title: Growth hormone/insulin-like growth factor-1 axis as related to body mass index in patients with idiopathic short stature.
abstract: OBJECTIVE
  Idiopathic short stature (ISS) is a heterogeneous disorder. An impairment of growth hormone (GH)/insulin-like growth factor 1 (IGF-1)/IGF-1 receptor (IGF-1 R) axis is postulated. To evaluate the somatotropic axis in relation to body mass index (BMI), serum IGF-1, IGF-binding protein-3 (IGFBP-3) and the expression of IGF-1 R genes in patients with ISS.
  
  
  METHODS
  Fifty-five ISS patients (24 F/31 M) aged 14.6 ± 5.5 years (range 3.5-28.5 years) and 25 BMI- and pubertal stage-matched peers were enrolled in the study. The ISS patients underwent a four-day standard GH stimulation test to evaluate IGF-1 generation. mRNA expression of the IGF-1 R gene in peripheral blood leukocytes was evaluated. ISS patients and controls were compared with respect to anthropometric and laboratory data. The results were also analyzed after subdividing the two groups into low-normal [BMI standard deviation score (SDS) between -2 to -1)] and normal (BMI SDS between -1 to +1) BMI subgroups.
  
  
  RESULTS
  Basal serum IGF-1 concentrations were lower in ISS subjects compared to controls who had similar BMI SDS values (p=0.000). Subgroup analyses revealed that there were no significant differences between low-normal BMI ISS subjects and low-normal BMI controls with respect to serum IGF-1 and IGFBP-3 concentrations. However, in the normal BMI ISS subgroup, basal and stimulated IGF-1 levels were significantly lower than the basal values in their control counterparts (basal: p=0.000; stimulated: p=0.007). mRNA expression of IGF-1 R gene was not found to be significantly different in ISS subjects and controls.
  
  
  CONCLUSIONS
  ISS patients were found to have lower IGF-1 concentrations than BMI-matched peers, a finding supporting presence of an impairment in the somatotropic axis. IGF-1 R expression does not seem to be impaired in ISS patients. ISS patients with low-normal BMI SDS also tend to display a relative IGF-1 resistance, whereas those with normal BMI SDS tend to be less GH-sensitive than healthy peers.
authors: Department of Pediatric Endocrinology, İstanbul University Istanbul Faculty of Medicine, İstanbul, Turkey. bruveyde@istanbul.edu.tr
authors: Pinar
authors: P
authors: Cengiz
authors: Firdevs
authors: F
authors: Bas
authors: Fatmahan
authors: F
authors: Atalar
authors: Ahmet
authors: A
authors: Ucar
authors: Feyza
authors: F
authors: Darendeliler
authors: Gökce
authors: G
authors: Akan
authors: Tuğba
authors: T
authors: Tarhan
authors: Rüveyde
authors: R
authors: Bundak
mesh_terms: D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004392:Dwarfism / Q000503:physiopathology*; D005260:Female; D006130:Growth Disorders / Q000097:blood / Q000503:physiopathology; D019382:Human Growth Hormone / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D017526:Receptor, IGF Type 1 / Q000097:blood / Q000235:genetics*
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1