Amiodarone-Induced Thyrotoxicosis

Abstract

Appropriate therapy for amiodarone-induced thyrotoxicosis (AIT) requires a diagnostic precision that may be difficult to achieve (1). Individual cases are rarely straight forward. On June 14, 1999, a 71-yr-old man was hospitalized with a 1-week history of exertional shortness of breath, foot swelling, and feeling poorly. In 1982, he was hospitalized with congestive heart failure and atrial fibrillation, attributed to myocarditis. In 1985, atrial fibrillation recurred and responded to chronic quinidine therapy. In early 1996, quinidine was stopped, followed by paroxysmal and then persistent atrial fibrillation with congestive heart failure (ejection fraction, 20–25%). Amiodarone (200 mg/day) and coumadin were prescribed. In May 1996, his serum TSH was 0.9 μU/mL. In September 1996, he suffered an acute myocardial infarction and underwent angioplasty of stenoses of the left anterior descending and diagonal coronary arteries. He remained in normal sinus rhythm; coumadin was discontinued. Amiodarone was discontinued in 1997 but successfully restarted in March 1998 when atrial fibrillation recurred (TSH 2.3μ U/mL). Atrial fibrillation recurred and persisted, and amiodarone was discontinued in September 1998, 9 months before admission. On admission (June 1999) he was in atrial fibrillation with a ventricular response of 180. His blood pressure was 90 systolic. He had mild proptosis (left greater than right), lid retraction, neck vein distension, and a slightly enlarged (20–25 g) thyroid. Although bilateral pleural effusions were present on the chest x-ray, interstitial edema was absent. A myocardial infarction was ruled out. His ventricular response was difficult to control despite escalating doses of β-blockers. Laboratory studies are summarized in Table 1. Laboratory data Normal range: T4, 4.5–10.9 μg/dL; free T4 index, 4.5–10.9; T3 RIA, 60–180 ng/dL; TSH, 0.5–5.0 μU/mL. Free T4, 0.7–1.5 (ng/dl); TSI, 0–129%; TBII, 0–9.9%; urine iodide, 42–350 μg/L. Laboratory data Normal range: T4, 4.5–10.9 μg/dL; free T4 index, 4.5–10.9; T3 RIA, 60–180 ng/dL; TSH, 0.5–5.0 μU/mL. Free T4, 0.7–1.5 (ng/dl); TSI, 0–129%; TBII, 0–9.9%; urine iodide, 42–350 μg/L. His 20-min 99m pertechnetate uptake was low at 0.19% (normal range, 0.5–3.75). AIT was diagnosed, possibly secondary to Graves’ disease. He was begun on methimazole (10 mg, po, tid), prednisone (40 mg, po, daily), iopanoic acid (500 mg, po, bid), metoprolol (200 mg, 4 id), and heparin, coumadin, and verapamil in doses up to 120 mg, tid. At the time of discharge his heart rate was 100–120. He was discharged on June 23, 1999, on methimazole (10 mg, po, tid), prednisone (40 mg, po, daily), iopanoic acid (500 mg, po, bid), lopressor (75 mg, 4 id), verapamil (20 mg, tid), lasix (20 mg, po, qd), and coumadin. Prednisone was discontinued after June 24. On July 2, he was in atrial fibrillation with a ventricular response of 104–108; his blood pressure was 90/60. He had lost 12 lbs since his hospital admission and noted less exertional shortness of breath. Mild proptosis, left greater than right, was noted (Hürthle exophthalmometer: left, 20 mm; right, 19 mm). TSH-binding inhibitory immunoglobulin titers (TBIIs) had been completed and were weakly positive. Graves’ disease was considered likely. On July 22, his pulse was 120 (AF). His dyspnea was unchanged, but he had a single episode of angina relieved by nitroglycerine. He noted increased fatigue and heat sensitivity. Methimazole was increased to 20 mg three times daily. Iopanoic acid was continued. On August 6, his radial pulse was 116–120. His ventricular rate on electrocardiogram was 139, increased compared with his previous electrocardiogram, and worsening ST segment depression was present. Although his dyspnea was stable, edema had increased to the mid-calf. His cardiologist considered hospital admission, but careful outpatient observation was the final recommendation. On August 17, thyroidectomy was recommended, in part, based on a serum T4 of 25.9 μg/dL, although his serum T3 had fallen to 140 ng/mL. A bilateral thyroidectomy was performed on September 10 without incident or complications. Pathological examination revealed an enlarged thyroid gland (right lobe, 5 × 2.5 × 1.5 cm; left lobe, 4.5 × 2.5 × 3 cm), but no weight was recorded. The final pathology report read: “Enlarged thyroid with fibrosis and mild chronic inflammation. There is no evidence of malignancy.” We asked to have the pathological material re-assessed. An addendum was reported: “The thyroid is diffusely affected with the lesions described as follows. Approximately half of the areas contained islands of dilated thyroid follicles that were lined by attenuated follicular epithelial cells. These islands are separated by areas of collapsed thyroid follicles admixed with fibrosis and prominent vasculature. Nonspecific findings including histocytes and eosinophilic bodies were present. These changes are consistent with those described in amiodarone-associated th