title: Efficacy of IGF-based growth hormone (GH) dosing in nonGH-deficient (nonGHD) short stature children with low IGF-I is not related to basal IGF-I levels.
abstract: OBJECTIVE
  Weight-based GH dosing is the standard for treating children with short stature. The current study validates the usefulness of IGF-based GH dosing for GH therapy in nonGH-deficient (nonGHD) children and its relationship with pretreatment serum IGF-I concentration.
  
  
  METHODS
  In this twelve-month, open-label, randomized controlled study, 151 nonGHD (based on GH-stimulation tests), prepubertal children with short stature and IGF-I levels ≤ 33rd percentile [-0.44 standard deviation score (SDS)] were randomly assigned to receive GH (dose based on IGF-I titration algorithm; n = 114) or to observation (n = 37). GH dose (initially 40 μg/kg/d) was adjusted every 3 months to achieve an IGF-I SDS in the upper normal range (66-99 th percentile).
  
  
  RESULTS
  In treated children, mean height SDS (HSDS) increased from -2.5 at baseline to -1.7 at 12 months and mean IGF-I SDS increased from -1.7 to 0.1. These parameters remained unchanged in untreated children. There was no relationship between change in HSDS (ΔHSDS) and degree of IGF-I deficiency at baseline. No safety problems were observed. Both groups had a similar advance in bone age. At the end of study, ΔHSDS in treated children showed a positive correlation with IGF-I SDS, but not with GH dose [mean 59 μg/kg/d (range 29-92)], basal IGF-I SDS or 1-month IGF parameters.
  
  
  CONCLUSIONS
  In nonGHD subjects with short stature and serum IGF-I concentrations within and below the lower third of normal, adjusting GH dose to achieve an IGF-I level in the upper normal range resulted in a significant increase in HSDS, regardless of basal IGF-I levels.
authors.affiliation: Department of Paediatric Endocrinology, Mattel Children's Hospital at UCLA, Los Angeles, CA 90095, USA. hassy@mednet.ucla.edu
authors.forename: Pinchas
authors.initials: P
authors.lastname: Cohen
authors.forename: Alan D
authors.initials: AD
authors.lastname: Rogol
authors.forename: Wayne
authors.initials: W
authors.lastname: Weng
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Kappelgaard
authors.forename: Ron G
authors.initials: RG
authors.lastname: Rosenfeld
authors.forename: John
authors.initials: J
authors.lastname: Germak
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004392:Dwarfism / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D013006:Growth Hormone / Q000008:administration & dosage* / Q000627:therapeutic use*; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male
chemical_list: D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone