The man described has congestive heart failure (CHF). Spironolactone is a mineralcorticoid antagonist that can cause gynecomastia as an adverse effect.
Drugs shown to reduce mortality in CHF include ACE inhibitors, beta-blockers, angiotensin II receptor blockers (ARBs), and spironolactone, which is known to have endocrine side effects including gynecomastia. Spironolactone prevents the binding of aldosterone to its receptor, and thus stops aldosterone-mediated sodium and water resorption in the cortical collecting tubule. By virtue of inhibiting aldosterone, spironolactone functions as a potassium-sparing diuretic. More selective mineralcorticoid antagonists like eplerenone are available and have lesser endocrine side effects.
Hoyt et al. describe the drug regimen recommended for reduced mortality and morbidity for patients with congestive heart failure. They recommend that patients with an ejection fraction less than 40 percent (decreased systolic function) should be treated with medication to improve symptoms and prevent progression of heart failure. ACE inhibitors, ARBs, beta-blockers and spironolactone are highlighted.
Salyer et al. detail pharmacologic causes of male gynecomastia, which they report accounts for 20% of all gynecomastia. Though commonly tested on exams, spironolactone is listed with verapamil, cimetidine, and first-generation antipsychotics as less common agents responsible for gynecomastia. Most common are anti-androgens, protease inhibitors, and nucleoside reverse transcriptase inhibitors. Discontinuation of the offending drug will sometimes lead to reversal of gynecomastia. If the drug cannot be changed, surgery or irradiation are included as other treatment options.
Figure A demonstrates an example of an elderly gentleman with gynecomastia.
Answer 1: An increased PR interval is the physiologic effect on a beta-blocker.
Answer 2: ACE inhibitors are a cornerstone of CHF therapy but are not known to cause gynecomastia.
Answer 4: Inhibition of the Na+/K+/2Cl- triple transporter is the mechanism of loop diuretics, more commonly used in edema therapy.
Answer 5: Increased tubular fluid osmolarity is the effect of osmotic diuretics like mannitol, which are contraindicated in CHF.
Hoyt RE, Bowling LS. Reducing readmissions for congestive heart failure. Am Fam Physician. 2001 Apr 15;63(8):1593-8. Erratum in: Am Fam Physician 2002 Jan 15;65(2):172. Level of Evidence: Undefined.
PMID:11327436 (Link to Abstract)
Salyer SA, Parks J, Barati MT, Lederer ED, Clark BJ, Klein JD, Khundmiri SJ. Aldosterone regulates Na(+), K(+) ATPase activity in human renal proximal tubule cells through mineralocorticoid receptor. Biochim Biophys Acta. 2013 May 16;1833(10):2143-2152
PMID:23684706 (Link to Abstract)
USMLE World Step 1 QBank Question #687. Copyright © USMLEWorld, LLC 2012