ESPE Abstracts (2015) 84 P-2-339

Hypothalamic Obesity, Hyperphagia, and Hyperinsulinaemia: Time for a Paradigm Shift in Assumptions?

Hoong-Wei Gana,b, Clare Leesonb, Helen Aitkenheadb, Helen Spoudeasb & Mehul Dattania,b

aUCL Institute of Child Health, London, UK; bGreat Ormond Street Hospital for Children NHS Foundation Trust, London, UK

Background: Hypothalamic obesity (HyOb) is a syndrome of inexorable, treatment-resistant obesity seen after congenital (e.g. septo-optic dysplasia (SOD)) or acquired (e.g. tumour-related) hypothalamic damage, often co-existing with hyperphagia, panhypopituitarism, autism, sleep, and temperature dysregulation. Its pathophysiology is poorly understood but hyperphagia and excess caloric intake may be less important than previously thought.

Objective and hypotheses: To determine the frequency of hyperphagia and its association with hyperinsulinaemia in HyOb in comparison to common obesity.

Method: Multiway case-control comparison of Dykens Hyperphagia Questionnaire Scores (DHQS), 2-h oral glucose tolerance test (OGTT)-stimulated plasma glucose and insulin indices in 49 obese (SOD 14, hypothalamic tumours 15, and common obesity 20) vs 29 lean (SOD 13, hypothalamic tumours 3, and controls 13) children.

Results: Patients were of median age 12.0 years (range 2.5–19.6, 50% females), with a median BMI +2.8 (+2.0 to +3.8) and +0.8 (−2.9 to +1.9) SDS in obese and lean groups, respectively, with no significant differences between SOD, tumour or control subgroups. DHQS and insulin-related indices were similar between patients with HyOb and common obesity (P>0.05). Of the DHQS sub-scores, only hyperphagic drive was correlated with BMI SDS (Spearman’s ρ=0.292, P<0.05), whilst Hyperphagic Drive, overall DHQS and BMI SDS correlated with fasting insulin, HOMA-IR, and the Matsuda index (all P≤0.01). 5/38 obese patients (13.2%) fulfilled WHO criteria for impaired glucose tolerance (IGT), whilst one tumour survivor (2.6%) had frank type 2 diabetes (T2DM). Autism (P=0.001), learning difficulties (P<0.05), and sleep disturbances (P<0.001) were frequent in SOD and tumour patients but were not significantly associated with DHQS or BMI SDS.

Conclusion: Hyperphagia is not, as commonly perceived, unique to HyOb or the hypothalamic syndrome, but its presence increases BMI and insulin insensitivity. Hyperinsulinaemia per se does not explain the pathophysiology and treatment-resistance of HyOb. IGT and T2DM are becoming increasingly prevalent in children with obesity from any cause.

Funding: This work was supported by the BUPA Cromwell Hospital (grant number 1DAAG), Great Ormond Street Hospital Children’s Charity (grant number 1DAAJ), Great Ormond Street Hospital Biomedical Research Centre (grant number 1DAAN), and the British Society of Paediatric Endocrinology (grant number 1DAAP).

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