TY - JOUR
T1 - Insulin growth factor-based dosing of growth hormone therapy in children
T2 - A randomized, controlled study
AU - Cohen, Pinchas
AU - Rogol, Alan D.
AU - Howard, Campbell P.
AU - Bright, George M.
AU - Kappelgaard, Anne Marie
AU - Rosenfeld, Ron G.
N1 - Funding Information:
This clinical trial was supported by Novo Nordisk Inc.
PY - 2007/7
Y1 - 2007/7
N2 - Context: Weight-based dosing of GH is the standard of care for short children, although IGF-I is thought to be the main mediator of GH actions on growth. Objective: The objective of the study was to test whether IGF-I levels achieved during GH therapy are determinants of the growth responses to GH treatment. Design: This was a 2-yr, open-label, randomized, IGF-I concentration-controlled trial. Prepubertal short children [n = 172, mean age 7.53 yr, 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 μg/kg/d (n = 34). Setting: The study was conducted in a multicenter, outpatient setting. Primary Outcome Measure: Change in HT-SDS over 2 yr was measured. Results: One hundred 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 other two groups). The IGF(high) arm required higher doses (<2.5 times) than the IGF(low) arm, and these GH doses were highly variable (20-346 μg/kg/d). Multivariate analyses suggested that the rise in the IGF-I SDS significantly impacted height outcome along with the GH dose and the pretreatment peak-stimulated GH level. Conclusion: 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 targets results in improved growth responses, although at higher average GH doses.
AB - Context: Weight-based dosing of GH is the standard of care for short children, although IGF-I is thought to be the main mediator of GH actions on growth. Objective: The objective of the study was to test whether IGF-I levels achieved during GH therapy are determinants of the growth responses to GH treatment. Design: This was a 2-yr, open-label, randomized, IGF-I concentration-controlled trial. Prepubertal short children [n = 172, mean age 7.53 yr, 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 μg/kg/d (n = 34). Setting: The study was conducted in a multicenter, outpatient setting. Primary Outcome Measure: Change in HT-SDS over 2 yr was measured. Results: One hundred 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 other two groups). The IGF(high) arm required higher doses (<2.5 times) than the IGF(low) arm, and these GH doses were highly variable (20-346 μg/kg/d). Multivariate analyses suggested that the rise in the IGF-I SDS significantly impacted height outcome along with the GH dose and the pretreatment peak-stimulated GH level. Conclusion: 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 targets results in improved growth responses, although at higher average GH doses.
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U2 - 10.1210/jc.2007-0204
DO - 10.1210/jc.2007-0204
M3 - Article
C2 - 17356043
AN - SCOPUS:34447119568
SN - 0021-972X
VL - 92
SP - 2480
EP - 2486
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 7
ER -