Adrenal Insufficiency Occurring During Septic Shock: Incidence, Outcome, and Relationship to Peripheral Cytokine Levels

Am J Med. 1995 Mar;98(3):266-71. doi: 10.1016/S0002-9343(99)80373-8.


Purpose: In patients with septic shock, to (1) determine the incidence of adrenal insufficiency (AI), (2) observe the effects of glucocorticoid therapy on outcome in those with impaired adrenal function, and (3) investigate a possible correlation between adrenal function and peripheral cytokine levels.

Patients and methods: Twenty-one patients admitted to the medical and surgical intensive care unit with septic shock and 11 healthy volunteers were studied. Cortisol, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) levels were measured before and after infusion of low (1 microgram) and standard doses (250 micrograms) of adrenocorticotropic hormone (ACTH) within 24 hours of the diagnosis of septic shock. Patients with subnormal adrenal responses to ACTH were treated with stress doses of steroids. Hormone, cytokine, and survival data in patients with normal response were compared to those with subnormal adrenal function.

Results: Five patients (23.8%) exhibited AI by ACTH stimulation testing. Three of them received steroid supplementation with rapid improvement in hemodynamic parameters. Autopsies of 2 patients with AI revealed intact adrenal cortices. Sixteen patients had adequate adrenal responses (AAR) to the standard-dose ACTH infusion. TNF-alpha levels were inversely correlated with mean arterial pressure (MAP) (r = -.52, P = 0.038) in AAR but not AI. There was no difference in mean peripheral TNF-alpha levels between AAR and AI. There was no correlation between TNF-alpha levels and mortality or adrenal function in those with septic shock. A trend toward lower IL-6 levels in AI suggests a link between reduced IL-6 levels and understimulation of the pituitary-adrenal axis in this group. Mortality in patients with AI was 80% at 4 weeks as compared with 43.8% in the group with normal adrenal response.

Conclusions: Adrenal hyporesponsiveness is a feature of septic shock in some patients. Its etiology is probably complex. Steroid supplementation appeared to improve short-term survival when AI occurred, although these patients' overall mortality was worse than that of patients with septic shock and AAR. The standard-dose (250 micrograms) rapid ACTH infusion test was adequate for detecting AI. Adrenal insufficiency should be suspected in patients with septic shock who do not respond to conventional treatment. Performing the ACTH infusion test and initiating a trial of stress doses of glucocorticoids pending the results is a reasonable strategy in this situation.

Publication types

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

MeSH terms

  • Adrenal Insufficiency / drug therapy
  • Adrenal Insufficiency / immunology*
  • Adrenal Insufficiency / microbiology
  • Adrenocorticotropic Hormone / administration & dosage
  • Adrenocorticotropic Hormone / therapeutic use*
  • Adult
  • Aged
  • Cytokines / blood*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Incidence
  • Infusions, Intravenous
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Reference Values
  • Shock, Septic / complications
  • Shock, Septic / immunology*
  • Shock, Septic / microbiology
  • Time Factors
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / metabolism


  • Cytokines
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Adrenocorticotropic Hormone