carcinoid syndrome

The term carcinoid syndrome refers to a constellation of symptoms mediated by various humoral factors, namely, serotonin and the tachykinins, elaborated by carcinoid tumors.

Carcinoid syndrome is most likely from metastases of a midgut (jejunum, ileum, ascending colon and appendix) tumor to the liver. Hindgut and foregut carcinoids rarely cause carcinoid syndrome. The frequency of carcinoids is GI > pulmonary. Within the GI tract, the frequency is small intestine > rectum > appendix > colon > stomach, but the incidence of rectal carcinoids is rising.

In the presence of localized disease, carcinoid neoplasms produce serotonin, which is taken up and stored in platelets while the excess is inactivated from the liver and lung and transformed into 5-HIAA.

In the presence of liver metastases, however, patients may develop malignant carcinoid syndrome, which results when vasoactive substances produced by the carcinoid tumor escape hepatic degradation and gain access to the systemic circulation.

It is also because of the high level of serotonin degradation by the liver that it is relatively uncommon for disease localized to the gut to display symptoms of serotonin secretion. Clinical findings of carcinoid syndrome include skin flushing, excessive diarrhea, right-sided heart disease, and bronchoconstriction.

Nearly 40% of patients exhibiting carcinoid syndrome develop carcinoid heart disease (CHD) with fibrotic endocardial plaques and associated heart valve dysfunction that classically involves the tricuspid valve.

Advanced changes in tricuspid valvular disease have been shown to be associated with poor long-term survival, and carcinoid valvular disease, rather than tumor dissemination, is the cause of death in approximately one third of these patients.

Though the mechanism behind CHD is not fully understood, serotonin is presumed to be the catalyst for the cardiac fibrotic process based on murine in vivo models of CHD.

Nearly 95% of patients present with right-sided heart valve disease, characterized by tricuspid insufficiency and pulmonary stenosis (the so called TIPS process) and the subsequent development of pulmonary hypertension.

Left-sided cardiac disease may be seen in up to 10% of patients, as is commonly associated with angina and coronary vasospasm.