Introduction: Non-islet cell tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome in which a tumor secretes high molecular weight (“big”) IGF-2, causing hypoglycemia. Big IGF-2 is a product of abnormal processing of IGF-2 precursors with defective gene transcription and expression. Tumors involved are usually of mesenchymal, vascular, or epithelial cell origin and have high tumor burden. We report an unusual case of NICTH in a patient with concomitant spindle cell tumors of the liver and thigh.
Case Description: A 65-year-old male with recently diagnosed malignant melanoma was referred for recurrent hypoglycemia. He was noted to have glucose values of 30 and 37 mg/dL on basic metabolic panels. He was experiencing episodes of confusion, incoherence, and disorientation, which required an emergency department visit. During his office visit, point of care glucose was 44 mg/dL. Patient denied any autonomic symptoms. Upon further evaluation, labs revealed IGF-2 mediated hypoglycemia. Insulin and c-peptide levels were undetectable. He was started on prednisone 20 mg daily with subsequent normalization of glucose levels. CT abdomen/pelvis revealed a 15 cm tumor in his left hepatic lobe. Biopsy showed a malignant spindle cell neoplasm, confirmed to be a solitary fibrous tumor on pathology. After liver mass resection, he was weaned off steroids and hypoglycemia resolved. After surgery, a left thigh mass was discovered, measuring 8x10cm, and was found to also be a spindle cell neoplasm on biopsy. He underwent excision of the thigh mass.
Discussion: NICTH is characterized by increased glucose utilization and inhibition of glucose release from the liver due to tumoral secretion of incompletely processed IGF-2. Diagnosis is confirmed by elevated IGF-2/IGF-1 ratio which was found in our patient. Hepatic or mesenchymal tumors that are remarkable in size (>10 cm) are most commonly identified. Mainstay of treatment is excision of the tumor. Alternate therapies include glucocorticoids when surgery is not possible. This case highlights an atypical presentation of IGF-2 mediated hypoglycemia in the setting of two large spindle cell neoplasms, with resolution of hypoglycemia after resection of the larger liver mass. This case calls attention to despite there being multiple spindle cell tumors, removal of the larger sized tumor might assist in resolution of hypoglycemia.