Drug controlled of Cushing's 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 weeks. 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 weeks, 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 year). This low regimen which consists of aminoglutethimide 500-750 mg daily, metyrapone 2 g daily, dexamethasone 0.5 mg b.d. and fludrocortisone 0.1 mg daily, is useful for preparing patients for operative treatments and may be used as a long-term treatment of milder cases.
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000616:Aminoglutethimide / Q000008:administration & dosage / Q000627:therapeutic use*; D003480:Cushing Syndrome / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D005260:Female; D005438:Fludrocortisone / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D008297:Male; D008797:Metyrapone / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors
D000616:Aminoglutethimide; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D005438:Fludrocortisone; D006854:Hydrocortisone; D008797:Metyrapone