aminoglutethimide + metyrapone

Aminoglutethimide + metyrapone is a combination of two oral small molecule steroidogenesis inhibitors used primarily for the medical management of Cushing's syndrome and related conditions characterized by cortisol overproduction. Both drugs act at different steps in adrenal steroid biosynthesis, leading to a more effective reduction in cortisol levels than either agent alone, often allowing lower and less toxic doses. Aminoglutethimide inhibits the conversion of cholesterol to pregnenolone (the first step in steroid synthesis), while metyrapone inhibits 11-beta-hydroxylase, blocking the final step in cortisol synthesis. This combination is particularly useful for short-term control or preoperative preparation in patients with Cushing's syndrome due to pituitary disease, ectopic ACTH production, or adrenal tumors[1][2][3]. Side effects can include rash and pruritus (aminoglutethimide) and hypertrichosis (metyrapone)[1][2].