Effect of aminoglutethimide on ACTH plasma levels in Cushing's disease and Nelson syndrome]

Out of all steroidogenesis inhibitors aminoglutethimide is most frequently used agent for so-called chemical adrenalectomy, especially in oncological cases. The present studies aimed at assessing an effect of the inhibition of cortisol synthesis on plasma ACTH in patients treated with aminoglutethimide. According to the rules of negative feedback, an increase in plasma ACTH should be expected. Aminoglutethimide has been administered to 24 patients with Cushing's disease for 1-6 months. Plasma ACTH did not increase but statistically significantly decreased despite a decrease in blood cortisol. It indicates that aminoglutethimide directly inhibits ACTH secretion. No return of the normal circadian rhythm of cortisol and ACTH release suggests that the drug exerts an effect on ACTH release regulating mechanisms. No definite results were achieved in patients with Nelson syndrome treated with aminoglutethimide for a short period of time. Plasma ACTH levels tend to decrease but no statistical significance was observed in comparison with placebo. It may depend on markedly increased corticotrophin secretion in Nelson tumors.