Cortisol metabolism in the postoperative period after cardiac surgery

Relative 11 beta-hydroxysteroid dehydrogenase deficiency has been shown pre viously to arise from endogenous hypercortisolism in diseases of the hypoth alamic/pituitary/adrenocortical system; whether stress induced hypercortiso lism may also result in substrate overload of 11 beta-hydroxysteroid dehydr ogenase has not yet been studied. We therefore studied the characteristics of cortisol metabolisation during the postoperative period of cardiac surge ry, representing a well standardized surgical procedure. In a prospective, observational, consecutive case study, 14 patients undergoing cardiac surge ry were investigated. During the first two days after cardiac surgery urine was collected from the patients during two 10 hour overnight periods (8 p. m. (day of surgery) until 6 a.m., and during the following night). Using ca pillary gas-chromatography, main urinary cortisol metabolites were quantifi ed (tetrahydrocortisone, tetrahydrocortisol, allo-tetrahydrocortisol, corto lones, cortols as sum of cortisol metabolites (CM)). Free urinary cortisol (FUC) was determined by an automated immunoassay after extraction. The rati o of cortisol metabolites (tetrahydrocortisol, allo-tetrahydrocortisol, cor tols) to cortisone metabolites (tetrahydrocortisone, cortolones) was calcul ated to characterize the overall activity of 11 beta-hydroxysteroid dehydro genase, an enzyme system catalyzing the conversion of cortisol to inactive cortisone (CMR, cortisol metabolisation ratio). Total cortisol metabolisati on (including hepatic ring A-reduction and conjugation) was estimated by a cortisol turnover quotient (CM/FUC). In all urinary samples the ratio of cortisol to cortisone metabolites was m arkedly elevated compared to controls (patients: median 1.9, interquartile range 1.5-2.4, absolute range 1.0-3.2; controls: median 0.45, interquartile range 0.36-0.52); this ratio was positively correlated to FUC (r(2) = 0.30 ; p = 0.003). The cortisol turnover quotient was markedly reduced (patients : median 38.0, interquartile range 20.0-103.9, absolute range 8.3-211.9; co ntrols: median 259, interquartile range 176-415) and inversely correlated t o FUC (r(2) = 0.64, p < 0.001). It is concluded that major surgical trauma results in a marked relative red uction of cortisol inactivation probably consequent to substrate overload o f the metabolizing enzymes; as the activity of these enzymes (mainly 11 bet a-hydroxysteroid dehydrogenase) is crucial for the modulation of cortisol r eceptor access, tissue corticoid sensitivity in the postoperative period ma y vary substantially from physiological conditions.