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Glucagonoma and the glucagonoma syndrome

Emily Bergsland, MD
Section Editors
David M Nathan, MD
David C Whitcomb, MD, PhD
Deputy Editor
Shilpa Grover, MD, MPH, AGAF


Glucagonomas are rare functioning neuroendocrine tumors that secrete glucagon. This topic will review the clinical manifestations, diagnosis, and management of glucagonomas. An overview of the clinical manifestations, diagnosis, and management of pancreatic neuroendocrine tumors and other functioning pancreatic neuroendocrine tumors are discussed in detail, separately. (See "Classification, epidemiology, clinical presentation, localization, and staging of pancreatic neuroendocrine tumors (islet-cell tumors)" and "Surgical resection of sporadic pancreatic neuroendocrine tumors" and "Metastatic well-differentiated pancreatic neuroendocrine tumors: Systemic therapy options to control tumor growth and symptoms of hormone hypersecretion" and "Metastatic gastroenteropancreatic neuroendocrine tumors: Local options to control tumor growth and symptoms of hormone hypersecretion" and "Insulinoma" and "Somatostatinoma: Clinical manifestations, diagnosis, and management" and "Zollinger-Ellison syndrome (gastrinoma): Clinical manifestations and diagnosis" and "Management and prognosis of the Zollinger-Ellison syndrome (gastrinoma)".)


Glucagonomas are rare, with an annual incidence of 0.01 to 0.1 new cases per 100,000 [1]. Glucagonomas are usually solitary, and the majority are located in the distal pancreas. Patients typically present in their fifth decade [2]. While most glucagonomas are sporadic, up to 20 percent may be associated with the multiple endocrine neoplasia syndrome type 1 (MEN1). However, glucagonomas occur in only 3 percent of MEN1 patients [3]. Glucagonomas are usually large (>3 cm), and approximately 50 to 80 percent are metastatic at diagnosis. Unlike carcinoid tumors, however, liver metastases are not a prerequisite for the clinical syndrome. (See "Clinical features of the carcinoid syndrome" and "Multiple endocrine neoplasia type 1: Clinical manifestations and diagnosis".)


Glucagonomas are neuroendocrine tumors (NETs) derived from multipotential stem cells of endodermal origin. The World Health Organization classifies NETs arising within the digestive system into two broad categories based upon the extent to which they resemble their normal non-neoplastic counterparts (table 1) (see "Pathology, classification, and grading of neuroendocrine tumors arising in the digestive system", section on '2010 WHO classification') [4]:

Well-differentiated NETs, which are further classified, according to proliferative rate, into low-grade (G1) and intermediate-grade (G2) subgroups

Poorly differentiated neuroendocrine carcinomas, all of which are high grade (G3) (see "Pathology of lung malignancies", section on 'Neuroendocrine tumors')

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Literature review current through: Nov 2017. | This topic last updated: Aug 10, 2016.
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