TREATMENT EFFECTS OF INTRANASAL GROWTH-HORMONE RELEASING PEPTIDE-2 INCHILDREN WITH SHORT STATURE

Growth hormone-releasing peptide (GHRP)-2 is a synthetic six amino aci d peptide that is a potent GH secretagogue. Although it shares no stru ctural homology with GH-releasing hormone, in clinical studies its act ions on the pituitary release of GH are similar. It is effective when administered orally and intranasally. For children with GH deficiency, such noninvasive treatments are most desirable and in need of develop ment. Fifteen children with short stature participated in this study. AU of the children had a height <2 S.D. below mean for age, poor heigh t velocity, delayed bone age, and low serum concentrations of IGF-1. T hese children had been tested with standard GH secretagogues, e.g. arg inine, insulin, and L-dopa. Fifty percent of the children were GH defi cient, the remainder had idiopathic short stature. The children receiv ed testing with GHRH and GHRP-2 as an acute i.v. bolus of 1 mu g/kg; a ll children in this study demonstrated a GH response >20 mu g/l. Each child in this study also demonstrated a GH response >10 mu g/l in resp onse to intranasal GHRP-2, in the dose range of 5-20 mu g/kg. The chil dren were administered intranasal GHRP-2, 5-15 mu g/kg, twice a day fo r 3 months, then three times a day. Fifteen children participated in t he study for 6 months; six; of the children have participated for 18-2 4 months. Height velocity, serum IGF-1, IGF-binding protein 3 (IGFBP-3 ) and GH-binding protein (GHBP) concentrations, and GH responses to GH RP-2 by i.v. bolus and intranasal spray were examined during treatment . Height velocity increased h-om 3.7 +/- 0.2 cm/year to 6.1 +/- 0.3 cm /year at 6 months, 6.0 +/- 0.4 cm/year at 18-24 months. There were no significant changes in IGF-I or IGF-PBS concentrations, or in acute GH responses to i.v. or intranasal GHRP-2. GHBP concentrations rose sign ificantly, from 439 +/- 63 pmol/l to 688 +/- 48 pmol/l. In this study, intranasal GHRP-2 administration was well tolerated, and produced a m odest but significant increase in growth velocity.