SAT-054 Gigantism and Hypothalamic Obesity: Rare Endocrine Manifestations of Neurofibromatosis Type 1

Abstract

Background: Neurofibromatosis type 1 (NF-1) is a heritable, autosomal dominant, multisystem disorder caused by mutations or deletions in NF1, with approximately 30-50% of cases arising from de novo mutations. In the pediatric population, growth hormone deficiency is among one of the most commonly described endocrine sequelae, although aberrations of pubertal development are also commonly seen. Clinical Case: A 3-year-old female, who was clinically diagnosed with NF-1 at the age of 4 months based on the presence of multiple café-au-lait macules, underwent screening MRI, which noted a left optic glioma and a hypothalamic mass favored to represent a hypothalamic glioma. Review of her growth chart showed a height much greater than the 99th percentile, with an increase in height velocity beginning 1 year prior. Weight was also noted to be much greater than the 99th percentile, with an increase in weight gain coinciding with the timing of alterations in linear growth. Mid-parental height is at the 95th percentile, and the patient’s height had tracked between the 86th and the 99th percentiles until age 2 years. Weight had tracked between the 68th and the 95th percentiles during that period. Initial laboratory evaluation showed an IGF-1 of 644 ng/mL (26-164 ng/mL). Gonadotropins were prepubertal; prolactin and thyroid studies were normal. ACTH stimulation demonstrated a rise in serum cortisol from 6.8 mcg/dL to 30.2 mcg/dL at 60 minutes. Growth hormone failed to suppress following an oral glucose load with a baseline GH of 4.4 ng/mL and values of 3.7, 6.5, 6.8, and 9.0 ng/mL at time +30, +60, +90, and +120 minutes respectively. Leuprolide stimulation did not show significant rises in gonadotropins. Bone age was advanced by more than 1 year. The patient was started on subcutaneous octreotide with a decrease in IGF-1 to 258 ng/mL after 1 month of therapy. On treatment, linear growth velocity slowed with no interval height gain over the initial 1-month period; however, the patient’s weight continued to increase with a gain of 1.8 kg. Parents additionally reported hyperphagia, which prompted concern for hypothalamic obesity in the setting of her known hypothalamic mass. Thyroid function remained normal on somatostatin therapy. To date, there has been no concern for diabetes insipidus. Conclusion: Growth hormone excess may rarely complicate a diagnosis of NF-1 in the setting of intracranial gliomas. Increased height velocity and/or tall stature for family should raise clinical suspicion and prompt evaluation. Hyperphagia and significant increases in weight in the setting of hypothalamic gliomas in patients with NF-1 should raise suspicion for hypothalamic obesity and prompt lifestyle modifications to curb ongoing weight gain.