The Physiologic Significance of 6β-Hydroxycortisol in Human Corticoid Metabolism*

Abstract

A previously described method for the measurement of 6β-hydroxycortisol (6β-OH-F) in human urine was modified by the use, for recovery purposes, of a radioactive tracer. A significant difference was noted between the mean urinary excretion in the normal male (298 μg per day) and in the normal female (399 μg per day). Administration of large doses of diethylstilbestrol increased the excretion of 6β-OH-F in normal men, without alteration of the adrenal secretory rate for cortisol. 6β-OH-F excretion was determined in various phases of the menstrual cycle, as well as after testosterone administration, and in hypertensive subjects. Abnormal values were observed in several of these urines. Studies of the metabolic fate of tracer doses of radiocortisol indicated that essentially all urinary 6β-OH-F arises from the peripheral metabolism of endogenous cortisol rather than as an independent secretion from the adrenal gland. This conclusion applies to normal and to estrogen-treated subjects as well as to patients with Cushing's syndrome. Hyperestrogenism, Cushing's syndrome, and liver disease are states in which the production of polar metabolites of cortisol is more important quantitatively than under ordinary circumstances. Evidence is cited that the utilization of this alternate pathway of cortisol metabolism may be increased when A-ring reduction is impaired.