What are the symptoms of a neuroendocrine tumor?

Symptoms of Neuroendocrine Tumors

Most gastroenteropancreatic NETs (45-70%) are non-functioning and present late with non-specific symptoms from mass effects, while functioning NETs (30-55%) cause distinct hormonal syndromes depending on the peptide or amine secreted. 1

Non-Functioning NETs (Most Common Presentation)

Non-functioning tumors typically present with:

• Intermittent abdominal pain (may be present for many years before diagnosis) due to local tumor invasion, bowel obstruction, or mesenteric ischemia 1
• Nausea and vomiting from mass effects 1
• Anemia from chronic intestinal blood loss 1, 2
• Symptoms from liver metastases when disease has spread 1

The median delay from first symptom to diagnosis is approximately 2 years, reflecting the non-specific nature of these symptoms 3

Functioning NETs: Carcinoid Syndrome

Carcinoid syndrome occurs in approximately 20-30% of small intestinal NETs and includes: 1

• Dry flushing without sweating (70% of cases with carcinoid syndrome) with or without palpitations 1
• Secretory diarrhea (50% of cases) 1
• Intermittent abdominal pain (40% of cases) 1
• Wheezing and dyspnea from bronchospasm 1
• Lacrimation and rhinorrhea in some patients 1

This syndrome is caused by serotonin and other vasoactive compounds released predominantly from liver metastases, as hormones from the primary intestinal tumor are metabolized in the liver before reaching systemic circulation 1

Carcinoid Crisis

A life-threatening complication characterized by profound bronchospasm, tachycardia, and widely fluctuating blood pressure, typically precipitated by anesthesia, surgery, or invasive procedures like embolization 1

Functioning Pancreatic NETs (40-55% of Pancreatic NETs)

Insulinoma (Up to 70% of Functioning Pancreatic NETs)

• Fasting or nocturnal hypoglycemia 1
• Dizziness, weakness, unconsciousness 1
• Relief with eating 1

Gastrinoma (Zollinger-Ellison Syndrome)

• Severe recurrent peptic ulceration 1
• Dyspepsia 1
• Diarrhea (may occur alone or with ulcer symptoms) 1

Glucagonoma

• Necrolytic migratory erythema (characteristic skin rash) 1
• Weight loss 1
• Diabetes mellitus 1
• Stomatitis 1
• Diarrhea 1

VIPoma (Verner-Morrison Syndrome/WDHA Syndrome)

• Profuse watery diarrhea 1
• Marked hypokalemia 1
• Achlorhydria 1

Somatostatinoma

• Cholelithiasis 1
• Weight loss 1
• Diarrhea and steatorrhea 1
• Diabetes mellitus 1

Important Clinical Pitfalls

Key diagnostic considerations:

• 70% of intestinal NETs do NOT have carcinoid syndrome despite being classified as "carcinoids" 1
• Immunohistochemical demonstration of hormone production does not prove functionality, as tumors can produce hormones without secreting them 1
• Symptoms may be episodic and intermittent, making diagnosis difficult and often delayed 4
• Patients with MEN-1 or von Hippel-Lindau disease present 15-20 years earlier than those with sporadic NETs 1
• Carcinoid syndrome rarely occurs without liver metastases unless there is direct retroperitoneal involvement with venous drainage bypassing the liver 1