Journal of Clinical Endocrinology & Metabolism, Vol 52, 1057-1061, Copyright © 1981 by Endocrine Society

ARTICLES

Plasma corticosteroid concentrations during spironolactone administration: evidence for adrenal biosynthetic blockade in man

ML Tuck, JR Sowers, DB Fittingoff, JS Fisher, GJ Berg, ND Asp and DM Mayes

Spironolactone, a mineralocorticoid antagonist, may also inhibit aldosterone biosynthesis. In vitro studies suggest that spironolactone and its major metabolites inhibit adrenal 18- and 11 beta-hydroxylase activity. We examined various adrenal corticosteroids and their precursors, plasma renin activity, aldosterone excretion rate, and serum and urine electrolytes in normal subjects before and on days 5 and 10 of spironolactone administration (400 mg/day). Plasma corticosteroids were also examined 60 min after ACTH (Cortrosyn) 0.25- mg iv bolus. RIAs were performed after extensive chromatography; there was no interference of spironolactone and its metabolites in the assays. All studies were performed in supine subjects in metabolic balance on a constant 120-meq sodium intake. Plasma renin activity was increased (P less than 0.001) on both days 5 and 10 of spironolactone. Plasma aldosterone (PA) and the aldosterone excretion rate increased (P less than 0.01) on day 5 of spironolactone but decreased (P less than 0.01) from day 5 to 10. Both 11-deoxycorticosterone and 18- hydroxycorticosterone were increased from day 5 to 10. Corticosterone, progesterone, and dehydroepiandrosterone did not increase significantly during spironolactone administration. Incremental PA response to ACTH was less than control on day 10 of spironolactone, but other corticosteroid responses to ACTH were not different during control and days 5 or 10 of treatment. Reduction in PA and further elevation in its precursors during the second 5-day period of spironolactone therapy suggests inhibition of aldosterone biosynthesis during this phase of treatment in normal man. The disproportionate increments in 18- hydroxycorticosterone and 11-deoxycorticosterone suggest biosynthetic inhibition at the 18-dehydrogenase and 11 beta-hydroxylase sites.

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