Glucagonoma and the glucagonoma syndrome (Review)

Song,Xujun; Zheng,Suli; Yang,Gang; Xiong,Guangbing; Cao,Zhe; Feng,Mengyu; Zhang,Taiping; Zhao,Yupei

doi:10.3892/ol.2017.7703

Glucagonoma and the glucagonoma syndrome (Review)

Authors:
- Xujun Song
- Suli Zheng
- Gang Yang
- Guangbing Xiong
- Zhe Cao
- Mengyu Feng
- Taiping Zhang
- Yupei Zhao
View Affiliations

Affiliations: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P.R. China
Published online on: December 28, 2017 https://doi.org/10.3892/ol.2017.7703
Pages: 2749-2755

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Glucagonoma is an extremely rare pancreatic α‑islet cell tumor and is often accompanied by certain clinical symptoms including necrotizing migratory erythema (NME), diabetes, weight loss and anemia. The objectives of the current review were to discern the clinical features, diagnosis, treatment and prognosis of glucagonoma by evaluating 623 reported cases. A 1998 study reviewed 407 cases and 216 cases were reported in studies published after 1998. The current review consisted of 268 males and 339 females, with an average age of 52.4 years. The male‑to‑female ratio was 0.79. The incidence of typical clinical findings were as follows: NME, 82.4% (350/425); diabetes, 68.5% (291/425); weight loss, 60.2% (256/425); anemia, 49.6% (211/425); and glossitis or stomatitis or cheilitis, 41.2% (175/425). A total of 499 cases reported the location of the tumor as the pancreas and 64.1% (320/499) involved the pancreatic tail. Tumor size was recorded in 58.3% (126/216) cases reported after 1998 and average tumor size was 5.0 cm. Metastasis was detected in 49.2% of patients (293/595 for whom metastasis or no metastasis were recorded) upon diagnosis. These patients were older than those without metastasis (average age, 54.0 years old vs. 50.8 years old). The average time between symptoms and diagnosis of glucagonoma was 31.4 months. Glucagonoma is a very rare disease. It is important for clinicians to learn more about this disease to be able to diagnose and treat it as early as possible, thus improving patient prognosis.

