Growth response to growth hormone (GH) treatment in children with GH deficiency (GHD) and those with idiopathic short stature (ISS) based on their pretreatment insulin-like growth factor 1 (IGFI) levels and at diagnosis and IGFI increment on treatment

J Pediatr Endocrinol Metab. 2021 Jul 22;34(10):1263-1271. doi: 10.1515/jpem-2021-0389. Print 2021 Oct 26.


Objectives: Some idiopathic short stature (ISS) patients may have varying degrees of insulin-like growth factor 1 (IGFI) deficiency. Others with growth hormone deficiency (GHD) (peak GH < 7 ng/dL after provocation) have normal IGFI levels. Do children with ISS or those with GHD with variable pretreatment IGFI standard deviation score (IGFISDS) have different IGFI and growth responses to recombinant human growth hormone (rhGH) therapy?

Methods: We studied the effect of GH therapy (0.035-0.06 mg/kg/day) on linear growth and weight gain per day (WGPD) in children with ISS (n=13) and those with GHD (n=10) who have low pretreatment IGFISDS (IGF SDS < -1.5) and compared them with age-matched prepubertal children with ISS (n=10) and GHD (n=17) who had normal pretreatment IGFISDS. An untreated group of children with ISS (n=12) served as a control group.

Results: At presentation, the height standard deviation score (HtSDS) of children with ISS who had low pretreatment IGFISDS was significantly lower compared to the normal IGFI group. The age, body mass index (BMI), BMISDS, peak GH response to clonidine provocation and bone age did not differ between the two study groups. After 1 year of treatment with rhGH (0.035-0.06 mg/kg/day) IGFISDS increased significantly in both groups (p<0.05). Both had significantly increased HtSDS (catch-up growth). The increase in the HtSDS and WGPD were significantly greater in the lower pretreatment IGFISDS group. The IGFSDS, BMISDS, HtSDS and difference between HtSDS and mid-parental HtSDS were significantly greater in the rhGH treated groups vs. the not treated group. In the GHD groups (normal and low IGFISDS), after 1 year of GH therapy (0.03-0.05 mg/kg/day), the HtSDS increased significantly in both, (p<0.01). The WGPD and increment in BMI were significantly greater in children who had low pretreatment IGFISDS. There was a significant increase in the IGFSDS in the two treated groups (p<0.05), however, the WGPD was greater in the pretreatment low IGFISDS.

Conclusions: IGFI deficiency represents a low anabolic state. Correction of IGFI level (through rhGH and/or improved nutrition) in short children (ISS and GHD) was associated with increased linear growth and WGPD denoting significant effect on bone growth and muscle protein accretion.

Keywords: GHD; HtSDS; IGFI; ISS; growth response; prepubertal; rhGH; short stature; weight gain per day.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Age Determination by Skeleton
  • Body Height / drug effects*
  • Bone Development / drug effects
  • Case-Control Studies
  • Child
  • Child Development / drug effects
  • Drug Monitoring / methods
  • Dwarfism, Pituitary / blood
  • Dwarfism, Pituitary / diagnosis
  • Dwarfism, Pituitary / drug therapy*
  • Female
  • Growth Disorders / blood
  • Growth Disorders / diagnosis
  • Growth Disorders / drug therapy*
  • Human Growth Hormone / deficiency
  • Humans
  • Insulin-Like Growth Factor I / analysis*
  • Insulin-Like Growth Factor I / metabolism
  • Male
  • Prognosis
  • Recombinant Proteins / therapeutic use
  • Treatment Outcome
  • Weight Gain / drug effects*


  • IGF1 protein, human
  • Recombinant Proteins
  • Human Growth Hormone
  • Insulin-Like Growth Factor I