eMedicine Specialties > Oncology > Carcinomas of the Gastrointestinal Tract

Malignant Carcinoid Syndrome

Author: Luigi Santacroce, MD, Assistant Professor, Medical School, State University at Bari, Italy
Coauthor(s): Laura Diomede, University of Bari School of Medicine, Italy; Lodovico Balducci, MD, Professor of Oncology and Medicine, University of South Florida College of Medicine; Division Chief, Senior Adult Oncology Program, H Lee Moffitt Cancer Center and Research Institute
Contributor Information and Disclosures

Updated: Nov 19, 2009

Introduction

Background

Malignant carcinoid syndrome is the constellation of symptoms typically exhibited by patients with metastases from carcinoid tumors.1,2,3 Carcinoid tumors usually secrete excessive amounts of the hormone serotonin. Carcinoid tumors arise from neuroendocrine cells, which are widespread in the human body, especially in the organs derived from the primitive intestine.

A section (on the right) of an intestinal carcino...

A section (on the right) of an intestinal carcinoid mass arising from the mucosa (150 X). Image courtesy of Professor Pantaleo Bufo, University of Foggia, Italy.

[ CLOSE WINDOW ]
A section (on the right) of an intestinal carcino...

A section (on the right) of an intestinal carcinoid mass arising from the mucosa (150 X). Image courtesy of Professor Pantaleo Bufo, University of Foggia, Italy.


In 1888 Lubarsch first described a carcinoid tumor,4 but Oberndorfer called a group of small, benign-appearing tumors karzinoide tumoren (carcinoid) for the first time in 1907.5

The name was chosen to separate these tumors from ordinary malignancies, but by the 1950s, the fact that carcinoids could be malignant was obvious, thanks to Erspamer and Asero (1952), who identified serotonin production by carcinoid tumors.6 This finding, built on research conducted in the first half of the 20th century, is summarized as follows:

  • In 1914, Gosset and Masson demonstrated that carcinoid tumors might arise from enterochromaffin cells (Kulchitsky cell) within glands of Lieberkühn using silver impregnation techniques.7
  • In 1928, Masson established characterization of carcinoids as argentaffin cell tumors.8
  • In 1980, the World Health Organization (WHO) applied the term carcinoid to all tumors of the diffuse endocrine system (synonymous with amine precursor uptake and decarboxylation [APUD] and neuroendocrine cell system).

These intensely vascularized tumors follow the so-called rule of one third, which states that one third of the tumors are multiple, one third of those in the gastrointestinal (GI) tract are located in the small bowel, one third of patients have a second malignancy, and one third of these tumors metastasize. In addition, some of these tumors produce hormones excessively, causing a condition known as malignant carcinoid syndrome. This syndrome is characterized by hot, red flushing of the face; severe and debilitating diarrhea; and asthma attacks. Malignant carcinoid syndrome occurs in fewer than 10% of patients with a carcinoid tumor. Typically, 90% of carcinoid tumors originate from the distal ileum or appendix (the embryologic midgut9 ); carcinoid tumors represent 90% of appendiceal tumors.

Tumors arising from the foregut and hindgut are considered atypical; however, tumors can originate from any cell of the amine precursor uptake and decarboxylation system and, therefore, produce several intestinal hormones. Most of these tumors produce 5-hydroxytryptamine, which, in physiologic conditions, is taken up and stored in the platelets while the excesses are inactivated in the liver and lung and transformed into 5-hydroxyindoleacetic acid (5-HIAA).

In order of frequency, carcinoids may occur in the appendix (35%), ileum (28%), rectum (13%), and bronchi (13%). Incidence is less than 1% in the pancreas, gallbladder, liver, larynx, testes, and ovaries; however, tumors in these locations frequently metastasize and spread through the mesenteric lymph nodes (see Media file 3) and portal vein.

A section of a rare lymph node metastasis from ad...

A section of a rare lymph node metastasis from adenocarcinoid tumor (250 X). Image courtesy of Professor Pantaleo Bufo, University of Foggia, Italy.

[ CLOSE WINDOW ]
A section of a rare lymph node metastasis from ad...

A section of a rare lymph node metastasis from adenocarcinoid tumor (250 X). Image courtesy of Professor Pantaleo Bufo, University of Foggia, Italy.


Carcinoids do not produce the malignant carcinoid syndrome until they are no longer confined to the small bowel or mesentery, perhaps because of the liver breakdown of tumor products. After spreading to the liver, carcinoids can metastasize to the lungs,10 bone, skin, or almost any organ. Ovarian carcinoids may be considered exceptions. In fact, a patient with ovarian teratomas, whose secretory products enter into the systemic circulation, may present with this syndrome without liver metastasis.11,12

If a patient is thought to have carcinoid syndrome, blood and urine tests must be performed to determine levels of bioactive substances secreted by carcinoid tumors. Imaging studies also must be performed to detect the sites of either primary tumors or metastases. Carcinoid tumors and related syndromes may be a part of multiple endocrine neoplasia.

