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Carcinoid syndrome and serotonin: Therapeutic effects of ketanserin

  • Serotonin and Vascular Disease
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Summary

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.

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References

  1. Ahlman H. Serotonin and carcinoid tumors. J Cardiovasc Pharmacol 1985;7(Suppl 7):S79-S85.

    Google Scholar 

  2. Grahame-Smith DG. Serotonin (5-hydroxytryptamine, 5-HT). Q J Med 1988;67:459–466.

    Google Scholar 

  3. Moertel CG, Weiland LH, Nagorney DM, Dockerty MB. Carcinoid tumor of the appendix: Treatment and prognosis. N Engl J Med 1987;317:1699–1701.

    Google Scholar 

  4. Rankin R, Nirodi NS, Browne MK. Carcinoid tumor of the oesophagus: Report of a case. Scott Med J, 1980;25:245–249.

    Google Scholar 

  5. Robertson JIS, Peart WS, Andrews TM. The mechanism of facial flushes in the carcinoid syndrome. Q J Med 1961;31:103–123.

    Google Scholar 

  6. Robertson JIS, Andrews TM. Free serotonin in human plasma: Quantitative and qualitative estimation. Lancet 1961;1:578–580.

    Google Scholar 

  7. Peart WS, Porter KA, Robertson JIS, Sandler M, Baldock E. A carcinoid tumor due to pancreatic duct neoplasm secreting 5-hydroxytryptophan and 5-hydroxytryptamine. Lancet 1963;1:239–242.

    Google Scholar 

  8. Oates JA, Melmon K, Sjoerdsma A, Gillespie L, Mason DT. Release of a kinin peptide in the carcinoid syndrome. Lancet 1964;1:514–517.

    Google Scholar 

  9. Sharma BK, Smits BJ, Robinson R, Burns S, Tournson EN. Carcinold tumor secreting dopa. Br Med J 1984;288:111–112.

    Google Scholar 

  10. Hodgson HJF. Controlling the carcinoid syndrome. Br Med J 1988;297:1213–1214.

    Google Scholar 

  11. Menzies DG, Campbell IW, Starkey IR. Infective endocarditis complicating tricuspid valve disease in the carcinoid syndrome. Br Med J 1988;296:682.

    Google Scholar 

  12. Gupta A, Saibil F, Kassim O, McKee J. Retroperitoneal fibrosis caused by carcinoid tumour. Q J Med 1985;56:367–375.

    Google Scholar 

  13. Robertson JIS. Serotonin, serotonin antagonists, hypertension and vascular diseases. Curr Opin Cardiol 1988; 3:702–714.

    Google Scholar 

  14. Peart WS, Robertson JIS, Andrews TM. Facial flushing produced in patients with carcinoid syndrome by intravenous adrenaline and noradrenaline. Lancet 1959; 2:715–716.

    Google Scholar 

  15. Frolich JC, Bloomgarten ZT, Oates JA, McGuigan JE, Rabinowitz D. The carcinoid flush: Provocation by pentagastrin and inhibition by somatostatin. N Engl J Med 1978;299:1055–1057.

    Google Scholar 

  16. Ahlman H, Dahlstrom A, Gronstad K, Jaffe BM, Nilsson O, Oberg K. The pentagastrin test in the diagnosis of the carcinoid syndrome. J Cardiovasc Pharmacol 1985;7(Suppl 7):S86-S88.

    Google Scholar 

  17. Vanhoutte P, Amery A, Birkenhäger W, et al. Serotonergic mechanisms in hypertension: Focus on ketanserin. Hypertension 1988;11:111–133.

    Google Scholar 

  18. Gustafsen J, Lendorf A, Raskov H, Boesby S. Ketanserin versus placebo in carcinoid syndrome: A clinical controlled trial. Scand J Gastroenterol 1986;21:816–818.

