The homeostatic control of energy balance is tightly regulated. Appetite and energy expenditure regulation involves neurons in the hypothalamus as well as other brain regions, including the limbic system, amygdala and the brainstem. Hypothalamic obesity is a well-recognized consequence of lesions such as craniopharyngiomas and other tumors in the hypothalamic region. Less known is obesity related to tumors in other brain regions. The child presented at 14 years of age with fainting episodes associated with severe obstructive sleep apnea and hypophonia. He was found to have a heterogeneous mass in the medulla extending inferiorly past the foramen of magnum into the cervical spinal cord, measuring 3.3×3.3×5.6 cm; lateral, third and fourth ventricles were diffusely enlarged. Surgical resection ensued and this was found to be a ganglioglioma, positive for a BRAF mutation. He was started on a tyrosine kinase inhibitor, vemurafenib. In monitoring for adverse effects of vemurafenib, he was found to have glucosuria. He had a HbA1C of 6.6%, and was referred for endocrine evaluation. Medical history was significant for early onset morbid obesity, with normal birth weight of 3.6 kg but obese by 2 years of age. While he did not have true hyperphagia except for the brief period that he was on dexamethasone just after tumor diagnosis, he described long-standing issues of obsession with food and nighttime food cravings. He maintained a high level of physical activity, 1 hour per day at least 5 days/week. He denied polyuria or nocturia but did have polydipsia. On examination, his BMI was 44 kg/m2, blood pressure 136/73. General appearance was that of a severely obese young man. Pertinent findings include severe acanthosis nigricans, mid-puberty. Diabetes autoantibodies were negative; random insulin level was 195 mcIU/ml. Brain imaging revealed the site of the tumor and subsequent resection bed involved the area encompassing the nucleus tractus solitarius (NTS). He was started on metformin, with improvement in his HbA1C but no change in weight or appetite. He was then started on once-weekly long-acting exenatide; HbA1C became normal at 5.0%, BMI z-score decreased by 0.12 within 3 months, and food preoccupation has resolved. This case represents obesity and diabetes in a child with a brainstem lesion involving the region of the NTS, a site known to be involved in body weight regulation. Treatment with a GLP-1 agonist was effective for diabetes as well as eating behaviors, and weight stabilized.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology