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The Growth Hormone Response to Hexarelin in Patients with Different Hypothalamic-Pituitary Abnormalities

Clinica Pediatrica (M.M., V.S., F.S.), Servizio Analisi Chimico Cliniche (M.A.), Servizio di Biometria (C.T.), Policlinico S. Matteo, Universitá di Pavia, Pavia; Divisione di Pediatria, Ospedale Bambino Gesù, IRCCS (M.C.), Palidoro; Servizio di Endocrinologia Pediatrica, Ospedale Regionale per le Microcitemie (P.C., S.L.), Cagliari, Italy; and Europeptides (R.D.), Argenteuil, France

Address all correspondence and requests for reprints to: Sandro Loche, M.D., Servizio di Endocrinologia Pediatrica, Ospedale Regionale per le Microcitemie, Via Jenner, 09121 Cagliari, Italy. E-mail: sloche{at}mcweb.unica.it

We evaluated the GH-releasing effect of hexarelin (Hex; 2 µg/kg, iv) and GHRH (1 µg/kg, iv) in 18 patients (11 males and 7 females, aged 2.5–20.4 yr) with GH deficiency (GHD) whose hypothalamic pituitary abnormalities had been previously characterized by dynamic magnetic resonance imaging (MRI). Ten patients had isolated GHD, and 8 had multiple pituitary hormone deficiency. All patients were receiving appropriate hormone replacement therapy. Twenty-four prepubertal short normal children (11 boys and 13 girls, aged 5.9–13 yr, body weight within ±10% of ideal weight) served as controls. MRI studies revealed an ectopic posterior pituitary at the infundibular recess in all patients. A residual vascular component of the pituitary stalk was visualized in 8 patients with isolated GHD (group 1), whereas MRI showed the absence of the pituitary stalk (vascular and neural components) in the remaining 10 patients (group 2), of whom 8 had multiple pituitary hormone deficiency and 2 had isolated GHD. In the short normal children, the mean peak GH response to GHRH (24.8 ± 4.4 µg/L) was significantly lower than that observed after Hex treatment (48.1 ± 4.9 µg/L; P < 0.0001). In the GHD patients of group 2, the mean peak GH responses to GHRH (1.4 ± 0.3 µg/L) and Hex (0.9 ± 0.3 µg/L) were similar and markedly low. In the patients of group 1, the GH responses to GHRH (8.7 ± 1.3 µg/L) and Hex (7.0 ± 1.3 µg/L) were also similar, but were significantly higher that those observed in group 2 (P < 0.0001). In the whole group of patients, a significant correlation was found between the GH peaks after Hex and those after GHRH (r = 0.746; P < 0.0001). In this study we have confirmed that the integrity of the hypothalamic pituitary connections is essential for Hex to express its full GH-releasing activity and that Hex is able to stimulate GH secretion in patients with GHD but with a residual vascular component of the pituitary stalk.

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