title: Antipituitary antibodies after traumatic brain injury: is head trauma-induced pituitary dysfunction associated with autoimmunity?
abstract: OBJECTIVE
  Traumatic brain injury (TBI) is a devastating public health problem that may result in hypopituitarism. However, the mechanisms responsible for hypothalamic-pituitary dysfunction due to TBI are still unclear. Although the antibodies against neurons have been demonstrated in injured animal studies, investigations regarding the occurrence of antipituitary antibodies (APAs) in patients with TBI are lacking in the literature. In order to investigate whether autoimmune mechanisms could play a role in the pituitary dysfunction after TBI, we have planned this study aimed at investigating the presence of APA at the third year of TBI and association between the TBI-induced hypopituitarism and APA.
  
  
  METHODS
  Twenty-nine (25 males and 4 females; age 36.5+/-2.3 years) patients who had completed a 3-year follow-up after TBI were included in the present study. APA and pituitary function were evaluated in all the patients 3 years after TBI; moreover, APAs were tested also in sera of 60 age-/sex-matched normal controls. The APAs were investigated by an indirect immunofluorescence method. Results APAs were detected in 13 out of the 29 TBI patients (44.8%), but in none of the normal controls. Pituitary dysfunction development ratio was significantly higher in APA-positive patients (46.2%) when compared with APA-negative ones (12.5%; P=0.04). There was a significant association between APA positivity and hypopituitarism due to TBI (odds ratio: 2.25, 95% confidence intervals 1.1-4.6). Moreover, there was a significant positive correlation (r=0.74, P=0.004) between APA titer ratio and peak GH response to GHRH+GH related peptide (GHRP)-6 test, suggesting that high APA titers were associated with low GH response to GHRH+GHRP-6 test.
  
  
  CONCLUSIONS
  This study shows for the first time the presence of the APA in TBI patients 3 years after head trauma. Moreover, present investigation indicates preliminary evidence that APA may be associated with the development of TBI-induced pituitary dysfunction, thus suggesting that autoimmunity may contribute in the development of TBI-induced hypopituitarism. The presence of the association between APA and TBI-induced hypopituitarism may provide a new point of view in this field and promote further clinical and experimental studies.
authors.affiliation: Department of Endocrinology, Erciyes University Medical School, 38039 Kayseri, Turkey.
authors.forename: Fatih
authors.initials: F
authors.lastname: Tanriverdi
authors.forename: Annamaria
authors.initials: A
authors.lastname: De Bellis
authors.forename: Antonio
authors.initials: A
authors.lastname: Bizzarro
authors.forename: Antonio Agostino
authors.initials: AA
authors.lastname: Sinisi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bellastella
authors.forename: Elena
authors.initials: E
authors.lastname: Pane
authors.forename: Antonio
authors.initials: A
authors.lastname: Bellastella
authors.forename: Kursad
authors.initials: K
authors.lastname: Unluhizarci
authors.forename: Ahmet
authors.initials: A
authors.lastname: Selcuklu
authors.forename: Felipe F
authors.initials: FF
authors.lastname: Casanueva
authors.forename: Fahrettin
authors.initials: F
authors.lastname: Kelestimur
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D015551:Autoimmunity / Q000276:immunology*; D001930:Brain Injuries / Q000097:blood / Q000276:immunology*; D016009:Chi-Square Distribution; D004958:Estradiol / Q000097:blood; D005260:Female; D006062:Gonadotropins / Q000097:blood; D006801:Humans; D007018:Hypopituitarism / Q000097:blood / Q000276:immunology*; D008297:Male; D016017:Odds Ratio; D010902:Pituitary Gland / Q000276:immunology* / Q000378:metabolism; D011388:Prolactin / Q000097:blood; D013739:Testosterone / Q000097:blood; D013972:Thyrotropin / Q000097:blood
chemical_list: D001323:Autoantibodies; D006062:Gonadotropins; D013739:Testosterone; D004958:Estradiol; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D013972:Thyrotropin