Autopsy and Case Reports
Autopsy and Case Reports
Article / Autopsy Case Report

Diarrhea: a missed D in the 4D glucagonoma syndrome

Marlone Cunha-Silva; Julia Guimarães da Costa; Guilherme Amorim Souza Faria; Juliana Yumi Massuda; Maria Letícia Cintra; Larissa Bastos Eloy da Costa; Vítor Marques Assad; Elaine Cristina de Ataíde; Daniel Ferraz de Campos Mazo; Tiago Sevá-Pereira

Downloads: 4
Views: 457


Glucagonoma is a rare and slow-growing pancreatic tumor that usually manifests as glucagonoma syndrome. It is mainly characterized by a typical Dermatosis named necrolytic migratory erythema (NME), Diabetes and glucagon oversecretion. Deep vein thrombosis and Depression complete this set. We report the case of an advanced glucagonoma with liver spread, where all these 4D symptoms occurred but a chronic secretory Diarrhea was the most relevant feature. A 65-year-old man was referred to our center to investigate multiple hepatic nodules evidenced by abdominal tomography. He had a recent diagnosis of diabetes and complained of significant weight loss (25 kg), crusted skin lesions and episodes of a large amount of liquid diarrhea during the past 6 months. On admission, there were erythematous plaques and crusted erosions on his face, back and limbs, plus angular cheilitis and atrophic glossitis. The typical skin manifestation promptly led dermatologists to suspect glucagonoma as the source of our patient’s symptoms. A contrast-enhanced abdominal computed tomography showed a hypervascularized pancreatic lesion and multiple hepatic nodules also hypervascularized in the arterial phase. Despite initial improvement of diarrhea after subcutaneous octreotide, the patient’s impaired nutritional status limited other therapeutic approaches and he died of respiratory failure due to sepsis. His high levels of serum glucagon were not yet available so we performed an autopsy, confirming the diagnosis of metastatic glucagonoma with NME on histology. Chronic diarrhea is not a common feature in glucagonoma syndrome; however, its severity can lead to serious nutritional impairment and set a poor outcome.


Glucagon, Necrolytic Migratory Erythema, Neoplasm Metastasis, Neuroendocrine Tumors, Paraneoplastic Syndromes


Wick MR, Patterson JW. Cutaneous paraneoplastic syndromes. Semin Diagn Pathol. 2019;36(4):211-28. []. [PMID:30736994]

Kiszkaą J, Karczmarek-Borowska B. Radioembolization treatment for liver metastases. Contemp Oncol (Pozn). 2017;21(4):274-8. []. [PMID:29416432]

Jensen RT, Cadiot G, Brandi ML, et al. ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms: functional pancreatic endocrine tumor syndromes. Neuroendocrinology. 2012;95(2):98-119. []. [PMID:22261919]

Cunha-Silva M, Mazo DFC, Gomes ILC, et al. Multiple hepatic metastases of cardiac angiosarcoma. Autops Case Rep. 2018;8(4):e2018048. []. [PMID:30775323]

John AM, Schwartz RA. Glucagonoma syndrome: a review and update on treatment. J Eur Acad Dermatol Venereol. 2016;30(12):2016-22. []. [PMID:27422767]

Al-Faouri A, Ajarma K, Alghazawi S, Al-Rawabdeh S, Zayadeen A. Glucagonoma and glucagonoma syndrome: a case report with review of recent advances in management. Case Rep Surg. 2016;2016:1484089. []. [PMID:26981306]

Mendoza-Guil F, Hernández-Jurado I, Burkhardt P, Linares J, Naranjo R. Necrolytic migratory erythema associated with glucagonoma. Actas Dermosifiliogr. 2005;96(3):175-8. []. [PMID:16476361]

Lévy-Bohbot N, Merle C, Goudet P, et al. Prevalence, characteristics and prognosis of MEN 1-associated glucagonomas, VIPomas, and somatostatinomas: study from the GTE (Groupe des Tumeurs Endocrines) registry. Gastroenterol Clin Biol. 2004;28(11):1075-81. []. [PMID:15657529]

Wei J, Song X, Liu X, et al. Glucagonoma and glucagonoma syndrome: one center’s experience of six cases. J Pancreat Cancer. 2018;4(1):11-6. []. [PMID:30631852]

Tolliver S, Graham J, Kaffenberger BH. A review of cutaneous manifestations within glucagonoma syndrome: necrolytic migratory erythema. Int J Dermatol. 2018;57(6):642-5. []. [PMID:29450880]

ElGuindy YM, Javadi S, Menias CO, Jensen CT, Elsamaloty H, Elsayes KM. Imaging of secretory tumors of the gastrointestinal tract. Abdom Radiol (NY). 2017;42(4):1113-31. []. [PMID:27878636]

