What are the symptoms of glucagonoma?

Symptoms of Glucagonoma

The classic symptoms of glucagonoma include necrolytic migratory erythema, diabetes mellitus, weight loss, stomatitis, and diarrhea. 1

Key Clinical Manifestations

Dermatological Manifestations

• Necrolytic migratory erythema (NME) is the most characteristic and often initial finding of glucagonoma syndrome, presenting as erosions and crusts primarily affecting the groin, perineum, buttocks, distal extremities, and central face 2, 3
• NME may appear as scaly papules and plaques that can resemble pemphigus foliaceus, acrodermatitis enteropathica, chronic mucocutaneous candidiasis, psoriasis, or severe seborrheic dermatitis 4
• The skin manifestations are often the first reason patients seek medical attention, with 100% of patients in some series presenting initially to dermatology 2

Metabolic Manifestations

• Diabetes mellitus occurs in 57-75% of patients with glucagonoma 2, 5
• The diabetes associated with glucagonoma often requires insulin therapy (75% of cases) 5
• Hyperglycemia results from the glucagon excess antagonizing insulin action 1

Gastrointestinal Manifestations

• Weight loss is reported in 57-71% of patients 2, 5
• Stomatitis (inflammation of the mouth and lips) occurs in 28-29% of patients 2, 5
• Painful glossitis (inflammation of the tongue) may also be present 6
• Diarrhea affects 14-29% of patients 2, 5

Hematological Manifestations

• Anemia (typically normochromic normocytic) is present in approximately 57% of patients 2, 6
• Increased tendency toward thrombosis, including deep vein thrombosis (DVT) 2, 6

Neuropsychiatric Manifestations

• Neuropsychiatric disturbances may occur as part of the syndrome 6

Diagnostic Considerations

• The combination of NME and diabetes mellitus leads to faster diagnosis (average 7 months) compared to either symptom alone (average 4 years) 5
• Plasma glucagon levels are significantly elevated in glucagonoma patients (range 216.92-3155 pg/mL) 2
• The average time from symptom onset to diagnosis is approximately 14 months (range 2-36 months) 2

Clinical Pitfalls and Caveats

• Early recognition of NME and subsequent workup for glucagonoma is crucial as metastases occur late, and early diagnosis before liver metastases can be life-saving 3
• Approximately 50% of glucagonomas have metastasized by the time of diagnosis, most commonly to the liver 6
• Glucagonoma must be distinguished from pseudoglucagonoma syndrome, where NME occurs without an alpha-cell pancreatic tumor 3
• Despite the malignant potential, patients may survive for several years after diagnosis (average 4.91 years even with tumor-related deaths) 5

Evaluation Algorithm

1. In patients presenting with persistent NME, especially when associated with diabetes mellitus, weight loss, or stomatitis:

   • Measure plasma glucagon levels 1, 2
   • Perform abdominal imaging (multiphasic CT or MRI) 1
   • Consider somatostatin scintigraphy and endoscopic ultrasound as appropriate 1

2. For confirmed cases, evaluate for:

   • Metastatic disease (particularly liver metastases) 2, 5
   • Associated metabolic abnormalities (diabetes, anemia) 5
   • Thrombotic complications 6