1. GENERAL MEDICINE CONFERENCE HYPERTHYROIDISM Selim Krim, MD Assistant Professor Texas Tech University Health Sciences Center

2. SIGNS AND SYMPTOMS Skin: Increased Sweating and heat intolerance, onycholysis, hyperpigmentation, pruritus and thinning of the hair. Eyes: Stare and lid lag, exophtalmos if graves disease Cardiac: Palpitations, exertional dyspnea, anginal-like chest pain, tachycardia, atrial fibrillation, CHF GI: Weight loss, diarrhea Neuro-psych: Anxiety, restlessness, irritability, emotional lability, psychosis, agitation, and depression Metabolic/Endocrine: Hyperglycemia, low serum total and high-density lipoprotein (HDL) cholesterol

3. GRAVES’ DISEASE Signs and symptoms of hyperthyroidism Exopthalmos, proptosis, lid lag, orbital edema Diffuse goiter TSH receptor antibodies Increased RAI uptake

4. MUST KNOW T4 and T3 are produced in thyroid gland but T3 is the active component. T3 can also come form T4. T4-to-T3 conversion is stopped by starvation, liver disease and certain drugs (propylthiouracil, propranolol, prednisone) T4 and T3 are circulating as bound proteins-TBG (thyroid binding globulin) If TBG goes up-T4 and T3 would go up. If TBG goes down-T4 and T3 would go down.

5. GENERAL RULE Hyperthyroidism with a high radioiodine uptake indicates de novo synthesis of hormone. Hyperthyroidism with a low radioiodine uptake indicates either inflammation and destruction of thyroid tissue with release of preformed hormone into the circulation, or an extrathyroidal source of thyroid hormone.

6. FACTITIOUS VS. SUBACUTE THYROIDITIS FACTITIOUSHYPERTHYROIDISMSUBACUTETHYROIDITIS THYROID GLAND Painless gland Painful gland SERUM THYROGLOBULIN Low/NormalHigh SEDIMENTATION RATE NormalHigh

7. DIFFERENTIATING THE THREE TYPES OF THYROIDITIS Subacute thyroiditis/Viral thyroiditis/de Quervain’s thyroiditis Silent or painless thyroiditis (Chronic lymphocytic) (Chronic lymphocytic) Hashimoto’s thyroiditis (Painless goiter) Viral Idiopathic mainly in women, typically 3-12 months after pregnancy (Postpartum thyroiditis) Autoimmune. Multinodular goiter is the outstanding feature. High ESR with fever Normal ESR High or normal ESR High T4 and T3 early on- later low T4 and T3. Low RAIU Anti-thyroglobulin antibodies are usually elevated. TPO antibodies usually normal. High T4 and T3 with low TSH initially, then Low RAIU, low T4 and T3. Anti-thyroglobulin antibodies may or may not be elevated. TPO elevated in 75% of cases. Initially eu, hyper- or hypo, eventually hypothyroid. Low RAIU. Anti-thyroglobulin antibodies are present in 85% of cases. TPO in 95% of cases. Aspirin/Steroids Beta-blockers if needed Levothyroxine if needed

8. INDICATIONS FOR SURGERY Patients with very large goiters Goiters causing upper airway obstruction or severe dysphagia In a patient who also has a nonfunctional thyroid nodule, which can be a thyroid cancer, surgery can both cure the hyperthyroidism and remove the nodule. Moderate to severe Graves' ophthalmopathy, Pregnant women who are allergic to antithyroid drugs and/or are tolerating hyperthyroidism poorly

9. Case 1 A 27-year-old woman is evaluated for palpitations and heat intolerance that develop 3 months after a successful pregnancy. She is breastfeeding. The patient's older sister has Graves' disease, but the patient herself has no history of thyroid disease. On physical examination, the blood pressure is 128/70 mm Hg, and the pulse rate is 104/min. Eye examination reveals stare and lid lag, but no proptosis. The thyroid gland is moderately enlarged and nontender. She has moist palms and brisk deep tendon reflexes. Serum free T4 is 2.7 ng/dL (34.2 pmol/L), free T3 46.22 ng/dL (7.1 pmol/L), and thyroid-stimulating hormone (TSH) is undetectable. Which one of the following is the most appropriate next step in this patient's management? A 27-year-old woman is evaluated for palpitations and heat intolerance that develop 3 months after a successful pregnancy. She is breastfeeding. The patient's older sister has Graves' disease, but the patient herself has no history of thyroid disease. On physical examination, the blood pressure is 128/70 mm Hg, and the pulse rate is 104/min. Eye examination reveals stare and lid lag, but no proptosis. The thyroid gland is moderately enlarged and nontender. She has moist palms and brisk deep tendon reflexes. Serum free T4 is 2.7 ng/dL (34.2 pmol/L), free T3 46.22 ng/dL (7.1 pmol/L), and thyroid-stimulating hormone (TSH) is undetectable. Which one of the following is the most appropriate next step in this patient's management? A- Serum anti-thyroid peroxidase antibodies A- Serum anti-thyroid peroxidase antibodies B- Serum thyroglobulin level B- Serum thyroglobulin level C- Serum TSH immunoglobulins C- Serum TSH immunoglobulins D- An empiric trial of antithyroid drugs D- An empiric trial of antithyroid drugs E- Radioiodine (I-131) uptake and thyroid scan E- Radioiodine (I-131) uptake and thyroid scan

