Pituitary-adrenal responses to human corticotropin-releasing hormone in critically ill patients

Objective: To investigate the pattern of pituitary-adrenal responses to human corticotropin-releasing hormone (hCRH) in critically ill patients and to examine the relation between responses and clinical outcome. Design and setting: Prospective study in consecutive critically ill patients in a general intensive care unit in a teaching hospital. Patients: The study included 37 critically ill, mechanically ventilated patients with diverse underlying diagnoses (28 men, 9 women; median age 56 years). Interventions: A morning blood sample was obtained to measure baseline cortisol, corticotropin (ACTH), and cytokines. Patients were then injected with 100 mu g hCRH, and plasma cortisol and ACTH were measured over a period of 2 h. Measurements and results: In the overall patient population baseline and peak cortisol concentrations following hCRH were 16 +/- 5 and 21 +/- 5 mu g/dl, respectively, and median baseline and peak ACTH levels 23 and 65 pg/ml, respectively. Higher ACTH levels and longer release of cortisol were noted in nonsurvivors (n = 18) than in survivors (n = 19). Furthermore, nonsurvivors had higher concentrations of interleukin 8 (115 vs. 38 pg/ml) and interleukin 6 (200 vs. 128 pg/ml) than survivors. Conclusions: Critically ill patients demonstrate altered pituitary-adrenal axis responses to hCRH. This is particularly evident in the sickest patients with the highest degree of inflammatory profile who ultimately do not survive.