Diagnosis of adrenal insufficiency in severe sepsis and septic shock

Am J Respir Crit Care Med. 2006 Dec 15;174(12):1319-26. doi: 10.1164/rccm.200509-1369OC. Epub 2006 Sep 14.


Rationale: Diagnosis of adrenal insufficiency in critically ill patients has relied on random or cosyntropin-stimulated cortisol levels, and has not been corroborated by a more accurate diagnostic standard.

Objective: We used the overnight metyrapone stimulation test to investigate the diagnostic value of the standard cosyntropin stimulation test, and the prevalence of sepsis-associated adrenal insufficiency.

Methods: This was an inception cohort study.

Measurements and results: In two consecutive septic cohorts (n = 61 and n = 40), in 44 patients without sepsis and in 32 healthy volunteers, we measured (1) serum cortisol before and after cosyntropin stimulation, albumin, and corticosteroid-binding globulin levels, and (2) serum corticotropin, cortisol, and 11beta-deoxycortisol levels before and after an overnight metyrapone stimulation. Adrenal insufficiency was defined by postmetyrapone serum 11beta-deoxycortisol levels below 7 microg/dl. More patients with sepsis (31/61 [59% of original cohort with sepsis] and 24/40 [60% of validation cohort with sepsis]) met criteria for adrenal insufficiency than patients without sepsis (3/44; 7%) (p < 0.001 for both comparisons). Baseline cortisol (< 10 microg/dl), Delta cortisol (< 9 microg/dl), and free cortisol (< 2 microg/dl) had a positive likelihood ratio equal to infinity, 8.46 (95% confidence interval, 1.19-60.25), and 9.50 (95% confidence interval, 1.05-9.54), respectively. The best predictor of adrenal insufficiency (as defined by metyrapone testing) was baseline cortisol of 10 microg/dl or less or Delta cortisol of less than 9 microg/dl. The best predictors of normal adrenal response were cosyntropin-stimulated cortisol of 44 microg/dl or greater and Delta cortisol of 16.8 microg/dl or greater.

Conclusions: In sepsis, adrenal insufficiency is likely when baseline cortisol levels are less than 10 microg/dl or delta cortisol is less than 9 microg/dl, and unlikely when cosyntropin-stimulated cortisol level is 44 microg/dl or greater or Delta cortisol is 16.8 microg/dl or greater.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Insufficiency / diagnosis*
  • Adrenal Insufficiency / etiology
  • Adrenocorticotropic Hormone / blood
  • Aged
  • Cosyntropin / pharmacology
  • Female
  • Humans
  • Hydrocortisone / blood*
  • Male
  • Metyrapone
  • Middle Aged
  • Sepsis / blood
  • Sepsis / complications*
  • Serum Albumin / analysis
  • Shock, Septic / blood
  • Shock, Septic / complications*
  • Transcortin / analysis


  • Serum Albumin
  • Cosyntropin
  • Adrenocorticotropic Hormone
  • Transcortin
  • Hydrocortisone
  • Metyrapone