10. Case 2 A 27-year-old male athlete is evaluated for frontal headache, palpitations, and heat intolerance and an elevated serum thyroid-stimulating hormone (TSH) level. On physical examination, the blood pressure is 147/78 mm Hg, a pulse rate of 88/min, and a mildly enlarged thyroid gland. He has a fine tremor, moist palms, and deep tendon reflexes are brisk. On laboratory testing, serum free T4 is 2.9 ng/dL (38.0 pmol/L) and TSH is 6.8 µU/mL (6.8 mU/L). Antithyroid peroxidase and antithyroglobulin antibodies are negative. Which of the following is the most appropriate next test in the evaluation of this patient? A 27-year-old male athlete is evaluated for frontal headache, palpitations, and heat intolerance and an elevated serum thyroid-stimulating hormone (TSH) level. On physical examination, the blood pressure is 147/78 mm Hg, a pulse rate of 88/min, and a mildly enlarged thyroid gland. He has a fine tremor, moist palms, and deep tendon reflexes are brisk. On laboratory testing, serum free T4 is 2.9 ng/dL (38.0 pmol/L) and TSH is 6.8 µU/mL (6.8 mU/L). Antithyroid peroxidase and antithyroglobulin antibodies are negative. Which of the following is the most appropriate next test in the evaluation of this patient? A- MRI of the pituitary A- MRI of the pituitary B- Thyroid function testing of family members B- Thyroid function testing of family members C- Radioactive iodine uptake and thyroid scan C- Radioactive iodine uptake and thyroid scan D- Serum thyroglobulin level D- Serum thyroglobulin level E- Thyroid stimulating immunoglobulins E- Thyroid stimulating immunoglobulins

11. Case 3 65-year-old man with refractory atrial fibrillation begins therapy with amiodarone. Baseline thyroid hormone levels are normal. One month later, the patient is asymptomatic but has the following laboratory findings: total T4, 13.4 µg/dL (172.46 nmol/L); free T4, 2.7 ng/dL (34.2 pmol/L); free T3, 11.72 ng/dL (1.8 nmol/L); TSH, 3.9 µU/mL (3.9 mU/L). Which of the following is the most likely explanation for these findings? 65-year-old man with refractory atrial fibrillation begins therapy with amiodarone. Baseline thyroid hormone levels are normal. One month later, the patient is asymptomatic but has the following laboratory findings: total T4, 13.4 µg/dL (172.46 nmol/L); free T4, 2.7 ng/dL (34.2 pmol/L); free T3, 11.72 ng/dL (1.8 nmol/L); TSH, 3.9 µU/mL (3.9 mU/L). Which of the following is the most likely explanation for these findings? A- Amiodarone-induced thyroiditis A- Amiodarone-induced thyroiditis B- Iodine-induced hyperthyroidism B- Iodine-induced hyperthyroidism C- Expected changes in euthyroid patients taking amiodarone C- Expected changes in euthyroid patients taking amiodarone D- Spurious laboratory results caused by amiodarone D- Spurious laboratory results caused by amiodarone E- Euthyroid sick syndrome E- Euthyroid sick syndrome

12. Case 4 A 24-year-old woman is evaluated for palpitations and sweating that began 4 weeks after she delivered her first child 8 weeks ago. She has had occasional loose stools. Otherwise, she has felt generally well. She nursed her baby for 6 weeks but decided to stop 2 weeks ago. Her family history is unremarkable. She is taking multivitamins but no other supplements. On physical examination, the blood pressure is 110/60 mm Hg, pulse rate 92/min, and BMI 23.7. The thyroid gland is normal size, slightly firm in consistency, and nontender. Thyroid-stimulating hormone<0.01µU/mL, free T4=3.4ng/dL, total T3=315ng/dL, radioiodine uptake<1%. Thyroid scan not visualized. Which of the following is the most appropriate therapy for this patient? A 24-year-old woman is evaluated for palpitations and sweating that began 4 weeks after she delivered her first child 8 weeks ago. She has had occasional loose stools. Otherwise, she has felt generally well. She nursed her baby for 6 weeks but decided to stop 2 weeks ago. Her family history is unremarkable. She is taking multivitamins but no other supplements. On physical examination, the blood pressure is 110/60 mm Hg, pulse rate 92/min, and BMI 23.7. The thyroid gland is normal size, slightly firm in consistency, and nontender. Thyroid-stimulating hormone<0.01µU/mL, free T4=3.4ng/dL, total T3=315ng/dL, radioiodine uptake<1%. Thyroid scan not visualized. Which of the following is the most appropriate therapy for this patient? A- Radioactive iodine (I-131) A- Radioactive iodine (I-131) B- β-Blocker B- β-Blocker C- Prednisone C- Prednisone D- Propylthiouracil D- Propylthiouracil E- Aspirin E- Aspirin

