Diagnosis of adrenal insufficiency in severe sepsis and septic shock

Rationale: Diagnosis of adrenal insufficiency in critically ill patients has relied on random or cosyntropin-stimulated cortisol levels, and has not been corroborated by a more accurate diagnostic standard. Objective: We used the overnight metyrapone stimulation test to investigate the diagnostic value of the standard cosyntropin stimulation test, and the prevalence of sepsis-associated adrenal insufficiency. Methods: This was an inception cohort study. Measurements and Results: In two consecutive septic cohorts (n = 61 and n = 40), in 44 patients without sepsis and in 32 healthy volunteers, we measured (1) serum cortisol before and after cosyntropin stimulation, albumin, and corticosteroid-binding globulin levels, and (2) serum corticotropin, cortisol, and 11 beta-deoxycortisol levels before and after an overnight metyrapone stimulation. Adrenal insufficiency was defined by postmetyrapone serum 11 beta-deoxycortisol levels below 7 mu g/dl. More patients with sepsis (31/61 [59% of original cohort with sepsis] and 24/40 [60% of validation cohort with sepsis]) met criteria for adrenal insufficiency than patients without sepsis (3/44; 7%) (p < 0.001 for both comparisons). Baseline cortisol (< 10 mu g/dl), Delta cortisol (< 9 mu g/dl), and free cortisol (< 2 mu g/dl) had a positive likelihood ratio equal to infinity, 8.46 (95% confidence interval, 1.19-60.25), and 9.50 (95% confidence interval, 1.05-9.54), respectively. The best predictor of adrenal insufficiency (as defined by metyrapone testing) was baseline cortisol of 10 mu g/dl or less or Delta cortisol of less than 9 mu g/dl. The best predictors of normal adrenal response were cosyntropin-stimulated cortisol of 44 mu g/dl or greater and Delta cortisol of 16.8 mu g/dl or greater. Conclusions: In sepsis, adrenal insufficiency is likely when baseline cortisol levels are less than 10 mu g/dl or delta cortisol is less than 9 mu g/dl, and unlikely when cosyntropin-stimulated cortisol level is 44 mu g/dl or greater or Delta cortisol is 16.8 mu g/dl or greater.