Relative
11beta-hydroxysteroid dehydrogenase deficiency has been shown previously to arise from endogenous
hypercortisolism in diseases of the hypothalamic/pituitary/adrenocortical system; whether stress induced
hypercortisolism may also result in substrate overload of
11beta-hydroxysteroid dehydrogenase has not yet been studied. We therefore studied the characteristics of
cortisol metabolisation during the postoperative period of cardiac surgery, representing a well standardized
surgical procedure. In a prospective, observational, consecutive case study, 14 patients undergoing cardiac surgery 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 capillary gas-chromatography, main urinary
cortisol metabolites were quantified (
tetrahydrocortisone,
tetrahydrocortisol, allo-
tetrahydrocortisol, cortolones, cortols as sum of
cortisol metabolites (CM)). Free urinary
cortisol (FUC) was determined by an automated immunoassay after extraction. The ratio of
cortisol metabolites (
tetrahydrocortisol, allo-
tetrahydrocortisol, cortols) to
cortisone metabolites (
tetrahydrocortisone, cortolones) was calculated to characterize the overall activity of
11beta-hydroxysteroid dehydrogenase, an
enzyme system catalyzing the conversion of
cortisol to inactive
cortisone (CMR,
cortisol metabolisation ratio). Total
cortisol metabolisation (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 markedly 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 (r2 = 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; controls: median 259, interquartile range 176-415) and inversely correlated to FUC (r2 = 0.64, p < 0.001). It is concluded that major surgical
trauma results in a marked relative reduction of
cortisol inactivation probably consequent to substrate overload of the metabolizing
enzymes; as the activity of these
enzymes (mainly
11beta-hydroxysteroid dehydrogenase) is crucial for the modulation of
cortisol receptor access, tissue
corticoid sensitivity in the postoperative period may vary substantially from physiological conditions.