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{{Glucagonoma}}
{{Glucagonoma}}
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{{CMG}}; {{AE}} {{PSD}} {{MAD}}
==Overview==
==Overview==
A glucagonoma is a rare tumor of the [[alpha cells]] of the [[pancreas]] that results in the overproduction of the hormone [[glucagon]]. Glucagon increases glycogenolysis, gluconeogenesis from amino acid substrates and inhibits glycolysis. This causes weight loss due to the [[Catabolism|catabolic]] action of glucagon. Glucagonoma may be part of multiple endocrine neoplasia type1 (MEN1). It is an autosomal dominant syndrome that is usually caused by mutations in the [[MEN1 syndrome|''MEN1'' gene]]. Glucagonomas are generally large tumors at diagnosis with a mean diameter of 5 cm, Most tuomrs have evidence of [[Metastasis|metastatic]] spread at presentation. Nearly all glucagonomas are located in the pancreas, 50–80% occur in the pancreatic tail, 32.2% in the body and 21.9% in the head. On the microscopic picture, glucagonomas are [[Pleomorphism|pleomorphic]] with cells containing granules that stain for other peptides, most frequently [[pancreatic polypeptide]]. Glucagon is usually detectable within the tumor cells by [[Immunoperoxidase|immunoperoxidase staining]], and glucagon [[mRNA]] may be detected.  
A glucagonoma is a rare tumor of the [[alpha cells]] of the [[pancreas]] that results in the overproduction of the hormone [[glucagon]]. Glucagon increases glycogenolysis, gluconeogenesis from amino acid substrates and inhibits glycolysis. This causes weight loss due to the [[Catabolism|catabolic]] action of glucagon. Glucagonoma may be part of multiple endocrine neoplasia type1 (MEN1). It is an autosomal dominant syndrome that is usually caused by mutations in the [[MEN1 syndrome|''MEN1'' gene]]. Glucagonomas are generally large tumors at diagnosis with a mean diameter of 5 cm, Most tuomrs have evidence of [[Metastasis|metastatic]] spread at presentation. Nearly all glucagonomas are located in the pancreas, 50–80% occur in the pancreatic tail, 32.2% in the body and 21.9% in the head. On the microscopic picture, glucagonomas are [[Pleomorphism|pleomorphic]] with cells containing granules that stain for other peptides, most frequently [[pancreatic polypeptide]]. Glucagon is usually detectable within the tumor cells by [[Immunoperoxidase|immunoperoxidase staining]], and glucagon [[mRNA]] may be detected.  
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==References==
==References==
{{reflist|2}}
{{reflist|2}}
[[Category:Disease]]
[[Category:Types of cancer]]
[[Category:Endocrinology]]
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Revision as of 18:59, 2 August 2017


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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Parminder Dhingra, M.D. [2] Mohammed Abdelwahed M.D[3]

Overview

A glucagonoma is a rare tumor of the alpha cells of the pancreas that results in the overproduction of the hormone glucagon. Glucagon increases glycogenolysis, gluconeogenesis from amino acid substrates and inhibits glycolysis. This causes weight loss due to the catabolic action of glucagon. Glucagonoma may be part of multiple endocrine neoplasia type1 (MEN1). It is an autosomal dominant syndrome that is usually caused by mutations in the MEN1 gene. Glucagonomas are generally large tumors at diagnosis with a mean diameter of 5 cm, Most tuomrs have evidence of metastatic spread at presentation. Nearly all glucagonomas are located in the pancreas, 50–80% occur in the pancreatic tail, 32.2% in the body and 21.9% in the head. On the microscopic picture, glucagonomas are pleomorphic with cells containing granules that stain for other peptides, most frequently pancreatic polypeptide. Glucagon is usually detectable within the tumor cells by immunoperoxidase staining, and glucagon mRNA may be detected.

Pathogenesis

  • A glucagonoma is a rare tumor of the alpha cells of the pancreas that results in the overproduction of the hormone glucagon.
  • Glucagon increases glycogenolysis, gluconeogenesis from amino acid substrates and inhibits glycolysis. This causes weight loss due to the catabolic action of glucagon.[1]
  • When glucagon is secreted by a tumor, it becomes independent and is no longer influenced by feedback control mechanisms.
  • Glucagonoma causes hyperglucagonemia, zinc deficiency, fatty acid deficiency, hypoaminoacidemia that may cause necrolytic migratory erythema.
  • The postulated mechanism for necrolytic migratory erythema involves excessive inflammation in the epidermis in response to trauma and to the necrolysis.[2][3]
  • Necrolytic migratory erythema (NME) probably results from hyponutrition and amino acid deficiency. It can be caused by a tryptophan loss in cutaneous tissues because of the excess circulating glucagon. Tryptophan is responsible for niacin function, which regulates cell turnover and the maturation of the epidermis and mucosal epithelia.[4][5]
  • Diarrhea may result from the secretion of gastrin occurs with hyperglucagonoma.

Genetics

Glucagonoma may be part of multiple endocrine neoplasia type1 (MEN1). It is an autosomal dominant syndrome that is usually caused by mutations in the MEN1 gene.

Gross Pathology

  • Glucagonomas are generally large tumors at diagnosis with a mean diameter of 5 cm, From 50 to 82% have evidence of metastatic spread at presentation.
  • Tumors below 2 cm in diameter are associated with a very low chance of malignancy.

Microscopic Pathology

Images

References

  1. Braverman IM (1982). ""Cutaneous manifestations of internal malignant tumors" by Becker, Kahn and Rothman, June 1942. Commentary: Migratory necrolytic erythema". Arch Dermatol. 118 (10): 784–98. PMID 6127984.
  2. Necrolytic migratory erythema. Wikipedia. https://en.wikipedia.org/wiki/Necrolytic_migratory_erythema. Accessed on October 13, 2015.
  3. Mullans EA, Cohen PR (1998). "Iatrogenic necrolytic migratory erythema: a case report and review of nonglucagonoma-associated necrolytic migratory erythema". J Am Acad Dermatol. 38 (5 Pt 2): 866–73. PMID 9591806.
  4. STURZBECHER M (1963). "[8 letters of Ferdinand von HEBRAS on his contributin to Virchow's Handbuch der Speziellen Pathologie and Therapie]". Z Haut Geschlechtskr. 34: 281–6. PMID 13978995.
  5. Wilson LA, Kuhn JA, Corbisiero RM, Smith M, Beatty JD, Williams LE; et al. (1992). "A technical analysis of an intraoperative radiation detection probe". Med Phys. 19 (5): 1219–23. doi:10.1118/1.596754. PMID 1435602.
  6. Soga J, Yakuwa Y (1998). "Glucagonomas/diabetico-dermatogenic syndrome (DDS): a statistical evaluation of 407 reported cases". J Hepatobiliary Pancreat Surg. 5 (3): 312–9. PMID 9880781.
  7. 7.0 7.1 Warner TF, Block M, Hafez GR, Mack E, Lloyd RV, Bloom SR (1983). "Glucagonomas. Ultrastructure and immunocytochemistry". Cancer. 51 (6): 1091–6. PMID 6295622.
  8. Mozell E, Stenzel P, Woltering EA, Rösch J, O'Dorisio TM (1990). "Functional endocrine tumors of the pancreas: clinical presentation, diagnosis, and treatment". Curr Probl Surg. 27 (6): 301–86. PMID 1973365.
  9. 9.0 9.1 9.2 9.3 Glucagonoma. Wikimedia Commons. https://commons.wikimedia.org/wiki/File:Confluent_epidermal_necrosis_-_high_mag.jpg
  10. Castro PG, de León AM, Trancón JG, Martínez PA, Alvarez Pérez JA, Fernández Fernández JC; et al. (2011). "Glucagonoma syndrome: a case report". J Med Case Rep. 5: 402. doi:10.1186/1752-1947-5-402. PMC 3171381. PMID 21859461.
  11. Fang S, Li S, Cai T (2014). "Glucagonoma syndrome: a case report with focus on skin disorders". Onco Targets Ther. 7: 1449–53. doi:10.2147/OTT.S66285. PMC 4140234. PMID 25152626.
  12. 12.0 12.1 12.2 Erdas E, Aste N, Pilloni L, Nicolosi A, Licheri S, Cappai A; et al. (2012). "Functioning glucagonoma associated with primary hyperparathyroidism: multiple endocrine neoplasia type 1 or incidental association?". BMC Cancer. 12: 614. doi:10.1186/1471-2407-12-614. PMC 3543729. PMID 23259638.