Glucagonoma

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.

Diagnosis

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

Histology

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

Monitoring

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

Background

Epidemiology

  • 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)

Pathophysiology

  • 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 Lab Tests

Use to diagnose and manage diabetes mellitus and other carbohydrate metabolism disorders

Aid in diagnosis and monitoring of glucagonoma

Aid in monitoring

Not recommended for diagnosis of carcinoid tumors

May be useful in monitoring nonsecretory sympathetic and parasympathetic neuroendocrine tumors

Aid in histologic diagnosis of pancreatic neuroendocrine tumors (PNETs)

Stained and returned to client pathologist; consultation available if needed

Aid in histologic diagnosis of PNETs

Stained and resulted by ARUP

Aid in histologic diagnosis of PNETs

Stained and returned to client pathologist; consultation available if needed

Aid in histologic diagnosis of PNETs

Stained and returned to client pathologist; consultation available if needed

Aid in histologic diagnosis of PNETs

Stained and returned to client pathologist; consultation available if needed

Medical Experts

Contributor

References

Additional Resources