Glucagonoma is a rare neuroendocrine tumor that originates in the alpha2 cells of the pancreas.
Neuroendocrine tumors are cancers that attack the interface between the nervous system and the hormone [endocrine] system, resulting in the severe overproduction of the hormone glucagon, in the case of glucagonoma.
The disease was first described in 1942 by Becker et. al. who noted that the overproduction of hormones (more specifically, of peptide hormones such as glucagon) promotes tumor growth and can result in grave toxic consequences.
Because of the disease’s rarity, no more than 250 cases of glucagonoma have been documented in credible medical literature since Becker’s first dexcription more than a half-century ago. Furthermore, long-term survival rates remain unknown.
Signs and Symptoms
Glucagomas affect the body with up to 1000-fold overproduction of the peptide hormone glucagon. The overproduction of glucagon results in elevated blood glucose levels by activating certain processes in the body that break down large molecules into smaller units (catabolism).
The catabolic processes primarily affected by glucagonoma are glucconeogenesis (a metabolic pathway that converts non-carbohydrate carbon substrates into glucose) and lipolysis (the conversion of fat stored in fat cells into energy). When these catabolic processes are altered, the body’s response is the onset of hyperglucagonemia (the excessive secretion of glucagon), hypoaminoacidemia (decreased amino acid levels in the blood), anemia, diarrhea, and weight loss.
In 70% of cases, a dissorder known as necrolytic migratory erythema (NME) is the patient’s initial symptom. This disorder, when associated with glucagonomas, results in the spread of erythematous blisters and swellings across areas of the body that commonly experience large amounts of friction: the lower abdomen, buttocks, perineum, and groin.
Another frequent aftereffect of glucagonomas is diabetes mellitus, which results from the extreme imbalance of insulin and glucagon associated with the disease.
The normal range of glucagon in the blood is 50-200 pg/mL. When a blood serum glucagon concentration exceeds 1000 pg/mL, glucagonoma is indicated. Recent studies, however, have shown that 40% of patients have glucagon levels in the blood that are as low as 500 pg/mL.
Thus, the range of glucagon in the blood of patients with glucagonomas has not been specifically determined. It should also be noted that extended fasting, renal insufficiency, severe stress, acute pancreatitus, hypercorticism, familial hyperglucagonemia, and hepatic diseases may also result in increased levels of glucagon. Rarely, though, do such cases affect the patient with glucagon levels above 500 pg/mL.
Several radiographic modalities can be used to locate the tumor itself. These modalities include angiography (a type of x-ray), CT scan, MRI, PET, and endoscopic ultrasound.
The administration of a somatostatin analogue such as octreotide can reduce glucagon levels in the blood and alleviate many of the symptoms associated with high glucagon levels. A somatostatin analogue is a substance similar to the peptide hormone somatostatin which inhibits in the release of secondary hormones such as glucagon.
The drugs Doxorubicin and Streptozotocin have been administered to selectively damage alpha2 cells of the pancreas, but they will not destroy the tumor. They can, however, reduce symptoms associated with the disease and minimize tumor growth.
Surgical resection, or the removal of the tumor, is the only curative therapy for glucagon. This therapy has been known to completely reverse the symptoms in some patients. Once again, the rarity of glucagonoma has resulted in limited credible documentation of the disease and the results of various treatments.