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October 1988

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

Author Affiliations

Department of Psychiatry
Department of Pathology Dartmouth Medical School Hanover, NH 03756

Arch Gen Psychiatry. 1988;45(10):966-967. doi:10.1001/archpsyc.1988.01800340094019

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.3We 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