Efficacy of IGF-based growth hormone (GH) dosing in nonGH-deficient (nonGHD) short stature children with low IGF-I is not related to basal IGF-I levels

Objective Weight-based GH dosing is the standard for treating children with short stature. The current study validates the usefulness of IGF-based GH dosing for GH therapy in nonGH-deficient (nonGHD) children and its relationship with pretreatment serum IGF-I concentration. Design and Patients In this twelve-month, open-label, randomized controlled study, 151 nonGHD (based on GH-stimulation tests), prepubertal children with short stature and IGF-I levels = 33rd percentile [0.44 standard deviation score (SDS)] were randomly assigned to receive GH (dose based on IGF-I titration algorithm; n = 114) or to observation (n = 37). GH dose (initially 40 mu g/kg/d) was adjusted every 3 months to achieve an IGF-I SDS in the upper normal range (66-99th percentile). Measurements and Results In treated children, mean height SDS (HSDS) increased from -2.5 at baseline to -1.7 at 12 months and mean IGF-I SDS increased from -1.7 to 0.1. These parameters remained unchanged in untreated children. There was no relationship between change in HSDS (?HSDS) and degree of IGF-I deficiency at baseline. No safety problems were observed. Both groups had a similar advance in bone age. At the end of study, HSDS in treated children showed a positive correlation with IGF-I SDS, but not with GH dose [mean 59 mu g/kg/d (range 2992)], basal IGF-I SDS or 1-month IGF parameters. Conclusions In nonGHD subjects with short stature and serum IGF-I concentrations within and below the lower third of normal, adjusting GH dose to achieve an IGF-I level in the upper normal range resulted in a significant increase in HSDS, regardless of basal IGF-I levels.