S2926 Craniopharyngioma-Induced Hypothalamic Obesity and a Red Herring Known as Binimetinib

Abstract

Introduction: Craniopharyngioma suprasellar extensions damage hypothalamic nuclei resulting in obesity. Binimetinib can reduce the size of craniopharyngiomas by 30%, but also contributes to an increase in adipose and muscle mass. Here is a case of hypothalamic obesity causing weight regain post sleeve gastrectomy (LSG) being successfully treated with a GLP-1 receptor agonist to decrease her weight and Hba1c. Case Description/Methods: A 26-year-old female patient with a BMI of 29 presents to the clinic with a craniopharyngioma-induced mass effect and panhypopituitarism. She had undergone transsphenoidal resections, external beam radiation, chemotherapy, gamma knife, and a ventriculoperitoneal shunt. Due to hypothalamic nucleus injury, she developed hyperphagia with a BMI of 36 kg/m2 and NAFLD-induced cirrhosis. She had a sleeve gastrectomy and reduced her BMI to 26. Her medications include desmopressin, insulin, levothyroxine, hydrocortisone, and recently started on binimetinib. She rapidly regained weight now with a BMI of 29. Abnormal labs include an Hba1c 9.7 g/dL, PT 15.6, INR 1.4, platelets 50, AST 51 u/L and ALT 48 u/L. MRI of her brain with contrast confirmed the suprasellar extension of the craniopharyngioma impinging on the hypothalamus (Figure 1). An esophagram demonstrated the patency of her LSG. After starting 1.8 mg of liraglutide, she lost 20 lbs with a BMI of 27 and dropped her Hba1c to 6.1 g/dL in 4 months. Discussion: Carniopharyngiomas can result in obesity due to damage to regulatory medial hypothalamic nuclei, specifically the arcuate nucleus, paraventricular nucleus, and the ventromedial nucleus. This occurs secondary to tumor mass effects, surgical resection of tumor, or from exposure to radiation >51Gy. This leads to leptin resistance causing hyperphagia, hyperinsulinemia, and decreased energy expenditure causing rapid and stubborn weight gain. A selective inhibitor of MEK, binimetinib, increases the muscle mass and muscle fiber size through inhibition of C26 and IL6, leading to an average muscle gain of 2.3 kg/100 days and 4.2% increase in adipose tissue. Radiation treatment in doses ≥ 54 Gy leads to an increased visceral fat and insulin resistance. Treatment includes a roux-en-y gastric bypass, GLP-1 receptor agonists, and metformin. GLP-1s have also recently shown improvement in NASH resolution. Identification of medication side effects and incorporation of weight loss medications can non-invasively treat hypothalamic obesity weight gain and prevent weight regain.Figure 1.: MRI depicting suprasellar extension of the craniopharyngioma into the hypothalamus.