View Figures

View References

1	Yao JC, Eisner MP, Leary C, Dagohoy C, Phan A, Rashid A, Hassan M and Evans DB: Population-based study of islet cell carcinoma. Ann Surg Oncol. 14:3492–3500. 2007. View Article : Google Scholar : PubMed/NCBI
2	Ito T, Sasano H, Tanaka M, Osamura RY, Sasaki I, Kimura W, Takano K, Obara T, Ishibashi M, Nakao K, et al: Epidemiological study of gastroenteropancreatic neuroendocrine tumors in Japan. J Gastroenterol. 45:234–243. 2010. View Article : Google Scholar : PubMed/NCBI
3	Klimstra DS, Arnold R, Capella C, et al: Neuroendocrine neoplasms of the pancreasWHO classification of tumours of the digestive system. Bosman FT, Carneiro F, Hruban RH and Theise ND: IARC Press; Lyon: pp. 322–326. 2010
4	Eldor R, Glaser B, Fraenkel M, Doviner V, Salmon A and Gross DJ: Glucagonoma and the glucagonoma syndrome-cumulative experience with an elusive endocrine tumour. Clin Endocrinol (Oxf). 74:593–598. 2011. View Article : Google Scholar : PubMed/NCBI
5	Wermers RA, Fatourechi V, Wynne AG, Kvols LK and Lloyd RV: The glucagonoma syndrome. Clinical and pathologic features in 21 patients. Medicine (Baltimore). 75:53–63. 1996. View Article : Google Scholar : PubMed/NCBI
6	Soga J and Yakuwa Y: Glucagonomas/diabetico-dermatogenic syndrome (DDS): A statistical evaluation of 407 reported cases. J Hepatobiliary Pancreat Surg. 5:312–319. 1998. View Article : Google Scholar : PubMed/NCBI
7	Anne Couvelard and Olivia Hentic: GlucagonomaPancreatic Neuroendocrine Neoplasms: Practical Approach to Diagnosis, Classification, and Therapy. Stefano LR and Fausto S: Springer International Publishing; Switzerland: pp. 81–87. 2015
8	Becker SW, Kahn D and Rothman S: Cutaneous manifestations of internal malignant tumors. Arch Dermatol Syphilol. 45:1069–1080. 1942. View Article : Google Scholar
9	McGavran MH, Unger RH, Recant L, Polk HC, Kilo C and Levin ME: A glucagon-secreting alpha-cell carcinoma of the pancreas. N Engl J Med. 274:1408–1413. 1966. View Article : Google Scholar : PubMed/NCBI
10	Wilkinson DS: Necrolytic migratory erythema with pancreatic carcinoma. Proc R Soc Med. 64:pp. 1197–1198. 1971; PubMed/NCBI
11	Kindmark H, Sundin A, Granberg D, Dunder K, Skogseid B, Janson ET, Welin S, Oberg K and Eriksson B: Endocrine pancreatic tumors with glucagon hypersecretion: A retrospective study of 23 cases during 20 years. Med Oncol. 24:330–337. 2007. View Article : Google Scholar : PubMed/NCBI
12	PubMed [Internet]. Bethesda (MD): National Library of Medicine (US). [1946]. 2016 January 23https://www.ncbi.nlm.nih.gov/pubmed/
13	Papotti M, Bongiovanni M, Volante M, Allìa E, Landolfi S, Helboe L, Schindler M, Cole SL and Bussolati G: Expression of somatostatin receptor types 1–5 in 81 cases of gastrointestinal and pancreatic endocrine tumors. A correlative immunohistochemical and reverse-transcriptase polymerase chain reaction analysis. Virchows Arch. 440:461–475. 2002. View Article : Google Scholar : PubMed/NCBI
14	Lepage C, Rachet B and Coleman MP: Survival from malignant digestive endocrine tumors in England and Wales: A population-based study. Gastroenterology. 132:899–904. 2007. View Article : Google Scholar : PubMed/NCBI
15	McGevna L and Tavakkol Z: Images in clinical medicine. Necrolytic migratory erythema. N Engl J Med. 362:e12010. View Article : Google Scholar : PubMed/NCBI
16	McGevna L, McFadden D, Ritvo J and Rabinowitz T: Glucagonoma-associated neuropsychiatric and affective symptoms: Diagnostic dilemmas raised by paraneoplastic phenomena. Psychosomatics. 50:548–550. 2009. View Article : Google Scholar : PubMed/NCBI
17	Remes-Troche JM, Garcia-de-Acevedo B, Zuñiga-Varga J, Avila-Funes A and Orozco-Topete R: Necrolytic migratory erythema: A cutaneous clue to glucagonoma syndrome. J Eur Acad Dermatol Venereol. 18:591–595. 2004. View Article : Google Scholar : PubMed/NCBI
18	Pujol RM, Wang CY, el-Azhary RA, Su WP, Gibson LE and Schroeter AL: Necrolytic migratory erythema: Clinicopathologic study of 13 cases. Int J Dermatol. 43:12–18. 2004. View Article : Google Scholar : PubMed/NCBI
19	Johnson DS, Coel MN and Bornemann M: Current imaging and possible therapeutic management of glucagonoma tumors: A case report. Clin Nucl Med. 25:120–122. 2000. View Article : Google Scholar : PubMed/NCBI
20	Halvorson SA, Gilbert E, Hopkins RS, Liu H, Lopez C, Chu M, Martin M and Sheppard B: Putting the pieces together: Necrolytic migratory erythema and the glucagonoma syndrome. J Gen Intern Med. 28:1525–1529. 2013. View Article : Google Scholar : PubMed/NCBI
21	Alkemade JA, van Tongeren JH, van Haelst UJ, Smals A, Steijlen PM and van de Kerkhof PC: Delayed diagnosis of glucagonoma syndrome. Clin Exp Dermatol. 24:455–457. 1999. View Article : Google Scholar : PubMed/NCBI
