Effect of Ketoconazole on a Hypophysectomized, Hypercortisolemic, Psychotically Depressed Woman

To the Editor.— Depressed patients often but not invariably demonstrate a significant elevation in plasma cortisol concentration and a greatly augmented secretion of cortisol in the urine. 1,2 The extent to which hypercortisolemia is a primary or secondary manifestation of the psychopathology is under investigation. 3 We had the unique opportunity to study a relationship between the level of plasma and urinary cortisol and the severity of the mood disorder in a depressed, 38-year-old woman who had undergone hypophysectomy. We administered ketoconazole, a broadspectrum antifungal agent that is a potent, rapidly acting, reversible inhibitor of cortisol-synthesizing 11-β-hydroxylase, a P-450-dependent enzyme. We did this during a recent hospitalization of the patient and noted a prompt reduction in cortisol production, with an equally prompt improvement in the patient's depressive illness. We present briefly the salient features of her diagnostic evaluation and inpatient treatment. Report of a Case.— The patient reported a long-standing