Systemic glucocorticoid therapy and adrenal insufficiency in adults: A systematic review.
The aim of this systematic literature review was to summarize the current knowledge regarding the prevalence of, time to recovery from, and influence of glucocorticoid dose and duration on glucocorticoid-induced adrenal insufficiency (AI).



Eligible studies were original research articles, which included adult patients with an indication for glucocorticoids and measured adrenal function following exposure to systemic glucocorticoids. Searches were performed in Web of Science and MEDLINE, with further articles identified from reference lists. Screening was performed in duplicate. Data were extracted for each group of glucocorticoid-exposed patients within eligible studies. The reported proportion of patients with AI was summarized as median and inter-quartile range. Results were then stratified by daily dose, cumulative dose, duration of exposure and time since last glucocorticoid use. The risk of bias within and across studies was considered: for randomised controlled trials risk of bias was assessed using the tool developed by the Cochrane Collaboration.



Overall, 73 eligible studies were identified out of 673 screened. The percentage of patients with AI ranged from 0% to 100% with a median (IQR) = 37.4% (13-63%). Studies were small-median (IQR) group size 16 (9-38)-and heterogeneous in methodology. AI persisted in 15% of patients retested 3 years after glucocorticoid withdrawal. Results remained widely distributed following stratification. AI was demonstrated at <5mg prednisolone equivalent dose/day, <4 weeks of exposure, cumulative dose <0.5g, and following tapered withdrawal.



The heterogeneity of studies and variability in results make it difficult to answer the research questions with confidence based on the current literature. There is evidence of AI following low doses and short durations of glucocorticoids. Hence, clinicians should be vigilant for adrenal insufficiency at all degrees of glucocorticoid exposure.
NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
Rebecca M
RM
Joseph
Manchester Centre for Endocrinology and Diabetes, Institute of Human Development, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
Ann Louise
AL
Hunter
Manchester Centre for Endocrinology and Diabetes, Institute of Human Development, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
David W
DW
Ray
Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. Electronic address: will.dixon@manchester.ac.uk.
William G
WG
Dixon
D000309:Adrenal Insufficiency / Q000139:chemically induced* / Q000453:epidemiology; D005938:Glucocorticoids / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D011239:Prednisolone / Q000009:adverse effects* / Q000627:therapeutic use; D015995:Prevalence
D005938:Glucocorticoids; D011239:Prednisolone
Adrenal insufficiency; Glucocorticoids; Systematic literature review