Symptoms of Metastatic Neuroendocrine Tumors of the Abdomen
Metastatic neuroendocrine tumors (NETs) of the abdomen commonly present with symptoms related to hormone hypersecretion (functional tumors) or mass effect from the primary tumor and metastases (non-functional tumors), with approximately 60% of patients presenting with metastatic disease at diagnosis. 1, 2
Functional Tumor Symptoms
Carcinoid Syndrome (Small Intestinal NETs)
- Flushing (especially of face and upper chest)
- Diarrhea (often watery and frequent)
- Abdominal cramping
- Wheezing or difficulty breathing
- Endocardial fibrosis (right-sided heart valve disease)
- Occurs in approximately 30% of patients with metastatic small intestinal NETs 1
- Caused by serotonin and peptide hormones released from liver metastases 1
Pancreatic NET Syndromes
Based on specific hormone production 1:
- Insulinoma: Confusion, sweating, dizziness, weakness, unconsciousness, relief with eating
- Gastrinoma (Zollinger-Ellison syndrome): Severe peptic ulceration, diarrhea
- Glucagonoma: Necrolytic migratory erythema (distinctive rash), weight loss, diabetes mellitus, stomatitis, diarrhea
- VIPoma (Werner-Morrison syndrome): Profuse watery diarrhea with marked hypokalemia
- Somatostatinoma: Cholelithiasis, weight loss, diarrhea, steatorrhea, diabetes mellitus
Non-Functional Tumor Symptoms
Non-functional tumors (approximately 30-40% of cases) may present with 1, 2:
- Abdominal pain (often vague and chronic)
- Change in bowel habits (often misdiagnosed as irritable bowel syndrome)
- Weight loss
- Nausea and vomiting
- Jaundice (if bile duct obstruction)
- Palpable abdominal mass
- Hepatomegaly (from liver metastases)
- Ascites (in advanced disease)
- Fatigue and weakness
Symptoms Related to Metastatic Disease
- Liver metastases: Right upper quadrant pain, early satiety, weight loss, hepatomegaly
- Mesenteric metastases: Abdominal pain, bowel obstruction, ischemia due to mesenteric fibrosis
- Peritoneal metastases: Ascites, abdominal distention, bowel obstruction
- Bone metastases: Bone pain, pathological fractures
Carcinoid Crisis
A potentially life-threatening complication characterized by 1:
- Profound flushing
- Bronchospasm
- Tachycardia
- Widely and rapidly fluctuating blood pressure
- Usually precipitated by anesthesia, tumor manipulation during surgery, or invasive procedures
Laboratory Abnormalities
Biochemical markers that may be elevated include 1, 2:
- Chromogranin A (general NET marker)
- 5-HIAA in 24-hour urine (for carcinoid tumors)
- Specific hormones based on tumor type (insulin, gastrin, glucagon, VIP, etc.)
- Neuron-specific enolase (especially in poorly differentiated tumors)
Important Clinical Considerations
- Symptoms may be intermittent and vague, leading to delays in diagnosis
- Many patients are initially misdiagnosed with irritable bowel syndrome or other functional disorders 1
- The presence of a genetic syndrome (MEN1, MEN2, NF1) should be thoroughly investigated in all patients with NETs 1, 2
- Metastatic disease may be the first presentation, with an occult primary tumor 3
Early recognition of these symptoms is crucial as the 5-year survival rate for metastatic NETs ranges from 25-75% depending on tumor type, grade, and treatment center expertise 1.