A 59-year-old man comes to the physician with painful enlargement of both breasts for the last 2-3 weeks. He also complains of significant fatigue, loss of libido, and erectile dysfunction. His past medical history is significant for type 2 diabetes mellitus, hypertension, hyperlipidemia, and ischemic cardiomyopathy. Echocardiogram 6 months ago showed global left ventricular hypokinesis (ejection fraction 25%) and moderate mitral regurgitation. The patient's current medications include sitagliptin, candesartan, amlodipine, spironolactone, furosemide, atorvastatin, and aspirin. Spironolactone was added 8 weeks ago after he complained of dyspnea on moderate physical activity. He has also started taking over-the-counter omeprazole to "protect my stomach from my medications."
On examination, bilateral tender gynecomastia is noted. There is no jugular venous distension or pedal edema. Examination of the heart shows a 3/6 pansystolic murmur at the apex radiating to the axilla. Lungs are clear to auscultation. Testicular examination is unremarkable.
Which of the following is the most appropriate next step in management of this patient?

Question

A 59-year-old man comes to the physician with painful enlargement of both breasts for the last 2-3 weeks.  He also complains of significant fatigue, loss of libido, and erectile dysfunction.  His past medical history is significant for type 2 diabetes mellitus, hypertension, hyperlipidemia, and ischemic cardiomyopathy.  Echocardiogram 6 months ago showed global left ventricular hypokinesis (ejection fraction 25%) and moderate mitral regurgitation.  The patient's current medications include sitagliptin, candesartan, amlodipine, spironolactone, furosemide, atorvastatin, and aspirin.  Spironolactone was added 8 weeks ago after he complained of dyspnea on moderate physical activity.  He has also started taking over-the-counter omeprazole to "protect my stomach from my medications."
On examination, bilateral tender gynecomastia is noted.  There is no jugular venous distension or pedal edema.  Examination of the heart shows a 3/6 pansystolic murmur at the apex radiating to the axilla.  Lungs are clear to auscultation.  Testicular examination is unremarkable.
Which of the following is the most appropriate next step in management of this patient?

Quizplus · Accepted Answer

This patient has gynecomastia, most likely from spironolactone due to its timing with initiation of therapy. Aldosterone receptor antagonists (spironolactone and eplerenone) are widely used in clinical practice as they have been shown to reduce mortality in patients with systolic congestive heart failure. Aldosterone receptor antagonists are associated with significant potential adverse effects, especially hyperkalemia. In addition, spironolactone blocks testosterone receptors, which may lead to breast enlargement, breast tenderness, and low libido in men. It also increases clearance of testosterone, increases conversion of testosterone to estrogen, and decreases overall testosterone production. In general, spironolactone is preferred over eplerenone due to lower cost and well-established clinical experience. However, both aldosterone receptor blockers appear equally efficacious; eplerenone may be substituted in patients who develop anti-androgenic side effects on spironolactone. (Choice A) The risk of developing gynecomastia with omeprazole is <1%. Among gastric acid reducers, cimetidine is associated with the highest risk of gynecomastia. (Choices C, D, and E) This patient's symptoms are likely due to blockade of testosterone receptors by spironolactone rather than testosterone deficiency. Measuring serum testosterone levels or adding exogenous testosterone is therefore unlikely to be effective. Similarly, measuring serum prolactin and thyroid-stimulating hormone is not indicated as the gynecomastia and decreased libido appear to be likely due to spironolactone. Further workup may be indicated if the symptoms do not resolve after discontinuing the spironolactone. Educational objective: Aldosterone receptor blockers - spironolactone and eplerenone - have been shown to improve survival in systolic heart failure with low left ventricular ejection fraction. Both may cause hyperkalemia. Spironolactone has significant anti-androgenic effects. Eplerenone is more specific than spironolactone for the mineralocorticoid receptor and has fewer endocrine side effects. __________ References: The risks and benefits of aldosterone antagonists. (http://www.ncbi.nlm.nih.gov/pubmed/16036053) Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. (http://www.ncbi.nlm.nih.gov/pubmed/12668699)

A 59-Year-Old Man Comes to the Physician with Painful Enlargement