Last Literature Review: July 2018 Last Update:

Medical Experts


Glucagonomas are a type of pancreatic neuroendocrine tumor (PNET) that produce excessive amounts of glucagon, which causes glucose intolerance, weight loss, and a distinctive rash (migratory necrolytic erythema). These tumors have a very high malignant potential and are the third most common functional PNET. They are rarely associated with genetic syndromes, in contrast to some other PNETs.


Indications for Testing

  • Pancreatic tumor
  • Clinical symptoms of glucose intolerance, hyperglycemia, weight loss and cachexia, and migratory necrotic erythema rash

Laboratory Testing

  • Serum glucose – elevated
  • Glucagon (fasting)
    • Elevated concentration suggestive of glucagonoma
  • Chromogranin A (Kunz, North American Neuroendocrine Tumor Society [NANETS], 2013)
    • Can be used as a marker of disease activity and for posttreatment surveillance


Diagnosis made by morphology and immunochemical testing

Imaging Studies

  • Multiphasic contrast enhanced computed tomography (CT) or magnetic resonance imaging (MRI)
    • If negative, proceed to scintography for tumor identification
  • Somatostatin-receptor scintigraphy (Indium-111 OctreoScan) may help localize small lesions

Differential Diagnosis


  • Chromogranin A (Kunz, NANETS, 2013)
    • Recommended for patients with advanced disease who had elevated levels at diagnosis
    • Consider for patients with resected disease



  • Incidence – <1/million (Falconi, European Neuroendocrine Tumor Society [ENETS] consensus, 2016)
  • Age – 50s-60s (median)
  • Sex – M:F, equal

Familial Genetics

Rarely associated with genetic variations; however, patients diagnosed with multiple endocrine neoplasia 1 (MEN1), von Hippel-Lindau, neurofibromatosis type 1 (NF1), or tuberous sclerosis are at higher risk for PNETs (Falconi, ENETS, 2016)


  • Usually sporadic
  • Tumor is usually large (5-10 cm) when discovered
  • Typically, a single tumor is found
  • Tumor size >5 cm associated with malignancy in 60-80% of cases
  • ~15% of functional PNETs
  • Tumor of alpha cells of pancreatic islets – small number in proximal duodenum
    • Most frequently malignant (50-80%) (Falconi, ENETS, 2016), calcified, and located in body and tail of pancreas with regional node involvement
    • Secretes excessive amounts of glucagon – stimulates glycogenolysis, gluconeogenesis, ketogenesis, lipolysis, and insulin secretion

Clinical Presentation

  • Laboratory – hyperglycemia, panhypoaminoaciduria
  • Glossitis, stomatitis, angular cheilitis
  • Skin rash
    • Migratory necrolytic erythema
    • Starts as annular erythema at intertriginous sites
    • Progresses to papulobullous stage that waxes and wanes
  • Increased risk of deep vein thrombosis
  • Diarrhea
  • Weight loss and cachexia
  • Frequently metastatic at presentation
    • Liver is most common site of metastasis, followed by lymph nodes or bone

ARUP Laboratory Tests


Additional Resources