Glucagonoma

Infobox_Disease
Name = Glucagonoma


Caption =
DiseasesDB = 5257
ICD10 = ICD10|C|25|4|c|15
ICD9 = ICD9|157.4, ICD9|211.7
ICDO = 8152
OMIM =
MedlinePlus =
eMedicineSubj = med
eMedicineTopic = 896
MeshID = D005935
A glucagonoma is a rare tumor of the alpha cells of the pancreas that results in up to a 1000-fold overproduction of the hormone glucagon. Alpha cell tumors are commonly associated with glucagonoma syndrome, though similar symptoms are present in cases of pseudoglucagonoma syndrome in the absence of a glucagon-secreting tumor.

History

Fewer than 250 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 are as yet unknown.

Symptoms

The primary physiological effect of glucagonoma is an overproduction of the peptide hormone glucagon, which enhances blood glucose levels through the activation of catabolic processes including gluconeogenesis and lipolysis. Gluconeogenesis produces glucose from protein and amino acid materials; lipolysis is the breakdown of fat. The net result is hyperglucagonemia, decreased blood levels of amino acids (hypoaminoacidemia), anemia, diarrhea, and weight loss of 5-15 kg.

Necrolytic migratory erythema (NME) is a classical symptom observed in patients with glucagonoma and is the presenting problem in 70% of cases.cite journal |author=van Beek AP, de Haas ER, van Vloten WA, Lips CJ, Roijers JF, Canninga-van Dijk MR |title=The glucagonoma syndrome and necrolytic migratory erythema: a clinical review |journal=Eur. J. Endocrinol. |volume=151 |issue=5 |pages=531–7 |year=2004 |month=November |pmid=15538929 |doi= |url=http://eje-online.org/cgi/pmidlookup?view=long&pmid=15538929] Associated NME is characterized by the spread of erythematous blisters and swelling across areas subject to greater friction and pressure, including the lower abdomen, buttocks, perineum, and groin.

Diabetes mellitus also frequently results from the insulin and glucagon imbalance that occurs in glucagonoma. [cite journal |author=Koike N, Hatori T, Imaizumi T, "et al" |title=Malignant glucagonoma of the pancreas diagnoses through anemia and diabetes mellitus |journal=Journal of hepato-biliary-pancreatic surgery |volume=10 |issue=1 |pages=101–5 |year=2003 |pmid=12918465 |doi=] Diabetes mellitus is present in 80-90% of cases of glucagonoma, and is exacerbated by preexisting insulin resistance.

Diagnosis

A blood serum glucagon concentration of 1000 pg/mL or greater is indicative of glucagonoma (the normal range is 50-200 pg/mL).

However, recent studies have shown that forty percent of patients have plasma glucagon levels ranging from 500 to 1000 pg/mL. Increased levels have been reported in cases of renal insufficiency, acute pancreatitis, hypercorticism, hepatic diseases, severe stress, extended fasting, and familial hyperglucagonemia. Rarely do these cases result in levels over 500 pg/mL, except in the case of patients with hepatic diseases [Goldman, Lee, and Ausiello Dennis. Cecil Textbook of Medicine. Philadelphia: Saunders, 2004.] .

Blood tests may also reveal abnormally low concentrations of amino acids, zinc, and essential fatty acids, which are thought to play a role in the development of NME. Skin biopsies may also be taken to confirm the presence of NME.

A CBC can uncover anemia, which is an abnormally low level of hemoglobin.

The tumor itself may be localized by any number of radiographic modalities, including angiography, CT, MRI, PET, and endoscopic ultrasound. Laparotomy is useful for obtaining histologic samples for analysis and confirmation of the glucagonoma.

Treatment

Heightened glucagon secretion can be treated with the administration of octreotide, a somatostatin analog, which inhibits the release of glucagon. [cite journal |author=Moattari AR, Cho K, Vinik AI |title=Somatostatin analogue in treatment of coexisting glucagonoma and pancreatic pseudocyst: dissociation of responses |journal=Surgery |volume=108 |issue=3 |pages=581–7 |year=1990 |pmid=2168587 |doi=] 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.

The only curative therapy for glucagonoma is surgical resection, where the tumor is removed. Resection has been known to reverse symptoms in some patients.

References