Aminoglutethimide: a ‘side-effect’ turned to therapeutic advantage

Abstract

Aminoglutethimide was introduced as an anti-convulsant drug in the U.S.A. in 1960. The occurrence of a number of side-effects, including several endocrine effects such as goitrogenesis, sexual precocity and virilization, led to its withdrawal. Further investigation indicated that the drug inhibited adrenal biosynthesis, particularly of aldosterone, cortisol and androgens, probably by interfering with the conversion of cholesterol to delta-5-pregnenolone. Aminoglutethimide has also been shown to modify the extra-adrenal metabolism of cortisol. The possible clinical applications of these ‘side-effects’ are discussed.