Abstract

The effect of diphenylhydantoin administration on the kinetics of labeled cortisol was investigated in 12 patients. During therapy with diphenylhydantoin the following significant mean changes (ranging from 13-28% of control) were noted: a decrease in disappearance time (T_1/2) of labeled cortisol from plasma, an increase in metabolic clearance rate, an increase in cortisol blood production rate and an increase in 24-hour cortisol secretion rate (urinary isotope dilution method). No change was noted in the rate of excretion of total radioactivity in urine at the time intervals selected. It is suggested that diphenylhydantoin therapy enhances tissue uptake of cortisol possibly mainly at the level of the hepatic smooth endoplasmic reticulum since there is also an increase in hydroxylated cortisol formation (e.g., 6-hydroxycortisol). An alteration in plasma cortisol binding does not appear to be a factor since plasma levels of cortisol were not significantly different during treatment, and supplementary studies demonstrated no changes in freely dialyzable cortisol or cortisol-binding globulin concentration.