SUN-328 Non-Islet Cell Tumor-Induced Hypoglycemia in a Patient with IGF-2 Producing Spindle Cell Neoplasm

Abstract

Background: Non-islet cell tumor-induced hypoglycemia is a rare paraneoplastic syndrome with approximately 300 reported cases in the literature. Classically these tumors secrete insulin-like growth factor-2 (IGF-2) to induce hypoglycemia, but the etiology and regulation of the hormone secretion remains poorly understood. We present a case of non-islet cell hypoglycemia from a spindle cell neoplasm of the lung, which appeared to show inconsistent secretion of IGF-2. Clinical case: A 72-year-old, non-diabetic male presented with episodes of altered mental status due to hypoglycemia with unintentional weight loss. Blood glucose was 35 mg/dL upon admission. CT chest showed an 18 cm tumor in the left hemithorax. The patient continued to have hypoglycemia throughout his hospital stay. At a time when the serum glucose was 48 mg/dL, a biochemical work up for hypoglycemia showed C-peptide 0.21 ng/mL (0.78-5.19 ng/mL), proinsulin 1.6 pmol/L (0-10 pmol/L), insulin 0.1 U/mL (1.9-23 U/mL), β-hydroxybutyrate 0.1 mmol/L (0-0.4 mmol/L), and a negative sulfonylurea screen. Given the large lung tumor, IGF hormones were measured: IGF-1 59 ng/mL (36-215 ng/mL), IGF-2 670 ng/mL (333-967 ng/mL). While both were within normal ranges, the IGF-2/IGF-1 ratio was 11.35. Biopsy of the lung mass showed benign spindle cell neoplasm, consistent with solitary fibrous tumor. The patient was diagnosed with paraneoplastic non-insulin mediated hypoglycemia and was transferred to our hospital for resection of the lung mass. During the first 96 hours after transfer, the patient had no hypoglycemic episodes and repeat laboratory values showed IGF-1 of 72 ng/mL, IGF-2 of 162 ng/mL, IGF-2/IGF-1 ratio of 2.25 with a glucose of 119 mg/dL, indicating the secretion of IGF-2 may have been intermittent. However, he later developed recurrent hypoglycemia and underwent resection of the tumor. Pathology showed a malignant solitary fibrous tumor. Blood sugars improved within 2 days after tumor resection and patient did not have further hypoglycemia. Discussion: Literature review shows that tumors causing non-islet cell hypoglycemia are large with one-third located in the chest and two-thirds in the retroperitoneum. They can secrete “big” IGF-2, which can activate insulin receptors to inhibit glucose output from the liver and increase uptake in muscle and adipose tissue leading to hypoglycemia. Interestingly, the IGF-2 level is not always outside the normal range, but a ratio of IGF-2/IGF-1 greater than 10 can be another marker of paraneoplastic hypoglycemia. We believe our case is unique in that during a 48-hour period of intense observation, the patient had no hypoglycemia and the IGF-2 levels and IGF-2/IGF-1 ratio decreased to the normal range. Thus, in patients with suspected tumor-mediated hypoglycemia, the IGF levels may need to be drawn during a hypoglycemic event, much like the workup for insulinoma.