(9.12) A Novel Use of Alpelisib to Mitigate Recurrent Hypoglycemia in an Adult with Nonislet Cell Tumor Hypoglycemia

Nonislet Cell Tumor Hypoglycemia (NICTH) is a rare complication due to the overproduction of incompletely processed insulin-like growth factor-2 (IGF-2). The challenge in treatment arises when a surgical cure is not feasible. Non-surgical treatment modalities can be targeted directly at the tumor (embolization, radiotherapy, and chemotherapy) or at reducing hypoglycemia (dietary modification, glucocorticoids, and recombinant growth hormone). We report a case where the novel use of Alpelisib, a phosphatidylinositol-3-kinase (PI3K) inhibitor, effectively reduced hypoglycemia.


 





Case(s) Description :

A 35-year-old man was found unresponsive. His history was notable for metastatic solitary fibrous tumor (brain primary) with hepatic, pulmonary, and osseous metastases. Prior cancer therapy included multiple brain surgeries, gamma knife radiation, hepatic tumor embolization, and several lines of systemic chemotherapy. On presentation, his venous glucose was 29 mg/dL, IGF-1 41 ng/ml (reference range 82-242), IGF-2 84 ng/mL (180-580), beta-hydroxybutyrate 0.39 mmol/L (< 0.27), and a hypoglycemic agent screen was negative. Insulin, proinsulin, insulin antibody, and C-peptide levels were undetectable. Following treatment with glucagon his venous glucose increased by >35 mg/dL and his confusion resolved. These findings were consistent with NICTH. He was initiated on prednisolone, and the dose was increased to 15 mg twice daily. He also consumed a high carbohydrate diet every 2-4 hours, including overnight. Despite these measures, he continued to have frequent hypoglycemic episodes. Therefore, we initiated off-label Alpelisib with escalation to 50 mg three times per day. With use of Alpelisib, the frequency of hypoglycemia was reduced and he was able to taper off prednisolone.

Discussion :

Alpelisib is an oral medication used to treat PI3KCA-mutated advanced or metastatic breast cancer and PIK3CA-related overgrowth spectrum diseases. Hyperglycemia is a common adverse effect of Alpelisib. Alpelisib causes hyperglycemia by directly interfering with the insulin signal transduction pathway. When insulin binds its receptor, activation of PI3K ultimately facilitates the movement of GLUT 4-containing vesicles to the cell membrane. By blocking PI3K, insulin action is inhibited. In our case, Alpelisib was used successfully as a novel therapy to mitigate recurrent hypoglycemia. The effect of Alpelisib on his solitary fibrous tumor burden itself is not yet known. In summary, Alpelisib should be considered as a treatment option for patients with NICTH who have hypoglycemia that is refractory to conventional management strategies.