Total suppression of cortisol excretion by ketoconazole in the therapy of the ectopic adrenocorticotropic hormone syndrome.

Ketoconazole, an antifungal imidazole derivative, has been shown to inhibit adrenal steroidogenesis in vitro and in vivo. This has led to its use clinically as an effective treatment for various forms of Cushing's syndrome. The clinically effective doses have been reported to be between 800 to 1,200 mg per day, usually without glucocorticoid replacement. Herein is reported the first case of Cushing's syndrome due to ectopic adrenocorticotropic production from a metastatic carcinoid tumor of the thymus that was treated with ketoconazole. Urinary cortisol excretion was totally suppressed at the initial dose and optimal control was achieved with relatively low doses of ketoconazole (200 to 400 mg per day), along with dexamethasone replacement. Use of glucocorticoid replacement is advisable in this setting to avoid symptomatic hypoadrenalism.