Unraveling The Mystery Part II: Hyperthyroidsim and Post Partum Thyroiditis

1. Unraveling The Mystery Part II: Hyperthyroidsimand Post Partum Thyroiditis Chris Sadler, MA, PA-C, CDE Diabetes and Endocrine Associates La Jolla, CA

2. Learning Objectives Describe the diagnostic work-up for hyperthyroidism and post partum thyroiditis Interpret laboratory, ultrasound and thyroid scan data in the diagnosis of hyperthyroidism and post partum thyroiditis Understand the benefit and risks of the different treatment options for hyperthyroidism

3. Clinical Symptoms of Hyperthyroidism Appetite change Exertional shortness ofbreath Fatigue Headache Heat intolerance Hyperactivity Increased perspiration Irritability Menstrual disturbances Nervousness Palpitations Pelvic and pectoral girdle muscle weakness Sleep disturbance Tremor Weakness Weight change Braverman LE, Utiger RD. In: Werner and Ingbar’s The Thyroid, 7th ed. 1996:522.

4. Clinical Signs of Hyperthyroidism Goiter Hyperactivity Hyperreflexia Muscle weakness Stare and eyelid retraction Systolic hypertension Tachycardia/atrial arrhythmia Tremor Warm, moist, smooth skin Braverman LE, Utiger RD. In: Werner and Ingbar’s The Thyroid, 7th ed. 1996:522.

5. It’s not always this obvious

6. CASE 1 70 yo male with fatigue, tachycardia (pulse 105 bpm) TSH: 0.098 (0.35 - 5.00) What do you do next? More Labs? I-123 Uptake and Scan? Ultrasound?

7. Possible Causes of Low TSH Hyperthyroidism Graves Toxic adenomas or autonomously functioning thyroid nodules Toxic Multinodular goiter (TMNG) Thyroiditis Central Hypothyroidism Euthyroid Sick Syndrome Medications (steroids, sympathomimetics) Ingestion of excess exogenous thyroid hormone (most common)

8. Drug Induced Thyrotoxicosis

9. What’s the likeliest diagnosis? Graves ~ 75% <Age 40-85% >Age 60-45% Other 3% Multiple nodules 10% Painful thyroiditis 4% Single nodule 1% Painless thyroiditis 7%

10. CASE 1 What do you do next? It depends How does the physical exam guide you?

11. Diagnosis of Hyperthyroidism Weight and blood pressure Pulse rate and cardiac rhythm Thyroid palpation and auscultation (to determine size, nodularity and vascularity) Neuromuscular exam (muscle weakness, hyperreflexia, tremor) Eye exam (exophthalmos, stare) Dermatologic (nails, diaphoresis) Cardiovascular

12. Adjunctive Tests Free T4 Total T3, (T3 toxicosis, euthyroid sick) TSH Receptor Auto Antibodies (TRAb) TSI (thyroid stimulating immunoglobulin) TBII (thyrotropin binding inhibitory immunoglobulin)

13. Lab error Autoimmunity Acute illness High estrogen states Acute psychiatric problems Hyperemesis gravidarum Familial thyroid binding abnormalities Generalized resistance to thyroid hormone Drugs Factors falsely affecting (increasing) Total T4 levels

14. Adjunctive Tests Free T4 Total T3, T3 toxicosis, euthyroid sick TSH Receptor Auto Antibodies (TRAb) TBII(thyrotropin binding inhibitory immunoglobulin) TSI (thyroid stimulating immunoglobulin)

15. Thyroid Uptake/Scan Rule out thyroiditis (low uptake) Rule in Graves (increased uptake, when other signs lacking) Looking for hot/cold nodules Percent uptake to prepare for I-131

16. Varieties of Thyrotoxicosis Fisher, J South Med J 2002

17. Treatment Recommendations

18. Beta Blockers

19. Normal/Cold Nodule

20. Toxic MNG

21. Toxic “Hot” Nodule

22. Thyroiditis Thyroiditis

23. Normal Ultrasound

24. Toxic Nodule

25. Toxic Nodule

26. Exam: no obvious goiter or exophthalmos Free T4: 1.58 (0.8 - 1.80) Total T3: 166 (60 - 180) Uptake/Scan: slightly elevated uptake at 6 and 24 hrs, with even distribution of tracer TSI: 150% (<130%) CASE 1

27. Subclinical Hyperthyroidism:Definition and Prevalence Usually asymptomatic1 Low or undetectable serum TSH1 Normal or borderline serum FT4 and FT31 Variable prevalence (0.7% to 6.0%)2 More common in women3 More common in older people than overt hyperthyroidism4 Most common cause is overtreatment withL-thyroxine 1. Ross DS. Mayo Clin Proc. 1988;63:1223. 2. Ross DS. In: Werner and Ingbar’s The Thyroid, 7th ed. 1996:1016. 3. Sawin CT. Adv Intern Med. 1991;37:223. 4. Sawin CT et al. N Engl J Med. 1994;331:1249.

28. Common Causes of Subclinical Hyperthyroidism Exogenous Excessive thyroid hormone replacement Thyroid hormone suppressive therapy Endogenous Thyroid gland autonomy: thyroid adenoma or multinodular goiter Graves disease Ross DS. In: Werner and Ingbar’s The Thyroid, 7th ed. 1996:1016.

