Clinical features of the carcinoid syndrome
- Jonathan R Strosberg, MD
Jonathan R Strosberg, MD
- Associate Professor
- Department of Gastrointestinal Oncology
- H. Lee Moffitt Cancer Center
- Section Editors
- Kenneth K Tanabe, MD
Kenneth K Tanabe, MD
- Section Editor — Gastrointestinal Malignancies
- Professor of Surgery
- Harvard Medical School
- David C Whitcomb, MD, PhD
David C Whitcomb, MD, PhD
- Section Editor — Pancreatic Diseases
- Professor of Medicine
- University of Pittsburgh School of Medicine
Carcinoid syndrome is the term applied to a constellation of symptoms mediated by various humoral factors elaborated by some well-differentiated neuroendocrine tumors (NETs) of the digestive tract and lungs, which synthesize, store, and release a variety of polypeptides, biogenic amines, and prostaglandins (table 1). Some of these tumor products are responsible for the carcinoid syndrome, but the relative contributions of each and the specificity of any for particular components of the syndrome are uncertain (table 2).
The pathophysiology and clinical manifestations of the carcinoid syndrome will be reviewed here. The diagnosis and treatment of this disorder are discussed separately. (See "Diagnosis of the carcinoid syndrome and tumor localization" and "Staging, treatment, and posttreatment surveillance of nonmetastatic, well-differentiated gastrointestinal tract neuroendocrine (carcinoid) tumors" and "Metastatic well-differentiated gastroenteropancreatic neuroendocrine tumors: Presentation, prognosis, imaging, and biochemical monitoring".)
Neuroendocrine tumors (NETs) may arise anywhere in the gastrointestinal tract, in the lungs, and occasionally, elsewhere (table 3). Carcinoid syndrome is most common in the setting of disseminated disease, particularly liver metastases, but it can occur in apparently locoregional disease. One reason may be understaging. Unappreciated hepatic metastases may be more common than previously reported [1-3], especially in small bowel primaries.
The liver inactivates bioactive products secreted into the portal circulation. This may explain why patients with gastrointestinal NETs most often develop carcinoid syndrome if they have hepatic metastases, resulting in the secretion of tumor products into the systemic circulation . In the large majority of cases, carcinoid syndrome is associated with metastatic tumors originating in the midgut (jejunum, ileum, and cecum); however, the expression is variable in individual patients . Less often, carcinoid syndrome is caused by a NET arising in the lung or in the distal colon or rectum (foregut and hindgut embryologic origin, respectively) . Gastric and lung NETs may be associated with atypical carcinoid syndromes. (See 'Variant syndromes' below.)
Approximately 1 percent of pancreatic NETs secrete excess serotonin and other vasoactive substances that produce the carcinoid syndrome. (See "Clinical characteristics of carcinoid tumors".)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Datta S, Williams N, Suortamo S, et al. Carcinoid syndrome from small bowel endocrine carcinoma in the absence of hepatic metastasis. Age Ageing 2011; 40:760.
- Feldman JM, Jones RS. Carcinoid syndrome from gastrointestinal carcinoids without liver metastasis. Ann Surg 1982; 196:33.
- Haq AU, Yook CR, Hiremath V, Kasimis BS. Carcinoid syndrome in the absence of liver metastasis: a case report and review of literature. Med Pediatr Oncol 1992; 20:221.
- Modlin IM, Kidd M, Latich I, et al. Current status of gastrointestinal carcinoids. Gastroenterology 2005; 128:1717.
- Feldman JM. Carcinoid tumors and syndrome. Semin Oncol 1987; 14:237.
- Halperin DM, Shen C, Dasari A, et al. Frequency of carcinoid syndrome at neuroendocrine tumour diagnosis: a population-based study. Lancet Oncol 2017; 18:525.
- Kvols LK. Metastatic carcinoid tumors and the malignant carcinoid syndrome. Ann N Y Acad Sci 1994; 733:464.
