Can neuroendocrine tumors cause intermittent diarrhea?

Can Neuroendocrine Tumors Cause Intermittent Diarrhea?

Yes, neuroendocrine tumors frequently cause diarrhea, and this diarrhea can present with an intermittent pattern, particularly in carcinoid syndrome where it occurs in approximately 50% of cases alongside intermittent abdominal pain (40% of cases). 1

Mechanisms and Patterns of NET-Related Diarrhea

Carcinoid Syndrome

• Diarrhea occurs in 50% of patients with carcinoid syndrome, typically from midgut NETs (jejunum/ileum) that have metastasized to the liver, allowing vasoactive compounds like serotonin and tachykinins to bypass hepatic metabolism and enter systemic circulation. 1
• The diarrhea in carcinoid syndrome is specifically described as occurring with intermittent abdominal pain (40% of cases), suggesting an episodic rather than purely continuous pattern. 1
• Carcinoid syndrome can also occur without liver metastases if there is direct retroperitoneal involvement with venous drainage bypassing the liver. 1

Functioning Pancreatic NETs

• Gastrinomas (Zollinger-Ellison syndrome) cause diarrhea in 50-65% of patients through gastric acid hypersecretion, though symptoms are typically chronic and persistent rather than intermittent. 2, 3
• VIPomas produce profuse secretory diarrhea (>1 liter/day) in 100% of cases with severe dehydration and hypokalemia—this is typically continuous and life-threatening rather than intermittent. 2, 4, 5
• Glucagonomas cause diarrhea along with necrolytic migratory erythema, weight loss, and diabetes mellitus. 1
• Somatostatinomas cause diarrhea and steatorrhea along with cholelithiasis and diabetes mellitus. 1

Clinical Context and Differential Diagnosis

Important Caveats

• Most gastroenteropancreatic NETs (the majority) are non-functioning and present with mass effects rather than hormonal symptoms. 1
• Diarrhea in NET patients can be multifactorial, including: hormone hypersecretion, pancreatic exocrine insufficiency from surgery, short bowel syndrome, bile acid malabsorption, or treatment effects from somatostatin analogs. 6
• Carcinoid syndrome occurs in only ~20% of well-differentiated midgut NETs, and is very rare with rectal NETs. 1

Diagnostic Approach

• Measure 24-hour urinary 5-HIAA (88% sensitivity and specificity for carcinoid syndrome) with dietary restrictions. 2
• Check fasting serum gastrin if acid reflux and diarrhea coexist; levels >1000 pg/mL suggest gastrinoma. 2
• Measure serum VIP during a diarrheal episode if secretory diarrhea exceeds 1 liter/day. 2
• Plasma chromogranin A serves as a general NET marker, particularly useful in gastric carcinoids with metastases. 2

Treatment Considerations

• Somatostatin analogs (octreotide) are first-line for carcinoid syndrome, though they paradoxically cause diarrhea in 34-61% of acromegalic patients treated with this medication. 7
• Tryptophan hydroxylase inhibitors and pancreatic enzyme replacement therapy may be needed based on specific etiology. 6
• Steroids may have a role in refractory VIPoma-related diarrhea based on emerging case evidence. 4

The key clinical pearl: NETs should be considered in the differential diagnosis of chronic or intermittent diarrhea after excluding more common etiologies, particularly when accompanied by flushing, palpitations, or abdominal pain. 1, 6