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

Abstract

Background Corticosteroid injection is a common treatment for individuals experiencing musculoskeletal pain, and it is part of the management of numerous orthopaedic conditions. However, there is concern about offering corticosteroid injections for musculoskeletal pain because of the possibility of secondary adrenal insufficiency. Questions/purposes In this systematic review and metaanalysis of prospective studies, we asked: (1) Are corticosteroid injections associated with secondary adrenal insufficiency as measured by 7-day morning serum cortisol? (2) Does this association differ depending on whether the shot was administered in the spine or the appendicular skeleton? Methods We searched the Allied and Complementary Medicine (AMED), Embase, EmCare, MEDLINE, CINAHL, and Web of Science from inception to January 22, 2021. We retrieved 4303 unique records, of which 17 were eventually included. Study appraisal was via the Downs and Black tool, with an average quality rating of fair. A Grading of Recommendations, Assessment, Development, and Evaluations assessment was conducted with the overall certainty of evidence being low to moderate. Reflecting heterogeneity in the study estimates, a pooled random-effects estimate of cortisol levels 7 days after corticosteroid injection was calculated. Fifteen studies or subgroups (254 participants) provided appropriate estimates for statistical pooling. A total of 106 participants received a spine injection, and 148 participants received an appendicular skeleton injection, including the glenohumeral joint, subacromial bursa, trochanteric bursa, and knee. Results Seven days after corticosteroid injection, the mean morning serum cortisol was 212 nmol/L (95% confidence interval 133 to 290), suggesting that secondary adrenal insufficiency was a possible outcome. There is a difference in the secondary adrenal insufficiency risk depending on whether the injection was in the spine or the appendicular Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request.

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

“…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.…”

“…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.…”