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The Effects of Dose, Nutrition, and Age on Hexarelin-Induced Anterior Pituitary Hormone Secretion in Adult Patients on Maintenance Hemodialysis¹

Department of Medicine, University of Sheffield, Clinical Sciences Center (R.C.J., R.J.M.R.), and Sheffield Kidney Institute (A.M.E.N., M.E.W., C.B.B.), Northern General Hospital, Sheffield, United Kingdom S5 7AU; the Department of Medicine, King’s College School of Medicine and Dentistry (J.J.), Denmark Hill, London, United Kingdom SE 9PJ; and the Division of Endocrinology, Department of Internal Medicine, University of Turin, Ospedale Molinette (E.G.), 10126 Torino, Italy

Address all correspondence and requests for reprints to: Dr. R. J. M. Ross, Department of Medicine, University of Sheffield, Clinical Sciences Center, Northern General Hospital, Herries Road, Sheffield, United Kingdom S5 7AU. E-mail: r.j.ross{at}sheffield.ac.uk

Malnutrition is common in chronic renal failure (CRF) and adversely affects prognosis. In view of the anabolic action of GH in CRF, we have studied the effects of hexarelin, a GH secretagogue, on CRF. An iv dose-response study in six 20- to 40-yr-old well nourished hemodialysis (HD) patients was followed by administration of the maximally effective dose to six 20- to 40-yr-old healthy controls, six 20- to 40-yr-old poorly nourished HD patients, and six 50- to 70-yr-old poorly nourished HD patients.

GH secretion (area under the curve over 180 min, mean ± SE) after 2 and 1 µg/kg doses (10.7 ± 4.2 and 8.2 ± 5.2 min/U·L, respectively) was greater than after placebo (0.60 ± 0.11 min/U·L; P < 0.001 and P < 0.05, respectively). The most effective dose (2 µg/kg) produced similar GH secretion (11.4 ± 3.3 min/U·L) in controls. GH secretion in the younger poorly nourished HD group (19.0 ± 4.4 min/U·L) was not significantly different from that in the well nourished 20- to 40-yr-old HD patients (P = 0.06). GH secretion in the older, poorly nourished HD patients (9.4 ± 2.2 min/U·L) was similar to that in the young, poorly nourished group (P = 0.18). ACTH and cortisol concentrations increased in all groups, whereas PRL concentrations were not affected in CRF.

The profound action of hexarelin on GH secretion has been shown to extend to CRF. Trends were evident toward increasing efficacy in malnourished subjects and decreasing efficacy with age. Further studies are required to determine whether the acute actions of hexarelin can be translated into long term anabolic changes.