title: Growth hormone receptor exon 3 isoforms may have no importance in the clinical setting of multiethnic Brazilian acromegaly patients.
abstract: BACKGROUND
  Acromegaly is associated with significant morbidity and increased mortality, but has a variable severity phenotype. The presence of the exon 3-deleted isoform of the growth hormone receptor (d3-GHR) may influence the disease phenotype and treatment outcomes, including the frequency of biochemical discordance after medical treatment.
  
  
  OBJECTIVE
  The objective of this study was to analyze the influence of the d3-GHR isoform on clinical and biochemical characteristics and in the treatment outcomes of Brazilian multiethnic acromegaly patients.
  
  
  METHODS
  We retrospectively analyzed our acromegaly outpatient clinic databank and collected demographic, clinical, biochemical and treatment outcome data from those patients who agreed to participate in the study. A blood sample was collected from all patients, the DNA was extracted and the GHR isoforms were evaluated by PCR, with the full length (fl)-GHR represented by a 935-bp fragment and the d3-GHR represented by a 532-bp fragment.
  
  
  RESULTS
  A total of 121 patients were included. Fifty-six patients (46.3 %) were full-length homozygous (fl/fl), 48 (39.7 %) were heterozygous (fl/d3) and 17 (14.0 %) were d3-GHR homozygous (d3/d3). There was no difference between patients homozygous for the fl isoform and those harboring at least one d3-GHR allele in the demographic, clinical and biochemical data or in the treatment outcomes, including somatostatin receptor ligands (SRL) monotherapy, combination therapy with SRL and cabergoline and pegvisomant treatment. There was also no difference between the groups for the frequency of GH and IGF-I discordance after medical treatment.
  
  
  CONCLUSIONS
  GHR exon 3 genotyping appears to have no clinical significance, at least in Brazilian acromegaly patients.
authors.affiliation: Neuroendocrinology Research Center/Endocrine Section, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco, 255, 9th floor, Ilha do Fundão, Rio de Janeiro, 21941-913, Brazil.
authors.forename: Evelyn
authors.initials: E
authors.lastname: de Oliveira Machado
authors.affiliation: Neuroendocrine Section and Molecular Genetics Laboratory, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil.
authors.forename: Carlos Henrique Azeredo
authors.initials: CH
authors.lastname: Lima
authors.affiliation: Neuroendocrine Section and Molecular Genetics Laboratory, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil.
authors.forename: Liana Lumi
authors.initials: LL
authors.lastname: Ogino
authors.affiliation: Neuroendocrinology Research Center/Endocrine Section, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco, 255, 9th floor, Ilha do Fundão, Rio de Janeiro, 21941-913, Brazil.|Neuroendocrine Section and Molecular Genetics Laboratory, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil.|Endocrine Section, Hospital Federal de Bonsucesso, Rio de Janeiro, Brazil.
authors.forename: Leandro
authors.initials: L
authors.lastname: Kasuki
authors.affiliation: Neuroendocrinology Research Center/Endocrine Section, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco, 255, 9th floor, Ilha do Fundão, Rio de Janeiro, 21941-913, Brazil. mgadelha@hucff.ufrj.br.|Neuroendocrine Section and Molecular Genetics Laboratory, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil. mgadelha@hucff.ufrj.br.
authors.forename: Mônica R
authors.initials: MR
authors.lastname: Gadelha
mesh_terms: D000172:Acromegaly / Q000235:genetics* / Q000378:metabolism; D000236:Adenoma / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D001483:Base Sequence; D001938:Brazil; D005006:Ethnicity / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000235:genetics* / Q000378:metabolism; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011986:Receptors, Somatotropin / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I
keywords: Acromegaly; Growth hormone receptor isoforms; Somatostatin receptor ligands; d3-GHR