High-dose GH treatment limited to the prepubertal period in young children with idiopathic short stature does not increase adult height

Abstract

Objective: To assess the long-term effect of prepubertal high-dose GH treatment on growth in children with idiopathic short stature (ISS). Design and methods: Forty children with no signs of puberty, age at start 4-8 years (girls) or 4-10 years (boys), height SDS !K2.0 SDS, and birth length OK2.0 SDS, were randomly allocated to receive GH at a dose of 2 mg/m 2 per day (equivalent to 75 mg/kg per day at start and 64 mg/kg per day at stop) until the onset of puberty for at least 2 years (preceded by two 3-month periods of treatment with low or intermediate doses of GH separated by two washout periods of 3 months) or no treatment. In 28 cases, adult height (AH) was assessed at a mean (S.D.) age of 20.4 (2.3) years. Results: GH-treated children (mean treatment period on high-dose GH 2.3 years (range 1.2-5.0 years)) showed an increased mean height SDS at discontinuation of the treatment compared with the controls (K1.3 (0.8) SDS versus K2.6 (0.8) SDS respectively). However, bone maturation was significantly accelerated in the GH-treated group compared with the controls (1.6 (0.4) versus 1.0 (0.2) years per year, respectively), and pubertal onset tended to advance. After an untreated interval of 3-12 years, AH was K2.1 (0.7) and K1.9 (0.6) in the GH-treated and control groups respectively. Age was a positive predictor of adult height gain. Conclusion: High-dose GH treatment restricted to the prepubertal period in young ISS children augments height gain during treatment, but accelerates bone maturation, resulting in a similar adult height compared with the untreated controls.

A 4-Year, Open-Label, Multicenter, Randomized Trial of Genotropin® Growth Hormone in Patients with Idiopathic Short Stature: Analysis of 4-Year Data Comparing Efficacy, Efficiency, and Safety between an Individualized, Target-Driven Regimen and Standard Dosing

“…Additional potential advantages of lowering the overall GH exposure in the treatment of ISS patients include a theoretical reduction of the risk of side effects and a lower risk of rapid acceleration of skeletal maturation [24,25], although it should be noted that we did not observe any differences in either the safety profile or the rates of skeletal maturation or pubertal advancement between the dose groups during the 4-year course of this trial.…”

A pilot study of growth hormone administration in boys with predicted adult short stature and near-ending growth

“…Despite an extensive Pubmed search including recent reviews [5,9,[13][14][15]], we have not been able to find studies dealing specifically with the start of rhGH administration at the very end of puberty in ISS. Indeed, most studies had focused on prepubertal children [3,5,9,[13][14][15][22][23][24]27,37]. As an example, the study that allowed rhGH to gain acceptance for ISS by the FDA [24] excluded boys with a bone age greater then 13 years and a testicular volume larger then 10 ml.…”

“…Although the clinical effectiveness of recombinant human growth hormone (rhGH) in ISS is well documented [3,5,[13][14][15][22][23][24]27,37], the use of this treatment varies largely across countries and health systems. For example the treatment of ISS with rhGH is not approved by the European Medicine Agency, whereas this indication has been approved in the United States since 2003, followed by a consensus on the management of ISS published in 2008 [9].…”

The Rationale for Growth Hormone Therapy in Children with Short Stature

“…More recently, van Gool et al ( 79 ) have reported that high dose GH therapy in prepubertal children with ISS does not improve adult height, as it increases height gain during treatment but, at the same time, accelerates bone maturation, resulting in a similar adult height compared with the untreated controls.…”