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

Abstract

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.