Glucagonoma

Glucagonoma is a very rare tumor of the alpha cells of the pancreas that results in the overproduction of the hormone glucagon. Typically associated with a rash called necrolytic migratory erythema, weight loss, and mild diabetes mellitus, most people with glucagonoma contract it spontaneously.<ref name=":02">Template:Citation</ref> However, about 10% of cases are associated with multiple endocrine neoplasia type 1 (MEN-1) syndrome.<ref name=":02"/>

Causes

Although the cause of glucagonoma is unknown, some genetic factors may lead to the condition. A family history of multiple endocrine neoplasia type 1 (MEN1) is a risk factor.<ref name=":02"/> Additionally, those with Mahvash disease have an increased risk for glucagonoma, as the glucagon receptor gene (GCGR) is mutated.<ref name=":22"/>

Mechanism

Glucagonoma results from the overproduction of glucagon, a peptide hormone located in the pancreatic alpha cells.<ref name=":42">Template:Cite journal</ref> Classic symptoms include, but are not limited to, necrolytic migratory erythema (NME), diabetes mellitus, and weight loss.<ref name=":42"/> NME presents in about 70% of cases of glucagonoma,<ref name="pmid1553892922">Template:Cite journal</ref> and is characterized by erythematous lesions over the distal extremities and the groin area.<ref name=":42"/> NME has occasionally been observed in people who do not have glucagonoma.<ref name=":22" /> People who develop glucagonoma from Mahvash disease also do not develop NME, implying that working glucagon receptors are needed in order for NME to be present in a person.<ref name=":42"/> Weight loss, the most commonly associated effect with glucagonoma, results from the glucagon hormone, which prevents the uptake of glucose by somatic cells.<ref name=":42"/> Diabetes is not present in all cases of glucagonoma,<ref name=":42"/> but does frequently result from the insulin and glucagon imbalance.<ref>Template:Cite journal</ref>

Diagnosis

The presence of glucagonoma syndrome, the symptoms that accompany the pancreatic tumor, as well as elevated levels of glucagon in the blood, are what is used to diagnose glucagonoma.<ref name=":32">Template:Cite journal</ref> When a person presents with a blood glucagon concentration greater than 500 mg/mL along with the glucagonoma syndrome, a diagnosis can be established.<ref name=":42"/> Not all cases of hyperglucagonemia will lead to a diagnosis of glucagonoma.<ref name=":42" /> Elevated blood levels of glucagon are associated with other disorders like pancreatitis and kidney failure.<ref name=":42" />

About 60% of people diagnosed with glucagonoma are women.<ref name=":5">Template:Cite journal</ref> Most of those that are diagnosed are between 45–60 years of age.<ref name=":5" />

Treatment

People who are diagnosed with sporadic glucagonoma often have an increased mortality rate compared to those with MEN1, as the latter group will go to the doctor for periodic visits.<ref name="pmid1553892922"/> People whose tumor have metastasized cannot easily be treated as the tumor is resistant to chemotherapy.<ref name="pmid1553892922"/> The only curative therapy for glucagonoma is surgery, and even this is not always successful.<ref name=":32"/><ref name="pmid1553892922"/>

Heightened glucagon secretion can be treated with the administration of octreotide, a somatostatin analog, which inhibits the release of glucagon.<ref>Template:Cite journal</ref> Doxorubicin and streptozotocin have also been used successfully to selectively damage alpha cells of the pancreatic islets. These do not destroy the tumor, but help to minimize progression of symptoms.<ref>Template:Cite web</ref>

History

Fewer than 251 cases of glucagonoma have been described in the literature since their first description by Becker in 1942. Because of its rarity (fewer than one in 20 million worldwide), long-term survival rates remain unknown. Glucagonoma accounts for approximately 1% of neuroendocrine tumors, although this may be an underestimate given that glucagonoma is associated with non-specific symptoms.<ref name=":22">Template:Cite web</ref>