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

Crit Care Med. 2003 Jun;31(6):1668-75. doi: 10.1097/01.CCM.0000063447.37342.A9.


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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenal Cortex Function Tests
  • Adrenal Insufficiency / diagnosis
  • Adrenal Insufficiency / epidemiology
  • Adrenal Insufficiency / etiology*
  • Adrenal Insufficiency / mortality
  • Adrenocorticotropic Hormone
  • Aged
  • Aldosterone / blood
  • Bacteremia / complications*
  • Female
  • Humans
  • Hydrocortisone / blood
  • Incidence
  • Male
  • Middle Aged
  • Prospective Studies
  • Shock, Septic / complications*
  • United States / epidemiology


  • Aldosterone
  • Adrenocorticotropic Hormone
  • Hydrocortisone