Pathophysiology

Pathophysiology is closely related to the sites of the primary tumors. When these tumors spread to the liver, patients usually begin to develop malignant carcinoid syndrome. In fact, this syndrome develops when vasoactive substances produced by a carcinoid tumor escape hepatic degradation and gain access to the systemic circulation.

Carcinoids arising in the stomach are usually associated with low gastric acid production, a condition termed hypochlorhydria or achlorhydria. These tumors rarely become malignant and never metastasize, but they sometimes produce histamine.

Carcinoid tumors arising in the lung generally produce serotonin, gastrin, adrenocorticotropic hormone (ACTH), and histamine. Carcinoids that develop outside the appendix are often malignant, while tumors developing in the appendix are usually benign if smaller than 2 cm in diameter. Rectal carcinoid tumors often produce polypeptides (PPs), polypeptide Y, neuropeptide Y, and other peptides, but none of the patients with this disease location have symptoms related to the production of such molecules. Few patients have liver metastases, but if they do have liver metastases, they do not have hormone-related symptoms.

Physiologically, serotonin causes vasodilation and can increase blood clotting by stimulating platelet aggregation, which may result in disseminated intravascular coagulation (DIC); however, serotonin is converted to 5-HIAA in the body. To date, it is well known that the carcinoids also may produce PPs and amines:

  • Acid phosphatase
  • α-glycoprotein
  • α1-antitrypsin
  • Amylin
  • Atrial natriuretic polypeptide
  • Calbindin-D28k
  • Catecholamines
  • Chromogranin A and B (CgA/CgB)
  • Dopamine
  • Fibroblast growth factor (FGF)
  • Gastrin
  • Gastrin-releasing peptide (bombesin)
  • Glucagon/glicentin
  • 5-Hydroxyindoleacetic acid (5-HIAA)
  • 5-Hydroxytryptamine (5-HT)
  • Histamine
  • Insulin
  • Kallikrein
  • Motilin
  • Neuron-specific enolase (NSE)
  • A-Neuropeptide
  • K-Neuropeptide
  • Neurotensin
  • Pancreastatin
  • Pancreatic polypeptide
  • Platelet-dermal growth factor (PDGF)
  • Prostaglandins
  • Pyroglutamyl-glutamyl-prolinamide
  • Secretin
  • Serotonin
  • Somatostatin
  • Substance P
  • Somatotropin release-inhibiting factor (SRIF)
  • Tachykinins
  • β-transforming growth factor (β-TGF)
  • Vasoactive intestinal polypeptide (VIP)

The molecules listed above are responsible for the extreme symptoms of this condition. For example, the reason some patients develop heart disease is not definitively known,13 but the serotonin produced by the tumor is probably involved. Bronchial constriction, which accounts for the asthmalike attacks, seems related to the tumoral tachykinins. Carcinoid diarrhea has been correlated with circulating tachykinins.14 Symptoms may also relate to overproduction of PPs in the pro-opiomelanocortin family (eg, endorphin, enkephalin). Frequently, the enteric blood supply is impaired, which is caused by the desmoplastic reaction of mesenteric peritoneum and determines kinking and angulation of the loops of the small bowel, with result in bowel obstruction.

Serotonin is derived from the amino acid tryptophan, which also serves as a precursor to niacin and several proteins. Increased metabolism of tryptophan by the tumor has been linked to symptoms in patients with carcinoid.15

The main clinical characteristics of the carcinoids arising in the digestive tract that most often cause malignant carcinoid syndrome are as follows:

