THE EFFECT OF HEXARELIN ON GROWTH-HORMONE (GH) SECRETION IN PATIENTS WITH GH DEFICIENCY

Hexarelin (Hex) is a new synthetic hexapeptide with potent GH-releasin g activity in both animals and men. We evaluated the GH response to ma ximal doses of Hex (2 mu g/kg, iv) and GHRH-(1-29) (1 mu g/kg, iv) in 15 children (11 boys and 4 girls, aged 6.0-17.3 yr) and 4 adults (3 me n and 1 woman, aged 20.2-30 yr) with GH deficiency (GHD). GHD was idio pathic in 8 patients and associated with pituitary stalk interruption syndrome in 8, with a pituitary cyst in 2, and with empty sella syndro me in 1. In 11 patients, GHD was isolated, whereas in 8, it was associ ated with other pituitary hormone deficiencies. Forty-five short norma l children (24 boys and 21 girls, aged 5.9-14 yr) served as controls. In patients with idiopathic GHD, the GH response to Hex was similar to that observed in short normal children, and it was significantly high er than the response to GHRH. In the patients with GHD associated with anatomical abnormalities, the GH responses to GHRH varied from normal to absent. Among these subjects, only 1 patient with a pituitary cyst had a sizable GH response to Hex, whereas in all others, the GH respo nse to Hex was absent or blunted compared with those in the short norm al children and the patients with idiopathic GHD. In all patients exce pt those with associated ACTH deficiency, Hex administration caused a slight, but significant, increase in cortisol concentrations. This stu dy shows that Hex stimulates GH secretion in patients with idiopathic GHD. The inability of Hex to stimulate GH secretion in patients with h ypothalamic-pituitary disconnection strongly supports the concept that in humans, the GH-releasing effect of GH-releasing peptides is mediat ed by the hypothalamus.