CARCINOID-SYNDROME AND SEROTONIN - THERAPEUTIC EFFECTS OF KETANSERIN

The carcinoid syndrome can arise when effluent blood from carcinoid tumor tissue gains access to the systemic, as opposed to the protal, venous system. Features include facial flushing, diarrhea, wheezing, right-sided cardiac lesions, and retroperitoneal fibrosis. Attacks of flushing, diarrhea, and wheezing can be provoked by bolus injections of adrenaline, noradrenaline, or pentagastrin. While serotonin usually predominates, carcinoid tumors can also secrete, in varying proportions, 5-hydroxytryptophan, kallikrein, kinins, substance P and other neuropeptides, prostaglandins, catecholamines, and histamine. Of these, serotonin, kinins, histamine, and substance P are possible mediators of flushes; serotonin and substance P of hyperperistalsis; and serotonin, kinins, or histamine of bronchial constriction. Despite the gross excess of circulating serotonin, nearly all is platelet bound and therefore inactive. Very little is free in plasma. Demonstration of a contribution of serotonin to carcinoid attacks requires assay of free plasma serotonin; measurements of whole blood or serum serotonin are of little value. Some, but not all, provoked flushes have been shown to be accompanied by a rise in free plasma serotonin or substance P; an increase in circulating kinins has been more consistently shown. The 5HT2 antagonist ketanserin has been found to inhibit both provoked and spontaneous attacks of flushing, diarrhea, and dyspnea in a proportion of patients with carcinoid syndrome. Intravenous ketanserin has controlled attacks of systemic hypertension during anesthesia and operation, and should also be useful in these circumstances for the relief of pulmonary hypertension or bronchial constriction. Because of the diversity and variability of hormones produced to excess in the carcinoid syndrome, a wide range of drugs is necessary for its treatment. Ketanserin is a valuable addition to the therapeutic repertoire in this fascinating, but often distressing, disease. © 1990 Kluwer Academic Publishers.