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

Lauzier, François MD, MSc1,2,3; Turgeon, Alexis F. MD, MSc1,2; Boutin, Amélie MSc1; Shemilt, Michèle BSc1; Côté, Isabelle MD1,3; Lachance, Olivier1; Archambault, Patrick M. MD, MSc1,2,4,5; Lamontagne, François MD, MSc6; Moore, Lynne PhD1,7; Bernard, Francis MD8,9; Gagnon, Claudia MD3,10; Cook, Deborah MD, MSc11,12

Critical Care Medicine:
doi: 10.1097/CCM.0000000000000046
Review Articles
Abstract

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 I2 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.

Author Information

1Centre de Recherche du CHU de Québec, Santé des Populations et Pratiques Optimales en Santé, Université Laval, Québec, QC, Canada.

2Division of Critical Care, Department of Anesthesiology, Université Laval, Québec, QC, Canada.

3Department of Medicine, Université Laval, Québec, QC, Canada.

4Department of Family Medicine and Emergency Medicine, Université Laval, Québec, QC, Canada.

5Centre de recherche du CSSS Alphonse-Desjardins (CHAU de Lévis), Lévis, QC, Canada.

6Centre de Recherche Clinique Étienne-Le Bel, Université de Sherbrooke, Sherbrooke, QC, Canada.

7Department of Social and Preventive Medicine, Université Laval, Québec, QC, Canada.

8Hôpital du Sacré-Coeur de Montréal Research Center, Department of Medicine, Université de Montréal, Montréal, QC, Canada.

9Hôpital du Sacré-Coeur de Montréal Research Center, Department of Critical Care Medicine, Université de Montréal, Montréal, QC, Canada.

10 Centre de Recherche du CHU de Québec, Endocrinology and Nephrology, Université Laval, Québec, QC, Canada.

11Department of Medicine, McMaster University, Hamilton, ON, Canada.

12 Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.

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This study was supported by the Consortium pour le développement de la recherche en traumatologie and the Fonds de la recherche du Québec-Santé. Drs. Lauzier, Turgeon, Archambault, and Lamontagne are recipients of a Research Career Award from the Fonds de la recherche du Québec-Santé. Ms. Boutin holds a Doctoral Research Award. Dr. Archambault served as a board member for the Association des médecins d’urgence du Québec, is employed by the Université Laval, received grant support from the Fonds de recherche en Santé Québec (career award), and lectured for Queen’s University and Centre de santé et services sociaux de Saguenay. Dr. Moore holds a New Investigator Award from the Canadian Institutes of Health Research. Dr. Cook is a Research Chair of the Canadian Institutes of Health Research. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: francois.lauzier@med.ulaval.ca

© 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins