blockers all cross the placenta. ATD’s still mainstay of tx PTU preferred (crosses placenta < Tapazole) Tapazole may be assoc w/ aplasia cutis The lowest possible dose should be given Goal of tx w/ ATD: maintain the mothers FT4 or FT3 in the high-normal range. TSH levels often remain suppressed w/ FT4 or FT3 in these ranges + can’t be accurately used for titrating ATD. If unable to use ATD- surgery (subtotal thyroidectomy) can be done during 2nd trimester. 1st trimester: ? risk of miscarriage 3rd trimester: ? risk of preterm labor

60. Causes of Increased LT4 requirement Post menopausal therapy: Estrogen Drugs known to interfere with absorption: FeSO4 Calcium carbonate Cholestyramine (and probably colestipol) Sodium polystryene sulfonate (Kayexalate) sulcrafate (Carafate) Aluminum hydroxide (Amphogel) soy-based feeding formulas (infants, post-menopausal women) Raloxifene (Evista) Separate LT4 and other medications or supplements at least 2-4 hrs apart!

61. Causes of Increased LT4 requirement Drugs that increase LT4 metabolism in the liver by inducing microsomal enzymes: Rifampin Carbamazepine (Tegretol) Phenytoin (Dilantin) Phenobarbitol Increased clearance: Nephrotic syndrome Pregnancy Drugs with unknown mechanism: Sertraline (Zoloft) Lovastatin (Mevacor)- 1 case report

62. Causes of Increased LT4 requirement Malabsorptive States: High fiber diets Intestinal diseases: celiac disease, inflammatory bowel disease, short bowel syndromes, protein losing enteropathy Pancreatic exocrine insufficiency Hepatic cirrhosis Weight gain Progression of the hypothyroid disease process itself!

63. Drugs Affecting Thyroid Function

69. Amiodarone and the Thyroid Iodine Effect Inability to “Escape” from the Wolff-Chaikoff effect results in an increased goiter or Hypothyroidism. Jod-Basedow phenom could occur in someone with occult MNG (AIT type 1) Direct Toxic Effect Thyroiditis (AIT type 2) “Innocent Changes” “Innocent” changes in TFT’s can occur in > 50% of pt’s Due to a Decreased conversion of T4 ?T3 (Inhibition of Type’s I + II 5’- deiodinase) T4 levels Increase 20-40% during the 1st month, then gradually fall towards baseline T3 levels Decrease by up to 30% within the 1st few weeks of tx and remain at this level rT3 levels Increase by 20% soon after initiation of tx and remain at this level TSH levels initially Increase, then return to NL in 2-3 mos

70. Jod-Basedow phenomenon (Historical) Definition- Hyperthyroidism induced by excess Iodine. Coindet (French physician) in 1821 published his cases about Hyperthyroidism. In the English speaking world this became known as Graves’ disease (1835), and in the German speaking world as von Basedow’s disease (1840). Coindet’s cases of hyperthyroidism were actually Iodine-induced, hence it came to be known as the Iodine-Basedow phenom. Jod is German for Iodine, hence the Jod-Basedow phenom! Coindet was deprived of credit for not only describing Hyper- thyroidism, but also the variant of hyperthyroidism caused by excess Iodine The credit was given to Dr “Jod” who never existed!

71. Conditions affecting Thyroid Function

72. Thyroid Disease in Pregnancy Euthyroid women, (+) TPO Ab’s Euthyroid pregnant women w/ (+) TPO Ab’s develop impaired thyroid function Tx w/ LT4 reduces the risk of miscarriage and prematurity in TPO Ab (+) women LT4 doses 0.5 mcg/kg/d for TSH < 1 mU/L 0.75 mcg/kg/d for TSH 1-2 mU/L 1 mcg/kg/d for TSH > 2 mU/L or TPO Ab titers > 1:1500 Is it reasonable to screen all pregnant women for TPO Ab’s and TSH? Negro R, et al. JCEM 2006

