Glucagonoma is a rare tumor of the pancreatic alpha cells 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. However, about 10% of cases are associated with multiple endocrine neoplasia type 1 (MEN-1) syndrome.
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.
Causes and Pathophysiology
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. Additionally, those with Mahvash disease have an increased risk for glucagonoma, as glucagon receptor gene (GCGR) is mutated.
Glucagonoma results from the overproduction of glucagon, a peptide hormone located in the pancreatic alpha cells. Classic symptoms include, but are not limited to, necrolytic migratory erythema (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.
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 renal failure.
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, a somatostatin analog, which inhibits the release of glucagon. 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.
- Vinik, Aaron; Pacak, Karel; Feliberti, Eric; Perry, Roger R. (2000), Feingold, Kenneth R.; Anawalt, Bradley; Boyce, Alison; Chrousos, George (eds.), "Glucagonoma Syndrome", Endotext, MDText.com, Inc., PMID 25905270, retrieved 2019-09-24
- "Glucagonoma: Practice Essentials, Pathophysiology, Epidemiology". 2019-02-01. Cite journal requires
- Albrechtsen, Nicolai Jacob Wewer; Challis, Benjamin; Damjanov, Ivan; Holst, Jens Juul (2016-02-01). "Do glucagonomas always produce glucagon?". Bosnian Journal of Basic Medical Sciences. 16 (1): 1–7. doi:10.17305/bjbms.2015.794. ISSN 1840-4812.
- van Beek AP, de Haas ER, van Vloten WA, Lips CJ, Roijers JF, Canninga-van Dijk MR (November 2004). "The glucagonoma syndrome and necrolytic migratory erythema: a clinical review". Eur. J. Endocrinol. 151 (5): 531–7. doi:10.1530/eje.0.1510531. PMID 15538929.
- Koike N, Hatori T, Imaizumi T, Harada N, Fukuda A, Takasaki K, Iwamoto Y (2003). "Malignant glucagonoma of the pancreas diagnoses through anemia and diabetes mellitus". Journal of Hepato-Biliary-Pancreatic Surgery. 10 (1): 101–5. PMID 12918465.
- Song, Xujun; Zheng, Suli; Yang, Gang; Xiong, Guangbing; Cao, Zhe; Feng, Mengyu; Zhang, Taiping; Zhao, Yupei (March 2018). "Glucagonoma and the glucagonoma syndrome". Oncology Letters. 15 (3): 2749–2755. doi:10.3892/ol.2017.7703. ISSN 1792-1074. PMC 5778850. PMID 29435000.
- Adams, David R.; Miller, Jeffrey J.; Seraphin, Kathryn E. (2005-10-01). "Glucagonoma syndrome". Journal of the American Academy of Dermatology. 53 (4): 690–691. doi:10.1016/j.jaad.2005.04.071. ISSN 0190-9622.
- Moattari AR, Cho K, Vinik AI (1990). "Somatostatin analogue in treatment of coexisting glucagonoma and pancreatic pseudocyst: dissociation of responses". Surgery. 108 (3): 581–7. PMID 2168587.