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Annals of Surgery logoLink to Annals of Surgery
. 1985 Jan;201(1):81–86.

The pentagastrin test in the diagnosis of the carcinoid syndrome. Blockade of gastrointestinal symptoms by ketanserin.

H Ahlman, A Dahlström, K Grönstad, L E Tisell, K Oberg, M J Zinner, B M Jaffe
PMCID: PMC1250622  PMID: 2578277

Abstract

The levels of 5-hydroxytryptamine (serotonin, 5-HT) and substance P (SP) were assayed (using high performance liquid chromatography-electron capture and radioimmunoassay methods) in the peripheral blood of 17 patients with known mid-gut carcinoids, 16 of whom had hepatic metastases. All patients had supranormal basal levels of 5-HT and SP. The clinical and hormonal changes induced by two provocation tests, intravenous pentagastrin (PG) and calcium infusion, were compared. Pentagastrin caused flushing in all the patients, induced gastrointestinal symptoms in all but one of the patients with hepatic involvement, and universally elevated circulating 5-HT levels. Pretreatment with a 5-HT2-receptor blocking agent, ketanserin, abolished the gastrointestinal effects but had virtually no influence on either 5-HT levels or flushing induced by intravenous pentagastrin. In contrast, calcium infusion induced carcinoid symptoms in only two of six patients, and this was consistently associated with stimulation of circulating serotonin levels. The authors conclude that 1) 5-HT may be responsible for the gastrointestinal symptoms in carcinoid patients, but it does not seem to play any role in flushing; 2) ketanserin may be a useful therapeutic agent in alleviating gastrointestinal symptoms in carcinoid patients; 3) differential responses to PG suggests that SP is released from a site different from that of 5-HT; 4) it is possible that SP may contribute to the mediation of flushing, but it cannot be the sole agent causing this symptom; and 5) the pentagastrin test with measurements of 5-HT levels in peripheral blood seems to be superior to calcium infusion as a provocative test in documenting the diagnosis of carcinoid disease.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akande B., Reilly P., Modlin I. M., Jaffe B. M. Radioimmunoassay measurement of substance P release following a meat meal. Surgery. 1981 Mar;89(3):378–383. [PubMed] [Google Scholar]
  2. Alumets J., Håkanson R., Ingemansson S., Sundler F. Substance P and 5-HT in granules isolated from an intestinal argentaffin carcinoid. Histochemistry. 1977 Jun 8;52(3):217–222. doi: 10.1007/BF00495858. [DOI] [PubMed] [Google Scholar]
  3. DUBACH U. C., GSELL O. R. Carcinoid syndrome: alleviation of diarrhoea and flushing with "Deseril" and Ro 5-1025. Br Med J. 1962 May 19;1(5289):1390–1391. doi: 10.1136/bmj.1.5289.1390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dharmsathaphorn K., Sherwin R. S., Cataland S., Jaffe B., Dobbins J. Somatostatin inhibits diarrhea in the carcinoid syndrome. Ann Intern Med. 1980 Jan;92(1):68–69. doi: 10.7326/0003-4819-92-1-68. [DOI] [PubMed] [Google Scholar]
  5. ERSPAMER V., ASERO B. Identification of enteramine, the specific hormone of the enterochromaffin cell system, as 5-hydroxytryptamine. Nature. 1952 May 10;169(4306):800–801. doi: 10.1038/169800b0. [DOI] [PubMed] [Google Scholar]
  6. Engelman K., Lovenberg W., Sjoerdsma A. Inhibition of serotonin synthesis by para-chlorophenylalanine in patients with the carcinoid syndrome. N Engl J Med. 1967 Nov 23;277(21):1103–1108. doi: 10.1056/NEJM196711232772101. [DOI] [PubMed] [Google Scholar]
  7. Feldman J. M. Serotonin metabolism in patients with carcinoid tumors: incidence of 5-hydroxytryptophan-secreting tumors. Gastroenterology. 1978 Dec;75(6):1109–1114. [PubMed] [Google Scholar]
  8. Frölich J. C., Bloomgarden Z. T., Oates J. A., McGuigan J. E., Rabinowitz D. The carcinoid flush. Provocation by pentagastrin and inhibition by somatostatin. N Engl J Med. 1978 Nov 9;299(19):1055–1057. doi: 10.1056/NEJM197811092991908. [DOI] [PubMed] [Google Scholar]
  9. GADDUM J. H., GIARMAN N. J. Preliminary studies on the biosynthesis of 5-hydroxytryptamine. Br J Pharmacol Chemother. 1956 Mar;11(1):88–92. doi: 10.1111/j.1476-5381.1956.tb01033.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hallberg D., Pernow B. Effect of substance P on various vascular beds in the dog. Acta Physiol Scand. 1975 Feb;93(2):277–285. doi: 10.1111/j.1748-1716.1975.tb05816.x. [DOI] [PubMed] [Google Scholar]
