COMPARISON OF THE EFFECTS OF GROWTH HORMONE-RELEASING HORMONE AND HEXARELIN, A NOVEL GROWTH HORMONE-RELEASING PEPTIDE-6 ANALOG, ON GROWTH-HORMONE SECRETION IN HUMANS WITH OR WITHOUT GLUCOCORTICOID EXCESS

The aim of our study was to investigate the effect of hexarelin, a nov el GH-releasing peptide-6 analog, and GH-releasing hormone (GHRH) (alo ne or in combination) on GH secretion in adult patients with increased somatostatin tone due to chronic glucocorticoid excess. We studied se ven adult patients undergoing long-term (no less than 6 months) immuno suppressive glucocorticoid treatment for non-endocrine diseases (six f emales and one male, age range 42-68 years) and one subject (female, a ge 31 years) with endogenous hypercortisolism due to adrenal adenoma. Six normal subjects (four females and two males) matched for sex and a ge with the patients and;lot undergoing any therapy served as controls . All the subjects underwent the following three tests in random order : (1) human GHRH (1-29)NH2 (100 mu g in 1 ml saline) injected as an i. v. bolus at 0 min, (2) hexarelin (100 mu g in 1 ml saline) injected as an i.v, bolus at 0 min and (3) hexarelin (100 mu g in 1 ml of saline) plus GHRH (100 mu g in 1 ml saline) injected as an i.v. bolus at 0 mi n. After GHRH alone the patients with glucocorticoid excess showed a b lunted GH response as compared with normal subjects (median delta GH: 0.9, range 0-5.6 mu g/l vs 7.1, range 0.3-14.9 mu g/l). No significant differences were observed in the steroid-treated group with respect t o normal subjects after hexarelin alone (median delta GH: 15.5, range 1.9-45.2 mu g/l vs 17.9, range 5.5-53.9 mu g/l). The GH responses afte r the combined stimuli were significantly decreased in the patients wi th glucocorticoid excess as compared with normal subjects (median delt a GH: 43.5, range 21-56.9 mu g/l vs 73.7, range 19.6-116.8 mu g/l). Th e two stimuli acted in a synergistic fashion in both soups of subjects . It may be hypothesized that hexarelin influences the GH inhibitory e ffect of glucocorticoids in humans, acting at the hypothalamic somatos tatin level.