Adrenal Insufficiency in Corticosteroids Use: Systematic Review and Meta-Analysis

J Clin Endocrinol Metab. 2015 Jun;100(6):2171-80. doi: 10.1210/jc.2015-1218. Epub 2015 Apr 6.


Objective: We aimed to estimate pooled percentages of patients with adrenal insufficiency after treatment with corticosteroids for various conditions in a meta-analysis. Secondly, we aimed to stratify the results by route of administration, disease, treatment dose, and duration.

Methods: We searched seven electronic databases (PubMed, MEDLINE, EMBASE, COCHRANE, CENTRAL, Web of Science, and CINAHL/Academic Search Premier) in February 2014 to identify potentially relevant studies. Original articles testing adult corticosteroid users for adrenal insufficiency were eligible.

Results: We included 74 articles with a total of 3753 participants. Stratified by administration form, percentages of patients with adrenal insufficiency ranged from 4.2% for nasal administration (95% confidence interval [CI], 0.5-28.9) to 52.2% for intra-articular administration (95% CI, 40.5-63.6). Stratified by disease, percentages ranged from 6.8% for asthma with inhalation corticosteroids only (95% CI, 3.8-12.0) to 60.0% for hematological malignancies (95% CI, 38.0-78.6). The risk also varied according to dose from 2.4% (95% CI, 0.6-9.3) (low dose) to 21.5% (95% CI, 12.0-35.5) (high dose), and according to treatment duration from 1.4% (95% CI, 0.3-7.4) (<28 d) to 27.4% (95% CI, 17.7-39.8) (>1 year) in asthma patients.

Conclusions: 1) Adrenal insufficiency after discontinuation of glucocorticoid occurs frequently; 2) there is no administration form, dosing, treatment duration, or underlying disease for which adrenal insufficiency can be excluded with certainty, although higher dose and longer use give the highest risk; 3) the threshold to test corticosteroid users for adrenal insufficiency should be low in clinical practice, especially for those patients with nonspecific symptoms after cessation.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adrenal Cortex Hormones / administration & dosage*
  • Adrenal Cortex Hormones / adverse effects*
  • Adrenal Insufficiency / chemically induced*
  • Adrenal Insufficiency / epidemiology*
  • Adult
  • Dosage Forms
  • Dose-Response Relationship, Drug
  • Drug Administration Routes
  • Drug Administration Schedule
  • Humans
  • Inflammation / drug therapy
  • Inflammation / epidemiology
  • Neoplasms / drug therapy
  • Neoplasms / epidemiology
  • Organ Transplantation / methods
  • Organ Transplantation / statistics & numerical data
  • Skin Diseases / drug therapy
  • Skin Diseases / epidemiology
  • Transplantation Conditioning / adverse effects
  • Transplantation Conditioning / statistics & numerical data


  • Adrenal Cortex Hormones
  • Dosage Forms