Eplerenone relieves spironolactone-induced painful gynaecomastia in a patient with primary aldosteronism

Abstract

Sir, Eplerenone is the second oral aldosterone antagonist available for the treatment of essential hypertension and congestive heart failure. Spironolactone, the first aldosterone antagonist, although effective for the above conditions, has progestational and antiandrogenic adverse effects due to its non-specific binding to various steroid receptors. We report the case of a 54-year-old Caucasian man, who was admitted to hospital because of severe hypertension and hypokalaemia. The plasma aldosterone/plasma renin activity ratio was well above the cut-off level of 30 ng/dl/ng ml � 1 h � 1 . The acute intravascular volume expansion with the intravenous administration of isotonic saline showed autonomous aldosterone production. The aforementioned results were considered diagnostic of primary aldosteronism. A computerized tomography scan with fine cuts (2.5–3 mm) showed bilateral adrenal gland hyperplasia. Therefore, the patient was started on spironolactone 100 mg t.d.s., and in the following days normokalaemia was restored and blood pressure was well-controlled. Two months later, the patient presented with bilateral painful gynaecomastia. We switched spironolactone to eplerenone 25 mg t.d.s., and the patient was completely relieved within 1 month, while his blood pressure remained well-controlled and serum potassium was normal. Spironolactone is the drug of choice for the treatment of primary aldosteronism, but presents sexual side effects, such as impotence, painful gynaecomastia and menstrual disturbances in pre-menopausal women. Several mechanisms have been proposed for these side effects, such as a dosedependent reduction of microsomal cytochrome P-450, alterations of the testosterone–estrogen ratio, a fall in plasma testosterone or a significant increase in its metabolic clearance, and the peripheral conversion of testosterone to estradiol or increased serum levels of estrone and estradiol [1]. Gynaecomastia may be quite remarkable and its occurrence is dose- and time-dependent. Eplerenone is a highly selective aldosterone antagonist. Spironolactone is approximately 40-fold more potent than eplerenone in blocking aldosterone activation of mineralocorticoid receptor. However, the selectivity of eplerenone is significantly greater than spironolactone at androgen, progesterone and glucocorticoid receptors. Eplerenone is 370-fold less potent at blocking dihydrotestosteroneactivation of androgen receptors compared with spironolactone [2]. Two large clinical studies have evaluated the efficacy and tolerability of these aldosterone antagonists. The Randomized Aldactone Evaluation Study (RALES) found that the administration of spironolactone 12.5–50 mg/day,