  1. Gastric carcinoid tumors are sporadic in 15-25% of cases, usually solitary and larger than 1 cm, arising in normal-appearing mucosa from enterochromaffin-like cells in the gastric fundus. These tumors are generally located in the body or fundus of the stomach and identified endoscopically. A large number of patients have metastases at the time of presentation, and over 50% have pernicious anemia. Gastric carcinoid tumors are more common in women during their sixth or seventh decade of life. It may be associated with atypical carcinoid syndrome manifested by flushing and mediated by histamine.
  2. Carcinoid tumors of the small bowel arise from intraepithelial endocrine cells producing 5-HT and account for one third or fewer of small-bowel tumors. Often located in the distal ileum, these tumors are frequently multicentric, and most patients present with metastases to the lymph nodes or liver. Although tumor size is an unreliable predictor of metastatic disease, the 5-year survival rate closely correlates with the stage of disease at presentation (35% of patients survive if one or more distant metastases are present; 65% for localized or regional disease). Patients usually present in the sixth or seventh decade of life, and 5-7% present with carcinoid syndrome.
  3. Appendiceal carcinoids are the most common cancers of the appendix and arise from the subepithelial endocrine cells from the lamina propria and submucosa. In 75% of cases, appendiceal carcinoids are located at the tip. Fewer than 10% of appendiceal carcinoids are located at the base. Appendiceal carcinoids are most frequently diagnosed in women in the fourth or fifth decade of life, and 10% or more are symptomatic. Patients may often be misdiagnosed as having appendicitis. The tumor size is the best prognostic predictor, with a 5-year survival rate of 94% for patients with local disease, 85% if there are regional metastases, and 34% if the patient has one or more distal metastases. It is noteworthy that more than 95% of appendiceal carcinoids are 2 cm or less, with rare metastases, while one third of tumors 2 cm or larger have either nodal or distant metastases. Carcinoid syndrome has been reported in patients with liver metastases.
  4. Carcinoid tumors of the colon account for 1% or fewer of colon tumors and usually arise from serotonin-producing epithelial endocrine cells present in the colon mucosa. Most of the affected patients are in the seventh decade of life and present with abdominal pain, anorexia, and weight loss. At the time of diagnosis, the average tumor diameter is approximately 5 cm, and more than two thirds of patients have either nodal or distant disease. The 5-year survival rate is reported to be near 70% for local disease, 44% if regional metastases exist, and 20% in cases with distant metastases. The 5% of patients with metastatic disease show a malignant carcinoid syndrome.
  5. Rectal carcinoid tumors are responsible for up to 2% of all rectal tumors. The disease usually affects persons in the sixth decade of life and most commonly presents as rectal bleeding, pain, or constipation, while 50% of patients are asymptomatic, with tumors found during routine endoscopy. Generally, the tumor cells contain glucagon and glicentin-related peptides rather than serotonin. The 5-year survival rate is 81% with local disease, 47% for regional disease, and 18% for distant metastases. Note that patients rarely present with carcinoid syndrome, and the syndrome is closely related to tumor size.

Frequency

United States

Probably 7-8 cases of carcinoid are diagnosed in the United States per year, but the actual frequency is almost certainly higher, because many patients never develop the related syndrome. Some researchers estimate that the incidence may be 1-2 cases per 100,000 individuals.

International

Epidemiologic studies have reported incidences of carcinoid tumors ranging from 0.79 to 1.88 per 100,000 population; a study from the Netherlands found an incidence of 1.95 per 100,000 population.16 These numbers are probably underestimates, because a large number of affected individuals do not develop the related syndrome. A Swedish autopsy study reported an incidence of 8.4 cases per 100,000 population.17 Carcinoid tumors are discovered in approximately 1-2 appendectomy cases per 200-300 per year.

Mortality/Morbidity

Tumors that are smaller than 1 cm in diameter rarely metastasize, while lesions larger than 2 cm often metastasize. The presence of a few small metastases to the liver is associated with a longer life expectancy. Morbidity is related to vasoactive amine production. The survival rate usually correlates inversely with the levels of daily urinary 5-HIAA excretion. Death is usually caused by cardiac or hepatic failure and by complications associated with tumor growth. Factors associated with higher mortality are high plasma levels of neuropeptide K and chromogranin A, location of the tumor in the large bowel, advanced disease, and a concomitant second malignancy. Mucus-producing tumors developing in the appendix also have some malignant characteristics.

Race

No racial prevalence is known.

Sex

This syndrome affects men and women equally.

Age

Carcinoids occur most frequently in patients aged 50-70 years. Age at diagnosis ranges from 10-93 years (mean age 55 y).

Clinical

History

Carcinoid tumors grow slowly, and symptoms may not occur for several years, if at all. When symptoms do develop, they are ill defined and may be neglected for a long time before being properly diagnosed. In some cases, carcinoid tumors present as acute appendicitis or chronic pain in the lower right abdominal quadrant. For this reason, the condition is frequently misdiagnosed as irritable bowel syndrome.18 Alcohol intolerance and weight loss also may be associated manifestations. Severity of symptoms varies. Onset of symptoms may be spontaneous or may be precipitated by certain foods and beverages (eg, alcohol), pharmacologic agents, and physical or emotional stress.

