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CORR Insights®: Are Corticosteroid Injections Associated With Secondary Adrenal Insufficiency in Adults With Musculoskeletal Pain? A Systematic Review and Meta-analysis of Prospective Studies

Chisari, Emanuele MD1

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Clinical Orthopaedics and Related Research: June 2022 - Volume 480 - Issue 6 - p 1075-1076
doi: 10.1097/CORR.0000000000002227

Where Are We Now?

Corticosteroid injections are one of the most commonly performed ambulatory orthopaedic procedures, regardless of the specialty of interest. In the current study, Whelan et al. [1] examine the association between this common practice and the risk of secondary adrenal insufficiency. This is important because prior to their work, this association had been poorly characterized, with shortcomings and disagreements among the primary source studies on the topic. For this reason, a meta-analysis in this month’s Clinical Orthopaedics and Related Research® is especially helpful.

This study analyzed multiple databases to identify 17 prospective studies for meta-analysis. The authors analyzed injections into the appendicular skeleton separately from those used in the spine and found that the risk of secondary adrenal insufficiency appeared to be much higher in the latter group than in the appendicular skeleton, where secondary adrenal insufficiency following corticosteroid injection does not appear likely at all.

Based on these findings, surgeons should be cautious when prescribing epidural steroid injections in patients who for other reasons may be at risk of adrenal insufficiency (such as history of chronic corticosteroid therapy, pituitary disturbances, female sex and age between 30 and 50 years), or in whom complications related to adrenal insufficiency—like infections—would be especially risky, such as patients who might poorly tolerate COVID-19 during an outbreak, or a bout of influenza during flu season.

Where Are We Going?

In this study, the authors highlight the risk of adrenal insufficiency after spinal corticosteroid injections [1], and this should be part of the clinician-patient conversation when discussing the potential risks of such injections. Future studies need to help us better understand just how serious the clinical implications of secondary adrenal insufficiency 7 days after a spinal injection might be. Researchers, perhaps in a long-term follow-up study, should investigate adverse events or other metabolic disturbances associated with adrenal function.

How Do We Get There?

Prospective studies can help researchers better understand how cortisol levels vary after injection and how secondary adrenal insufficiency affects our patients’ outcomes and complications. Historically, orthopaedic research has not been focused on complications, but rather on functional and patient-reported outcomes. But on topics like secondary adrenal insufficiency after corticosteroid injections, we need to pay closer attention. Based on this study’s finding, particular attention should be given to injections of the spine. To ensure that enough adverse events are detected (if such events occur), these studies should focus on enrolling patients who are especially at risk for such complications, perhaps including patients aged between 30 and 50 years of age, females, and those with a history of chronic glucocorticoids therapy for asthma or autoimmune diseases, for example.

Another study design researchers should consider is a large insurance database analysis because large sample sizes are especially handy when looking for less-common complications. Studies in this setting could potentially determine whether infection-related complications occur for at-risk patient populations in the days or weeks following spinal injections. Such an analysis could yield promising results regarding the possible frequency of complications related to secondary adrenal insufficiency and could identify populations that deserve particular focus in follow-up research using prospective, observational designs. Filling these important gaps in our knowledge will surely help guide physician decision-making in the future.


1. Whelan G, Sim J, Smith B, Moffatt M, Littlewood C. Are corticosteroid injections associated with secondary adrenal insufficiency in adults with musculoskeletal pain? A systematic review and meta-analysis of prospective studies. Clin Orthop Relat Res. 2022;480:1061-1074.
© 2022 by the Association of Bone and Joint Surgeons