Biochemical mediators of carcinoid syndrome
Carcinoid syndrome results from humoral mediators secreted by NETs that reach the systemic circulation. Carcinoid syndrome does not usually occur with midgut NETs unless there are extensive liver metastases that impair mediator metabolism in the liver or that secrete mediators directly into the circulation via the hepatic vein. Extraintestinal carcinoids may cause carcinoid syndrome without liver metastases because mediators from these tumors are not secreted into the portal veins.
Serotonin, histamine, kallikrein, bradykinin, tachykinins, and prostaglandins are considered the most important humoral mediators. Histamine is the main mediator of flushing; kallikrein, bradykinin, and tachykinins may contribute in some cases. Serotonin is the primary mediator of diarrhea and fibrous tissue formation in the heart, serosal tissues (pleural, peritoneal), and retroperitoneal spaces; kinins and prostaglandins may also contribute to the secretory diarrhea.