What are the symptoms of neuroendocrine pancreatic tumors?

Symptoms of Pancreatic Neuroendocrine Tumors

Pancreatic neuroendocrine tumors present either with hormone-specific syndromes (40-55% of cases) or as non-functioning tumors (45-60%) that cause symptoms from mass effect or metastases, with up to 30% remaining completely asymptomatic at diagnosis. 1, 2

Functioning Pancreatic Neuroendocrine Tumors

The clinical presentation depends entirely on which hormone is being secreted, creating distinct syndromes:

Insulinoma (Most Common Functioning PNET)

• Confusion, sweating, dizziness, weakness, and unconsciousness occurring during fasting or nocturnal periods 1, 3
• Relief of symptoms with eating is pathognomonic 1
• Approximately 90% are benign with only 10% developing metastases 1, 2

Gastrinoma (Zollinger-Ellison Syndrome)

• Severe peptic ulceration that is refractory to standard therapy 1, 3
• Diarrhea occurring in 50-65% of patients due to gastric acid hypersecretion 1, 4
• 60% develop metastases, with 80-90% having high metastatic risk 1, 2

Glucagonoma

• Necrolytic migratory erythema (characteristic skin rash) 1, 3
• Weight loss, diabetes mellitus, stomatitis, and diarrhea 1, 3
• Over 60% have metastases at presentation 1

VIPoma (Werner-Morrison Syndrome)

• Profuse watery diarrhea exceeding 1 liter per day 1, 4
• Marked hypokalemia and dehydration 1, 4
• Up to 70% have metastases, with the majority found at initial presentation 1

Somatostatinoma

• Cholelithiasis (gallstones) 1, 3
• Weight loss, diarrhea and steatorrhea, diabetes mellitus 1, 4
• Approximately 50% develop metastases 1

Non-Functioning Pancreatic Neuroendocrine Tumors

These represent 45-60% of all pancreatic NETs and produce no clinically evident hormonal syndrome 2, 5:

• Symptoms from pancreatic mass effect: abdominal pain (often radiating to the back), obstruction, jaundice 1, 3
• Symptoms from liver metastases: hepatomegaly, abdominal fullness 1
• Non-specific constitutional symptoms: weakness, nausea, weight loss, night sweats 1
• Up to 30% remain completely asymptomatic and are discovered incidentally 1

Critical Clinical Pitfalls

Do not assume hormone production equals clinical syndrome. Immunohistochemical demonstration of hormone production does not prove functionality—there can be hormone production without secretion into circulation 1. The diagnosis of a functioning tumor requires both biochemical evidence of elevated circulating hormone levels AND corresponding clinical symptoms 1.

Non-functioning tumors can transform into functioning tumors. Rare cases demonstrate that initially non-secreting pancreatic NETs can later develop insulin secretion, causing severe hypoglycemia with negative prognostic implications 6. This emphasizes the need for ongoing clinical vigilance even in established non-functioning tumors.

Consider genetic syndromes in all patients. Patients with MEN-1 or von Hippel-Lindau disease present 15-20 years earlier than those with sporadic tumors 1. A detailed family history and screening for associated tumors is mandatory in all NET patients 1.