Background: One percent of the adult population are, at any one time, prescribed oral glucocorticoids (GC). GCs are known to be associated with hypothalamicpituitaryadrenal axis suppression. However, there remains uncertainty regarding: i) the prevalence of GC-induced adrenal insufficiency (AI); ii) the effects of GC dose and duration; and iii) the time course of adrenal recovery and how GCs should be withdrawn. We undertook a systematic literature review to address these questions.
Methods: Searches were performed in MEDLINE and Web of Science in November 2014. Eligible papers studied adult patients with an indication for long-term GCs, exposure to oral GCs, and adrenal function tests. Screening was performed in duplicate and additional articles identified through citation screening. Three categories each for increasing dose, duration, and cumulative dose were assessed.
Results: From 645 screened papers, 42 met the inclusion criteria (14 randomised controlled trials and 28 observational studies). The prevalence of AI ranged from 0 to 100%. When examined within exposure categories, the prevalence still ranged from 0 to 100%, with medians of 3343%. Only exposure <5 mg prednisolone equivalent dose/day had reduced AI (range 036%, median 15%). There was evidence of persisting adrenal suppression 13 years after GC cessation. Only five studies reported weaning of GCs and these were too heterogeneous in study design to draw useful conclusions.
Conclusions: Significant variation exists in the reported prevalence of AI after oral GC therapy, irrespective of exposure category. There is evidence, albeit limited, that even low doses can suppress adrenal function, and some patients may have AI after several years of cessation. We suggest clinicians be vigilant for AI with all doses and durations of oral GC therapy. The evidence base supporting current practice, particularly with regards to withdrawal of steroids, is scant. There is imperative need for large-scale prospective studies to guide future practice.