title: Predictors of Insulin-Like Growth Factor-I Responses to Growth Hormone Replacement in Young Adults with Growth Hormone Deficiency.
abstract: OBJECTIVE
  Physiological growth hormone (GH) secretion and insulin-like growth factor-I (IGF-I) levels are greater in young compared to older adults. We evaluated IGF-I levels and predictors of IGF-I responses in young adults on GH replacement.
  
  
  METHODS
  From the KIMS database, 310 young adults (age 15-26 years) with severe GH deficiency related to childhood-onset disease and commenced on 'adult GH replacement' were identified. 'IGF-I responses' were estimated from first-year increments in IGF-I standard deviation scores (SDS) and adjusted for GH dose. Body composition was assessed by bioimpedance in 143 patients.
  
  
  RESULTS
  IGF-I levels increased markedly from baseline to 1 year of replacement (-3.75 ± 1.94 vs. -1.36 ± 1.86 SDS, p < 0.0001), but remained low compared to normative data despite dose titration. In multivariate models, IGF-I responses were positively associated with age [B (SE) SDS/(mg/m2); 0.52 (0.15), p = 0.0007] and BMI SDS [1.06 (0.25), p < 0.0001] and inversely associated with female gender [-4.45 (0.79), p < 0.0001] and baseline IGF-I SDS [-1.44 (0.20), p < 0.0001]. IGF-I responses were positively associated with first-year increases in lean body mass (r = 0.19, p = 0.003) and haemoglobin A1c (r = 0.15, p = 0.031).
  
  
  CONCLUSIONS
  Low IGF-I levels in young adults on treatment may reflect suboptimal GH replacement. Identification of predictors for IGF-I responses could lead to a more appropriate replacement strategy. Association between IGF-I responses and lean body mass suggests that maintaining age-appropriate IGF-I levels is important during therapy.
authors.affiliation: Department of Paediatrics, University of Cambridge, Cambridge, UK.
authors.forename: Ajay
authors.initials: A
authors.lastname: Thankamony
authors.forename: Donatella
authors.initials: D
authors.lastname: Capalbo
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Jonsson
authors.forename: Helen L
authors.initials: HL
authors.lastname: Simpson
authors.forename: David B
authors.initials: DB
authors.lastname: Dunger
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D016208:Databases, Factual; D005260:Female; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male
chemical_list: D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I