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Hyperthyroidism and Graves’ Disease

Hyperthyroidism and Graves’ Disease. Anthony Yin, MD Sutter Pacific Medical Foundation Division of Endocrinology, Diabetes and Osteoporosis. No financial disclosures. Case presentation.

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Hyperthyroidism and Graves’ Disease

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  1. Hyperthyroidism and Graves’ Disease Anthony Yin, MD Sutter Pacific Medical Foundation Division of Endocrinology, Diabetes and Osteoporosis

  2. No financial disclosures

  3. Case presentation 62 year old woman presents with fatigue and occasional palpitations for 3 months. Past medical history notable for long-standing hypertension and osteopenia based on a bone density study performed two years ago. She went through menopause at the age of 55 and has had no fractures. She has been an avid gardener for many years but has lost pleasure in this activity lately. She is a non smoker and only occasionally drinks alcohol. There is no family history of thyroid disease or malignancy Her medications are hydrochlorothiazide 25 mg/d, aspirin 81 mg/d, calcium 500 mg BID and vitamin D 800 IU/d No known medication allergies

  4. Case presentation BP 135/82, HR 110, BMI 24 NAD, flat affect No proptosis, lid lag or periorbital edema Minimally enlarged smooth goiter with no palpable nodules; bruits are present CV: regular with occasional premature beats, no murmurs Mild tremor in both hands Moderate khyposcoliosis without paravertebral tenderness No dermatologic abnormalities

  5. Laboratory data CBC wnl CMP notable for AST 62 and ALT 65 with normal bilirubin and alkaline phosphatase 25-OH vit D3 is 22 TSH 0.03 (normal 0.45-4.5 uIU/mL), anti TPO ab 22 (normal <35) ESR 16

  6. Questions What is the differential diagnosis? What further studies are recommended? How should she be treated?

  7. Outline of Discussion • What’s normal? • Scope of the Problem • Causes • Diagnostic Approach • Management

  8. WHAT’S NORMAL? http://www.sciencedirect.com/science/article/pii/S0003986110002407

  9. Scope of the problem: HYPERTHYROIDISM Singer PA, Cooper DS, Levy EG, Ladenson PW, BravermanLE, Daniels G, Greenspan FS, McDougall IR, Nikolai TF 1995 Treatment guidelines for patients with hyperthyroidism and hypothyroidism. JAMA 273:808–812. 1Hollowell JG, et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Heatlh and Nutrition Examination Survey (NHANES III). J ClinEndocrinolMetab 2002; 87:489 AsvoldBIO, et al. Tobacco smoking and thyroid function: a population-based study. Arch Intern Med 2007; 167:1428. Holm IA, et al. Smoking and other lifestyle factors and the risk of Graves’ hyperthyroidism. Arch Intern Med 2005; 165:1606 • U.S.: prevalence 1.2% • Overt 0.5%, 0.7% subclinical • Women 5x > men • More common in smokers • Graves’ disease (GD) most common • Toxic multinodular goiter (TMNG) & toxic adenoma (TA)

  10. Clinical Manifestations Anxiety Emotional lability Weakness Tremor Palpitations Increased perspiration Weight loss (gain) Normal or increased appetite

  11. Clinical Manifestations • Hyperdefecation • Urinary frequency • Oligomenorrhea or amenorrhea (women) • Gynecomastia and erectile dysfunction (men) • New onset atrial fibrillation • Myopathy • Elderly patients may be “apathetic”; depression Anxiety Emotional lability Weakness Tremor Palpitations Increased perspiration Weight loss (gain) Normal or increased appetite

  12. Stare & Lid Lag http://www.patient.co.uk/doctor/Thyroid-Eye-Disease.htm

  13. ExophthalmosSpecific to Graves’ disease http://www.myhousecallmd.com/archives/3761 Expected normal ranges: Caucasian males 12 - 21 mm Caucasian females 12 - 20 mm African American males 12 - 24 mm African American females 12 - 23 mm http://jnnp.bmj.com/content/75/suppl_4/iv2.full http://www.opt.indiana.edu/riley/HomePage/External_Eye_Exam/Text_External_Eye_Exam.html

  14. Graves’ ophthalmopathy (GO) • 50% of all with GD • 5% severe • Risk factors: • radioiodine therapy for hyperthyroidism (318,319) • smoking • high pretreatment T3 values (>325 ng/dL) (319) • high serum pretreatment TRAblevels (>50% TBII inhibition or TSI >8.8 IU/Liter) (320) • hypothyroidism following radioiodine treatment

