Tumor-associated hypoglycemia is a rare, but important cause of morbidity in cancer patients. Three different clinical syndromes cause most cancer-related hypoglycemia. The first is production of insulin by an islet tumor. Although primary insulinomas are rare, dedifferentiation and bulky hepatic metastasis of an islet cell carcinoma may be associated with excessive insulin production ( Chapter 249). A second cause of hypoglycemia, insufficient gluconeogenesis to maintain the plasma glucose concentration in the fasting state, is caused by nearly complete replacement of the liver by metastatic tumor. A third cause of hypoglycemia is increased concentrations of insulin-like growth factor type II (IGF-II), a ligand that activates the insulin receptor in large abdominal tumors, most commonly fibrosarcoma, hemangiopericytoma, or hepatoma. This increase appears to be due to the failure to form normal IGF binding protein 3 (IGFBP-3) and the …