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Ghrelin Has Partial or No Effect on Appetite, Growth Hormone, Prolactin, and Cortisol Release in Patients with Anorexia Nervosa

Department of Neuroendocrinology (D.M., S.P., M.Dj., M.Do., V.P), Institute of Endocrinology, Diabetes, and Metabolic Diseases, Clinical Center of Serbia, 11000 Belgrade, Serbia and Montenegro; Department of Medical Statistics (N.M.), Belgrade School of Medicine, 11000 Belgrade, Serbia and Montenegro; Faculty of Medicine and Complejo Hospitalario (F.F.C.), Endocrine Section, Santiago de Compostela University, 15782 Santiago de Compostela, Spain; and Department of Metabolic Medicine (M.G.), Imperial College, London SW7 2AZ, United Kingdom

Address all correspondence and requests for reprints to: Professor Vera Popovic, Department of Neuroendocrinology, Institute of Endocrinology, 11000 Belgrade, Serbia and Montenegro. E-mail: popver{at}eunet.yu.

Context: Anorexia nervosa (AN) is an eating disorder characterized by self-induced starvation. Gastric hormone ghrelin, potent orexigen, and natural GH secretagogue are increased in AN. Although exogenous ghrelin stimulates appetite, GH, prolactin, and cortisol release in humans, its effects have not been studied, during infusions, in AN patients.

Objective: The objective of the study was to determine the effects of ghrelin on appetite, sleepiness, and neuroendocrine responses in AN patients.

Design: This was an acute interventional study.

Setting: The study was based at a hospital.

Investigated Subjects: Twenty-five young women, including nine patients diagnosed with AN with very low body weight, six AN patients who partially recovered their body weight but were still amenorrheic, and 10 constitutionally thin female subjects, without history of eating disorder, weight loss, with regular menstrual cycles, were included in the study.

Intervention: Each patient received 300-min iv infusion of ghrelin 5 pmol/kg·min and was asked to complete Visual Analog Scale questionnaires hourly.

Main Outcome Measures: Visual Analog Scale scores for appetite and sleepiness, GH, prolactin, and cortisol responses were measured.

Results: At baseline, AN patients had significantly higher ghrelin, GH, and cortisol levels and significantly lower leptin than constitutionally thin subjects. GH responses to ghrelin infusion were blunted in patients with AN. Ghrelin administration did not significantly affect appetite but tended to increase sleepiness in AN patients.

Conclusions: Ghrelin is unlikely to be effective as a single appetite stimulatory treatment for patients with AN. Our results suggest that AN patients are less sensitive to ghrelin in terms of GH response and appetite than healthy controls. Ghrelin effects on sleep need further studies.

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