Non–Islet-Cell Tumor Induced Hypoglycemia in Patients With Advanced Gastrointestinal Stromal Tumor Possibly Worsened By Imatinib

Numerous causes for hypoglycemia exist including hepatic, renal, or adrenal dysfunction, toxins such as alcohol and drugs, congestive heart failure, sepsis, malnutrition, prolonged exercise, hypopituitarism, autoimmune disorders, and increased insulin production by islet-cell tumors or small-cell carcinomas. Next to these causes, hypoglycemic episodes in cancer patients can be caused by non-islet-cell tumor induced hypoglycemia (NICTH). NICTH results from overproduction of incompletely processed forms of proinsulin-like growth factor-II (pro-IGF-II), which may lead to an excessive stimulation of the insulin receptors at various target tissues. NICTH is predominantly encountered in patients with large mesenchymal tumors, including gastrointestinal stromal tumors (GISTs), 1-4 but epithelial tumors have also been reported to be associated with NICTH. We describe two GIST patients with hypoglycemia related to a raised concentration of pro-IGF-II; in one case imatinib (Gleevec; Novartis Pharma, Basel, Switzerland) is likely to have contributed to the severity of the hypoglycemia.