Effect of etomidate on cortisol biosynthesis: site of action after induction of anaesthesia.

To determine the site of inhibition of etomidate on cortisol biosynthesis, plasma cortisol, aldosterone, 17 alpha-hydroxyprogesterone, 11-deoxycortisol and ACTH levels were measured in healthy women before and after the administration of a single dose of either 0.20 mg kg-1 etomidate (mean value, n = 10) or 3.15 mg kg-1 thiopental (n = 9) for induction of anaesthesia in a randomized trial. Etomidate produced a smaller increase in plasma cortisol and had a later onset of action than thiopental. Plasma ACTH levels, however, rose higher in the etomidate-induced patients to reach peak levels 6 h after drug administration. In the same group, plasma aldosterone remained below the control levels but still within the normal range, whereas it rose about 2-fold in the thiopental group. Plasma levels of 17 alpha-hydroxyprogesterone and 11 beta-deoxycortisol were hardly modified after thiopental but increased significantly and remained high for 6 h after etomidate injection. This marked rise in precursors together with a blunted and delayed cortisol response to high ACTH levels, and slightly lowered plasma aldosterone concentration indicates a blockage of 11 beta-hydroxylation in adrenal cortisol synthesis after induction of anaesthesia with etomidate.