title: Clinical outcomes, predictors, and prevalence of anterior pituitary disorders following traumatic brain injury: a systematic review.
abstract: OBJECTIVE
  To assess the clinical outcomes, predictors, and prevalence of anterior pituitary disorders following traumatic brain injury.
  
  
  METHODS
  We searched Medline, Embase, Cochrane Registry, BIOSIS, and Trip Database up to February 2012 and consulted bibliographies of narrative reviews and selected articles.
  
  
  METHODS
  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.
  
  
  METHODS
  Two independent reviewers selected citations, extracted data, and assessed the risk of bias using a standardized form.
  
  
  RESULTS
  We performed meta-analyses using random effect models and assessed heterogeneity using the I 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.
authors.affiliation: 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.
authors.forename: François
authors.initials: F
authors.lastname: Lauzier
authors.forename: Alexis F
authors.initials: AF
authors.lastname: Turgeon
authors.forename: Amélie
authors.initials: A
authors.lastname: Boutin
authors.forename: Michèle
authors.initials: M
authors.lastname: Shemilt
authors.forename: Isabelle
authors.initials: I
authors.lastname: Côté
authors.forename: Olivier
authors.initials: O
authors.lastname: Lachance
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Archambault
authors.forename: François
authors.initials: F
authors.lastname: Lamontagne
authors.forename: Lynne
authors.initials: L
authors.lastname: Moore
authors.forename: Francis
authors.initials: F
authors.lastname: Bernard
authors.forename: Claudia
authors.initials: C
authors.lastname: Gagnon
authors.forename: Deborah
authors.initials: D
authors.lastname: Cook
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D001930:Brain Injuries / Q000175:diagnosis / Q000453:epidemiology* / Q000628:therapy*; D016022:Case-Control Studies; D016638:Critical Illness / Q000401:mortality / Q000628:therapy; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D015600:Glasgow Coma Scale; D017052:Hospital Mortality; D006801:Humans; D015601:Injury Severity Score; D008297:Male; D008875:Middle Aged; D010900:Pituitary Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000628:therapy*; D011237:Predictive Value of Tests; D015995:Prevalence; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome