Cortisol metabolism in the morning and evening; relation to cortisol secretion rate measurements

Abstract

The question was studied whether the discrepancies observed in cortisol secretion rate determinations from several metabolites were due to changes in metabolic pathway of cortisol during the course of the day. Cortisol-4- 14C was administered to two subjects in the morning at about 0800 hr. The studies were repeated in the same subjects twice in the evening at about 1800 hr and one subject received cortisol-4- 14C at 1415 hr as well. The specific activities of 6 metabolites were determined and the apparent cortisol secretion rates were calculated. The production rates from the various metabolites were not in precise agreement at any of the times of day studied; the disagreement was apparently greatest when the tracer was given in the evening. That the time of day at which labeled cortisol is injected is not the factor responsible for the different estimates was shown in an adrenalectomized subject maintained on dexamethasone. Tracer cortisol-4- 14C was given to this patient at 1750 hr and 36 hours later another tracer of cortisol 1,2- 3H was given at 0900 hr. Complete urine collections were obtained from the time of administration of the first tracer until 36 hours after the second. The urine was processed as a single collection. The 3H/ 14C ratios of all the metabolites were identical demonstrating that the labeled cortisol followed identical metabolic pathway in the morning and in the evening. It thus appears that a diurnal variation in cortisol metabolizing enzymes is not responsible for the demonstrated discrepancies between metabolites when secretion rate is measured by the isotope dilution method from urinary metabolites.