73. Autoimmune Polyglandular Syndromes 2 Classic Triad: Adrenal Insufficiency Autoimmune thyroid disease (hypo or hyperthyroidism) Type 1 DM Only 2 of the 3 are required for diagnosis F:M 3:1 Age of onset tends to be between 20 and 30 years Other components of APS-2 Primary Hypogonadism Myasthenia Gravis Celiac disease Pernicious Anemia Alopecia Vitiligo Serositis Stiffman Syndrome ITP IgA deficiency/ Goodpasture’s syndrome

74. Hyperthyroidism Hypokalemic Periodic Paralysis Reported in conjunction w/ thyrotoxicosis More common in Asian men Symptoms sudden Muscle stiffness/cramps Flaccid paralysis Due to shift of K+ intracellularly Treatment K+ for hypokalemia ?-blockers Rapid reduction in thyroid hormone

75. Hyperthyroid Eye Disease Does 131-RAIA worsen ophthalmopathy? The natural course of Graves’ disease is such that 15-20% have significant ophthalmopathy. The majority of cases arise in the 18 mos before to 18 mos after the onset of thyrotoxicosis. Thus a fair number of cases can be expected to coincide w/ the timing of 131-RAIA. Two prospective randomized trials have shown that 131 RAIA is more likely than other tx modalities to worsen ophthalmopathy. Prudent to avoid 131-RAIA in pt’s w/ active moderate? severe Graves’ ophthalmopathy. Tx others at ? risk (esp smokers) w/ course of oral corticosteroids.

76. Cutis Aplasia

77. Thyroid Binding Globulin (TBG) Hepatitis/ Biliary Cirrhosis OCP’s Pregnancy Estrogens (also Tamoxifen + Raloxifene) Drugs (Narcotics/Heroin, Methadone, Clofibrate, Major Tranquilizers, 5-FU) Steroids/Glucocorticoids Hypoalbuminemia Androgens (Testosterone, Danazol) Nephrotic syndrome Acromegaly Drugs (Niacin, L-asparginase)

79. Thyroid Regulation

91. Hyperthyroid Eye Disease

96. Thyroid Disease in Pregnancy 1st trimester increase in hCG Glycoproteins LH/FSH, TSH + hCG Share a similar alpha subunit (a-SU) Beta subunit (ß-SU) are immunologically + biologically distinct

102. Amiodarone the Thyroid “Innocent” changes in TFT’s can occur in > 50% of pt’s Due to a Decreased conversion of T4 ?T3 (Inhibition of Type’s I + II 5’- deiodinase) T4 levels Increase 20-40% during the 1st month, then gradually fall towards baseline T3 levels Decrease by up to 30% within the 1st few weeks of tx and remain at this level rT3 levels Increase by 20% soon after initiation of tx and remain at this level TSH levels initially Increase, then return to NL in 2-3 mos

103. Amiodarone Effects on Thyroid 37% of Amiodarone’s mass is Iodine (contains 2 iodine molecules). Dietary Recommendations for Daily Iodide (World Health Organization) for Adults – 150 mcg. Avg US intake: 240- 700 mcg Each 200mg tab contains 75 mg Iodine 10% (7mg) as free is released iodine, almost 50x’s the daily recommended allowance! Accumulates in the Liver and Adipose Tissue T-1/2 ~ 100 days. Total body Iodine stores can remain elevated for up to 9 months after stopping the drug

104. Amiodarone Effects on Thyroid Pt’s with underlying thyroid disease often have defects in the autoregulation of Iodine. National Health + Nutrition Examination Study: 11.3% positive for Anti-TPO Ab’s Iodine Effect Inability to “Escape” from the Wolff-Chaikoff effect results in an increased goiter or Hypothyroidism. Jod-Basedow phenom could occur in someone with occult MNG (AIT type 1) Direct Toxic Effect Thyroiditis (AIT type 2)

105. Thyroid Hormone There is no absorption from the stomach. Absorption occurs in the small bowel. The main absorptive sites appear to be the proximal and mid-jejunum. Progressively decreasing degrees of absorption occur along the distal bowel and proximal colon. Hypothyroidism can lead to a slight increase in absorption.