    Google Scholar 

  19. Friis J, Stage JG, Fischerman NK, Winther K. Trial of ketanserin treatment in carcinoid syndrome: Reversal of platelet activation by ketanserin. Proceedings, International Workshop on Serotonin, Platelets and Disease, Stockholm, 1983:1–2.

  20. Ahlman H, Dahlstrom A, Gronstadt K, Tisell LE, Oberg K, Zinner MJ, Jaffe BM. The pentagastrin test in the diagnosis of the carcinoid syndrome: Blockade of gastrointestinal symptoms by ketanserin. Ann Surg 1985; 201:81–86.

    Google Scholar 

  21. Sullivan PA, O'Donovan M. Ketanserin, a 5-HT antagonist, onistin symptomatic treatment of carcinoid syndrome. Irish J Med Sci 1985;155:436.

    Google Scholar 

  22. Janssen Pharmaceutica, Beerse, Belgium. Clinical and Research File on Ketanserin.

  23. Howse JJ. Ketanserin in a patient with carcinoid syndrome during open heart surgery. Janssen Clinical ReportN26 290.

  24. Zuurmond WWA, Van Der Kun JEM, Scheijgrond H. Treatment of circulatory complications during anaesthesia for the removal of a carcinoid tumour with ketanserin, a new selective competitive serotonin antagonist. Janssen Clinical Report N27505.

  25. Fischler M, Dentan M, Westerman MN, Vourch G, Freitag B. Prophylactic use of ketanserin in a patient with carcinoid syndrome. Br J Anaesth 1983;55:920.

    Google Scholar 

  26. Houghton K, Carter JA. Peri-operative management of carcinoid syndrome using ketanserin. Anaesthesia 1986; 41:596–599.

    Google Scholar 

  27. Castheley PA, Jablons M, Griepp RB, Ergin MA, Goodman K. Ketanserin in the pre-operative and intra-operative management of a patient with carcinoid tumor undergoing tricuspid valve replacement. Anesth Analg 1986;65:809–811.

    Google Scholar 

  28. Demoulin JC, Bertholet M, Soumagne D, David JL, Kulbertus HE. 5-HT2 receptor blockade in the treatment of heart failure. Lancet 1981;1:1186–1188.

    Google Scholar 

  29. Maton PN, Camilleri M, Griffin G, Allison DJ, Hodgson HJF, Chadwick VS. Role of hepatic arterial embolisation in the carcinoid syndrome. Br Med J 1983;287:932–935.

    Google Scholar 

  30. Peart WS, Robertson JIS. The effect of a serotonin antagonist, methysergide (UML 491), in carcinoid disease. Lancet 1961;2:1172–1174.

    Google Scholar 

  31. Noppen M, Jacobs A, Van Belle S, Herregodts P, Somers G. Inhibitory effects of ranitidine on flushing and serum serotonin concentrations in carcinoid syndrome. Br Med J 1988;296:682–683.

    Google Scholar 

  32. Oberg K, Funa K, Alm G. Effects of leukocyte interferon on clinical symptoms and hormone levels in patients with mid-gut carcinoid tumors and carcinoid syndrome. N Engl J Med 1983;309:129–133.

    Google Scholar 

  33. Stahl SM, Levin B, Freedman DX. Serotonin depletion by fenfluramine in the carcinoid syndrome. N Engl J Med 1982;306:429.

    Google Scholar 

  34. Kvols LK, Moertel CG, O'Connell MJ, Schutt AJ, Rubin J, Hahn RG. Treatment of the malignant carcinoid syndrome: Evaluation of a long-acting somatostatin analogue. N Engl J Med 1986;315:663–666.

    Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Prince of Wales Hospital, Chinese University of Hong Kong, Beerse, Belgium

    J. Ian S. Robertson

  2. Janssen Research Foundation, Beerse, Belgium

    J. Ian S. Robertson

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Robertson, J.I.S. Carcinoid syndrome and serotonin: Therapeutic effects of ketanserin. Cardiovasc Drug Ther 4, 53–58 (1990). https://doi.org/10.1007/BF00053427

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