Abstract
ObjectivesThe 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).MethodsEligible 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.ResultsOverall, 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 <5 mg prednisolone equivalent dose/day, <4 weeks of exposure, cumulative dose <0.5 g, and following tapered withdrawal.ConclusionsThe 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.
Highlights
Adrenal insufficiency (AI) is failure of the adrenal cortex to produce sufficient levels of cortisol
There were thirteen randomised controlled trials (RCTs) [19,22,23,24,25,26,27,28,29,30,31,32,33] with random allocation and blinding maintained throughout; the remaining 60 studies were classified as observational studies [12,13,14,15,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84] with some open trials [85,86,87,88] and pilot studies [89]
Across the 100 GC-exposed participant groups included in this review, the median prevalence of AI was 37%
Summary
Adrenal insufficiency (AI) is failure of the adrenal cortex to produce sufficient levels of cortisol. Can cause non-specific symptoms such as fatigue and nausea whilst lack of the usual cortisol response to stress can lead to a potentially fatal adrenal crisis [1]. Taking glucocorticoids (GCs) can lead to suppression of the hypothalamic–pituitary–adrenal (HPA) axis. The HPA-axis may remain suppressed following cessation of GC therapy, leaving the patient with adrenal insufficiency [2]. GCs are widely used many patients could potentially be at risk of AI.
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