A 56-year-old man comes to the office due to progressively worsening fatigue, difficulty concentrating, and increasing forgetfulness over the past several weeks. In addition, the patient has had vague abdominal pain and constipation and has gained 2.7 kg (6 lb) unintentionally over the last 3 months. Medical history is significant for hypertension, nonischemic cardiomyopathy with left ventricular systolic dysfunction, and atrial fibrillation. Blood pressure is 140/90 mm Hg and pulse is 75/min. Physical examination reveals regular heart sounds with normal S1 and S2. The lungs are clear to auscultation. There is no lower extremity edema, and the skin appears dry. Laboratory studies are as follows: Which of the following medications is most likely responsible for this patient's current symptoms?

Question

A 56-year-old man comes to the office due to progressively worsening fatigue, difficulty concentrating, and increasing forgetfulness over the past several weeks.  In addition, the patient has had vague abdominal pain and constipation and has gained 2.7 kg (6 lb) unintentionally over the last 3 months.  Medical history is significant for hypertension, nonischemic cardiomyopathy with left ventricular systolic dysfunction, and atrial fibrillation.  Blood pressure is 140/90 mm Hg and pulse is 75/min.  Physical examination reveals regular heart sounds with normal S1 and S2.  The lungs are clear to auscultation.  There is no lower extremity edema, and the skin appears dry.  Laboratory studies are as follows:  Which of the following medications is most likely responsible for this patient's current symptoms?

Quizplus · Accepted Answer

11ec25c8_d355_1d02_bc81_8d1e9d2e4bde_MD0003_00 This patient's symptoms consistent with hypothyroidism (eg, fatigue, concentration difficulties, constipation, weight gain, dry skin) and his liver function test abnormalities likely represent amiodarone side effects. Amiodarone is indicated for patients with serious ventricular arrhythmias and for rhythm control in those with atrial fibrillation and left ventricular systolic dysfunction. However, it can cause thyroid dysfunction (hyper-or hypothyroidism) due to its high iodine content and intrinsic effects on thyroid metabolism. Amiodarone causes hypothyroidism because the large iodine load suppresses synthesis of thyroid hormone (Wolff-Chaikoff effect), and amiodarone also inhibits the conversion of T4 to T3 in peripheral tissues. Conversely, amiodarone can cause hyperthyroidism due to increased thyroid hormone synthesis in patients with nodular thyroid disease or latent Graves disease (amiodarone-induced thyrotoxicosis type 1) or due to destructive thyroiditis with release of preformed thyroid hormone (amiodarone-induced thyrotoxicosis type 2). Other toxic effects of amiodarone can include hepatocellular injury (eg, elevated hepatic aminotransferases, as in this patient), cardiac conduction abnormalities, interstitial pneumonitis, peripheral neuropathy, and skin discoloration. About 50% of patients on long-term amiodarone therapy develop significant side effects, and approximately 1 in 5 discontinue the drug due to toxicity. (Choice B) Digoxin toxicity can cause nausea, diarrhea, anorexia, confusion, visual disturbances, and a variety of cardiac arrhythmias, but thyroid and hepatic effects are not common. (Choice C) Dofetilide is a class III antiarrhythmic agent and is associated with a risk of torsade de pointes in ≤3% of patients. (Choice D) Hydralazine can cause salt and fluid retention, peripheral edema, palpitations, orthostatic hypotension, and drug-induced lupus-like syndrome. (Choice E) Beta blockers (eg, metoprolol) can cause fatigue, decreased concentration, and weight gain. However, this patient's dry skin and constipation are more consistent with hypothyroidism, and hepatic toxicity is uncommon with beta blockers. (Choice F) Common side effects of verapamil include constipation and impaired cardiac conduction and contractility, with potential worsening of bradyarrhythmias and congestive heart failure. Educational objective: Amiodarone causes thyroid dysfunction due to its iodine content and effects on thyroid metabolism. It impairs synthesis of thyroid hormone and decreases peripheral conversion of T4 to T3. It also can increase synthesis of thyroid hormone in patients with nodular thyroid disease or latent Graves disease and can cause destructive thyroiditis with release of preformed hormone. References: Amiodarone and the thyroid. (http://www.ncbi.nlm.nih.gov/pubmed/25931048)

A 56-Year-Old Man Comes to the Office Due to Progressively