Is there a role for ghrelin and peptide-YY in the pathogenesis of obesity in adults with acquired structural hypothalamic damage?

Context: Obesity is a common sequel to hypothalamic tumors and their treatment, but the underlying mechanisms are not fully established. Objective: Our objective was to evaluate the role of ghrelin and peptide-YY ( PYY) in human hypothalamic obesity. Setting: The study took place at a University Medical Center. Participants: Subjects included 14 adult patients ( six male, eight female) with tumors of the hypothalamic region and 15 healthy controls ( six male and nine female) matched for age, body mass index, and percentage of body fat. Interventions: Plasma ghrelin and total PYY were measured using RIAs after an overnight fast and 15, 30, 60, 120, and 180 min after a mixed meal. Main Outcome Measures: We assessed ghrelin, PYY, and appetite ratings. Results: The fall in ghrelin levels after the test meal was similar in the two groups. There was no statistically significant change postprandially in circulating PYY in the patients with hypothalamic damage. Fasting leptin levels and postprandial insulin responses were also similar in the two groups. Patients with hypothalamic damage reported higher hunger ratings at 3 h after the meal ( P = 0.01) and a stronger desire to eat at 2 h ( P = 0.01) and 3 h ( P = 0.02) compared with the control group. Conclusions: Adult patients with structural hypothalamic damage show impaired satiety, but the changes observed in circulating ghrelin and PYY concentrations in response to a test meal do not indicate a central role for these gut hormones in the control of appetite and the pathogenesis of obesity in these patients.