  11. Jaffe B. M., Condon S. Prostaglandins E and F in endocrine diarrheagenic syndromes. Ann Surg. 1976 Oct;184(4):516–524. doi: 10.1097/00000658-197610000-00015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kaplan E. L., Jaffe B. M., Peskin G. W. A new provocative test for the diagnosis of the carcinoid syndrome. Am J Surg. 1972 Feb;123(2):173–179. doi: 10.1016/0002-9610(72)90329-7. [DOI] [PubMed] [Google Scholar]
  13. Kaplan E. L., Sizemore G. W., Peskin G. W., Jaffe B. M. Humoral similarities of carcinoid tumors and medullary carcinomas of the thyroid. Surgery. 1973 Jul;74(1):21–29. [PubMed] [Google Scholar]
  14. Kellum J. M., Jaffe B. M. Validation and application of a radioimmunoassay for serotonin. Gastroenterology. 1976 Apr;70(4):516–522. [PubMed] [Google Scholar]
  15. Kellum J. M., Jr, Jaffe B. M. Release of immunoreactive serotonin following acid perfusion of the duodenum. Ann Surg. 1976 Nov;184(5):633–636. doi: 10.1097/00000658-197611000-00018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. OATES J. A., MELMON K., SJOERDSMA A., GILLESPIE L., MASON D. T. RELEASE OF A KININ PEPTIDE IN THE CARCINOID SYNDROME. Lancet. 1964 Mar 7;1(7332):514–517. doi: 10.1016/s0140-6736(64)92907-1. [DOI] [PubMed] [Google Scholar]
  17. PAGE I. H., CORCORAN A. C., UDENFRIEND S., SZOEDSMA A., WEISSBACH H. Argentaffinoma as endocrine tumour. Lancet. 1955 Jan 22;268(6856):198–199. doi: 10.1016/s0140-6736(55)91924-3. [DOI] [PubMed] [Google Scholar]
  18. PAGE I. H., MCCUBBIN J. W. Arterial pressure response to infused serotonin in normotensive dogs, cats, hypertensive dogs and man. Am J Physiol. 1956 Feb;184(2):265–270. doi: 10.1152/ajplegacy.1956.184.2.265. [DOI] [PubMed] [Google Scholar]
  19. PEART W. S., PORTER K. A., ROBERTSON J. I., SANDLER M., BALDOCK E. Carcinoid syndrome due to pancreatic-duct neoplasm secreting 5-hydroxytryptophan and 5-hydroxytryptamine. Lancet. 1963 Feb 2;1(7275):239–243. doi: 10.1016/s0140-6736(63)90952-8. [DOI] [PubMed] [Google Scholar]
  20. Polak J. M., Heitz P., Pearse A. G. Differential localisation of substance P and motilin. Scand J Gastroenterol Suppl. 1976;39:39–42. [PubMed] [Google Scholar]
  21. Ponzio F., Jonsson G. A rapid and simple method for the determination of picogram levels of serotonin in brain tissue using liquid chromatography with electrochemical detection. J Neurochem. 1979 Jan;32(1):129–132. doi: 10.1111/j.1471-4159.1979.tb04519.x. [DOI] [PubMed] [Google Scholar]
  22. Reimann I. W., Frölich J. C. Mechanism of antihypertensive action of ketanserin in man. Br Med J (Clin Res Ed) 1983 Aug 6;287(6389):381–383. doi: 10.1136/bmj.287.6389.381-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Roberts L. J., 2nd, Bloomgarden Z. T., Marney S. R., Jr, Rabin D., Oates J. A. Histamine release from a gastric carcinoid: provocation by pentagastrin and inhibition by somatostatin. Gastroenterology. 1983 Feb;84(2):272–275. [PubMed] [Google Scholar]
  24. SANDLER M., SNOW P. J. An atypical carcinoid tumour secreting 5-hydroxytryptophan. Lancet. 1958 Jan 18;1(7012):137–139. doi: 10.1016/s0140-6736(58)90616-0. [DOI] [PubMed] [Google Scholar]
  25. SJOERDSMA A., WEISSBACH H., TERRY L. L., UDENFRIEND S. Further observations on patients with malignant carcinoid. Am J Med. 1957 Jul;23(1):5–15. doi: 10.1016/0002-9343(57)90353-4. [DOI] [PubMed] [Google Scholar]
  26. Somers G., Pipeleers-Marichal M., Gepts W., Pipeleers D. A case of duodenal somatostatinoma: diagnostic usefulness of calcium--pentagastrin test. Gastroenterology. 1983 Nov;85(5):1192–1198. [PubMed] [Google Scholar]
  27. Tilson M. D. Carcinoid syndrome. Surg Clin North Am. 1974 Apr;54(2):409–423. doi: 10.1016/s0039-6109(16)40288-4. [DOI] [PubMed] [Google Scholar]
  28. Van Nueten J. M., Janssen P. A., Van Beek J., Xhonneux R., Verbeuren T. J., Vanhoutte P. M. Vascular effects of ketanserin (R 41 468), a novel antagonist of 5-HT2 serotonergic receptors. J Pharmacol Exp Ther. 1981 Jul;218(1):217–230. [PubMed] [Google Scholar]
  29. Wells S. A., Jr, Ontjes D. A., Cooper C. W., Hennessy J. F., Ellis G. J., McPherson H. T., Sabiston D. C., Jr The early diagnosis of medullary carcinoma of the thyroid gland in patients with multiple endocrine neoplasia type II. Ann Surg. 1975 Oct;182(4):362–370. doi: 10.1097/00000658-197510000-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wilander E., Portela-Gomes G., Grimelius L., Westermark P. Argentaffin and argyrophil reactions of human gastrointestinal carcinoids. Gastroenterology. 1977 Oct;73(4 Pt 1):733–736. [PubMed] [Google Scholar]
  31. Zinner M. J., Yeo C. J., Jaffe B. M. The effect of carcinoid levels of serotonin and substance P on hemodynamics. Ann Surg. 1984 Feb;199(2):197–204. doi: 10.1097/00000658-198402000-00012. [DOI] [PMC free article] [PubMed] [Google Scholar]

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