PC1196: Obesity and Hyperosmolar Hyperglycemia: The Brain Can Explain

Introduction: The prevalence of obesity and its related comorbidities in children has risen worldwide. Hypothalamic obesity (HO) is a form of obesity commonly seen in patients with hypothalamic dysfunction secondary to tumors, inflammation, or infection. As life expectancy of childhood brain cancer survivors increases, it is imperative to understand the long-term endocrine and metabolic consequences of the disruption of the hypothalamic-pituitary axis.

Case Description: A 13-year-old female, with a history of a non-germinomatous germ cell tumor of the suprasellar region and panhypopituitarism, presented for evaluation of progressive weakness and instability. She was hypothermic, bradycardic, and hypotensive. Labs revealed blood glucose of 589 mg/dL, serum osmolality 387 mOsm/kg, and normal free T4 level. She was diagnosed with hyperglycemic hyperosmolar state, new onset diabetes mellitus, and impending adrenal insufficiency. She had persistent hypotension and bradycardia despite increasing doses of hydrocortisone, consistent with hypothalamic dysfunction. In addition, her chart revealed a weight gain of 32 kg in less than 2 years (BMI increase from -1.9 SD to +1.9 SD). Initial management included steroid stress doses, fluid resuscitation, and insulin. Upon discharge, her metabolic derangements resolved, and she went home on midodrine and metformin.

Discussion: Hypothalamic obesity occurs in patients with insults to the ventromedial hypothalamus and arcuate nucleus, such as tumors, inflammation, or infection, and presents 6-12 months after surgical management of suprasellar masses. It occurs in about 50% of craniopharyngioma survivors. Patients present with rapid weight gain due to hyperphagia, central insulin resistance, decreased sympathetic activity, and low energy expenditure. Hyperphagia might subside, however weight gain progresses due to low resting energy expenditure. Remarkably, HO is the most common example of refractory obesity in childhood, leading to severe atherosclerotic disease, type 2 diabetes mellitus (T2DM), and metabolic syndrome. The patient presented with hyperglycemic hyperosmolar syndrome, which is a life-threatening condition and a severe complication of hyperglycemia. It occurs in about 2% of adolescents with T2DM and is even less common in prepubertal children.

Conclusion: The adage ‘prevention is better than cure’ is apposite to hypothalamic obesity. Tracking growth parameters and monitoring trends in children with CNS injury, particularly brain cancer survivors, can dramatically reduce the chances of illness. Medical professionals should be aware of hypothalamic obesity to intervene early and avoid severe presentations and other comorbidities. Appropriate therapy approaches, including limited caloric intake, increased physical activity, behavior modifications, CNS stimulants, and bariatric surgery, should be strategically implemented. Future studies evaluating novel therapies are necessary for this condition.