Diurnal Variation of the Metabolic Clearance Rate of Cortisol. Effect on Measurement of Cortisol Production Rate

Abstract

The effects of changes in plasma concentration of cortisol (F) on the metabolic clearance rate (MCR) of this hormone were investigated in 11 normal adult males as follows: constant blood withdrawal was carried out using a portable pump attached to a non-thrombogenic catheter which itself was placed in the antecubital vein. Two pulse-injections of radioactive F were administered, first 14C-F at 8 pm and then 3H-F at 5 am. Six-hr blood collections were started immediately before each of these injections. The integrated plasma concentrations (I.C.) of endogenous and radioactive F were determined in each 6-hr pool. The MCR was calculated as radioactive F injected/I.C. of radioactive F. The MCR values of the 5 am-11 am period (149 ± 28 l/M2/24 hr) were significantly (p < 0.005) higher than those obtained during the 8 pm-2 am period (91 ± 19 l/M2/24 hr). The I.C. of endogenous F were 10.9 ± 1.7 (SD) μg/100 ml and 3.3 ± 1.0 μg/100 ml for the 2 periods of study respectively. The marked changes in MCR invalidate the determinations of the blood production of F on the basis of a 24-hr integrated concentration of this steroid and the value of its MCR measured during a fraction of the day. When the production rate of F was calculated from the cumulative specific activities of urinary THF and THE glucuronides, it was found that the values derived from the 14C-THE (14C-F being given at 8 pm) were about 1/4 less than those from 14C-THF. In contrast, when 3H-F was injected at 5 am, the urinary productions derived from 3H-THF was slightly but significantly smaller than those from 3H-THE. However, when the production was calculated from the mean of THF and THE, there was only minimal effect of the time of injection of radioactive F.