Prepubertal Children with Growth Hormone Deficiency Treated for Four Years with Growth Hormone Experience Dose-Dependent Increase in Height, but Not in the Rate of Puberty Initiation

Abstract

Background/Aims: Limited data exist on long-term dose response to recombinant human growth hormone (rhGH) in prepubertal GH-deficient (GHD) children. The effect of low, intermediate, and high-dose rhGH (25, 50, and 100 μg/kg/day, respectively) on growth and puberty in children with GHD was investigated for 48 months. Methods: A prospective, dose-response study in 111 patients (aged 3-16 years) evaluated growth velocity (cm/year), height standard deviation score (HSDS), corrected HSDS, bone age/chronologic age ratio, body mass index SDS, and the percentage starting puberty. Results: Dose-related increases were observed in growth velocity (p < 0.001), HSDS (p < 0.001), and corrected HSDS (p < 0.001) from baseline to 48 months. Increases in the bone age/chronologic age ratio (p = 0.043) and body mass index SDS (p = 0.018) occurred up to 36 months at intermediate and high doses versus low-dose rhGH; increases at 48 months were not significant. No significant differences in growth were found between intermediate and high doses of rhGH. Percentages of rhGH-treated patients starting puberty at each dose were equivalent (p = 0.607). Conclusions: rhGH, 50 and 100 μg/kg/day, induced greater growth than 25 μg/kg/day without altering the proportion of children starting puberty. The maximum approved dose for pubertal patients (100 μg/kg/day) is not required or recommended for prepubertal children with GHD.

Metabolomic Differential Compounds Reflecting the Clinical Efficacy of Polyethylene Glycol Recombinant Human Growth Hormone in the Treatment of Childhood Growth Hormone Deficiency

“…The analysis of metabolomics provides a powerful tool for determining biomarkers that predict the effects of PEG-rhGH therapy through large-scale molecular analyses. The present study confirmed and extended previous studies by showing the favorable effects of PEG-rhGH therapy on GHD patients ( Rogol et al, 2013 ; Luo et al, 2017 ). To explore the potential mechanism, changes of metabolites of GHD patients in HE and LE groups were monitored using a GC/TOFMS-based metabolomics method.…”

“…Growth failure, the primary apparent feature of GHD, may influence the life quality and psychosocial development of affected children ( Chaplin et al, 2015 ; Chinoy and Murray, 2016 ; Leonibus et al, 2016 ). As recorded in recent pharmaceutical studies, recombinant human growth hormone (rhGH) showed a significant therapeutic effect against growth hormone deficiency ( Rogol et al, 2013 ). To achieve this effect, rhGH is required to be administered as a daily injection ( López-Siguero et al, 2011 ; Wit et al, 2013 ).…”

“…Frequent injections cause distress to the children and therefore reduce compliance. PEG-rhGH preparation is a covalent conjugate of rhGH and branched polyethylene glycol (PEG), which can potentially increase the molecular weight of rhGH, reduce drug toxicity and prolong the half-life of elimination in vivo ( Cutfield et al, 2011 ; Rogol et al, 2013 ; Lundberg et al, 2018 ; Wang et al, 2021 ). The treatment of polyethylene glycol-modified long-acting rhGH (PEG-rhGH) requires only weekly injections, which can reduce the frequency of injections and can enhance children’s compliance with rhGH treatment.…”

Somatotropic‐Testicular Axis: A crosstalk between GH/IGF‐I and gonadal hormones during development, transition, and adult age

“…One study observed a negative correlation between GH dose and pubertal onset but no correlation with treatment duration 124 . In addition, a more recent study that evaluated pubertal onset in 111 GHD children aged 3‐16 years after 48 months of rhGH administration at different doses (25, 50, and 100 µg/kg/day) did not find any significant differences, even if the wide age range of inclusion and lack of control group may bias the findings 125 (Table 1).…”

Genetic Polymorphisms as Predictive Markers of Response to Growth Hormone Therapy in Children with Growth Hormone Deficiency

“…Limitations of our study included low rhGH doses and high peak serum GH levels in stimulation tests, i. e. patients with peak serum GH levels of up to 9.9 µg/l were included based on a GH cut-off level of 10 µg/l. This is relevant because higher rhGH doses and lower peak GH levels are associated with better response to therapy [2,25]. Moreover, our patient population was small: 81 prepubertal patients and 20 patients already at the onset of puberty (max.…”