29. Mortality in Patients >60 yrs

30. Subclinical HyperthyroidismWhen to treat

31. Treatment of Graves’ Disease:Summary

32. Antithyroid Drugs • Thionamides • Methimazole (Tapazole) preferred except in the first trimester of pregnacy • 5 -15 mg bid typical dose (max 30 mg bid) • Propylthiouracil (PTU) – avoid use except in 1st trimester of pregnancy secondary to rare but serious hepatotoxicity 100 -150 mg q 8 hrs typical dose (max 900 mg/day) • ~30-40% achieve long lasting remission

33. Antithyroid Drugs

34. Factors that Favor ATD’s • Patients with high likelihood of remission (females, mild disease, small goiters and negative TRAb) • The elderly with co-morbidities increasing surgical risk or with limited life expectancy • Patients with previously operated or irradiated necks • Lack of access to high-volume thyroid surgeon • Patients with moderate to severe active Graves ophthalmopathy

35. Factors that Favor Radioiodine • Females planning a pregnancy in the future (4-6 months later, provided thyroid function is normal) • The elderly • Those with co-morbidities increasing surgical risks and with previously operated or irradiated necks • Lack of access to high-volume thyroid surgeon

36. Factors that Favor Surgery • Symptomatic compression or large goiters • Relatively low uptake of radioiodine • When thyroid malignancy is documented or suspected • Large non-functioning, photopenic, or hypo functioning “cold” nodule • Co-existing hyperparathyroidism requiring surgery • Females planning pregnancy within 4-6 months • Patients with moderate to severe active GO

37. Management Trends

38. Rx: Methimazole 5 mg qd (check baseline WBC, and LFT’s, repeat if symptomatic) Repeat TFT’s in 3-4 weeks Once TSH stable, can check labs q 3 months Discontinue methimazole if signs of remission CASE 1

39. CASE 2 35 yo female c/o hair loss, 15 lb wt. loss over last 6 week, feels hot all the time, mild diarrhea, has skipped her last 2 menses Meds: none

40. CASE 2 Exam: Somewhat anxious appearing female, 66”, 125 lbs, Pulse: 125, BP: 140/66, mild stare, skin warm to touch with diaphoresis of her palms, Thyroid: 2x normal size, firm, smooth, symmetrical w/o obvious nodules, Heart: tachcardia, hyperdynamic, Ext: tremor of outstretched hands, unable to rise from squatting position w/o assistance, DTR’s increased

41. Case 2 What is the differential diagnosis? Graves’ Toxic multinodular goiter Thyroiditis Large toxic nodule

42. Diagnostic Clinical Signs of Graves’ Disease Smooth symmetrical goiter Proximal muscle weakness Orbitopathy Pretibial myxedema Lifting of nailbeds Braverman LE, Utiger RD. In: Werner and Ingbar’s The Thyroid, 7th ed. 1996:522.

43. What to order? • Labs • Free T4 • Total T3 • TRAb • Uptake/Scan • Ultrasound?

44. Case 2: Test Results TSH <0.001 (0.35-5.50 mIU/ml) Total T3 605 (60-181 ng/dl) Free T4 3.50 (0.89-1.76 ng/dl) TSI 180% (<130%) Uptake/Scan: markedly increased uptake at 6 and 24 hours, diffuse homogeneous distribution Rx: Methimazole 10mg ii bid, Atenolol 100 mg bid

45. Case 2: Hyperthyroidism Labs 3 weeks later, (symptoms markedly improved) TSH <0.004 (0.35-5.50 mIU/ml) Total T3 219 (60-181 ng/dl) Free T4 1.58 (0.89-1.76 ng/dl) Rx: Continue Methimazole 10mg ii bid Decrease Atenolol to 50 mg bid as pulse now at 85 bpm

46. Case 2: Hyperthyroidism Labs 3 weeks later, (symptoms resolved) TSH <0.009 (0.35-5.50 mIU/ml) Total T3 135.4 (60-181 ng/dl) Free T4 1.30 (0.89-1.76 ng/dl) Rx: Continue Methimazole 10mg ii bid Wean Atenolol gradually over next 2 weeks

47. Case 2: Hyperthyroidism Labs 4 weeks later, (c/o fatigue, constipation bloating, cold intolerance, – self decreased dose to 10 mg bid 2 weeks prior to visit) TSH <0.040 (0.35-5.50 mIU/ml) Total T3 113.0 (60-181 ng/dl) Free T4 0.48 (0.89-1.76 ng/dl) Rx: Further decrease Methimazole to 10mg QD

49. Hyperthyroidism Flowsheet Total T3, TRAb?

50. Case 3 32 yo female 11 weeks postpartum reports symptoms of heat intolerance, fatigue and palpitations TSH <0.001 (0.35-5.50 mIU/ml) What other labs should be ordered? Free T4 4.01 (0.89-1.76 ng/dl) Total T3 332.0 (60-181 ng/dl) TPO Ab 965 (<60) Consider TRAb and/or RAI uptake if suspicion of Graves dz