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A single bolus dose of etomidate decreases cortisol synthesis by inhibiting the 11-beta hydroxylase, a mitochondrial enzyme in the final step of cortisol synthesis. In our institution, all the patients undergoing cardiac surgery receive etomidate at anesthesia induction. The purpose of this study was to assess the incidence of adrenocortical dysfunction after a single dose of etomidate in selected patients undergoing major cardiac surgery and requiring high-dose norepinephrine postoperatively.Retrospective descriptive study in the surgical ICU of a university hospital.Sixty-three patients presented acute circulatory failure requiring norepinephrine (0,2 microg/kg/min) during the 48 hours following cardiac surgery. Absolute adrenal insufficiency was defined as a basal cortisol below 414 nmo/l (15 microg/dl) and relative adrenal insufficiency as a basal plasma cortisol between 414 nmo/l (15 microg/dl) and 938 nmo/l (34 microg/dl) with an incremental response after 250 microg of synthetic corticotropin (measured at 60 minutes) below 250 nmol/l (9 microg/dl).Fourteen patients (22%) had normal corticotropin test results, 10 (16%) had absolute and 39 (62%) relative adrenal insufficiency. All patients received a low-dose steroid substitution after the corticotropin test. Substituted patients had similar clinical outcomes compared to patients with normal adrenal function.A high incidence of relative adrenal failure was observed in selected cardiac surgery patients with acute postoperative circulatory failure.

Synthesis of aldosterone (Aldo) and corticosterone (B) has been recently reported in rat heart. However, regulation of this synthesis in pathophysiological states remains unknown. Thus, this study aimed to analyze effects of a one-month myocardial infarction (MI) on cardiac steroidogenic system. Levels of terminal enzymes of B (11 beta-hydroxylase: 11 beta H) and aldo (Aldo-synthase: AS) synthesis were assayed by quantitative RT-PCR. Cardiac Aldo and B levels were assessed by celite colum chromatography and radioimmunoassay. MI raised AS mRNA levels by 2.0-fold (p0.05) but downregulated that of 11 beta H by 2.4 fold (p0.05) in the noninfarcted part of the left ventricle (LV). Cardiac steroids production followed a similar pattern of regulation. Aldo level was increased in MI (319 +/- 85 vs 87 +/- 11 pg/mg of protein in control, p0.05) whereas that of B fell (2,412 +/- 318 vs 4,624 +/- 857 pg/mg of protein in control, p0.05). MI also induced an 1.9-fold increase in cardiac Ang II level. Such cardiac regulations were prevented by Ang II-AT1 receptor antagonist losartan (8 mg/kg/day) treatment. The Aldo receptor antagonist spironolactone (20 mg/kg/day) had no effect. Plasma Aldo and B, and adrenal 11 beta H and AS mRNA levels were unchanged whatever the treatment. The MI-induced collagen deposition in noninfarcted area of the LV was reduced by both spironolactone and losartan treatments by 1.6- and 2.5-fold, respectively. These data indicate that MI is associated with tissue-specific activation of myocardial aldosterone synthesis. This activation is mediated by cardiac Ang II via AT1 receptor and the resultant increase of intracardiac aldosterone level may be involved in post-MI ventricular remodeling.

Newborn rat adrenocortical cells in primary culture have allowed us to establish the place of 11 beta/18-hydroxylation in the biosynthesis and metabolism of corticosteroid hormones. The affinity of the 11 beta/18-hydroxylation system has been determined with respect to known or potential intermediates. It has equally been examined in relation to 2 alpha-, 6 alpha-, 6 beta-, 16 alpha or 17 alpha-hydroxyprogesterone and 6 alpha-, 6 beta- or 17 alpha-hydroxy-11-deoxycorticosterone.