The advent of puberty in growth hormone deficient (GHD) children initiates the process that leads to epiphyseal fusion, which may limit their growth. LHRH-A therapy in children with central precocious puberty is effective in slowing bone maturation and improving final height. In order to study the effect of delaying puberty on the growth of GHD children, we studied 23 pubertal GHD patients (14F, 9M) in a prospective, randomized, placebo-controlled trial. Their chronological age was 14.2 ± 1.6 years and their bone age was 11.0± 1.5 years (mean+SD). Patients were randomly assigned to receive GH+LHRH-A (n=11), or GH+placebo (P) (n=12) during 3 years Nutropin (donated by Genentech) was administered at a dose of 0.1Ul/Kg/day sc, and depot Lupron (donated by TAP Pharmaceuticals) was administered at a dose of 300 ug/Kg every 28 days GH deficiency was defined as children with a growth velocity < 4cm/year, significantly delayed bone age. GH response to 2 stimulation tests <4 ng/ml, and low IGF-I and IGFBP-3 for age. Patients were evaluated clinically every 3 months and every 6 months we performed a CBC, blood chemistry profile, LHRH test, testosterone (boys), estradiol (girls), cortisol, T4, T3,TSH and bone age. In the following table we present the preliminary data generated during the first 2 years of the study. Statistical analysis was performed by ANOVA or Kruskal Wallis when variances were not homogeneous. (* p<0.001)
We observed an increase in predicted height during the first 2 years of the study, which was more marked in the GHD children treated with GH+LHRH-A. These preliminary findings suggest that delaying puberty with LHRH-A in pubertal growth hormone deficient children treated with growth hormone may increase their final height compared to treatment with growth hormone alone. We are following these children until epiphyseal fusion at which time we will evaluate whether this therapy improves final height. (Supported by Fondecyt 1940543).
