Glucagonoma

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

• Skin rash
  • Necrolytic migratory erythema in association with cirrhosis, pancreatitis, or celiac disease
  • Psoriasis
  • Paraneoplastic syndromes
  • Vitamin/mineral deficiency syndromes (eg, pellagra, zinc)
  • Toxic epidermal necrolysis associated with other disorders (eg, hepatitis B)
  • Immunobullous disease
    • Pemphigus
    • Pemphigoid
  • Herpes simplex virus
  • Seborrheic/contact dermatitis
• Hyperglycemia
  • Diabetes mellitus (type 1 or type 2)
  • Metabolic syndrome
• Deep vein thrombosis
  • Thrombophilia
  • Antiphospholipid syndrome
  • Malignancy
• Other malignancy
  • Pancreatic adenocarcinoma

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