GH response to ghrelin in subjects with congenital GH deficiency: evidence that ghrelin action requires hypothalamic–pituitary connections

Abstract

Objectives: Evaluation of GH response to ghrelin in patients with GH deficiency (GHD) may help to elucidate the site and mechanism of action of ghrelin. We aimed to investigate the GH-releasing effect of ghrelin in children and young adults with childhood-onset GHD. Design: All subjects underwent ghrelin testing and neuro-imaging examination. Magnetic resonance imaging evidenced the presence of a vascular pituitary stalk (VPS) or its complete absence (PSA). Patients and methods: Seventeen prepubertal children and nine adult patients with childhood-onset GHD were selected for the study. The children were enrolled at a median age of 5.8 years. The adult subjects were included at a median age of 23.3 years. The diagnosis of GHD in the adult patients had been established at a median age of 8.5 years. Ghrelin was administered at a dose of 1 μg/kg body weight, i.v. at time zero, and blood for GH determination was obtained at 0, 15, 30, 45, 60, 75, 90, 105 and 120 min. Results: Median GH response after ghrelin was similar between children and adults. Median peak GH response to ghrelin (7.45 μg/l, IQR: 3.9–11.3 μg/l) was significantly higher in patients with VPS (10.9 μg/l, IQR: 2.4–15.1 μg/l) than in those with PSA (IQR: 2.3–6.7 μg/l; P = 0.001). It was significantly higher in subjects with isolated GHD (12.5 μg/l, IQR: 10.8–15.5 μg/l) than in those with multiple pituitary hormone deficiencies (5.15 μg/l, IQR: 2.4–9.0 μg/l; P = 0.003). No correlation was found between the GH peak after ghrelin and body mass index. Conclusion: The GH response to ghrelin in patients with congenital hypopituitarism depends on the degree of the anatomical abnormalities and lends further support to the assumption that the main action of the peptide is exerted at the hypothalamic level and requires the integrity of hypothalamic–pituitary connections.