Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2021) 78 CME3.2 | DOI: 10.1530/endoabs.78.CME3.2

BSPED2021 CME Training Day Sessions Session 3 (2 abstracts)

Hypothalamic obesity post cancer treatment - optimising outcomes

Robert Lustig


UCSF, San Francisco, USA


The hypothalamus integrates the neuroendocrine control of numerous hormonal systems. Energy balance is regulated by a complex neuroendocrine feedback loop, in which the ventromedial hypothalamus (VMH) responds peripheral neural and hormonal afferent signals of satiety and energy reserve (through insulin and leptin), interprets these as anorexigenic (a-MSH) or orexigenic (NPY, AgRP) signals (through the melanocortin-4 receptor), and then directs efferent autonomic signals (sympathetic or vagal) to effect energy storage or expenditure. Damage to this hypothalamic control system results in a syndrome of intractable weight gain, termed ‘hypothalamic obesity’. A retrospective analysis of weight gain in children with brain tumors established that a younger age at diagnosis, hypothalamic tumor location and degree of damage, tumor histology (particularly those such as craniopharyngioma), dose of radiation to the VMH (> 51 Gy), and presence of endocrinopathy as risk factors for the development of future obesity. These results verify that hypothalamic damage, due to tumor, surgery, or radiation, is the primary cause of obesity in survivors of childhood brain tumors. The pathogenesis of hypothalamic obesity is analogous to an animal model in which the VMH is destroyed or deafferented resulting in anatomic leptin resistance. The brain senses starvation (despite excess adiposity); in response, the VMH decreases sympathetic innervation in order to conserve energy (decreased locomotion), and increases vagal innervation of the periphery to store more energy in adipose tissue (increased appetite). One other result of this vagal innervation is increased activation of the b-cell, resulting in insulin hypersecretion in response to glucose, which promotes partitioning of energy substrate into adipose tissue. Numerous approaches have been attempted to treat this disorder, including b-cell insulin suppression (octreotide), GLP-1 agonist (exenatide), and bariatric surgery (roux-en-Y, vagotomy), all with variable and inconsistent efficacy. More recently, a triple serotonin-dopamine-norepinephrine reuptake inhibitor (tesofensine) has been approved in adults.

Volume 78

48th Meeting of the British Society for Paediatric Endocrinology and Diabetes

Online, Virtual
24 Nov 2021 - 26 Nov 2021

British Society for Paediatric Endocrinology and Diabetes 

Browse other volumes

Article tools

My recent searches

No recent searches.