Song X, Zheng S, Yang G, et al. Glucagonoma and the glucagonoma syndrome. Oncol Lett. 2018;15(3):2749-55. [PMID:29435000]

Lobo I, Carvalho A, Amaral C, Machado S, Carvalho R. Glucagonoma syndrome and necrolytic migratory erythema. Int J Dermatol. 2010;49(1):24-9. []. [PMID:20465606]

Fuller C, Glick J, Rivas S, Burris K. Necrolytic migratory erythema associated with fatty liver disease and the pseudoglucagonoma syndrome. Dermatol Online J. 2016;22(9):13030. [PMID:28329615]

Wermers RA, Fatourechi V, Wynne AG, Kvols LK, Lloyd RV. The glucagonoma syndrome. Clinical and pathologic features in 21 patients. Medicine (Baltimore). 1996;75(2):53-63. []. [PMID:8606627]

Klein S, Jahoor F, Baba H, Townsend CM Jr, Shepherd M, Wolfe RR. In vivo assessment of the metabolic alterations in glucagonoma syndrome. Metabolism. 1992;41(11):1171-75. []. [PMID:1435287]

Vinik A, Pacak K, Feliberti E, Perry RR. Glucagonoma syndrome [Internet]. South Dartmouth: Endotext; 2017 [cited 2019 Jul 24]. Available from:

Barabas M, Huang-Doran I, Pitfield D, et al. Glucagonoma-associated dilated cardiomyopathy refractory to somatostatin analogue therapy. Endocrinol Diabetes Metab Case Rep. 2019;2019(1):EDM180157. []. [PMID:30836327]

Tremblay C, Marcil I. Necrolytic migratory erythema: a forgotten paraneoplastic condition. J Cutan Med Surg. 2017;21(6):559-61. []. [PMID:28662584]

Wei J, Lin S, Wang C, et al. Glucagonoma syndrome: a case report. Oncol Lett. 2015;10(2):1113-6. []. [PMID:26622635]

Guilbaud T, Berbis P, Birnbaum DJ. Glucagonoma with paraneoplasic dermatitis: diagnosis and management. J Gastrointest Surg. 2019;219(1):1-3. []. [PMID:31152349]

Wu SL, Bai J, Xu J, Ma Q, Wu Z. Necrolytic migratory erythema as the first manifestation of pancreatic neuroendocrine tumor. World J Surg Oncol. 2014;12(1):220. []. [PMID:25029913]

Tomassetti P, Migliori M, Simoni P, et al. Diagnostic value of plasma chromogranin A in neuroendocrine tumours. Eur J Gastroenterol Hepatol. 2001;13(1):55-8. []. [PMID:11204811]

Gut P, Waligórska-Stachura J, Czarnywojtek A, et al. Management of the hormonal syndrome of neuroendocrine tumors. Arch Med Sci. 2017;13(3):515-24. []. [PMID:28507564]

Moreno-Suárez F, Pulpillo-Ruiz Á, Alberdi MF. Necrolytic migratory erithema: A diagnostic clue in glucagonoma syndrome. Med Clin (Barc). 2017;148(8):e45. []. [PMID:27567335]

Han X, Wang D, Kuang T, Rong Y, Lou W. Glucagonoma syndrome: report of one case. Transl Gastroenterol Hepatol. 2016;1:70. []. [PMID:28138636]

Öberg K. Management of functional neuroendocrine tumors of the pancreas. Gland Surg. 2018;7(1):20-7. []. [PMID:29629316]

Zhang P, Li YL, Qiu XD, et al. Clinicopathological characteristics and risk factors for recurrence of well-differentiated pancreatic neuroendocrine tumors after radical surgery: a case-control study. World J Surg Oncol. 2019;17(1):66. []. [PMID:30975157]

Toberer F, Hartschuh W, Wiedemeyer K. Glucagonoma-associated necrolytic migratory erythema: the broad spectrum of the clinical and histopathological findings and clues to the diagnosis. Am J Dermatopathol. 2019;41(3):e29-32. []. [PMID:30124507]

Caplin ME, Pavel M, Ruszniewski P. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med. 2014;371(16):1556-7. [PMID:25317881]

Radny P, Eigentler TK, Soennichsen K, et al. Metastatic glucagonoma: treatment with liver transplantation. J Am Acad Dermatol. 2006;54(2):344-7. []. [PMID:16443073]




Publication date:

5dde7c1c0e8825ac677b23c9 autopsy Articles
Links & Downloads

Autops Case Rep

Share this page
Page Sections