Effects of dose and gender on the growth and growth factor response to GH in GH-deficient children: Implications for efficacy and safety

Pinchas Cohen, George M. Bright, Alan D. Rogol, Anne Marie Kappelgaard, Ron G. Rosenfeld

Research output: Contribution to journalArticle

142 Scopus citations

Abstract

We evaluated the dose-response effects of GH on the growth and growth factor levels of GH-deficient patients. One hundred eleven short (-3.0 ± 0.9 height SD score), prepubertal GH-deficient children were randomized to receive low- (L; 0.025 mg/kg per day), medium- (M; 0.05 mg/kg per day), or high (H; 0.1 mg/kg per day) dose GH. One hundred four children completed the 2-yr study. At 2 yr, the three groups displayed increases in height SD scores of 1.4 ± 0.1 for L, 2.2 ± 0.1 for M, and 2.3 ± 0.1 for H (P < 0.001 relative to L, P = NS relative to M). The serum levels of IGF-I and IGF binding protein-3 during treatment also demonstrated dependency on the GH dose and were independently correlated with the increase in height SD scores attained. Bone age advancement, the occurrence of puberty, fasting glucose, and hemoglobin A1c did not change during therapy, but fasting insulin levels rose in a dose-dependent manner. Surprisingly, the GH dose-response curve for both auxological and biochemical parameters differed between prepubertal females (n = 33) and males (n = 71). Males had a linear GH dose response, whereas females had an apparent plateau of both linear growth and IGF-I SD score responses at 0.05 mg/kg per day. In this large, randomized, 2-yr study, we observed a dose-response effect of GH on growth and serum growth factor levels and a prepubertal gender difference in GH sensitivity. These results suggest that the efficacy and theoretical safety of GH therapy can be optimized by modulating the GH dose in a gender-specific manner, based on the growth response and serum growth factor levels.

Original languageEnglish (US)
Pages (from-to)90-98
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume87
Issue number1
DOIs
StatePublished - Jan 1 2002

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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