A Case of Non-Islet Cell Tumor Hypoglycemia Due to Gastrointestinal Stromal Tumor in a Patient with Neurofibromatosis

Introduction: Non-Islet Cell Tumor Hypoglycemia (NICTH) is a rare but serious complication of malignancy leading to recurrent episodes of severe hypoglycemia and impaired quality of life. It is commonly due to mesenchymal and epithelial tumors. The underlying mechanism is overproduction of insulin-like growth factor-2 (IGF-2) and its precursors that activate the insulin receptor. Patients with Neurofibromatosis type 1 (NF-1) have a high incidence of GISTs. GISTs are rare mesenchymal tumors. This case describes a case of NICTH due to GIST with hypoglycemia as the first presentation.
Case Description: A 57-year-old man with NF-1 was evaluated for frequent severe hypoglycemic episodes including seizures and loss of consciousness. He also reported reduced appetite, weight loss and melena. He denied history of diabetes mellitus, alcohol abuse or illegal drug abuse. Initial biochemical assessment showed anemia with normal liver, renal and thyroid profile with normal cortisol level. Further laboratory assessment during an episode of hypoglycemia with plasma glucose of 35 mg/dL revealed very low levels of insulin, C-peptide and beta-hydroxybutyrate. IGF-1 was suppressed. Unfortunately, IGF-2 level could not be done due to unavailability in Sri Lankan settings. He had a dramatic rise in blood glucose level with glucagon administration, suggesting the presence of insulin like substance. Computed Tomography (CT) of the chest, abdomen and pelvis showed multiple large liver lesions and a large enhancing paraaortic lesion. Biopsy of the liver lesion with immune staining confirmed metastatic GIST. He was started on imatinib. He is treated with prednisolone for NICTH with good response in hypoglycemia.
Conclusion: In patients with an underlying malignancy, if clinical and biochemical findings are compelling for NICTH, additional assessment with IGF-2 levels is not usually necessary to make the diagnosis. The Glucagon challenge test is a supportive investigation for the diagnosis. Glucocorticoids might be effective to control hypoglycemia and improve quality of life if tumor can’t be surgically treated