The effect of administered ACTH on aldosterone metabolism and secretion

To determine better the overall regulation of aldosterone by ACTH, the effect of administered ACTH on the aldosterone metabolic clearance rate (MCR), the excretion rates of tetrahydroaldosterone (THAldo), and the acid-labile conjugate (ALC) of aldosterone were studied in healthy male volunteers on a sodium intake in excess of 200 mEq/day. In 7 subjects, the aldosterone MCR increased significantly on the third day of ACTH treatment, as did the excretion of THAldo, but there was a decrease in the excretion of the ALC. One subject receiving ACTH for 6 days showed a steady increase in the aldosterone MCR on days 3 and 6 of treatment. In 2 of 3 subjects receiving ACTH treatment for 3-4 days, plasma aldosterone levels and plasma renin activity showed little change, whereas in 1 subject, both plasma aldosterone and plasma renin activity became suppressed. During ACTH administration there was a sustained increase in the excretion of THAldo, a metabolite formed in the liver, (in contrast to a decreasing excretion of the ALC which is made principally in the kidneys) which suggests that the increased aldosterone metabolism in response to ACTH occurred in the liver. Measurements made of the excretion of THAldo show that the ACTH stimulatory effect on aldosterone secretion may not be as transient as previously reported.