DIAGNOSTIC STUDIES WITH INTRAVENOUS AND INTRANASAL GROWTH HORMONE-RELEASING PEPTIDE-2 IN CHILDREN OF SHORT STATURE

GH secretion is primarily regulated by the hypothalamic-releasing hormones GHRH and somatostatin. Additionally, several neurotransmitters act at the hypothalamus and pituitary to modulated GH release. The agents commonly used in clinical practise to diagnose GH deficiency, such as arginine, insulin and L-dopa, act through the neural GH network. Many children with a poor GH response to conventional agents have a significant serum GH response to iv GHRH. GH-releasing peptides (GHRPS) are synthetic peptides that like GHRH act directly on pituitary somatotrophs to stimulate GH release. GHRP-2, an investigational drug, is one of the most potent members of the GHRP family. It has been shown to be effective in adults via the oral and intranasal as well as the iv route of administration. In this study, GH responses to GHRP-2 were compared with GH responses to other provocative agents in children of short stature. GHRP-2 was administered iv or intranasally to children with; short stature. In the same subjects, GHRP-8 was administered iv in combination with GHRH. Twenty-four children undergoing evaluation for GH deficiency received at least one conventional agent (arginine, in addition to iv GHRH and GHRP-2. The GH responses to GHRH or GHRP-2 were similar in each child, and both were equally reliable predictors of pituitary reserve. The conventional agents used in GH testing were less likely to predict the capacity of the pituitary to release GH than were either GHRH or GHRP-2. There was no correlation between maximal GH response to standard tests with GH responses to GHRH or GHRP-2. A subset of the group of 21 children who had a robust response to iv GHRP-2 were later administered GHRH + GHRP-2 simultaneously. The GH response to GHRH + GHRP-2 was synergistic in this group of 12 children, similar to previously reported observations in adults of normal stature. Fifteen of the 21 children who had a robust response to the iv GH-releasing factors also received intranasal GHRP-2. All 15 of these children had a significant GH response to intranasal GHRP-2 over a dose range of 5-20 mu g/kg per dose. The mean peak GH response to 15 mu g/kg was 31.3 mu g/L. The intranasal preparation was well tolerated. The fact that GHRP-2 given intranasally exerts a significant GH response suggests that It may be of benefit in assessing pituitary GH function in the outpatient setting. A convenient, well tolerated GH releasing agent such as intranasal GHRP-2 represents a possible attractive treatment option for Children with hypothalamic GH deficiency.