Hexarelin, a synthetic six‑amino‑acid peptide, can boost growth hormone (GH) release when given intravenously at 2 µg/kg, but only in people whose hypothalamus‑pituitary connection is still working. It works well in kids with idiopathic GH deficiency, similar to normal short kids, but fails in those whose pituitary area is damaged or disconnected.

Hexarelin (Hex) is a new synthetic hexapeptide with potent GH-releasing activity in both animals and men. We evaluated the GH response to maximal doses of Hex (2 micrograms/kg, iv) and GHRH-(1-29) (1 microgram/kg, iv) in 15 children (11 boys and 4 girls, aged 6.0-17.3 yr) and 4 adults (3 men and 1 woman, aged 20.2-30 yr) with GH deficiency (GHD). GHD was idiopathic in 8 patients and associated with pituitary stalk interruption syndrome in 8, with a pituitary cyst in 2, and with empty sella syndrome in 1. In 11 patients, GHD was isolated, whereas in 8, it was associated with other pituitary hormone deficiencies. Forty-five short normal 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 higher 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 response to Hex was absent or blunted compared with those in the short normal children and the patients with idiopathic GHD. In all patients except those with associated ACTH deficiency, Hex administration caused a slight, but significant, increase in cortisol concentrations. This study shows that Hex stimulates GH secretion in patients with idiopathic GHD. The inability of Hex to stimulate GH secretion in patients with hypothalamic-pituitary disconnection strongly supports the concept that in humans, the GH-releasing effect of GH-releasing peptides is mediated by the hypothalamus.