Etomidate: a selective adrenocortical 11 beta-hydroxylase inhibitor.
To investigate the adrenocortical suppression caused by the anesthetic etomidate, plasma levels of progesterone (P), 17-hydroxyprogesterone (17-OHP), 11-deoxycorticosterone (DOC), corticosterone (B), aldosterone (Aldo), 11-deoxycortisol (S), cortisol (F), and cortisone (E) were measured simultaneously before and after a short-term ACTH stimulation test in a 6.5-year-old boy whose convulsions could be kept under control only with constant etomidate infusions. During etomidate therapy, plasma levels of DOC and S were extremely elevated, the progestins P and 17-OHP were slightly elevated, whereas B and Aldo were in the lower normal range, and F and E were markedly decreased. A short-term ACTH stimulation test during etomidate infusion gave a blunted response of B, Aldo, F and E, whereas the level of DOC remained high and S even further increased. P and 17-OHP showed a positive response to ACTH. The ratios of B/DOC and F/S, which reflect adrenocortical 11 beta-hydroxylase activity, were extremely decreased during etomidate and did not change after ACTH stimulation. In contrast, the ratios of DOC/P and S/17-OHP, which reflect 21-hydroxylase activity, were elevated and remained elevated after ACTH stimulation. After discontinuation of etomidate therapy, all the baseline steroid levels were somewhat elevated, but responded normally to ACTH. These results demonstrate that etomidate causes a specific and reversible blockade of the 11 beta-hydroxylation of adrenal steroid synthesis.
D019326:17-alpha-Hydroxyprogesterone; D000302:Adrenal Cortex / Q000187:drug effects*; D000324:Adrenocorticotropic Hormone; D000450:Aldosterone / Q000097:blood; D002648:Child; D003345:Corticosterone / Q000097:blood; D003348:Cortisone / Q000097:blood; D003350:Cortodoxone / Q000097:blood; D003900:Desoxycorticosterone / Q000097:blood; D005045:Etomidate / Q000627:therapeutic use*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D006908:Hydroxyprogesterones / Q000097:blood; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D011374:Progesterone / Q000097:blood; D013226:Status Epilepticus / Q000188:drug therapy* / Q000201:enzymology; D013252:Steroid 11-beta-Hydroxylase / Q000037:antagonists & inhibitors*; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors*
D006908:Hydroxyprogesterones; D007093:Imidazoles; D003900:Desoxycorticosterone; D000450:Aldosterone; D011374:Progesterone; D019326:17-alpha-Hydroxyprogesterone; D000324:Adrenocorticotropic Hormone; D013250:Steroid Hydroxylases; D013252:Steroid 11-beta-Hydroxylase; D003348:Cortisone; D003345:Corticosterone; D003350:Cortodoxone; D006854:Hydrocortisone; D005045:Etomidate