- Swain CP, Tavill AS, Neale G. Studies of tryptophan and albumin metabolism in a patient with carcinoid syndrome, pellagra, and hypoproteinemia. Gastroenterology 1976; 71:484.
- HENDRIX TR, ATKINSON M, CLIFTON JA, INGELFINGER FJ. The effect of 5-hydroxytryptamine on intestinal motor function in man. Am J Med 1957; 23:886.
- von der Ohe MR, Camilleri M, Kvols LK, Thomforde GM. Motor dysfunction of the small bowel and colon in patients with the carcinoid syndrome and diarrhea. N Engl J Med 1993; 329:1073.
- Lie JP. Carcinoid tumor, carcinoid syndrome, and carcinoid heart disease. Prim Cardiol 1982; 8:163.
- Roberts LJ 2nd, Marney SR Jr, Oates JA. Blockade of the flush associated with metastatic gastric carcinoid by combined histamine H1 and H2 receptor antagonists. Evidence for an important role of H2 receptors in human vasculature. N Engl J Med 1979; 300:236.
- Grahame-Smith DG. What is the cause of the carcinoid flush? Gut 1987; 28:1413.
- Oates JA, Pettinger WA, Doctor RB. Evidence for the release of bradykinin in carcinoid syndrome. J Clin Invest 1966; 45:173.
- Oates JA. The carcinoid syndrome. N Engl J Med 1986; 315:702.
- Metz SA, McRae JR, Robertson RP. Prostaglandins as mediators of paraneoplastic syndromes: review and up-date. Metabolism 1981; 30:299.
- Sandler M, Karim SM, Williams ED. Prostaglandins in amine-peptide-secreting tumours. Lancet 1968; 2:1053.
- Vinik AI, McLeod MK, Fig LM, et al. Clinical features, diagnosis, and localization of carcinoid tumors and their management. Gastroenterol Clin North Am 1989; 18:865.
- Makridis C, Theodorsson E, Akerström G, et al. Increased intestinal non-substance P tachykinin concentrations in malignant midgut carcinoid disease. J Gastroenterol Hepatol 1999; 14:500.
- Cunningham JL, Janson ET, Agarwal S, et al. Tachykinins in endocrine tumors and the carcinoid syndrome. Eur J Endocrinol 2008; 159:275.
- Maton PN. The carcinoid syndrome. JAMA 1988; 260:1602.
- Törnebrandt K, Nobin A, Ericsson M, Thomson D. Circulation, respiration and serotonin levels in carcinoid patients during neurolept anaesthesia. Anaesthesia 1983; 38:957.
- Marsh HM, Martin JK Jr, Kvols LK, et al. Carcinoid crisis during anesthesia: successful treatment with a somatostatin analogue. Anesthesiology 1987; 66:89.
- Warner RRP. Carcinoid tumors. In: Gastroenterology, Berk JE (Ed), WB Saunders, Philadelphia 1985.
- Morin LJ, Zuerner RT. Retroperitoneal fibrosis and carcinoid tumor. JAMA 1971; 216:1647.
- Daskalakis K, Karakatsanis A, Stålberg P, et al. Clinical signs of fibrosis in small intestinal neuroendocrine tumours. Br J Surg 2017; 104:69.
- Melmon KL, Sjoerdsma A, Mason DT. Distinctive clinical and therapeutic aspects of the syndrome associated with bronchial carcinoid tumors. Am J Med 1965; 39:568.
- Borch K, Ahrén B, Ahlman H, et al. Gastric carcinoids: biologic behavior and prognosis after differentiated treatment in relation to type. Ann Surg 2005; 242:64.
- Gough DB, Thompson GB, Crotty TB, et al. Diverse clinical and pathologic features of gastric carcinoid and the relevance of hypergastrinemia. World J Surg 1994; 18:473.
- Tryptophan metabolism
- CLINICAL FEATURES
- Cutaneous flushing
- Venous telangiectasia
- Cardiac valvular lesions
- Minor manifestations
- VARIANT SYNDROMES
- Gastric NET variant syndrome
- Lung NET variant syndrome