Hypothalamic-pituitary-adrenal axis suppression and intranasal corticosteroid use: A systematic review and meta-analysis.

Background: Intranasal corticosteroids (INCS) are used in the management of sinonasal conditions. Use of exogenous steroids can be associated with hypothalamic-pituitary-adrenal axis dysfunction and adrenal insufficiency (AI). We aimed to estimate the rate of AI after INCS use in a meta-analysis, stratified by steroid type and treatment duration.

Methods: Ovid Medline, Embase Classic, PubMed, Web of Science, and CINAHL databases were searched following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify studies investigating INCS use and AI. AI was defined as morning serum cortisol <550 nmol/L and <80 nmol/L with and without adrenocorticotropic hormone stimulation. INCS were classified as first (beclomethasone dipropionate, triamcinolone acetonide, beclomethasone, budesonide, dexamethasone) and second (ciclesonide, mometasone furoate, and fluticasone propionate) generation. Duration of treatment was classified as short (<1 month), medium (1-12 months), and long-term (>12 months) time periods.

Results: This search identified 3668 articles. A total of 39 studies (1678 patients) were included in the final analysis. The pooled percentage of AI for routinely utilized first- and second-generation INCS was 0.70% (95% confidence interval [CI], 0.29-1.12%). Stratified by type, AI was observed in 0.78% (95% CI, 0.25-1.30%) of first-generation and 0.58% (95% CI, -0.1% to 1.26%) of second-generation steroids. AI was seen in 0.48% (95% CI, -0.01% to 0.96%) of short-term, 1.13% (95% CI, 0.2-2.1%) of medium-term, and 1.67% (95% CI, 0.37-2.9%) of long-term use of INCS.

Conclusion: Overall, the use of INCS carries a low risk for AI. Although modest, this risk may differ depending on the length of duration and type of INCS used. Informing patients of these risks is of importance for the treatment of chronic sinonasal conditions.