C. Pihoker et al., DIAGNOSTIC STUDIES WITH INTRAVENOUS AND INTRANASAL GROWTH HORMONE-RELEASING PEPTIDE-2 IN CHILDREN OF SHORT STATURE, The Journal of clinical endocrinology and metabolism, 80(10), 1995, pp. 2987-2992
GH secretion is primarily regulated by the hypothalamic-releasing horm
ones GHRH and somatostatin. Additionally, several neurotransmitters ac
t at the hypothalamus and pituitary to modulated GH release. The agent
s commonly used in clinical practise to diagnose GH deficiency, such a
s arginine, insulin and L-dopa, act through the neural GH network. Man
y children with a poor GH response to conventional agents have a signi
ficant serum GH response to iv GHRH. GH-releasing peptides (GHRPS) are
synthetic peptides that like GHRH act directly on pituitary somatotro
phs to stimulate GH release. GHRP-2, an investigational drug, is one o
f 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 rout
e of administration. In this study, GH responses to GHRP-2 were compar
ed 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 com
bination with GHRH. Twenty-four children undergoing evaluation for GH
deficiency received at least one conventional agent (arginine, in addi
tion to iv GHRH and GHRP-2. The GH responses to GHRH or GHRP-2 were si
milar in each child, and both were equally reliable predictors of pitu
itary reserve. The conventional agents used in GH testing were less li
kely to predict the capacity of the pituitary to release GH than were
either GHRH or GHRP-2. There was no correlation between maximal GH res
ponse 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 wer
e 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 f
actors also received intranasal GHRP-2. All 15 of these children had a
significant GH response to intranasal GHRP-2 over a dose range of 5-2
0 mu g/kg per dose. The mean peak GH response to 15 mu g/kg was 31.3 m
u g/L. The intranasal preparation was well tolerated. The fact that GH
RP-2 given intranasally exerts a significant GH response suggests that
It may be of benefit in assessing pituitary GH function in the outpat
ient setting. A convenient, well tolerated GH releasing agent such as
intranasal GHRP-2 represents a possible attractive treatment option fo
r Children with hypothalamic GH deficiency.