Predicting the growth response to growth hormone in patients with intrauterine growth retardation

Abstract

Objective: Human GH treatment of short children who had intrauterine growth retardation (IUGR) results in a highly variable growth response. The object of this study was to test the hypothesis that differences in responsiveness to exogenously administered GH might reflect differences in endogenous GH secretion or sensitivity. DESIGN Prospective study evaluating the growth response to GH therapy in short individuals with prior IUGR. Patients: Ten short, prepubertal children with prior IUGR were studied. Mean age was 6 years (3.39-8.61). Mean bone age was 4.6 years (2.3-8.3). Mean body mass index was 13.2 kg/m 2 (9.9-14.0; normal 13.5-19.0). Measurements: Overnight spontaneous GH release was measured using a constant withdrawal pump and stimulated GH release was measured following clonidine (0.15 mg/m 2) administration. IGF-I concentrations were measured at baseline and 12, 24, 36 and 48 hours after sequential doses of GH (0.05 and 0.2 mg/kg/dose) given 48 hour apart. Patients were treated with GH (0.125 mg/kg three times a week) and growth response was assessed. In the second and third year, attempts were made to improve the growth rate by nutritional supplementation and increasing the dose of GH to 0.25 mg/kg three times a week. Results: All patients had normal integrated nocturnal GH secretion (> 3 μg/l, 6 mU/l) and normal peak GH secretion in response to clonidine (> 7 μg/l). In the first year of the trial, mean growth velocity (GV) increased from 5.39 cm/ year ± 0.29 to 7.32 cm/year ± 0.39 (P = 0.004). Changes in GV correlated inversely with integrated GH (r = -0.69; P = 0.038), baseline IGF-I concentration (r = -0.88; P = 0.002) and baseline GV-SDS (r = -0.68; P = 0.043). There was no correlation between change in GV and GH binding protein, baseline height SDS or age. The effect of GH waned in the second year, but tended to remain greater than the pretreatment growth rate (6.54 ± 0.49 vs 5.53 cm/year ± 0.29; P = 0.09). No significant advancement of bone age over chronological age was observed over the first 2 years. Increasing nutritional intake by 17% did not result in significant weight gain nor increase in height velocity. Doubling the dose of GH in the second or third year did not result in a significant increase in GV. Conclusion: The variable response to GH therapy in short children with a history of intrauterine growth retardation may partly reflect relative sufficiency or insufficiency of GH. Baseline IGF-I levels and baseline growth velocity appear to be useful and practical predictors of response to GH.