Paraneoplastic hypoglycemia in a diabetic dog with an insulin growth factor-2-producing mammary carcinoma

A 6-year-old intact female Labrador Retriever had diabetes mellitus, which had been difficult to control with insulin. The dog also had a solid ductal mammary carcinoma with very rapid growth, which was temporally related to onset of hypoglycemia. Eight months after initial diagnosis of diabetes, the dog had a hypoglycemic crisis. Insulin administration was stopped and serum glucose concentration returned to normal. Three months after discontinuing insulin, another hypoglycemic crisis occurred. During subsequent months, serum glucose concentrations remained at life-threatening levels (1.64-2.12 mmol/L, reference interval 4.44-6.66 mmol/L) simultaneously with an increase in the size of the mammary tumor, which reached a diameter of about 16 cm. At the time of surgery for removal of the tumor serum glucose concentration was 2.20 mmol/L and was then monitored every 3 hours after excision of the tumor. The glucose concentration continued to rise and reached 9.99 mmol/L 12 hours after the removal of the mammary tumor. Immunohistochemical staining demonstrated expression of insulin growth factor-2 by tumor cells, which apparently had caused the hypoglycemia during tumor growth even in a diabetic dog. Hyperglycemia associated with diabetes was pronounced after excision of the tumor and had been masked by the paraneoplastic effect of the tumor.