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 novel GH-releasing peptide-6 analog, and GH-releasing hormone (GHRH) (alone or in combination) on GH secretion in adult patients with increased somatostatin tone due to chronic glucocorticoid excess. We studied seven adult patients undergoing long-term (no less than 6 months) immunosuppressive glucocorticoid treatment for non-endocrine diseases (six females and one male, age range 42-68 years) and one subject (female, age 31 years) with endogenous hypercortisolism due to adrenal adenoma. Six normal subjects (four females and two males) matched for sex and age 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 min. After GHRH alone the patients with glucocorticoid excess showed a blunted 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 to 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 after the combined stimuli were significantly decreased in the patients with glucocorticoid excess as compared with normal subjects (median delta GH: 43.5, range 21-56.9 mu g/l vs 73.7, range 19.6-116.8 mu g/l). The two stimuli acted in a synergistic fashion in both soups of subjects. It may be hypothesized that hexarelin influences the GH inhibitory effect of glucocorticoids in humans, acting at the hypothalamic somatostatin level.