  15. Acropachy & Pretibial myxedema: Specific to Graves’ disease http://see.visualdx.com/diagnosis/thyroid_acropachy http://jcem.endojournals.org/content/87/2/438/F1.expansion

  16. CAUSES • Trophoblastic disease and germ cell tumors • Extrathyroidal GD TMNG or TA Thyroiditis Iodine-induced

  17. Diagnostic Approach Goiter + opthalmopathy+ moderate to severe hyperthyroidism = GD Radioactive iodine uptake (RAIU) Antibodies (TSI or TSH-R ab) ESR (subacute thyroiditis)

  18. GRAVES’ DISEASE (GD)

  19. TSI

  20. GD: TREATMENT Medical Radioactive Iodine Surgery

  21. Beta Blockade PEARL: Beta-adrenergic blockade should be given to elderly patients with symptomatic thyrotoxicosis and to other thyrotoxic patients with resting heart rates in excess of 90 bpm or coexistent cardiovascular disease. RECOMMENDATION 2

  22. Anti Thyroid Drugs (ATDs) Methimazole (MMI) Propylthiouracil (PTU)

  23. Cooper, David. AntithyroidDrugs. N Engl J Med 352;9

  24. Cooper, David. AntithyroidDrugs. N Engl J Med 352;9

  25. Anti Thyroid Drugs (ATDs) Methimazole (MMI) Propylthiouracil (PTU) • Initial dose: 300 mg/d • Preferred in pregnancy • Higher potential for side effects • 300 mg/d $408/yr “should be used in virtually every patient who chooses antithyroid drug therapy for GD, except during the first trimester of pregnancy when propylthiouracil is preferred, in the treatment of thyroid storm, and in patients with minor reactions to methimazole who refuse radioactive iodine therapy or surgery” Now only FDA approved for treating hyperthyroidism during pregnancy *RECOMMENDATION 13 Initial dose: 10–20 mg/d Maintenance dose: generally 5–10 mg/d Easier for patients Side effects less common 15 mg/d $360/yr

  26. Possible side effects Recommendation 14 pruritic rash jaundice acolic stools or dark urine arthralgias abdominal pain nausea fatigue fever pharyngitis

  27. Anti Thyroid Medications: Timeline & Monitoring Start ATD Week 0

  28. Anti Thyroid Medications: Timeline & Monitoring Start ATD Free T4 + T3 Week 0 Week 4 q 4-8 weeks q 2-3 months

  29. Anti Thyroid Medications: Timeline & Monitoring Start ATD Free T4 + T3 Stop ATD 12-18 months Week 0 Week 4 q 4-8 weeks q 2-3 months

  30. Anti Thyroid Medications: Timeline & Monitoring Start ATD Free T4 + T3 Stop ATD TSH Free T4 T3 12-18 months q 2 mo x 6 mo Week 0 Week 4 q 4-8 weeks q 2-3 months

  31. Anti Thyroid Medications: Timeline & Monitoring No Start ATD Free T4 + T3 Stop ATD TSH Free T4 T3 TSH Free T4 T3 Yes Remission? 12-18 months q 2 mo x 6 mo Week 0 q 12 mo Week 4 No q 4-8 weeks I-131 ablation q 2-3 months

  32. Radioactive Iodine Ablation

  33. ATDsGenerally not necessary prior to 131I insufficient evidence for radioactive iodine worsening either the clinical or biochemical aspects of hyperthyroidism “it only delays treatment with radioactive iodine”

  34. pretreatment may reduce the efficacy of subsequent radioactive iodine therapy Marcocci C, Gianchecchi D, Masini I, Golia F, Ceccarelli C, Bracci E, Fenzi GF, Pinchera A 1990 A reappraisal of the role of methimazole and other factors on the efficacy and outcome of radioiodine therapy of Graves’ hyperthyroidism. J Endocrinol Invest 13:513–520

  35. When to use MMI prior to 131I If given as pretreatment, MMI should be discontinued 3–5 days before the administration of radioactive iodine, restarted 3–7 days later, and generally tapered over 4–6 weeks as thyroid function normalizes. • Risk for CV complications such as atrial fibrillation, heart failure, or pulmonary hypertension • renal failure • infection • trauma • poorly controlled diabetes mellitus • cerebrovascular or pulmonary disease

