title: Evaluation of insulin-like growth factor (IGF)-I and IGF binding protein-3 generation test in short stature.
abstract: BACKGROUND
  Differentiation between growth hormone deficiency (GHD) and idiopathic short stature (ISS) based on GH tests and basal IGF-I and IGFBP-3 levels may be difficult. The aim of this study was to evaluate the role of pharmacological GH tests, IGF-I and IGFBP-3 generation test and height velocity off-treatment in the evaluation of GHD and ISS.
  
  
  METHODS
  Thirty-three (17 M, 16 F) prepubertal short (height SDS < -2) children were divided into two groups: Group 1 (n = 19) with peak GH level <10 tg/l (GHD) and Group 2 (n = 14) GH > or =10 microg/l in two sex steroid primed pharmacological GH tests. Having excluded other diagnoses, Group 2 was regarded as having ISS. The generation test was performed concomitantly (0.1 IU/kg GH s.c. for 4 days) with IGF-I and IGFBP-3 measured on the 4th day in both groups. The patients were followed for a year for height velocity (HV).
  
  
  RESULTS
  Group 1 and 2 had comparable height SDS (-2.3 +/- 0.4 and -2.3 +/- 0.3) at comparable ages (7.8 +/- 2.8 and 7.0 +/- 2.7 yr). Although the deltaIGF-I response was low (<2.0 nmol/l 115 ng/ ml]) in seven (37%) children in the GHD group, all GHD patients with low height velocity had adequate (> or =14 nmol/I [400 ng/ml]) deltaIGFBP-3 response. deltaIGFBP-3 in the generation test showed a negative correlation with HV (p = 0.021, r = -0.570) and also with basal IGFBP-3 (p <0.001, r = -0.743) in the GHD group. In the ISS group, deltaIGF-I and deltaIGFBP-3 responses were low in 31% and 7%, respectively, and the correlation between basal IGF-I, IGFBP-3 and HV and between delta values in the generation test were significantly positive, pointing to a difference in the growth response of these children.
  
  
  CONCLUSIONS
  In the GHD group, based on pharmacological tests, an adequate deltaIGFBP-3 response in the generation test predicts poor height velocity at follow up and thus strengthens the diagnosis of true GHD.
authors.affiliation: Pediatric Endocrinology Unit, Department of Pediatrics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. feyzad@istanbul.edu.tr
authors.forename: Feyza
authors.initials: F
authors.lastname: Darendeliler
authors.forename: Cem
authors.initials: C
authors.lastname: Ocal
authors.forename: Firdevs
authors.initials: F
authors.lastname: Baş
mesh_terms: D015415:Biomarkers; D001827:Body Height; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006130:Growth Disorders / Q000097:blood* / Q000175:diagnosis*; D013006:Growth Hormone / Q000172:deficiency*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D011237:Predictive Value of Tests
chemical_list: D015415:Biomarkers; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone