Glucagonoma is a very rare

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

of the pancreatic alpha cells that results in the overproduction of the

hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are require ...

, glucagon. Typically associated with a rash called

necrolytic migratory erythema Necrolytic migratory erythema is a red, blistering rash that spreads across the skin. It particularly affects the skin around the mouth and distal extremities; but may also be found on the lower abdomen, buttocks, perineum, and groin. It is stron ...

, weight loss, and mild diabetes mellitus, most people with glucagonoma contract it spontaneously. However, about 10% of cases are associated with

multiple endocrine neoplasia type 1 Multiple endocrine neoplasia type 1 (MEN-1) is one of a group of disorders, the multiple endocrine neoplasias, that affect the endocrine system through development of neoplastic lesions in pituitary, parathyroid gland and pancreas. It was first d ...

(MEN-1) syndrome.

Causes

Although the cause of glucagonoma is unknown, some genetic factors may lead to the condition. A family history of

(MEN1) is a risk factor. Additionally, those with

Mahvash disease Mahvash disease is an autosomal recessive, hereditary pancreatic neuroendocrine tumor syndrome. The genetic defect that causes Mahvash disease is biallelic inactivating mutations of the glucagon receptor gene (''GCGR''). Mahvash disease was discov ...

have an increased risk for glucagonoma, as the

glucagon receptor The glucagon receptor is a 62 kDa protein that is activated by glucagon and is a member of the class B G-protein coupled family of receptors, coupled to G alpha i, Gs and to a lesser extent G alpha q. Stimulation of the receptor results in the ...

gene (GCGR) is mutated.

Mechanism

Glucagonoma results from the overproduction of glucagon, a

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. ...

hormone located in the pancreatic alpha cells. Classic symptoms include, but are not limited to,

(NME), diabetes mellitus, and weight loss. NME presents in about 70% of cases of glucagonoma, and is characterized by erythematous lesions over the distal extremities and the groin area. NME has occasionally been observed in people who do not have glucagonoma. 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. Weight loss, the most commonly associated effect with glucagonoma, results from the glucagon hormone, which prevents the uptake of glucose by somatic cells. Diabetes is not present in all cases of glucagonoma, but does frequently result from the insulin and glucagon imbalance.

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. When a person presents with a blood glucagon concentration greater than 500 mg/mL along with the glucagonoma syndrome, a diagnosis can be established. It is important to note that not all cases of hyperglucagonemia will lead to a diagnosis of glucagonoma. Elevated blood levels of glucagon are associated with other disorders like pancreatitis and

kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

. About 60% of people diagnosed with glucagonoma are women. Most of those that are diagnosed are between 45–60 years of age.

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. People whose tumor have metastasized cannot easily be treated as the tumor is resistant to chemotherapy. The only curative therapy for glucagonoma is surgery, and even this is not always successful. Heightened glucagon secretion can be treated with the administration of

octreotide Octreotide, sold under the brand name Sandostatin among others, is an octapeptide that mimics natural somatostatin pharmacologically, though it is a more potent inhibitor of growth hormone, glucagon, and insulin than the natural hormone. It was ...

, a somatostatin analog, which inhibits the release of glucagon.

Doxorubicin Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used toge ...

and

streptozotocin Streptozotocin or streptozocin ( INN, USP) (STZ) is a naturally occurring alkylating antineoplastic agent that is particularly toxic to the insulin-producing beta cells of the pancreas in mammals. It is used in medicine for treating certain can ...

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.

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.

References

External links

{{Endocrine gland neoplasia Endocrine neoplasia Rare cancers