Glucagon Secreting Tumors and Glucagonoma Syndrome

Glucagonomas are the functioning neuroendocrine tumors. These arise from pancreatic islet α-cells. These tumors are extremely rare and have an annual incidence of 1 per 20-40 million population 80% of glucagon-expressing tumors are sporadic, and 20% are associated with genetic syndromes such as Multiple Endocrine Neoplasia-type 1. Glucagonoma typically occurs in the distal pancreas, and around 85% are in the body or tail. It tends to be large at the time of diagnosis. Most reported cases of glucagonoma are malignant and about 65-75% patients present with metastatic disease. The liver is usually the first site of metastases, followed by the involvement of peripancreatic lymph nodes. The term Glucagonoma syndrome and glucagonoma are often interchangeably used, but in fact, these are two distinct entities. Glucagonoma syndrome comprises of necrolytic migratory erythema, hyperglucagonemia, diabetes mellitus, anemia, weight loss, glossitis, diarrhea, venous thrombosis and neuropsychiatric disturbances in the presence of a glucagon-producing tumor of the pancreas. Tumors secreting glucagon can occur without the glucagonoma syndrome. The glucagonoma secretion depends on the expression of protein convertase enzyme PC1/3 or PC2 within the tumor itself. As a result of this expression, the clinical manifestations can be variable. The tumor can either present with hyperinsulinemic hypoglycemia in a patient with a previous history of diabetes or with the features of the glucagonoma syndrome. In cases where a tumor is localized surgery is the curative treatment. Reduction of the tumor bulk, removal of the primary by surgery and targeted therapy for the hepatic metastases are the favored approach even when there is the metastasis.