Reduced Energy Expenditure and Impaired Feeding-Related Signals But Not High Energy Intake Reinforces Hypothalamic Obesity in Adults with Childhood Onset Craniopharyngioma

• DOI: 10.1210/jc.2010-0993
• Publication Date: 2010-09-09T01:41:59Z
• Authors: Helene Holmer; Gabriella Pozarek; Elisabet Wirfält; Vera Popovic; Bertil Ekman; Jonas Björk; Eva-Marie Erfurth
• Keywords: Adult; Leptin; Male; Adolescent; Hypothalamus; Craniopharyngioma; 03 medical and health sciences; 0302 clinical medicine; Surveys and Questionnaires; Humans; Insulin; Obesity; Age of Onset; Child; 2. Zero hunger; Estrogens; Feeding Behavior; Middle Aged; Ghrelin; 3. Good health; Androgens; Female; Energy Intake; Energy Metabolism

Obesity is a frequent manifestation of hypothalamic damage from a craniopharyngioma (CP). It is not yet clarified whether the obesity is due to alterations in energy expenditure, i.e. basal metabolic rate (BMR) and physical activity, or to increased energy intake (EI).The aim was to investigate whether energy expenditure and EI differed between childhood onset CP patients and matched population controls and whether these measures were related to hypothalamic damage, as tumor growth into the third ventricle (TGTV).Forty-two CP patients (20 women) aged 28 yr (range, 17-57 yr) operated between 1958 and 2000 in the South Medical Region of Sweden (population, 2.5 million) were studied. Body composition, satiety hormones, BMR (indirect calorimetry), physical activity, EI, and attitudes toward eating were assessed. Comparisons were made with matched controls and between patients with (n=25) and without (n=17) TGTV.After adjustment, patients had lower BMR compared to controls (-90 kcal/24 h; P=0.02) and also had lower EI (1778 vs. 2094 kcal/24 h; P=0.008), and the EI/BMR ratio was significantly lower in TGTV patients. Similar dietary macronutrient composition was found, and only significantly higher scales in restricting food intake were recorded in patients. Ghrelin levels were significantly lower in patients, whereas serum insulin and leptin levels were higher (P<0.001), and both ghrelin and insulin correlated significantly to tumor growth. Lower levels of physical activity (P<0.01) were recorded in patients.The major mechanisms that reinforced obesity were hypothalamic damage causing disrupted or impaired sensitivity to feeding-related signals for leptin, insulin, and ghrelin, and reductions in both BMR and physical activity.