Background: Glucocorticoids are a mainstay of inflammatory bowel disease (IBD) treatment, with oral tapering courses frequently used to induce remission or control flares. Impairment of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in adrenal suppression (AS), is an established side effect of exogenous glucocorticoids. Currently however there is no standard guidance or recommendations to suggest routine screening of IBD patients for this potentially fatal complication following steroid use. We aimed to systematically review the published evidence for risk of AS in both adult and paediatric IBD patients treated with glucocorticoids.
Methods: An electronic literature search using PubMed, Ovid Medline and Embase was performed up to November 2016 using MeSH terms relating to IBD and adrenal function/insufficiency/suppression. A hand search of references of relevant papers was also performed. Papers presenting original data including biochemical evidence of adrenal function during or after glucocorticoid therapy for IBD, were included. Evidence was assessed using GRADE recommendations.
Results: 198 papers were initially retrieved and reviewed. Ten met the inclusion criteria (6 randomised controlled trials, 4 case series). 4 of the randomised trials (one paediatric) compared oral budesonide with prednisolone or placebo and measured AS as a secondary outcome. Results varied, with one study showing no increase in AS after budesonide, two suggesting AS in up to 62% of patients after budesonide, and one study showing AS in 89% of patients treated with prednisolone. 2 retrospective case series (one paediatric) specifically investigated adrenal function following oral prednisolone: one measured morning cortisol and found 20% to be low; the other demonstrated AS in 60%. Both papers measured the time taken for the HPA axis to return to normal (5.6 weeks and 7.2 months respectively). The remaining 2 randomised studies and 2 case series measured adrenal function after different steroid enemas and found some degree of AS after prednisolone and betamethasone preparations. Most papers had high risk of confounding/bias and heterogeneity.
Conclusions: AS in patients with IBD during or after therapy with either oral or rectal glucocorticoids has been shown to occur in up to 89% of patients. However good quality, adequately powered studies are lacking and methods of measuring adrenal function varied considerably. Stimulation testing with adrenocorticotropic hormone analogues is most sensitive but is a more complex procedure than a morning cortisol assay. Clinical presentation of AS was not explored in the selected studies but case reports and experience from other patient groups suggest that it can be non-specific, mimic IBD symptoms or even cause mortality.