22	Kimbara S, Fujiwara Y, Toyoda M, Chayahara N, Imamura Y, Kiyota N, Mukohara T, Fukunaga A, Oka M, Nishigori C and Minami H: Rapid improvement of glucagonoma-related necrolytic migratory erythema with octreotide. Clin J Gastroenterol. 7:255–259. 2014. View Article : Google Scholar : PubMed/NCBI
23	Chang-Chretien K, Chew JT and Judge DP: Reversible dilated cardiomyopathy associated with glucagonoma. Heart. 90:e442004. View Article : Google Scholar : PubMed/NCBI
24	Demir OM, Paschou SA, Ellis HC, Fitzpatrick M, Kalogeropoulos AS, Davies A, Thompson J, Davies SW and Grapsa J: Reversal of dilated cardiomyopathy after glucagonoma excision. Hormones (Athens). 14:172–173. 2015.PubMed/NCBI
25	Gaiser CA and Dhawan N: Paradoxical presentation of glucagonoma with delayed onset of necrolytic migratory erythema. Am J Med. 128:e1–e2. 2015. View Article : Google Scholar : PubMed/NCBI
26	Beattie PE, Fleming CJ, Evans AT, Sheppard DG, Leese GP, Dow E and Tait IS: Glucagonoma syndrome presenting as psoriasis. QJM. 95:834–835. 2002. View Article : Google Scholar : PubMed/NCBI
27	Shyr YM, Su CH, Lee CH, Wu CW and Lui WY: Glucagonoma syndrome: A case report. Zhonghua Yi Xue Za Zhi (Taipei). 62:639–643. 1999.PubMed/NCBI
28	Nightingale KJ, Davies MG and Kingsnorth AN: Glucagonoma syndrome: Survival 24 years following diagnosis. Dig Surg. 16:68–71. 1999. View Article : Google Scholar : PubMed/NCBI
29	Recant L, Perrino PV, Bhathena SJ, Danforth DN Jr and Lavine RL: Plasma immunoreactive glucagon fractions in four cases of glucagonoma: Increased ‘large glucagon-immunoreactivity’. Diabetologia. 12:319–326. 1976. View Article : Google Scholar : PubMed/NCBI
30	Kitamura Y, Sato M, Hatamochi A and Yamazaki S: Necrolytic migratory erythema without glucagonoma associated with hepatitis B. Eur J Dermatol. 15:49–51. 2005.PubMed/NCBI
31	Technau K, Renkl A, Norgauer J and Ziemer M: Necrolytic migratory erythema with myelodysplastic syndrome without glucagonoma. Eur J Dermatol. 15:110–112. 2005.PubMed/NCBI
32	Yamashita S, Tanaka N, Takahashi M, Nagai M, Furuya T, Suzuki Y and Nomura Y: Pancreatic insulinoma combined with glucagon positive cell: A case report. World J Gastrointest Surg. 5:68–72. 2013. View Article : Google Scholar : PubMed/NCBI
33	Lolis MS, Krishtul A, Vidal C, Shim-Chang H, Phelps R and Lebwohl M: Necrolytic migratory erythema associated with a metastatic neuroendocrine tumor. Cutis. 87:78–80. 2011.PubMed/NCBI
34	Adams DR, Miller JJ and Seraphin KE: Glucagonoma syndrome. J Am Acad Dermatol. 53:690–691. 2005. View Article : Google Scholar : PubMed/NCBI
35	Schwartz RA: Glucagonoma and pseudoglucagonoma syndromes. Int J Dermatol. 36:81–89. 1997. View Article : Google Scholar : PubMed/NCBI
36	Miller HC, Kidd M, Modlin IM, Cohen P, Dina R, Drymousis P, Vlavianos P, Klöppel G and Frilling A: Glucagon receptor gene mutations with hyperglucagonemia but without the glucagonoma syndrome. World J Gastrointest Surg. 7:60–66. 2015. View Article : Google Scholar : PubMed/NCBI
37	Glueck CJ, Phillips HG, Cameron D and Wang P: Estrogen replacement in a protein S deficient patient leads to diarrhea, hyperglucagonemia, and osteonecrosis. JOP. 2:323–329. 2001.PubMed/NCBI
38	Vanderlan WB, Zhang Z and Abouljoud MS: Duodenal enteroglucagonoma revealed by differential comparison of serum and tissue glucagon reactivity with Siemens' Double Glucagon Antibody and DakoCytomation's Polyclonal Rabbit Anti-Human Glucagon: A case report. J Med Case Rep. 4:1782010. View Article : Google Scholar : PubMed/NCBI
39	Plöckinger U, Rindi G, Arnold R, Eriksson B, Krenning EP, de Herder WW, Goede A, Caplin M, Oberg K, Reubi JC, et al: Guidelines for the diagnosis and treatment of neuroendocrine gastrointestinal tumours. A consensus statement on behalf of the European Neuroendocrine Tumour Society (ENETS). Neuroendocrinology. 80:394–424. 2004. View Article : Google Scholar : PubMed/NCBI
40	Melen-Mucha G, Lawnicka H, Kierszniewska-Stepien D, Komorowski J and Stepien H: The place of somatostatin analogs in the diagnosis and treatment of the neuoroendocrine glands tumors. Recent Pat Anticancer Drug Discov. 1:237–254. 2006. View Article : Google Scholar : PubMed/NCBI
41	Fernández-Cruz L, Blanco L, Cosa R and Rendón H: Is laparoscopic resection adequate in patients with neuroendocrine pancreatic tumors? World J Surg. 32:904–917. 2008. View Article : Google Scholar : PubMed/NCBI
42	Sarmiento JM, Que FG, Grant CS, Thompson GB, Farnell MB and Nagorney DM: Concurrent resections of pancreatic islet cell cancers with synchronous hepatic metastases: Outcomes of an aggressive approach. Surgery. 132:976–983. 2002. View Article : Google Scholar : PubMed/NCBI
43	Kindmark H, Sundin A, Granberg D, Dunder K, Skogseid B, Janson ET, Welin S, Oberg K and Eriksson B: Endocrine pancreatic tumors with glucagon hypersecretion: A retrospective study of 23 cases during 20 years. Med Oncol. 24:330–337. 2007. View Article : Google Scholar : PubMed/NCBI