Glucocorticoid insufficiency in patients who present to the hospital with severe sepsis: a prospective clinical trial.

OBJECTIVE To identify the incidence of secondary adrenal insufficiency in severe sepsis. DESIGN Prospective clinical trial testing 100 patients with a 250-microg adrenocorticotropic hormone (ACTH) stimulation test. SETTING County-university teaching hospital. PATIENTS One hundred patients with sepsis and septic shock. Forty patients had bacteremia and 17% shock. INTERVENTIONS ACTH, cortisol, aldosterone, and electrolyte concentrations were measured at baseline. Cortisol and aldosterone were measured 30 and 60 mins after ACTH (250 microg). MEASUREMENTS AND MAIN RESULTS Nine of the 100 patients (9%) failed the ACTH stimulation test (all serum cortisol <20 microg/dL). The 91 patients with sepsis began with a serum cortisol at 29.3 +/- 2.5, and it increased to 40.1 +/- 2.6 and 46.9 +/- 2.7 microg/dL at times 30 and 60 mins, respectively. Serum cortisol in nine septic patients who failed the ACTH stimulation test had an initial concentration of 11.3 +/- 1.8 microg/dL, and it increased at time 30 mins to 14.0 +/- 1.9 microg/dL and at 60 mins to 15.7 +/- 1.8 microg/dL. Four of the nine patients had secondary adrenal insufficiency as determined by a normal aldosterone response to ACTH. The remaining five patients had an absent aldosterone response to ACTH and baseline ACTH concentrations that were not elevated, suggesting adrenal dysfunction. Serum sodium (128 +/- 4 vs. 138 +/- 1 mmol/L, p <.05) and glucose concentrations (121 +/- 20 vs. 163 +/- 11 mg/dL, p <.05) were reduced in the nine patients. Of the four patients with secondary adrenal insufficiency, two had a history of amenorrhea after birth of their children many years earlier. CONCLUSIONS These data demonstrate that 9% of adults with sepsis fail the ACTH stimulation test due to a mixture of etiologies. A reduced sodium or glucose concentration may be helpful in identifying glucocorticoid (adrenal) insufficiency in patients with sepsis.