  36. GO: Worsening with I-131 Traisk F, et al. Thyroid-Associated Ophthalmopathy after Treatment for Graves’ Hyperthyroidism with Antithyroid Drugs or Iodine-131. J ClinEndocrinolMetab 94: 3700–3707, 2009

  37. GO and I-131: increased proptosis Traisk F, et al. Thyroid-Associated Ophthalmopathy after Treatment for Graves’ Hyperthyroidism with Antithyroid Drugs or Iodine-131. J ClinEndocrinolMetab 94: 3700–3707, 2009

  38. GO: Effects of I-131 and smoking Traisk F, et al. Thyroid-Associated Ophthalmopathy after Treatment for Graves’ Hyperthyroidism with Antithyroid Drugs or Iodine-131. J ClinEndocrinolMetab 94: 3700–3707, 2009

  39. RADIOACTIVE IODINE ABLATION: Timeline & Monitoring I-131 Week 0 *Ross DS. Radioiodine therapy for hyperthyroidism. N Engl J Med 2011;364(6): 542–50 **RECOMMENDATION 11 ***RECOMMENDATION 12

  40. RADIOACTIVE IODINE ABLATION: Timeline & Monitoring (expect normalization) I-131 Free T4 and T3 Week 0 Weeks 4-8 q 4-6 weeks** *Ross DS. Radioiodine therapy for hyperthyroidism. N Engl J Med 2011;364(6): 542–50 **RECOMMENDATION 11 ***RECOMMENDATION 12

  41. RADIOACTIVE IODINE ABLATION: Timeline & Monitoring (expect normalization) No*** I-131 TSH + free T4 Free T4 and T3 Yes Hypothyroid? initiate LT4 Week 0 Weeks 4-8 q6 weeks 6 months q 4-6 weeks** *Ross DS. Radioiodine therapy for hyperthyroidism. N Engl J Med 2011;364(6): 542–50 **RECOMMENDATION 11 ***RECOMMENDATION 12

  42. GD:TREATMENT Torring O, Tallstedt L, Wallin G, Lundell G, Ljunggren JG, Taube A, Saaf M, Hamberger B 1996 Graves’ hyperthyroidism: treatment with antithyroid drugs, surgery, or radioiodine— a prospective, randomized study. Thyroid Study Group. J Clin EndocrinolMetab 81:2986–2993.

  43. GD:TREATMENT Torring O, Tallstedt L, Wallin G, Lundell G, Ljunggren JG, Taube A, Saaf M, Hamberger B 1996 Graves’ hyperthyroidism: treatment with antithyroid drugs, surgery, or radioiodine— a prospective, randomized study. Thyroid Study Group. J Clin EndocrinolMetab 81:2986–2993.

  44. 37% 21% 6% Torring O, Tallstedt L, Wallin G, Lundell G, Ljunggren JG, Taube A, Saaf M, Hamberger B 1996 Graves’ hyperthyroidism: treatment with antithyroid drugs, surgery, or radioiodine— a prospective, randomized study. Thyroid Study Group. J Clin EndocrinolMetab 81:2986–2993.

  45. Chosing therapy ATDs High likelihood of remission Elderly or increased surgical risk or with limited life expectancy Nursing home residents/unable to follow radiation safety regulations Previously operated or irradiated necks Lack of access to a high volume thyroid surgeon Moderate to severe active Graves’ opthalmopathy Females planning a pregnancy in the future > 4–6 months following RAI Comorbidities increasing surgical risk Previous neck surgery or external radiation Lack of access to a high-volume thyroid surgeon Contraindications to ATD use Radioactive iodine ablation • Substantial comorbidity • Pregnancy: relative contraindication Previous adverse reactions to ATDs • Pregnancy, lactation • Coexisting thyroid cancer, or suspicion cancer • Individuals unable to comply with radiation safety guidelines • Women planning a pregnancy within 4–6 months Symptomatic compression or large goiters (>80 g) Relatively low uptake of radioactive iodine Documented/suspected thyroid malignancy Large nonfunctioning, photopenic, or hypofunctioning nodule Coexisting hyperparathyroidism requiring surgery Females planning a pregnancy in <4–6 months Moderate to severe active Graves’ opthalmopathy Thyroidectomy

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