Glucagonoma

At a Glance

Glucagonoma (“sweet” syndrome) is one of the functioning pancreatic neuroendocrine tumors (NETs) that account for 1-3% of all pancreatic NETs. Most cases are sporadic, but 5-17% are associated with multiple endocrine neoplasia type 1 (MEN1). Glucagonomas are typically single, large tumors (average size 6 cm) and are found almost exclusively in the pancreas. The tumors are malignant in 80-90% of cases; however, as for other NETs, the degree of malignancy cannot be predicted by histological appearance. Glucagonomas present with liver metastases in more than 60% of cases

Glucagonomas present clinically with glucose intolerance (40-90%) or diabetes (with associated marked weight loss in 80% of cases), accompanied by the “4D syndrome,” including dermatosis (necrolytic migratory erythema in 70-90% of cases), depression, deep venous thrombosis (30% of cases), and diarrhea. Glucose intolerance in the glucagonoma syndrome may relate to tumor size. Many symptoms are nonspecific, but the presence of necrolytic migratory erythema should prompt evaluation of glucagonoma.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Diagnosis of a glucagonoma requires demonstration of increased plasma glucagon concentrations (usually 500-1000 pg/mL, reference interval <50 pg/mL) in the presence of clinical symptoms. Concentrations are markedly higher than those reported in healthy, fasting subjects (<150 pg/ mL) or in other disorders causing hyperglucagonemia, including diabetes mellitus, burn injury, acute trauma, bacteremia, acute pancreatitis, cirrhosis, Cushing syndrome, and renal and hepatic failure (<500 pg/mL). However, some glucagonoma patients have glucagon concentrations in the “physiologically elevated” range. Therefore, in patients with a classic clinical presentation, a serum glucagon concentration less than 500 pg/mL does not exclude a glucagonoma. Concentrations greater than 1000 pg/mL are virtually diagnostic of the disease.

Serum chromogranin A (CGA) is a nonspecific marker for well-differentiated neuroendocrine tumors that does not distinguish the various tumor subtypes. CGA is usually increased in gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including glucagonomas. CGA concentration correlates with tumor volume and may be useful for staging, prognosis, and monitoring. CGA is elevated in other conditions, including renal insufficiency and severe malabsorption syndrome.

After the diagnosis is made, the glucagonoma must be located and staged with the use of imaging studies (for patients who are surgical candidates).(Table 1)