SAT-254 Combination of Octreotide and Dexamphetamine to Control Weight Gain in Pediatric Patients with Hypothalamic Obesity

Abstract

Abstract Hypothalamic obesity (HO) is a devastating complication, that occurs in patients with hypothalamic damage. It is characterized by polyphagia, and adynamia leading to a severe form of obesity, which is intractable to caloric restriction or lifestyle modification. HO is suggested to be a result of hypothalamic damage, leading to declined efferent sympathetic activity and reduced energy expenditure as well as raised vagal activity resulting in increased insulin secretion and adipogenesis. Trials of both single octreotide (OCT) and single dexamphetamin (DEX) were conducted and showed some effect to weight control. However no trial of combined OCT and DEX (OCT/DEX) was reported until now. A monocentric retrospective cohort study was conducted. All patients, who were diagnosed to suffer from HO in between January 1st, 2010 and September 30st, 2018, were included (n =11; mean age: 14.7 years; mean weight 104.6 +/- 11.6 kg; body mass index (BMI), 36.4 +/- 1.3 kg/m2). All subjects were suffering from a brain tumor (craniopharyngioma: 6/11; germinoma 3/11; astrocytoma 1/11) followed by neurosurgery and/or irradiation. Panhypopituitarism and type 2 diabetes, which was verified in all subjects, was replaced in usual hormone dosages and metformin, respectively. A specialized diet and raised physical activity was recommended. Six subjects received a combination of OCT (15-20 µg/kg/d) and DEX (5-15 mg/d) for at least 36 months, when the observation was stopped. Seven patients were not treated with this combination. In the first 12 months patients with OCT/DEX the Δweight (mean ± sem) was -0.7 ± 0.5 kg vs. 9.4 ± 1.6 kg for untreated patients. After 36 months with OCT/DEX the Δweight was +8.2 ± 0.6 kg vs. 27.1 ± 4.7 kg for the untreated group, and ΔBMI was +0.5 ± 0.4 vs. +6.8 ± 3.4 kg/m2, respectively. With oGTT we observed Δinsulin response (peak−basal) of -397± 244 pmol/L and +188±201 pmol/L in the treated and untreated patient groups, respectively. Parents reported marked improvement in physical activity of patients on OCT/DEX, but not in the untreated group. Complications and adverse events were mostly mild and self-limited. One patient with OCT/DEX developed gallstones 32 months after start, when OCT was stopped. Three patients without OCT/DEX leg died probably due to sleep apnea by known obesity-hypoventilation syndrome. Regarding the hypothalamus being extremely sensitive to irradiation and neurosurgical intervention, we consider a brain-saving surgery remains the best treatment. We combined both OCT and DEX in attempt to reduce hyperinsulinemia and increase patients` activity level. We report about a significant lower weight gain in patients treated with OCT/DEX than in the comparative cohort and therefore suggest OCT/DEX as an effective combination to control weight in patients with HO due to hypothalamic damage. Further prospective controlled studies are required to confirm this observation.