Insulin growth factor-based dosing of growth hormone therapy in children: A randomized, controlled study

Pinchas Cohen, Alan D. Rogol, Campbell P. Howard, George M. Bright, Anne Marie Kappelgaard, Ronald (Ron) Rosenfeld

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

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 ((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.

Original languageEnglish (US)
Pages (from-to)2480-2486
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume92
Issue number7
DOIs
StatePublished - Jul 2007
Externally publishedYes

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Insulin-Like Growth Factor I
Growth Hormone
Intercellular Signaling Peptides and Proteins
Insulin
Therapeutics
Growth
Titration
Insulin-Like Growth Factor II
Standard of Care
Labels
Reference Values
Outpatients
Multivariate Analysis
Outcome Assessment (Health Care)
Weights and Measures

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Insulin growth factor-based dosing of growth hormone therapy in children : A randomized, controlled study. / Cohen, Pinchas; Rogol, Alan D.; Howard, Campbell P.; Bright, George M.; Kappelgaard, Anne Marie; Rosenfeld, Ronald (Ron).

In: Journal of Clinical Endocrinology and Metabolism, Vol. 92, No. 7, 07.2007, p. 2480-2486.

Research output: Contribution to journalArticle

Cohen, Pinchas ; Rogol, Alan D. ; Howard, Campbell P. ; Bright, George M. ; Kappelgaard, Anne Marie ; Rosenfeld, Ronald (Ron). / Insulin growth factor-based dosing of growth hormone therapy in children : A randomized, controlled study. In: Journal of Clinical Endocrinology and Metabolism. 2007 ; Vol. 92, No. 7. pp. 2480-2486.
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abstract = "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 ((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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AU - Cohen, Pinchas

AU - Rogol, Alan D.

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AU - Bright, George M.

AU - Kappelgaard, Anne Marie

AU - Rosenfeld, Ronald (Ron)

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