title: Hormonal, pituitary magnetic resonance, LHX4 and HESX1 evaluation in patients with hypopituitarism and ectopic posterior pituitary lobe.
abstract: OBJECTIVE
  LHX4 and HESX1 are important in early stages of pituitary development and their mutations can be associated with an ectopic posterior lobe (EPL) in the pituitary of patients with hypopituitarism. The EPL can be located at the median eminence or at the path of the pituitary stalk. The aim of this study was to analyse LHX4 and HESX1 and characterize the hormonal deficiency profiles, establishing relationships with magnetic resonance imaging (MRI) findings in these patients.
  
  
  METHODS
  Sixty-two patients with hypopituitarism associated with EPL were submitted to evaluation of pituitary function, analysis of MRI with EPL location and molecular analysis of LHX4 and HESX1 using polymerase chain reaction (PCR), digestion with restriction enzyme and automatic sequencing.
  
  
  RESULTS
  Forty-two patients had a nonvisualized pituitary stalk (NPS), and 20 a visualized pituitary stalk (VPS). Most patients (95%) with NPS had combined pituitary hormone deficiency (CPHD), with ACTH deficiency in 85%. In patients with VPS, CPHD was found in 50% and ACTH deficiency occurred in only 20%. The frequency of the location of EPL was similar in patients with VPS and NPS: 35% at median eminence and 65% at the path of the stalk. No mutations in LHX4 and HESX1 were identified. Three new polymorphisms in LHX4 were found.
  
  
  CONCLUSIONS
  ACTH deficiency is frequent in patients with hypopituitarism and NPS (85%), the location of EPL at the median eminence was not predictive of the hormonal profile [isolated GH deficiency (IGHD) or CPHD], and LHX4 and HESX1 genes mutations remain rare causes of hypopituitarism associated with EPL.
authors.affiliation: Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular LIM 42, Disciplina de Endocrinologia - HCFMUSP, Brazil. medna@usp.br
authors.forename: Maria Edna
authors.initials: ME
authors.lastname: Melo
authors.forename: Suemi
authors.initials: S
authors.lastname: Marui
authors.forename: Luciani Renata
authors.initials: LR
authors.lastname: Carvalho
authors.forename: Ivo Jorge Prado
authors.initials: IJ
authors.lastname: Arnhold
authors.forename: Claudia Costa
authors.initials: CC
authors.lastname: Leite
authors.forename: Berenice Bilharinho
authors.initials: BB
authors.lastname: Mendonça
authors.forename: Mirta
authors.initials: M
authors.lastname: Knoepfelmacher
mesh_terms: D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000483:Alleles; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D002828:Choristoma / Q000097:blood / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007018:Hypopituitarism / Q000097:blood* / Q000473:pathology; D060850:LIM-Homeodomain Proteins; D008279:Magnetic Resonance Imaging; D008297:Male; D008473:Median Eminence / Q000473:pathology; D010902:Pituitary Gland / Q000473:pathology; D010904:Pituitary Gland, Posterior; D010907:Pituitary Hormones / Q000097:blood*; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D011247:Pregnancy; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C489736:HESX1 protein, human; D018398:Homeodomain Proteins; C486362:LHX4 protein, human; D060850:LIM-Homeodomain Proteins; D010907:Pituitary Hormones; D014157:Transcription Factors; D000324:Adrenocorticotropic Hormone