Relative adrenal insufficiency in patients with septic shock:: Comparison of low-dose and conventional corticotropin tests

Objective: To compare a low-dose (1 mu g) corticotropin stimulation test with the more standard (250 mu g) test for the diagnosis of relative adrenal insufficiency. Design: Diagnostic study. Setting: Thirty-one-bed mixed medico-surgical department of intensive care. Patients: Forty-six consecutive patients with septic shock. Interventions: Corticotropin stimulation tests (low-dose test, 1 mu g, and standard 250-mu g test), performed consecutively at an interval > 4 hrs. Measurements and Main Results: In each test, serum cortisol levels were measured before (T0) and 30 (T30), 60 (T60), and 90 (T90) mins after corticotropin injection. The maximal increase in cortisol (Delta max) was calculated as the difference between T0 and the highest cortisol value at T30, T60, or T90 and considered as adequate if > 9 mu g/dl (250 nmol/L). Nonresponders to the low-dose test had a lower survival rate than responders to both tests (27 vs. 47%, p =.06; Kaplan Meier curves). Interestingly, nonresponders to high-dose test received hydrocortisone treatment and had a similar survival to responders. Multivariable logistic regression disclosed that the response to the combined low-dose test and high-dose test was an independent predictor of survival (odds ratio 28.91, 95% confidence interval 1.81-462.70, p =.017), whereas basal or maximal cortisol levels in both tests were not. Conclusions: The low-dose test identified a subgroup of patients in septic shock with inadequate adrenal reserve who had a worse outcome and would have been missed by the high-dose test. These patients may also benefit from glucocorticoid replacement therapy.