Evidence of altered cortisol metabolism in critically ill patients: a prospective study

Abstract

Context: Changes in cortisol metabolism due to altered activity of the enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD) have been implicated in the pathogenesis of hypertension, obesity and the metabolic syndrome. No published data exist on the activity of this enzyme in critical illness.

Objective: To investigate cortisol metabolism in critically ill patients utilising plasma cortisol: cortisone ratio as an index of 11beta-HSD activity.

Setting: Tertiary level intensive care unit.

Patients: Three cohorts of critically ill patients: sepsis (n = 13); multitrauma (n = 20); and burns (n = 19).

Main outcome measures: Serial plasma cortisol: cortisone ratios.

Measurements and main results: Plasma total cortisol cortisone ratios were determined serially after admission to the intensive care unit. As compared with controls, the plasma cortisol:cortisone ratio was significantly elevated in the sepsis and trauma cohorts on day 1 (22 +/- 9, p = 0.01, and 23 +/- 19, p = 0.0003, respectively) and remained elevated over the study period. Such a relationship was not demonstrable in burns. The ratio was significantly correlated with APACHE II (r = 0.77, p = 0.0008) and Simplified Acute Physiology Score (r = 0.7, p = 0.003) only on day 7 and only in the burns cohort. There were no significant correlations observed between total plasma cortisol or cortisone and sickness severity in the sepsis and trauma cohorts.

Conclusions: In critically ill patients, there is evidence of altered cortisol metabolism due to an increase in 11beta-HSD activity as demonstrated by an elevation of plasma cortisol: cortisone ratios. Further studies with larger sample sizes specifically designed to examine altered tissue 11beta-HSD activity and its clinical significance and correlation with outcome are warranted.