Insulin Autoimmune Syndrome Developing after Surgery for Ileal Invasion of Rectal Cancer in a Patient with the HLA-DRB1^*0406, B1^*04051 Genotype

Abstract

A 73-year-old female was admitted to our hospital for the treatment of repetitive hypoglycemic episodes. Three years before admission, she was diagnosed with advanced rectal cancer with retroperitoneal and peritoneal invasion. She received two partial courses of chemotherapy following resection of the rectal cancer and subsequent alleviation of ileus. The regimen included fluorouracil, its prodrug and calcium folinate. Two weeks before the current admission, the patient underwent resection of the retroperitoneal mass and a portion of the ileum. Seven days after the surgery, she lapsed into a hypoglycemic coma (blood glucose level: 22 mg/dl). Hypoglycemic episodes recurred thereafter, even after meals. No drugs containing a sulfhydryl group were administered. The plasma glucose and insulin levels were 45 mg/dl and 305 μIU/ml, respectively, during one hypoglycemic episode. Insulin autoantibodies were positive for both IgG and IgE. Therefore, the recurrent hypoglycemic episodes were diagnosed as insulin autoimmune syndrome (IAS). The patient carried both susceptible (DRB1^*0406) and resistant (DRB1^*04051) HLA class II genotypes to IAS. The hypoglycemic attacks subsided spontaneously within six months. We speculate that the ileal surgery triggered the development of IAS by disrupting the patient's normal intestinal immunity.