A randomized controlled trial of three years growth hormone and gonadotropin-releasing hormone agonist treatment in children with idiopathic short stature and intrauterine growth retardation

We assessed the effectiveness and safety of 3 yr combined GH and GnRH agoni st (GnRHa) treatment in a randomized controlled study in children with idio pathic short stature (ISS) or intrauterine growth retardation (IUGR). Gonad al suppression, GH reserve, and adrenal development were assessed by hormon e measurements in both treated children and controls during the study perio d. Thirty-six short children, 24 girls (16 ISS/8 IUGR) and 12 boys (8 ISS/4 IU GR), with a height so score of -2 sn or less in early puberty (girls, B2-3; boys, G2-3), were randomly assigned to treatment (n = 18) with GH (genotro pin 4 IU/m(2) day) and GnRHa (triptorelin, 3.75 mg/28 days) or no treatment (n = 18). At the start of the study mean (SD) age was 11.4 (0.56) or 12.2 (1.12) yr whereas bone age was 10.7 (0.87) or 10.9 (0.63) Srs in girls and boys, respectively. During 3 yr of study height so score for chronological age did not change i n both treated children and controls, whereas a decreased rate of hone matu ration after treatment was observed [mean (sn) 0.55 (0.21)'yr'/yr vs. 1.15 (0.37) 'yr'/yr in controls, P < 0.001, girls and boys together]. Height so score for bone age and predicted adult height increased significantly after 3 yr of treatment; compared with controls the predicted adult height gain was 8.0 cm in girls and 10.4 cm in boys. Furthermore, the ratio between sit ting height/height sn score decreased significantly in treated children, wh ereas body mass index was not influenced by treatment. Puberty was effectively arrested in the treated children, as was confirmed by physical examination and prepubertal testosterone and estradiol levels. GH-dependent hormones including serum insulinlike growth factor I and II, c arboxy terminal propeptide of type I collagen, amino terminal propeptide of type III collagen, alkaline phosphatase, and osteocalcin were not differen t between treated children and controls during the study period. Thus, a GH dose of 4 U/m(2) seems adequate for stabilization of the GH reserve and gr owth in these GnRHa-treated children. We conclude that 3 yr treatment with GnRHa was effective in suppressing pub ertal development and skeletal maturation, whereas the addition of GH prese rved growth velocity during treatment. This resulted in a considerable gain in predicted adult height, without demonstrable side effects. Final height results will provide the definite answer on the effectiveness of this comb ined treatment.