title: Involvement of hypothalamus autoimmunity in patients with autoimmune hypopituitarism: role of antibodies to hypothalamic cells.
abstract: BACKGROUND
  Antipituitary antibodies (APA) but not antihypothalamus antibodies (AHA) are usually searched for in autoimmune hypopituitarism.
  
  
  OBJECTIVE
  Our objective was to search for AHA and characterize their hypothalamic target in patients with autoimmune hypopituitarism to clarify, on the basis of the cells stained by these antibodies, the occurrence of autoimmune subclinical/clinical central diabetes insipidus (CDI) and/or possible joint hypothalamic contribution to their hypopituitarism.
  
  
  METHODS
  We conducted a cross-sectional cohort study.
  
  
  METHODS
  Ninety-five APA-positive patients with autoimmune hypopituitarism, 60 without (group 1) and 35 with (group 2) lymphocytic hypophysitis, were studied in comparison with 20 patients with postsurgical hypopituitarism and 50 normal subjects.
  
  
  METHODS
  AHA by immunofluorescence and posterior pituitary function were evaluated; then AHA-positive sera were retested by double immunofluorescence to identify the hypothalamic cells targeted by AHA.
  
  
  RESULTS
  AHA were detected at high titer in 12 patients in group 1 and in eight patients in group 2. They immunostained arginine vasopressin (AVP)-secreting cells in nine of 12 in group 1 and in four of eight in group 2. All AVP cell antibody-positive patients presented with subclinical/clinical CDI; in contrast, four patients with GH/ACTH deficiency but with APA staining only GH-secreting cells showed AHA targeting CRH- secreting cells.
  
  
  CONCLUSIONS
  The occurrence of CDI in patients with lymphocytic hypophysitis seems due to an autoimmune hypothalamic involvement rather than an expansion of the pituitary inflammatory process. To search for AVP antibody in these patients may help to identify those of them prone to develop an autoimmune CDI. The detection of AHA targeting CRH-secreting cells in some patients with GH/ACTH deficiency but with APA targeting only GH-secreting cells indicates that an autoimmune aggression to hypothalamus is jointly responsible for their hypopituitarism.
authors.affiliation: Department of Cardiothoracic and Respiratory Sciences, Second University of Naples via Pansini N. 5, 80131 Naples, Italy. annamaria.debellis@unina2.it
authors.forename: A
authors.initials: A
authors.lastname: De Bellis
authors.forename: A A
authors.initials: AA
authors.lastname: Sinisi
authors.forename: E
authors.initials: E
authors.lastname: Pane
authors.forename: A
authors.initials: A
authors.lastname: Dello Iacovo
authors.forename: G
authors.initials: G
authors.lastname: Bellastella
authors.forename: G
authors.initials: G
authors.lastname: Di Scala
authors.forename: A
authors.initials: A
authors.lastname: Falorni
authors.forename: C
authors.initials: C
authors.lastname: Giavoli
authors.forename: V
authors.initials: V
authors.lastname: Gasco
authors.forename: R
authors.initials: R
authors.lastname: Giordano
authors.forename: M R
authors.initials: MR
authors.lastname: Ambrosio
authors.forename: A
authors.initials: A
authors.lastname: Colao
authors.forename: A
authors.initials: A
authors.lastname: Bizzarro
authors.forename: A
authors.initials: A
authors.lastname: Bellastella
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000328:Adult; D000918:Antibody Specificity / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000453:epidemiology / Q000276:immunology*; D015331:Cohort Studies; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D003430:Cross-Sectional Studies; D020790:Diabetes Insipidus, Neurogenic / Q000453:epidemiology / Q000276:immunology*; D005260:Female; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D007018:Hypopituitarism / Q000453:epidemiology / Q000276:immunology* / Q000601:surgery; D007031:Hypothalamus / Q000276:immunology*; D008297:Male; D016036:Seroepidemiologic Studies
chemical_list: D001323:Autoantibodies; D019382:Human Growth Hormone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone