PREDICTING THE GROWTH-RESPONSE TO GROWTH-HORMONE IN PATIENTS WITH INTRAUTERINE GROWTH-RETARDATION

OBJECTIVE Human GH treatment of short children who had intrauterine gr owth retardation (IUGR) results in a highly variable growth response. The object of this study was to test the hypothesis that differences i n responsiveness to exogenously administered GH might reflect differen ces in endogenous GH secretion or sensitivity. DESIGN Prospective stud y evaluating the growth response to GH therapy in short individuals wi th prior IUGR. PATIENTS Ten short, prepubertal children with prior IUG R were studied. Mean age was 6 years (3 . 39-8 . 61). Mean bone age wa s 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 spontaneou s GH release was measured using a constant withdrawal pump and stimula ted GH release was measured following clonidine (0 . 15 mg/m(2)) admin istration. 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/d ose) 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 a nd third year, attempts were made to improve the growth rate by nutrit ional supplementation and increasing the dose of GH to 0 . 25 mg/kg th ree times a week. RESULTS All patients had normal integrated nocturnal GH secretion (> 3 mu g/l, 6mU/l) and normal peak GH secretion in resp onse to clonidine (> 7 mu g/l). In the first year of the trial, mean g rowth 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 concentr ation (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 bindin g protein, baseline height SDS or age. The effect of GH waned in the s econd 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 observe d over the first 2 years. Increasing nutritional intake by 17% did not result in significant weight gain nor increase in height velocity. Do ubling 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 the rapy in short children with a history of intrauterine growth retardati on may partly reflect relative sufficiency or insufficiency of GH. Bas eline IGF-I levels and baseline growth velocity appear to be useful an d practical predictors of response to GH.