Variable degree of growth hormone (GH) and insulin-like growth factor (IGF) sensitivity in children with idiopathic short stature compared with GH-deficient patients: evidence from an IGF-based dosing study of short children

J Clin Endocrinol Metab. 2010 May;95(5):2089-98. doi: 10.1210/jc.2009-2139. Epub 2010 Mar 5.


Context: We recently showed that, in IGF-based GH therapy, the IGF-I target chosen affects GH dose requirements, and higher IGF-I targets are associated with more robust growth parameters.

Objective: The objective of the study was to compare the response of GH-deficient (GHD) vs. idiopathic short-stature (ISS) children to IGF-based GH therapy.

Design: This was a 2-yr, open-label, randomized trial.

Setting: The setting was multicenter and outpatient.

Patients: Prepubertal short children [height sd score (SDS) < -2] with low IGF-I levels (<or=-1 SDS), subclassified based on the peak stimulated serum GH concentration at baseline, into two subgroups: GHD (n = 63, GH < 7 ng/ml) and ISS (n = 102, GH >or= 7 ng/ml).

Interventions: Patients were randomized 2:2:1 to three treatment groups: IGF-I target of 0 SDS (IGF0T), 2 SDS (IGF2T), or a conventional weight-based GH dosing of 40 microg/kg x d (Conv).

Main outcome measures: Change in (Delta) height SDS, IGF-I SDS, and GH dose was measured.

Results: ISS subjects required higher GH doses than GHD patients in the IGF2T (but not IGF0T) arm (medians 119 and 65 microg/kg x d, respectively), indicating that ISS represents a partial GH-insensitive state that manifests during treatment with higher doses of GH. GHD children grew more than those with ISS in both IGF-targeted dosage groups despite similar IGF-I levels (suggesting a degree of IGF insensitivity in ISS subjects): Delta height SDS of 2.04 +/- 0.17 for GHD and 1.33 +/- 0.09 for ISS groups in IGF2T, 1.41 +/- 0.13 for children with GHD, and 0.84 +/- 0.07 for those with ISS in IGF0T.

Conclusion: IGF-based GH dosing is clinically feasible in both GHD and ISS patients, although GH dose requirements and auxological outcomes are distinct between these groups. This suggests a degree of both GH and IGF insensitivity in subjects with ISS that requires specific management strategies to optimize growth during GH therapy.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Body Height* / drug effects
  • Body Mass Index
  • Breast / anatomy & histology
  • Child
  • Child, Preschool
  • Dwarfism, Pituitary / drug therapy*
  • Female
  • Growth / drug effects
  • Growth / physiology*
  • Growth Hormone / blood
  • Growth Hormone / therapeutic use
  • Human Growth Hormone / blood*
  • Human Growth Hormone / therapeutic use*
  • Humans
  • Insulin-Like Growth Factor I / deficiency
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor I / therapeutic use*
  • Male
  • Somatomedins / pharmacology
  • Somatomedins / therapeutic use*
  • Testis / anatomy & histology


  • Somatomedins
  • Human Growth Hormone
  • Insulin-Like Growth Factor I
  • Growth Hormone