Prevalence of Anterior Pituitary Dysfunction Twelve Months or More following Traumatic Brain Injury in Adults: A Systematic Review and Meta-Analysis

The objective of this study is to systematically review clinical studies that have reported on the prevalence of chronic post-traumatic brain injury anterior pituitary dysfunction (PTPD) 12 months or more following traumatic brain injury (TBI). We searched Medline, Embase, and PubMed up to April 2017 and consulted bibliographies of narrative reviews. We included cohort, case-control, and cross-sectional studies enrolling at least five adults with primary TBI in whom at least one anterior pituitary axis was assessed at least 12 months following TBI. We excluded studies in which other brain injuries were indistinguishable from TBI. Study quality was assessed using the Newcastle-Ottawa Scale (NOS) score. We also considered studies that determined growth hormone deficiency and adrenocorticotrophic hormone reserve using provocation test to be at low risk of bias. Data were extracted by four independent reviewers and assessed for risk of bias using a data extraction form. We performed meta-analyses using random effect models and assessed heterogeneity using the index. We identified 58 publications, of which 29 (2756 participants) were selected for meta-analysis. Twelve of these were deemed to be at low risk of bias and therefore "high-quality," as they had NOS scores greater than 8 and had used provocation tests. The overall prevalence of at least one anterior pituitary hormone dysfunction for all 29 studies was 32% (95% confidence interval [CI] 25-38%). The overall prevalence in the 12 high-quality studies was 34% (95% CI 27-42%). We observed significant heterogeneity that was not solely explained by the risk of bias. Studies with a higher proportion of participants with mild TBI had a lower prevalence of PTPD. Our results show that approximately one-third of TBI sufferers have persistent anterior pituitary dysfunction 12 months or more following trauma. Future research on PTPD should differentiate between mild and moderate/severe TBI.