Endocrine Abstracts

Introduction: Hypothalamic obesity (HyOb) is a rare form of treatment-resistant morbid obesity associated with hypothalamic damage. Its pathophysiology is incompletely understood, and is associated with hyperphagia and hyperinsulinaemia. We sought to compare the physiology of various appetite-regulating hormones in HyOb and ‘simple’ obesity.

Methods: Oral glucose-stimulated serum insulin and plasma oxytocin concentrations, and fasting concentrations of serum leptin, plasma α-MSH, BDNF, ghrelin, AgRP and copeptin were compared by internally validated ELISA in obese (BMI≥+2SDS) and lean children with hypothalamic damage (HyOb and HyLean) to ‘simple’ obese (Ob) and lean controls. Hyperphagia was quantified using the Dykens’ Hyperphagia Questionnaire Score (DHQS).

Results: Patients (49 HyOb, 29 HyLean, 24 Ob, 19 Lean) were of mean age 11.3±3.9 years with a BMI SDS of 2.8±0.6 and 0.4±1.4 in the obese and lean groups respectively. HyOb patients were more hyperphagic compared to Lean controls (median DHQS 24 (17–34) vs 17 (12–21), P=0.04), but not Ob patients (DHQS 24 (18–31), P=1.0), with a strong positive correlation between BMI SDS and DHQS (ρ=0.4, P<0.001) regardless of aetiology. Insulin (R=0.4, P<0.001) and leptin (R=0.8, P<0.001) were positively correlated whilst ghrelin (R=−0.3, P=0.045) and AgRP (R=−0.2, P=0.03) were negatively correlated with BMI SDS. A lower leptin was independently associated with more rapid increases in BMI SDS (β=−0.7 (95% CI −1.3–0.0, P=0.04) at one year. There were no significant differences in hormone concentrations between HyOb and Ob subcohorts. HyLean patients exhibited intermediate insulin and leptin concentrations between HyOb and Lean controls despite normal BMIs, with 3/15 becoming obese within one year.

Conclusion: There are no differences in appetite-regulating hormone concentrations or hyperphagia in HyOb and simple obesity, with anorexigens being increased and orexigens being suppressed. HyLean patients exhibit early hormone dysregulation and remain at risk of HyOb. These data suggest a relationship between baseline leptin concentrations and weight gain requiring further investigation.