DRUG CONTROL OF CUSHINGS-SYNDROME - COMBINED AMINOGLUTETHIMIDE AND METYRAPONE THERAPY

Eighteen patients with Cushing''s syndrome (16 pituitary-dependent Cushing''s disease, 1 ectopic ACTH syndrome, 1 primary adrenal adenoma) were given a combination of aminoglutethimide and metyrapone, with the object of controlling cortisol overproduction using less toxic doses than would be required with each drug alone. A preliminary trial of this combination using doses of aminoglutethimide of 1 g or more a day was assessed over 2 wk. Control of cortisol overproduction and clinical improvement was achieved, but side effects led to withdrawal of the drugs in 6 out of the 12 patients. A lower dose trial of this combination over 2 wk, using 750 mg/day of aminoglutethimide also controlled cortisol overproduction, and side effects led to drug withdrawal in only 2 out of 6 patients. Four of these patients were successfully controlled with even lower doses (500-750 mg/day of aminoglutethimide) for longer periods (26 days-1 yr). This low regimen which consists of aminoglutethimide 500-750 mg daily, metyrapone 2 g daily, dexamethasone 0.5 mg b.d. [twice a day] and fludrocortisone 0.1 mg daily, is useful for preparing patients for operative treatments and may be used as long-term treatment of milder cases.