Comparative fates of intravenously and orally administered aldosterone: evidence for extrahepatic formation of acid-hydrolyzable conjugate in man.

Abstract

Although the liver is the major site of metabolic inactivation of aldosterone, 2 lines of evidence have been developed indicating that considerable conversion of aldosterone to its acid-hydrolyzable conjugate (AHC) occurs in extrahepatic tissues. First, when aldosterone is administered orally, the proportion that is converted to AHC is considerably less than when it is administered intravenously. This sort of discrepancy is not observed in the formation of tetrahydroaldosterone, the other major metabolite of aldosterone. Second, direct measurements of aldosterone and AHC in arterial blood, renal venous blood, and urine, during constant infusion of labeled aldosterone, have indicated that aldosterone is converted to AHC in the kidney. In the absence of liver disease, up to 50% of the total formation of AHC may take place in extrahepatic tissues. The fact that significant quantities of AHC are formed by the kidney has explanatory value with respect to the high proportion of aldosterone that is excreted as AHC in patients with liver disease; the high apparent renal clearance of AHC that has been reported previously; the spuriously high estimates of aldosterone secretion rate than can be obtained by the isotope dilution method if isotopic aldosterone is administered by the oral route.