What are the differences in clinical presentation between glucagonoma (Glucagon-secreting tumor), somatostatinoma (Somatostatin-secreting tumor), and vipoma (Vasoactive Intestinal Peptide-secreting tumor)?

From the Guidelines

Glucagonomas, somatostatinomas, and VIPomas are rare neuroendocrine tumors with distinct clinical presentations, and their management should prioritize reducing morbidity, mortality, and improving quality of life through early diagnosis and targeted treatment. The clinical presentation of these tumors varies significantly, with glucagonomas typically presenting with necrolytic migratory erythema, diabetes mellitus, weight loss, anemia, and thromboembolism, as noted in the guidelines for the management of gastroenteropancreatic neuroendocrine tumors 1. Somatostatinomas present with a classic triad of diabetes mellitus, gallbladder disease (cholelithiasis), and steatorrhea, along with hypochlorhydria and weight loss, as outlined in the same guidelines 1. VIPomas, on the other hand, present with watery diarrhea, hypokalemia, and achlorhydria (WDHA syndrome or pancreatic cholera), with patients experiencing severe secretory diarrhea (>3L/day) that persists during fasting, as described in the guidelines for the management of gastroenteropancreatic neuroendocrine tumors 1.

Key Clinical Features

• Glucagonomas:
  • Necrolytic migratory erythema
  • Diabetes mellitus
  • Weight loss
  • Anemia
  • Thromboembolism
  • Elevated glucagon levels (>500 pg/mL) 1
• Somatostatinomas:
  • Diabetes mellitus
  • Gallbladder disease (cholelithiasis)
  • Steatorrhea
  • Hypochlorhydria
  • Weight loss
  • Elevated plasma somatostatin levels 1
• VIPomas:
  • Watery diarrhea
  • Hypokalemia
  • Achlorhydria (WDHA syndrome or pancreatic cholera)
  • Severe secretory diarrhea (>3L/day) that persists during fasting
  • Elevated VIP levels, hypokalemia, and hypochlorhydria 1

Treatment and Management

Treatment for all three tumors includes surgical resection when possible, with somatostatin analogs like octreotide (100-500 mcg subcutaneously three times daily) used to control symptoms. Specific symptom management differs: glucagonomas may require amino acid supplementation and diabetes management; somatostatinomas need diabetes and malabsorption treatment; and VIPomas require aggressive fluid and electrolyte replacement, as recommended in the guidelines for the management of gastroenteropancreatic neuroendocrine tumors 1. Early diagnosis is challenging due to their rarity, but recognizing these distinct clinical syndromes can lead to earlier intervention and improved outcomes. The use of somatostatin analogues and interferons has been effective in controlling associated clinical syndromes related to hormone production and release in up to 60% of patients, as noted in the ESMO clinical recommendations for diagnosis, treatment, and follow-up of neuroendocrine gastroenteropancreatic tumors 1.

From the Research

Clinical Presentation of Glucagonoma, Somatostatinoma, and Vipoma

The clinical presentation of glucagonoma, somatostatinoma, and vipoma can be distinguished by their unique sets of symptoms.

• Glucagonoma is characterized by:
  • Weight loss 2, 3, 4
  • Necrolytic migratory erythema (NME) 2, 3, 4
  • Diabetes mellitus 2, 3, 4
  • Diarrhea 2, 3
  • Cheilosis or stomatitis 2
• Somatostatinoma is characterized by:
  • Inhibitory symptoms, including diabetes and steatorrhea 5, 6
  • Less specific symptoms, as somatostatin has a wide range of inhibitory effects on hormone secretion 5
• Vipoma is characterized by:
  • Diarrheogenic symptoms, including severe diarrhea 5
  • Other symptoms related to the excessive secretion of vasoactive intestinal peptide (VIP) 5

Comparison of Clinical Presentations

The clinical presentations of glucagonoma, somatostatinoma, and vipoma can be compared as follows:

• Glucagonoma and somatostatinoma both often present with diabetes, but glucagonoma is more commonly associated with NME and weight loss 2, 3, 4, 6
• Vipoma is distinct from glucagonoma and somatostatinoma due to its diarrheogenic symptoms 5
• The measurement of plasma concentrations of specific peptides can help diagnose and differentiate between these tumors 5