Adrenal function in protracted critical illness: evaluation with the low-dose (1 μg) corticotropin stimulation test

To investigate the adrenocortical function in protracted critical illness, 43 patients (29 men and 14 women), having a mean (± SD) age of 55 ± 21 years were studied. First, a morning blood sample was obtained to determine baseline plasma cortisol. Subsequently, 1 μg of corticotropin (ACTH, synacthen) was injected intravenously and a second blood sample was drawn 30 min following the injection to measure stimulated plasma cortisol. Patients having a stimulated cortisol level of at least 18 μg/dl were defined as responders. In 36 patients, morning interleukin-6 (IL-6) concentrations were also measured. Mean baseline and stimulated plasma cortisol were 16.8 ± 4.1 μ/dl and 21.2 ± 5.1 μg/dl respectively. The median increment in cortisol was 4.1 μg/dl. Median IL-6 was high (39.3 pg/ml, interquartile range 24.9–86.6 pg/ml). There was a negative correlation between IL-6 and stimulated plasma cortisol (r = -0.40, P = 0.01). Of the 43 patients, 31 patients (72%) were responders, and 12 patients (28%) were non-responders to the low-dose synacthen test. Non-responders had significantly higher IL-6 levels compared to responders (76.6 vs 37.3 pg/ml, P = 0.01). Overall, 18 patients died and 25 patients survived to hospital discharge. Non-survivors had significantly lower baseline (15.1 ± 2.9 vs 18.0 ± 4.5 μg/dl, P = 0.02) and stimulated (19.1 ± 3.3 vs 23.0 ± 5.6, P = 0.01) cortisol levels compared to survivors. In conclusion, patients with protracted critical illness may have an altered adrenal responsiveness to stimulation by ACTH. This finding is in part explained by an increase in the production of IL-6 and carries a poor prognosis.