RENAL CLEARANCE OF ENDOGENOUS 17-HYDROXYCORTICOSTEROIDS IN HYPERTENSION*

Abstract

Renal clearances of endogenous free and conjugated 17-hydroxycorticosteroids (17-OH-CS) were determined in 15 normotensive and 13 hypertensive subjects (12 with essential hypertension and one with Cushing''s syndrome) and were related to endogenous creatinine clearance. Free 17-OH-CS were cleared at similar rates in the two groups of subjects. These rates were 15-25 times lower than those for conjugated 17-OH-CS. After stimulation with ACTH the clearance of free 17-OH-CS increased significantly in both groups as compared with the clearance under basal conditions. The clearance of total conjugated 17-OH-CS (extractable with butanol-chloroform mixture) was significantly lower in the hypertensive than in the normotensive subjects. In patients with renal damage the percentage decrease in the clearance of total conjugated 17-OH-CS exceeded the decrease in creatinine clearance. The decreased clearance of total conjugated 17-OH-CS resulted in the accumulation of these steroids in the blood, thus decreasing the ratio of free to conjugated 17-OH-CS in plasma. The 17-OH-CS glucuronides (released by [beta]-glucuronidase hydrolysis) were cleared at similar rates in normotensive and hypertensive subjects. In patients with decreased renal function these rates were proportional to those of creatinine clearance. Moreover, the concentration of 17-OH-CS glucuronides in the urine of hypertensive patients was almost identical with the concentration of total conjugated 17-OH-CS in the same specimens. After administration of ACTH, the clearance of total conjugated 17-OH-CS decreased in normotensive subjects but increased slightly in hypertensive patients, as compared with the corresponding clearances under basal conditions. Thus, the hypertensive patients under basal conditions cleared total conjugated 17-OH-CS in a manner similar to that observed in the normotensive subjects after administration of ACTH.