Pancreatic neuroendocrine tumors: glucagonoma
What is a glucagonoma?
About 5-10% of pancreatic neuroendocrine tumors are "glucagonomas," tumors that produce an inappropriate abundance of the hormone glucagon. It is estimated that one person out of 20 million will develop a glucagonoma each year. Glucagon is a protein segment that is produced by the "α(alpha) cells" of the "islets of Langerhans," the endocrine elements of the pancreas. The role of glucagon is to balance the effects of insulin, keeping blood sugar levels normal. Patients with glucagonomas are classically 40-70 years of age, with no significant preference for gender. Most of these tumors develop spontaneously in patients with no family history of endocrine tumors, although a few may occur in the setting of the MEN1 syndrome. These tumors originate in the pancreas, usually in the body or tail of the gland.
Figure 1: Necrolytic migratory erythema. McGevna L, Tavakkol Z. Necrolytic migratory erythema. N Engl J Med 2010;362 (1):e1. Copyright © 2010 Massachusetts Medical Society. All rights reserved.
Glucagonomas are characterized by the "4 D's": Diabetes, Dermatitis (rash), Deep vein thrombosis (e.g., blood clot in the legs), and Depression, although not all of these findings may co-exist in each patient. Most patients (75%-95%) develop diabetes. About two-thirds of patients have a combination of weight loss and a classic skin rash that is termed "necrolytic migratory erythema." (Figure 1)
Figure 2: Cheilitis. McGevna L, Tavakkol Z. Necrolytic migratory erythema. N Engl J Med 2010;362 (1):e1. Copyright © 2010 Massachusetts Medical Society. All rights reserved.
The rash develops in about 70% of patients, often before other symptoms arise. The skin condition commonly begins as red lumps and plaques in the perineum (the area between the genitals and anus), groins, or abdomen, and it may migrate to the extremities. The plaques broaden and then connect over 1-2 weeks. The center eventually clears and leaves bronze-colored thickened skin, while the edges of the skin changes become blistered and crusted. The rash is usually itchy and painful. Most patients also experience "cheilitis," an inflammation of the lips associated with redness and cracking at the corners of the mouth. (Figure 2)
A diagnosis of a glucagonoma is established with a significant elevation of glucagon levels in the blood. Other common laboratory abnormalities include elevated blood sugar and chromogranin A values, and anemia (decreased red blood cells). Symptoms of glucagonomas are often vague and may be evident for years before a diagnosis is secured. Consequently, the tumors may be relatively large (an average diameter of 4-6cm) when they are discovered.