SUN-285 Autoimmune Brain Disease Associated with Severe Obesity and Progressive Hypothalamic and Pituitary Dysfunction

Abstract

Hypothalamic dysfunction can lead to rapidly progressive severe obesity, which has been observed in the pediatric age group after an insult to the hypothalamus, such as tumors, trauma, inflammatory disease, or surgical treatment. We present here the progression of hypothalamic and pituitary dysfunction associated with severe obesity due to a primary inflammatory process in the brain and the therapeutic effect of immunosuppressants and aggressive weight management. The patient presented with new onset focal epilepsy refractory to anti-epileptic medications at age 6 years 8 months (illness month 0) at 23.6 kg and BMI-Z of -0.07. At month 2, he had a 2 kg weight gain thought to be due to anti-epileptics. At month 7 (35.6 kg, BMI-Z 2.10), he had gained 12 kg, precocious puberty was noted and he was started on a GnRH agonist. He was also having behavioral changes, including decreased cognition, hyperphagia, and difficulty sleeping. At month 10 (45.5 kg, BMI-Z 2.57), a brain biopsy showing lymphocytic infiltration confirmed the primary diagnosis of autoimmune brain disease as the cause of hypothalamic dysfunction and seizure disorder; therefore, a methylprednisone burst was started at month 11 (48.2 kg, BMI-Z 2.63), followed by monthly cyclophosphamide and a 7 month oral prednisone taper. By month 12, he developed respiratory symptoms requiring hospital admission. Indirect calorimetry revealed resting energy expenditure of 802 kcal/day; topiramate was initiated, and he was discharged home on a 1200 kcal/day diet. At month 13, central hypothyroidism was diagnosed (TSH 0.34, free T4 0.61) and levothyroxine started. At month 13.5, he was at maximum weight (60.1 kg, BMI-Z 2.88, 36.5 kg total gain) and he again had worsened respiratory distress requiring admission; at this time phentermine was started, CPAP was initiated, diet was decreased to 1000 kcal/day and changed to ketogenic. From months 13 to 18, he had his first weight reduction of 5.5 kg with a noted decrease in appetite. He was continued on monthly cyclophosphamide and IV methylprednisone through month 16 when a brain MRI was showed improvement; cyclophosphamide discontinued and prednisone weaned. Adrenal insufficiency was found, although it was unclear if iatrogenic or central. By month 19 (57.1 kg, BMI-Z 2.73) off immunosuppression, he had worsened hyperphagia and seizure activity and decreased cognitive abilities, possibly suggestive of a flare of the brain inflammation; thus aggressive immunosuppression was reinitiated. This case demonstrates severe obesity related to progressive hypothalamic and pituitary dysfunction secondary to inflammatory brain disease. The management of weight gain for this patient remains difficult due to hyperphagia related to behavior dysregulation and low basal metabolic rate, in addition to continued need for immunosuppressants to treat the underlying autoimmune condition. Funding: NIDDK K23