Decreased GH Dose After Catch-up Growth in GH Deficiency
Decreased GH Dose After Catch-up Growth in GH Deficiency
Objective Few studies have evaluated metabolic outcomes following growth hormone (GH) treatment in short prepubertal children during different periods of growth. Previously, we found that individualized GH dosing in the catch-up period reduced the variation in fasting insulin levels by 34% compared with those receiving a standard GH dose. We hypothesized that the GH dose required to maintain beneficial metabolic effects is lower during the prepubertal growth phase after an earlier catch-up growth period.
Design Short prepubertal children with isolated GH deficiency or idiopathic short stature were randomized to individualized GH treatment (range, 17–100 μg/kg/day) or a standard dose in a preceding 2-year study. After achieving near mid-parental heightSDS, children receiving an individualized dose were randomized to either a 50% reduced individualized dose (RID,n = 28) or an unchanged individualized dose (UID,n = 37) for 2 years. The dose remained unchanged in 33 children initially randomized to receive a standard dose (FIX, 43 μg/kg/day).We evaluated whether the variations in metabolic parameters measured during maintenance growth diminished in RID compared with UID or FIX.
Results We observed less variation in fasting insulin levels (−50%), insulin sensitivity as assessed by homoeostasis model assessment (−55·1%), lean soft tissue (−27·8%) and bone mineral content (−31·3%) in RID compared with UID (all P < 0·05), but no differences compared with FIX.
Conclusions Continued reduced individualized GH treatment after the catch-up growth period is safe and reduces hyperinsulinism. Individualized GH dose can be reduced once the desired heightSDS is achieved to avoid overtreatment in terms of metabolic outcome
Using prediction models to estimate individual growth hormone (GH) responsiveness makes it possible to avoid giving insufficient or excessive GH doses to children being treated for short stature. Growth in response to individualized GH treatment has been investigated in several previous studies in short prepubertal children. However, there have been few evaluations of metabolic outcomes following individualized GH treatment during different periods of growth. GH effects beyond the promotion of linear growth comprise changes in body composition, insulin sensitivity, and protein and lipid metabolism. The antagonistic effect of GH on insulin in particular has been considered to be an adverse effect particularly in small for gestational age (SGA) children, but high insulin levels without impaired insulin sensitivity may be needed for growth promotion, as is most obvious in foetal life.
Data show that the range of growth responses around the mid-parental height SDS (MPHSDS) narrows after approximately 2 years of individualized GH treatment, suggesting that the dose is being optimized in terms of the effects on height. Similarly, metabolic response also appears to be optimized based on recent findings of a reduction in variation of fasting insulin levels by 34% in those receiving an individualized dose during the catch-up growth period compared with controls receiving a standard dose. Furthermore, this effect was independent of endogenous GH secretion capacity. Clearly, therefore, there are benefits to individualize GH dose.
As healthy children approach the onset of puberty, it appears that they experience a decrease in GH secretion that does not compromise their growth and maintain standard deviation score (SDS) channel-parallel growth although height velocity decreases slightly. Channel-parallel growth has been observed in children receiving a 50% reduction in their individualized GH dose after catch-up growth had been achieved.
The aim of the present study was to evaluate whether the reduced GH dose compromised the markers of metabolic effects in prepubertal children who had achieved their catch-up growth during 2 preceding years of GH treatment. We hypothesize that the GH dose required to maintain the beneficial 'normalized' effects of GH on metabolism, that is, keeping fasting insulin, lean soft tissue mass (LST) and fat mass within the reference ranges, during the prepubertal growth period is lower than during the catch-up growth period. We expected that the variation in metabolic variables would be narrower in patients in whom the individualized GH dose is reduced than in those where the individualized dose remains unchanged following catch-up growth.
Abstract and Introduction
Abstract
Objective Few studies have evaluated metabolic outcomes following growth hormone (GH) treatment in short prepubertal children during different periods of growth. Previously, we found that individualized GH dosing in the catch-up period reduced the variation in fasting insulin levels by 34% compared with those receiving a standard GH dose. We hypothesized that the GH dose required to maintain beneficial metabolic effects is lower during the prepubertal growth phase after an earlier catch-up growth period.
Design Short prepubertal children with isolated GH deficiency or idiopathic short stature were randomized to individualized GH treatment (range, 17–100 μg/kg/day) or a standard dose in a preceding 2-year study. After achieving near mid-parental heightSDS, children receiving an individualized dose were randomized to either a 50% reduced individualized dose (RID,n = 28) or an unchanged individualized dose (UID,n = 37) for 2 years. The dose remained unchanged in 33 children initially randomized to receive a standard dose (FIX, 43 μg/kg/day).We evaluated whether the variations in metabolic parameters measured during maintenance growth diminished in RID compared with UID or FIX.
Results We observed less variation in fasting insulin levels (−50%), insulin sensitivity as assessed by homoeostasis model assessment (−55·1%), lean soft tissue (−27·8%) and bone mineral content (−31·3%) in RID compared with UID (all P < 0·05), but no differences compared with FIX.
Conclusions Continued reduced individualized GH treatment after the catch-up growth period is safe and reduces hyperinsulinism. Individualized GH dose can be reduced once the desired heightSDS is achieved to avoid overtreatment in terms of metabolic outcome
Introduction
Using prediction models to estimate individual growth hormone (GH) responsiveness makes it possible to avoid giving insufficient or excessive GH doses to children being treated for short stature. Growth in response to individualized GH treatment has been investigated in several previous studies in short prepubertal children. However, there have been few evaluations of metabolic outcomes following individualized GH treatment during different periods of growth. GH effects beyond the promotion of linear growth comprise changes in body composition, insulin sensitivity, and protein and lipid metabolism. The antagonistic effect of GH on insulin in particular has been considered to be an adverse effect particularly in small for gestational age (SGA) children, but high insulin levels without impaired insulin sensitivity may be needed for growth promotion, as is most obvious in foetal life.
Data show that the range of growth responses around the mid-parental height SDS (MPHSDS) narrows after approximately 2 years of individualized GH treatment, suggesting that the dose is being optimized in terms of the effects on height. Similarly, metabolic response also appears to be optimized based on recent findings of a reduction in variation of fasting insulin levels by 34% in those receiving an individualized dose during the catch-up growth period compared with controls receiving a standard dose. Furthermore, this effect was independent of endogenous GH secretion capacity. Clearly, therefore, there are benefits to individualize GH dose.
As healthy children approach the onset of puberty, it appears that they experience a decrease in GH secretion that does not compromise their growth and maintain standard deviation score (SDS) channel-parallel growth although height velocity decreases slightly. Channel-parallel growth has been observed in children receiving a 50% reduction in their individualized GH dose after catch-up growth had been achieved.
The aim of the present study was to evaluate whether the reduced GH dose compromised the markers of metabolic effects in prepubertal children who had achieved their catch-up growth during 2 preceding years of GH treatment. We hypothesize that the GH dose required to maintain the beneficial 'normalized' effects of GH on metabolism, that is, keeping fasting insulin, lean soft tissue mass (LST) and fat mass within the reference ranges, during the prepubertal growth period is lower than during the catch-up growth period. We expected that the variation in metabolic variables would be narrower in patients in whom the individualized GH dose is reduced than in those where the individualized dose remains unchanged following catch-up growth.
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