title: Long-Term Outcomes, Genetics, and Pituitary Morphology in Patients with Isolated Growth Hormone Deficiency and Multiple Pituitary Hormone Deficiencies: A Single-Centre Experience of Four Decades of Growth Hormone Replacement.
abstract: BACKGROUND
  Growth hormone (GH) has been used to treat children with GH deficiency (GHD) since 1966.
  
  
  OBJECTIVE
  Using a combined retrospective and cross-sectional approach, we explored the long-term outcomes of patients with GHD, analysed factors influencing therapeutic response, determined persistence into adulthood, investigated pituitary morphology, and screened for mutations in causative genes.
  
  
  METHODS
  The files of 96 GH-deficient children were reviewed. In a subset of 50 patients, re-assessment in adulthood was performed, including GHRH-arginine testing, pituitary magnetic resonance imaging (MRI), and mutational screening for the growth hormone-1 gene (GH1) and the GHRH receptor gene (GHRHR) in isolated GHD (IGHD), and HESX1, PROP1, POU1F1, LHX3, LHX4, and GLI2 in multiple pituitary hormone deficiency (MPHD) patients.
  
  
  RESULTS
  GH was started at a height SDS of -3.2 ± 1.4 in IGHD patients and of -4.1 ± 2.1 in MPHD patients. Relative height gain was 0.3 SDS/year, absolute gain 1.6 SDS, and 1.2/2.6 SDS in IGHD/MPHD, respectively. Mid-parental target height was reached in 77%. Initial height SDS, bone age retardation and duration of GH replacement were correlated with height SDS gain. GHD persisted into adulthood in 19 and 89% of subjects with IGHD and MPHD, respectively. In 1/42 IGHD patients a GH1 mutation was detected; PROP1 mutations were found in 3/7 MPHD subjects. Anterior pituitary hypoplasia, combined with posterior pituitary ectopy and pituitary stalk invisibility on MRI, was an exclusive finding in MPHD patients.
  
  
  CONCLUSIONS
  GH replacement successfully corrects the growth deficit in children with GHD. While the genetic aetiology remains undefined in most cases of IGHD, PROP1 mutations constitute a major cause for MPHD. Persistence of GHD into adulthood is related to abnormal pituitary morphology.
authors.affiliation: Division of Paediatric Endocrinology and Diabetology, Children's Hospital, Technische Universität Dresden, Dresden, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Rohayem
authors.forename: Hendrik
authors.initials: H
authors.lastname: Drechsel
authors.forename: Bettina
authors.initials: B
authors.lastname: Tittel
authors.forename: Gabriele
authors.initials: G
authors.lastname: Hahn
authors.forename: Roland
authors.initials: R
authors.lastname: Pfaeffle
authors.forename: Angela
authors.initials: A
authors.lastname: Huebner
mesh_terms: D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D018398:Homeodomain Proteins / Q000235:genetics; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000172:deficiency / Q000235:genetics / Q000627:therapeutic use; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D060850:LIM-Homeodomain Proteins / Q000235:genetics; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics; D010902:Pituitary Gland / Q000378:metabolism / Q000473:pathology; D010907:Pituitary Hormones / Q000172:deficiency*; D011986:Receptors, Somatotropin / Q000235:genetics; D013997:Time Factors; D050817:Transcription Factor Pit-1 / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D000075746:Zinc Finger Protein Gli2
chemical_list: C082593:GLI2 protein, human; C489736:HESX1 protein, human; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; C486362:LHX4 protein, human; D060850:LIM-Homeodomain Proteins; C094898:Lhx3 protein; D009687:Nuclear Proteins; C494187:POU1F1 protein, human; D010907:Pituitary Hormones; C102134:Prophet of Pit-1 protein; D011986:Receptors, Somatotropin; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D000075746:Zinc Finger Protein Gli2; D019382:Human Growth Hormone