Clinical Background
Glucagonomas are pancreatic neuroendocrine tumors that produce excessive amounts of glucagon and are associated with a distinctive clinical syndrome.
Epidemiology
- Incidence – <1/1,000,000
- Age – median age is 50s-60s
- Sex – M:F, equal
- Occurrence – third most common functional neuroendocrine tumor
Risk Factors
- Genetic – rarely associated with MEN1 or von Hippel-Lindau (VHL) syndrome
- Usually sporadic
Pathophysiology
- Tumor of the alpha cells of the pancreatic islets
- Most frequently in the body and tail of the pancreas
- Tumor is usually large when discovered
Clinical Presentation
- Diabetes mellitus, skin rash, hypoaminoacidemia, increased risk of deep vein thrombosis (DVT)
- Skin rash
- Migratory necrolytic erythema
- Starts as annular erythema at intertriginous sites
- Rash progresses to papulobullous stage that waxes and wanes
- Frequently metastatic at presentation – liver is the most common site of metastasis
Treatment
- Symptomatic relief
- Somatostatin analogues
- Resection
Diagnosis
- Indications for testing – neuroendocrine symptoms compatible with tumor; pancreatic tumor with neuroendocrine symptoms
- Laboratory testing
- Glucagon level >500 pg/mL
- Histology
- Nested or trabecular arrangement of small- to medium-sized cells
- Finely granular eosinophilic cytoplasm
- Central round to oval nuclei
- Stippled chromatin (“salt and pepper”)
- Immunohistochemistry – chromogranin, synaptophysin and glucagon are most valuable; others include NSE, AE1/AE3, PGP 9.5
- Imaging studies
- CT and/or MRI
- Somatostatin-receptor scintigraphy may help localize small lesions
Differential Diagnosis
- Diabetes mellitus (type 1 or type 2)
- Thrombophilic syndrome
- Hereditary thrombophilia
- Paraneoplastic syndromes
- Psoriasis
- Toxic epidermal necrolysis
- Vitamin deficiency syndromes
- Pancreatic adenocarcinoma
Pharmacogenetics and Therapeutic Drug Monitoring
Indications for Laboratory Testing
- Tests generally appear in the order most useful for common clinical situations
- Click on number for test-specific information in the ARUP Laboratory Test Directory
| Test Name and Number |
Recommended Use |
Limitations |
Follow Up |
| Glucagon 0099165 Method: Radioimmunoassay |
Diagnose glucagonoma
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| Immunohistochemistry Stain Offering arup005 Method: Immunohistochemistry |
For fixed tissue samples, consultative services as well as immunohistochemical staining for synaptophysin, chromogranin, glucagon, NSE, AE1/AE3, and PGP 9.5 are available |
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General References
Cruz-Bautista I, Lerman I, Perez-Enriquez B, Padilla LS, Torres CL, Lopez A, Cabrera T, Mehta RP, Gomez-Perez FJ, Rull JA, Orozco-Topete R. Diagnostic challenge of glucagonoma: case report and literature review. Endocr Pract. 2006; 12 (4) :422-426.PubMed
Comprehensive Review: July 2009
Last Update: August 2009