What is the role of spironolactone in the treatment of idiopathic hyperaldosteronism?

Updated: Sep 08, 2020
  • Author: George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London); Chief Editor: Robert P Hoffman, MD  more...
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Spironolactone is generally considered first-line therapy for patients with BAH at doses ranging between 25-400 mg/d (usually 12,5-50 mg/d). It is a nonselective, competitive mineralocorticoid receptor antagonist that is structurally similar to progesterone and metabolized in the liver to active metabolites. Additionally, spironolactone also acts as an antagonist of the androgen receptor, a weak antagonist of the glucocorticoid receptor, and an agonist of the progesterone receptor. These receptor-mediated actions also result in the associated adverse effects of spironolactone including hyperkalemia, hyponatremia, gynecomastia, impotence, menstrual disturbances and breast tenderness in women, hirsutism, and decreased libido. It should be used with caution in peripubertal children. [24, 25]

Gynecomastia is one of the major side effects of spironolactone in men and occurs in a dose-dependent manner in approximately 7% of cases with doses of less than 50 mg/d and as many as 50% of cases with doses of more than 150 mg/d. Spironolactone-mediated inhibition of central sympathetic nervous system activity has been suggested to be an important mechanism underlying its antihypertensive effects in patients with resistant hypertension. [30, 49]

Patients unable to tolerate spironolactone can be treated with eplerenone, a more expensive but selective mineralocorticoid receptor blocker with fewer antiandrogenic effects. Eplerenone is derived from spironolactone and considered a selective mineralocorticoid receptor antagonist with limited crossreactivity for the androgen and progesterone receptors, thus lacking many of the significant sexually-related adverse effects known to be associated with the use of spironolactone. However, eplerenone has a low affinity for the mineralocorticoid receptor and is less efficient than spironolactone with respect to BP lowering in patients with mild-to-moderate hypertension; thus, higher doses of eplerenone are needed to achieve the same effect as spironolactone (usually 25-50 mg twice daily).

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