An Effect of o,p′-DDD on the Extra-adrenal Metabolism of Cortisol in Man

o,p′-DDD was administered orally in doses of 6–9 g daily to 5 patients with untreated Cushing's syndrome and to 8 patients with Addison's disease who received constant doses of exogenous cortisol. Sequential measurements of plasma and urinary 17-hydroxycorticosteroids, cortisol secretion rates, plasma cortisol disappearance rates, and serum transcortin levels were performed before and during treatment with o,p′-DDD. There was invariably a prompt 50–80% decrease in urinary 17-OHCS, regardless of whether the patient's source of cortisol was endogenous or exogenous. Plasma 17-OHCS levels and cortisol secretion rates, however, did not fall. Evaluation of the pattern of cortisol metabolites excreted in the urine of these patients revealed that o,p′-DDD altered the extra-adrenal metabolism of cortisol so as to decrease the proportion of cortisol excreted as tetrahydrocortisol and tetrahydrocortisone and to increase the proportion excreted as 6β-hydroxycortisol.