Influence of spironolactone on endogenous steroid metabolism in man

1. Mild secondary hyperaldosteronism was induced in ten healthy young males by a low sodium diet for 14 days. After 7 days on the diet, five subjects each were treated with spironolactone (group S) or triamterene (group T) daily. 2. The daily negative sodium balance was identical during the first 3 days of medication with both drugs but sodium loss was more severe during the following days in group S. Consequently, the plasma renin activity was higher during the last days of spironolactone compared with triamterene medication. 3. Changes in plasma electrolytes were similar in both groups. 4. No influence of either drug on the synthesis chain leading to cortisol was observed. 5. Plasma concentrations of deoxycorticosterone and corticosterone, however, increased considerably in group S, whereas triamterene did not influence these steroids. 6. Whereas triamterene induced a prompt increase of plasma aldosterone, an increase was delayed for the first 3 days of treatment with spironolactone. Later, plasma aldosterone concentrations rose rapidly in group S and were no longer different from those in group T. 7. Results are interpreted as being due to an initial inhibition of aldosterone synthesis by spironolactone, which is finally compensated, at least in part, by increased activation of the renin-angiotensin system.