13. Case 5 A 59-year-old woman is evaluated for a 2-week history of diffuse arthralgias, malaise, anorexia, and left-sided neck pain and swelling. The pain radiates upwards towards the left ear. She has no fever, chills, palpitations, or nervousness. On physical examination, the temperature is 37.3 °C (99.2 °F), and the pulse rate is 92/min. Thyroid examination shows warmth, tenderness, and moderate enlargement of the left lobe of the gland, without fluctuance. Laboratory testing shows a leukocyte count of 12,300/µL (12.3 × 109/L), with 82% segmented cells and 3% bands; erythrocyte sedimentation rate is 113 mm/h. Serum free T4 is 3.0 ng/dL (38.6 pmol/L), and TSH is 0.04 µU/mL (0.04 mU/L). CT scan of the neck shows no evidence of abscess. Which of the following is the most appropriate therapy at this time? A 59-year-old woman is evaluated for a 2-week history of diffuse arthralgias, malaise, anorexia, and left-sided neck pain and swelling. The pain radiates upwards towards the left ear. She has no fever, chills, palpitations, or nervousness. On physical examination, the temperature is 37.3 °C (99.2 °F), and the pulse rate is 92/min. Thyroid examination shows warmth, tenderness, and moderate enlargement of the left lobe of the gland, without fluctuance. Laboratory testing shows a leukocyte count of 12,300/µL (12.3 × 109/L), with 82% segmented cells and 3% bands; erythrocyte sedimentation rate is 113 mm/h. Serum free T4 is 3.0 ng/dL (38.6 pmol/L), and TSH is 0.04 µU/mL (0.04 mU/L). CT scan of the neck shows no evidence of abscess. Which of the following is the most appropriate therapy at this time? A- Propylthiouracil 100 mg three times daily A- Propylthiouracil 100 mg three times daily B- Radioiodine ablation therapy B- Radioiodine ablation therapy C- Thyroidectomy C- Thyroidectomy D- Systemic antibiotic therapy D- Systemic antibiotic therapy E- Prednisone 40 mg once daily E- Prednisone 40 mg once daily

14. Case 6 A young female has weight loss, irritability, diarrhea, very high T4, low TSH, and a low RAIU. O/E thyroid gland is painless. Serum thyroglobulin level is low. TPO antibodies are normal. What is your diagnosis? A young female has weight loss, irritability, diarrhea, very high T4, low TSH, and a low RAIU. O/E thyroid gland is painless. Serum thyroglobulin level is low. TPO antibodies are normal. What is your diagnosis? A- Graves disease. A- Graves disease. B- Subacute thyroiditis. B- Subacute thyroiditis. C- Chronic lymphocytic thyroiditis C- Chronic lymphocytic thyroiditis D- Factitious hyperthyroidism D- Factitious hyperthyroidism E- Hashimoto’s thyroiditis. E- Hashimoto’s thyroiditis.

15. Case 7 A 33 year old female gave birth to a healthy child 6 weeks ago. She complains of tremors and anxiety. T4 is elevated while TSH is low normal. In addition to prescribing beta-blockers, which of the following would you order to confirm your diagnosis? A 33 year old female gave birth to a healthy child 6 weeks ago. She complains of tremors and anxiety. T4 is elevated while TSH is low normal. In addition to prescribing beta-blockers, which of the following would you order to confirm your diagnosis? A- Lugol iodine A- Lugol iodine B- Radioactive iodine B- Radioactive iodine C- RAU uptake C- RAU uptake D- Observation D- Observation

16. Case 8 A 32 year old, 4 months post-partum nurse comes to you for depression. O/E thyroid is enlarged but painless to palpation. Blood tests reveal high T3 and low TSH. What is your next step in the management of this patient? A 32 year old, 4 months post-partum nurse comes to you for depression. O/E thyroid is enlarged but painless to palpation. Blood tests reveal high T3 and low TSH. What is your next step in the management of this patient? A- Free T4 A- Free T4 B- RAI uptake B- RAI uptake C- A trial of propylthiouracil C- A trial of propylthiouracil D- Propranolol D- Propranolol E- Observation E- Observation

17. Case 9 2 months later she comes back with continued symptoms of depression. The previously ordered RAIU was low. Blood tests now reveal low T3 and high TSH. What is your next step in the management of this patient? 2 months later she comes back with continued symptoms of depression. The previously ordered RAIU was low. Blood tests now reveal low T3 and high TSH. What is your next step in the management of this patient? A- No medication, reassurance, and to return for rechecking thyroid function test in 3 months A- No medication, reassurance, and to return for rechecking thyroid function test in 3 months B- Give synthroid for short term and reassure that she will be fine soon B- Give synthroid for short term and reassure that she will be fine soon C- refer her to a psychiatrist C- refer her to a psychiatrist D- Check for spurious intake of thyroid hormone D- Check for spurious intake of thyroid hormone

18. Questions? Questions?