Abstract
Introduction: Insulin like growth factor (IGF-2) mediated hypoglycemia secondary to solitary fibrous tumor (SFT), also known as Doege-Potter syndrome is a rare paraneoplastic syndrome. The tumor cells produce large amounts of high molecular weight IGF 2 precursor protein called “big IGF-2” which binds to insulin and IGF receptors in liver, muscle and other peripheral tissues. This causes reduced gluconeogenesis and increased uptake of glucose by the muscle and other tissues leading to hypoglycemia. Big IGF-2 also exerts central negative feedback of growth hormone causing reduction of IGF-I production. Most SFTs are benign and localized (approximately 78-88%). As a result, tumor excision alone would often lead to resolution of the hypoglycemia. We present a case of metastatic SFT with multiple metastasis managed with oral prednisone.
Clinical Case: A 44-year-old man with metastatic SFT presented with bilateral humeral fractures. He has known metastatic disease to the brain, lung, liver, bony lytic lesions over a course of eleven years. It has progressed despite multiple chemotherapy and radiation therapies. Prior to admission, he had multiple syncopal episodes associated with fasting hypoglycemia. He reported capillary blood glucose values ranging between 30-50 mg/dl during these episodes which would improve after drinking juice or eating candy. There was no history of diabetes mellitus or use of oral hypoglycemic agents or insulin. On admission, he had a capillary blood glucose value of less than 20 mg/dl, which was confirmed by a serum glucose value of 18 mg/dl on basic metabolic panel. His renal, liver and thyroid function tests were normal. Significant labs include: serum glucose 17 mg/dl, C-peptide <0.10 ng/ml (n: 1-4 ng/ml), serum insulin <1.6 Uu/ml (n: <20 Uu/ml), beta-hydroxybutyrate <0.2 mmol/L (n: <0.3), cortisol 10.8 ug/dl(n: 5-15 ug/dl) glucagon 6 pg/ml(ref 8-57 pg/ml), insulin-like growth factor-1 (IGF 1) 20 ng/ml (n: 52-328), and IGF-2 level 380 ng/ml (267-616 ng/ml), improvement in blood glucose from 46 to 111 mg/dl after 1-gram glucagon administration. The IGF-2/IGF-1 ratio of 19 confirmed our clinical suspicion of non-islet cell tumor hypoglycemia (NICTH). He was started on prednisone 20 mg twice daily with marked improvement in hypoglycemia.
Conclusion: NICTH is a rare cause of hypoglycemia and should be considered in the differential while evaluating hypoglycemia in malignancy. For diagnosing NICTH, assays for big IGF-II are not commercially available. However, the IGF-II:IGF-I ratio is considered to be a surrogate marker of big IGFII concentration. The normal ratio is 3 and ratio >10 is diagnostic of NICTH. In cases like ours where tumor resection is not possible, glucocorticoids are most effective in management of hypoglycemia by inhibiting big IGF2 production and stimulating gluconeogenesis.
Late Onset of Non-islet Cell Tumor Hypoglycemia Managed via Multidisciplinary Treatment in a Patient with a Solitary Fibrous Tumor
