Insulin growth factor-I-based dosing of growth hormone therapy in children: a randomized, controlled study
https://doi.org/10.14341/probl200955227-34
Abstract
Weight-based dosing of growth hormone (GH) is the standard of therapy in short children although insulin-like growth factor-I (IGF-I) is a major mediator of GH actions on growth. Objective: to test whether the IGF-I levels achieved during GH therapy are determinants of the growth responses to GH therapy. This was a two-year open-label, randomized IGF-I concentration-controlled trial. Prepubertal short children [n = 172; mean age 7.53 years; mean height SD score (HT-SDS - 2.64] with low IGF-I levels (mean IGF-I SDS - 3.56) were randomized to receive one of two GH dose-titration arms in which GH dosage was titrated to achieve an IGF-I SDS at the mean [IGF(low) group, n = 70) or the upper limit of the normal range [+2 SDS, IGF(high) group, n = 68] or to a comparison group of conventional GH dose of 40 mg/kg/day (n = 34). The multicenter study was performed in the outpatient centers. The primary outcome measure was to determine changes in HT-SDS during 2-year therapy. One hundred and forty-seven patients completed the trial. Target IGF-I levels were achieved in the dose-titration arms within 6-9 months. The changes in HT-SDS were +1.0, +1.1, and +1.6 for conventional, IGF(low), and IGF(high), respectively, with IGF(high) showing significantly greater linear growth response (p < 0.001), compared with the two other groups). The IGF-I(high) arm required higher doses ( > 2.5 times) than the IGF-I(low) arm, and these GH doses were highly variable (20-346 mg/kg/day). Multivariate analyses suggest that the rise in IGF-I SDS significantly impacted height outcome along with the GH dose and the pretreatment peak-stimulated GH level. IGF-I-based GH dosing is clinically feasible and allows maintaining serum IGF-I concentrations within the desired target range. Titrating the GH dose to achieve higher IGF-I target results in improved growth responses, although at higher average GH doses.
About the Authors
P CohenMattel Childrens Hospital at UCLA
United States
Department of pediatric Endocrinology
A D Rogol
University of Virginia
United States
Department of Pediatrics
C P Howard
Novo Nordisk Inc.
United States
Medical Department
G M Bright
Novo Nordisk Inc.
United States
Medical Department
A.-M Kappelgaard
Novo Nordisk A/S
Denmark
Scientific Marketing GHT
R G Rosenfeld
Lucile Packard Foundation for Children’s Health
United States
Medical Affairs
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Review
For citations:
Cohen P., Rogol A.D., Howard C.P., Bright G.M., Kappelgaard A., Rosenfeld R.G. Insulin growth factor-I-based dosing of growth hormone therapy in children: a randomized, controlled study. Problems of Endocrinology. 2009;55(2):27-34. (In Russ.) https://doi.org/10.14341/probl200955227-34
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