Clinical Outcomes, Predictors, and Prevalence of Anterior Pituitary Disorders Following Traumatic Brain Injury: A Systematic Review

Objectives: To assess the clinical outcomes, predictors, and prevalence of anterior pituitary disorders following traumatic brain injury. Data Sources: We searched Medline, Embase, Cochrane Registry, BIOSIS, and Trip Database up to February 2012 and consulted bibliographies of narrative reviews and selected articles. Study Selection: We included cohort, case-control, cross-sectional studies and randomized trials enrolling at least five adults with blunt traumatic brain injury in whom at least one anterior pituitary axis was assessed. We excluded case series and studies in which other neurological conditions were indistinguishable from traumatic brain injury. Data Extraction: Two independent reviewers selected citations, extracted data, and assessed the risk of bias using a standardized form. Data Synthesis: We performed meta-analyses using random effect models and assessed heterogeneity using the I-2 index. Results: We included 66 studies (5,386 patients) evaluating prevalence, 14 evaluating clinical outcomes, and 27 evaluating predictors. Thirty studies were at low risk of bias. Anterior pituitary disorders were associated with a trend toward increased ICU mortality (risk ratio, 1.79; 95% CI, 0.99-3.21; four studies) and no difference in Glasgow Outcome Scale score (mean difference, -0.45; 95% CI, -1.10 to 0.20; three studies). Age (mean difference, 3.19; 95% CI, 0.31-6.08; 19 studies), traumatic brain injury severity (risk ratio, 2.15; 95% CI, 1.20-3.86 for patients with severe vs nonsevere traumatic brain injury; seven studies), and skull fractures (risk ratio, 1.73; 95% CI, 1.03-2.91; six studies) predicted anterior pituitary disorders. Over the long term, 31.6% (95% CI, 23.6-40.1%; 27 studies) of patients had at least one anterior pituitary disorder. We observed significant heterogeneity that was not solely explained by the risk of bias or traumatic brain injury severity. Conclusions: Approximately one third of traumatic brain injury patients have persistent anterior pituitary disorder. Older age, traumatic brain injury severity, and skull fractures predict anterior pituitary disorders, which in turn may be associated with higher ICU mortality. Further high-quality studies are warranted to better define the burden of anterior pituitary disorders and to identify high-risk patients.