hexarelin and Hypopituitarism

Growth hormone (GH)-releasing peptides possess specific pituitary, hypothalamic, and myocardial receptors. Seven adult male patients with GH deficiency (GHD) (age, mean+/-S.E.M.: 42.0+/-4.0 year) were studied by equilibrium radionuclide angiocardiography after i.v. administration of hexarelin, a peptide GH secretagogue. Data for these patients were compared with those for nine adult male controls (37.0+/-2.7 year). The GH response to hexarelin was negligible in patients with GHD compared to control subjects (CS) (peak: 1.9+/-0.9 vs. 45.7+/-3.6 microg/l, P<0.001). Basal left ventricular ejection fraction (LVEF) in patients with GHD was lower than that in CS (50+/-1% vs. 63+/-2%, P<0.001). Hexarelin administration increased LVEF both in patients with GHD and in CS (peak: 57+/-2 vs. 70+/-2, respectively, P<0.05 vs. baseline) without changing catecholamine levels, mean blood pressure (MBP), or cardiac output in either group. In conclusion, the acute administration of hexarelin exerts a short-lasting positive inotropic effect in humans, probably GH-independent and mediated by specific myocardial receptors for GH secretagogues.

Topics: Adult; Flushing; Heart; Hemodynamics; Human Growth Hormone; Humans; Hypopituitarism; Insulin-Like Growth Factor I; Male; Middle Aged; Oligopeptides; Radionuclide Angiography

Hexarelin (Hex) is a new synthetic hexapeptide with potent growth hormone (GH)-releasing activity in both animals and men. We evaluated the GH response to a maximal dose of Hex (2 micrograms/kg iv) and GH-releasing hormone (GHRH) (1-29, 1 microgram/kg iv) in 45 short normal children (24 males and 21 females, age 5.9-14 yr, 24 prepubertal and 21 in Tanner stage 2 or 3 of pubertal maturation), in 10 prepubertal obese children (7 males and 3 females, age 7.5-12 yr), and in 5 subjects with organic hypopituitarism (4 males and 1 female, age 8.4-21 yr). In 5 male subjects with constitutional growth delay (age 12.0-13.7 yr), the GH response to Hex was reevaluated 1 week after priming with testosterone enanthate (100 mg im). In all short normal children Hex caused a prompt and clear-cut increase of serum GH concentrations, with peaks occurring between 15-30 min from injection. The GH response to Hex was significantly higher than that observed after GHRH and was not different between males and females or between prepubertal and pubertal subjects. Priming with testosterone resulted in an increased GH response to Hex in all 5 subjects studied. No GH increase was observed in the hypopituitary subjects after either GHRH or Hex administration. In the obese children the GH responses to GHRH and to Hex were significantly lower than in the prepubertal children. Also, in the obese, the GH response to Hex was significantly higher than that observed after GHRH. In all short normal and obese children, but not in the hypopituitary subjects, Hex administration caused a slight but significant increase from baseline of both cortisol and PRL concentrations that returned to the baseline values within 2 h. None of the subjects experienced adverse side effects after Hex administration. This study shows that, in short normal and obese children, Hex is a potent GH-releasing stimulus with potential clinical utility.

Topics: Body Height; Child; Child, Preschool; Female; Growth Hormone; Growth Hormone-Releasing Hormone; Growth Substances; Humans; Hydrocortisone; Hypopituitarism; Male; Obesity; Oligopeptides; Prolactin; Puberty; Reference Values