Pathophysiology
Clinical meaning
Carcinoid syndrome results from systemic release of bioactive amines (serotonin, histamine, tachykinins, prostaglandins) from well-differentiated neuroendocrine tumors (NETs). Most gastrointestinal NETs drain into the portal system where the liver metabolizes these amines โ syndrome occurs only when liver metastases allow vasoactive substances to bypass hepatic first-pass metabolism and enter systemic circulation (or in primary bronchial/ovarian NETs which drain directly into systemic circulation). Serotonin (5-HT), synthesized from tryptophan via tryptophan hydroxylase, is the primary mediator: it causes intestinal hypermotility (diarrhea via 5-HT3 and 5-HT4 receptors), bronchoconstriction, and fibrosis. Carcinoid heart disease (Hedinger syndrome) occurs in 20-50%: serotonin-mediated endocardial fibrosis predominantly affects right-sided cardiac valves (tricuspid regurgitation and pulmonic stenosis) because serotonin is metabolized by pulmonary MAO before reaching left heart. Flushing is mediated primarily by tachykinins (substance P, neurokinin A) and histamine rather than serotonin. Tryptophan diversion to serotonin synthesis can cause niacin (vitamin B3) deficiency with pellagra-like symptoms.