title: Pituitary stalk dysgenesis-induced hypopituitarism in adult patients: prevalence, evolution of hormone dysfunction and genetic analysis.
abstract: OBJECTIVE
  To investigate the prevalence of pituitary stalk dysgenesis (PSD) in adult hypopituitary patients by describing the chronology of hormone deficiencies and their potential correlation with traumatic delivery, mutations in genes required for pituitary development and function and pituitary stalk visibility on MRI.
  
  
  METHODS
  Retrospective and prospective study involving 231 hypopituitary patients, including 26 diagnosed with PSD. Clinical, biochemical and radiological studies were reviewed. Molecular analyses of HESX1, LHX4,PROP1 and POU1F1 genes were performed prospectively.
  
  
  RESULTS
  PSD was present in 11.2% of hypopituitary patients. PSD was diagnosed before 14 years of age in 46.2% of cases, between 14 and 18 years of age in 23%, and in adulthood in 30.8%. Perinatal complications or gene mutations were present in 26.9 and 4.3% of patients, respectively. At first assessment, 92.3% of patients had growth hormone (GH) deficiency. 26.9% presented as combined pituitary deficiencies and 7.6% as panhypopituitarism. Hormone deficiencies were progressive during follow-up in 84.6%. 96% progressed to multiple deficiencies and 46% to panhypopituitarism. No significant association was found between hormonal dysfunction and previous perinatal damage or breech delivery (p = 0.17), PROP1 mutations (p = 0.26) or pituitary stalk visibility on MRI (p = 0.52). No mutations in POU1F1, HESX1 and LHX-4 genes were detected.
  
  
  CONCLUSIONS
  In this study, PSD prevalence in adult hypopituitary patients was 11.2%. Typical clinical presentation includes isolated or combined pituitary hormone deficiencies during the pediatric age, which usually progress to combined or complete hypopituitarism in adulthood. Phenotype is highly variable depending on hormone profile and age at onset.
authors.affiliation: Endocrinology Division, Complejo Hospitalario Universitario de Santiago de Compostela, SERGAS, Departamento de Medicina, Universidad de Santiago de Compostela, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Fernandez-Rodriguez
authors.forename: Celsa
authors.initials: C
authors.lastname: Quinteiro
authors.forename: Jesus
authors.initials: J
authors.lastname: Barreiro
authors.forename: Mónica
authors.initials: M
authors.lastname: Marazuela
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Pereiro
authors.forename: Roberto
authors.initials: R
authors.lastname: Peinó
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Cabezas-Agrícola
authors.forename: Fernando
authors.initials: F
authors.lastname: Dominguez
authors.forename: Felipe F
authors.initials: FF
authors.lastname: Casanueva
authors.forename: Ignacio
authors.initials: I
authors.lastname: Bernabeu
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007018:Hypopituitarism / Q000453:epidemiology* / Q000209:etiology* / Q000503:physiopathology; D060850:LIM-Homeodomain Proteins; D008297:Male; D010900:Pituitary Diseases / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology*; D010902:Pituitary Gland / Q000002:abnormalities*; D015995:Prevalence; D050817:Transcription Factor Pit-1 / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: C489736:HESX1 protein, human; D018398:Homeodomain Proteins; C486362:LHX4 protein, human; D060850:LIM-Homeodomain Proteins; C494187:POU1F1 protein, human; C102134:Prophet of Pit-1 protein; D050817:Transcription Factor Pit-1; D014157:Transcription Factors