Clinical Pearls & Morning Reports
Published October 25, 2023
Features of carcinoid syndrome include facial flushing, bronchospasm, diarrhea, and telangiectasias. Read the NEJM Case Records of the Massachusetts General Hospital here.
Q: Where do neuroendocrine tumors most commonly arise?
A: Neuroendocrine tumors are relatively uncommon tumors that can arise in multiple organs, although the most commonly affected organs are the lungs, pancreas, and intestines. Carcinoid tumors are rare secretory neuroendocrine tumors that typically arise in the gastrointestinal tract or lungs. These tumors secrete vasoactive compounds — including serotonin, histamine, tachykinins, kallikreins, and prostaglandins — into the systemic circulation, which leads to carcinoid syndrome.
Q: Which cardiac valves are most often involved in patients with carcinoid heart disease?
A: Up to half of patients with carcinoid syndrome ultimately have some degree of heart disease, and up to 20% of patients have heart disease at the time of presentation, although it is often asymptomatic. In patients with carcinoid heart disease, involvement of the tricuspid and pulmonic valves is common. Involvement of the mitral and aortic valves occurs in less than half these patients and is typically associated with the presence of a patent foramen ovale. Cardiac valves on the left side are less likely to be affected because the lungs can inactivate vasoactive compounds.
A: Carcinoid syndrome is seen in approximately 20% of all patients with grade 1 or 2 neuroendocrine tumors and occurs infrequently in patients with higher-grade tumors. Most cases occur in the context of liver metastases; when the liver is unaffected, it has the capacity to inactivate bioactive compounds, including serotonin, which decreases the risk of carcinoid syndrome occurring in association with tumors without liver metastases.
A: Well-differentiated neuroendocrine tumors can secrete various biologically active compounds, including serotonin, into the systemic circulation. Elevation of the serum serotonin level is thought to play a direct role in the development of carcinoid syndrome. The urinary 5-hydroxyindoleacetic acid (5-HIAA) level is used as a proxy for the serum serotonin level; serum serotonin is metabolized by the liver to a terminal metabolite, 5-HIAA, which is then cleared by the kidneys. Measurement of the urinary 5-HIAA level is the preferred initial laboratory test for carcinoid syndrome. However, if a 24-hour urine sample cannot be obtained, serum serotonin or 5-HIAA testing may be useful. Interpretation of the results of urinary 5-HIAA testing can be challenging. An elevated urinary 5-HIAA level can result from dietary consumption of serotonin-rich foods. Many nuts, fruits, and vegetables contain enough serotonin to increase the urinary 5-HIAA level above the upper limit of the normal range, if they are ingested within 48 to 72 hours before testing. It has been suggested that certain medications can either increase or decrease the urinary 5-HIAA level through multiple mechanisms and, therefore, should not be taken within 72 hours before testing.