  • Diarrhea is common, as is flushing of the face and neck.19 These manifestations result from tumoral hormone production; however, even if a carcinoid tumor produces these molecules, some patients do not experience any symptoms.
  • Right heart problems may develop because the tricuspid valve is stenosed by serotonin action, causing shortness of breath after a few years.
  • Other common problems include the following:
    • Asthma
    • Wheezing
    • Dyspnea
    • Palpitations
    • Low blood pressure
    • Fatigue
    • Dizziness
    • Asthenia
  • Uncommon symptoms include the following:
    • Myopathy
    • Arthritis
    • Arthralgias
    • Irritability, aggression, and lack of impulse control; these have been linked with low levels of plasma tryptophan and presumably with low brain serotonin.15
  • Flushing is a phenomenon of transient vasodilation causing reddening of the face, head, neck, and the upper chest and epigastric areas.20
    • Flushing is the most frequent symptom and may be brief (eg, 2-5 min) or may last for several hours, usually in later disease stages.
    • Flushing may be accompanied by tachycardia, while the blood pressure usually falls or does not change.
    • Malignant carcinoid syndrome is not a cause of sustained hypertension, and a rise in blood pressure during flushing is rare.
    • In addition to cutaneous vasodilation, some patients also develop telangiectasia, primarily on the face and neck, which is most marked in the malar area.
  • Intestinal obstruction may result from the primary tumor or from the sclerosing reaction in the surrounding mesentery. Necrosis of hepatic tumor masses may produce a typical acute syndrome with fever, abdominal pain, tenderness, and leukocytosis.

Physical

Wheezing, facial telangiectasis with cyanosis and edema, pallor, flushing, macular erythema, and periorbital edema, accompanied by hepatomegaly, pellagralike skin lesions, steatorrhea, and chronic diarrhea, all suggest the diagnosis.

  • During chest examination, a pulmonary systolic and diastolic heart murmur may be heard if cardiac involvement is present. Cardiac involvement is associated with pulmonic valve stenosis and/or tricuspid insufficiency.21
  • Bronchospasms, which cause asthmalike attacks, are generally most pronounced during flushing attacks. Bronchospasms are a less common sign of malignant carcinoid syndrome but may be severe.
  • Any sign of niacin deficiency (pellagra) must be investigated carefully.22
  • Debilitating diarrhea is common and may have a secretory component.
    • As many as 20 episodes of diarrhea per day are possible and cause marked debilitation due to fluid, electrolyte, and protein depletion.
    • The diarrhea persists with fasting, fails to disappear when the patient is fed intravenously, and is usually accompanied by flushing; however, diarrhea occurs alone in approximately 15% of patients.
    • Abdominal borborygmi and cramping or pain may be present. When severe, malabsorption may occur and may even cause death.
  • Primary tumors seldom cause gastrointestinal bleeding.
  • Hepatomegaly from metastases is usually present, but extensive metastatic liver involvement may occur before liver function test results become abnormal.
  • Carcinoid heart disease is reported in approximately 50-60% of all patients with malignant carcinoid syndrome and is severe in approximately 25%.
    • Carcinoid heart disease occurs primarily on the right side of the heart but may involve the left side to a minimal degree.
    • Fibrous deposits adhering to the surface of the valvular endocardium may occur as part of this condition.23
    • Thickening of the endocardium of the cardiac chambers and papillary muscles and thickening and deformation of the valve cusps and chordae tendineae can lead to heart failure, influencing valvular function and causing regurgitation, stenosis, or combined functional lesions.
    • The tricuspid valve is affected most commonly.

Causes

  • As with many other cancers, the exact cause is unknown. Malignant carcinoid syndrome does not generally appear to be hereditary.
  • A study of genetic alterations in small bowel carcinoid tumors found that loss of all or most of chromosome 18 was the most common finding. Heterozygosity was also lost on chromosome arms 9p and 16q. Although the amplitude of observed gains was modest in comparison with those reported in some other tumor types, one focal region of recurrent gain on 14q mapped to the locus of the gene encoding the antiapoptotic protein DAD1.24

More on Malignant Carcinoid Syndrome

Overview: Malignant Carcinoid Syndrome
Differential Diagnoses & Workup: Malignant Carcinoid Syndrome
Treatment & Medication: Malignant Carcinoid Syndrome
Follow-up: Malignant Carcinoid Syndrome
Multimedia: Malignant Carcinoid Syndrome
References
[ CLOSE WINDOW ]

References

  1. Bendelow J, Apps E, Jones LE, et al. Carcinoid syndrome. Eur J Surg Oncol. Mar 2008;34(3):289-96. [Medline].

  2. Feldman JM. Carcinoid tumors and syndrome. Semin Oncol. Sep 1987;14(3):237-46. [Medline].

  3. Feldman JM. Carcinoid tumors and the carcinoid syndrome. Curr Probl Surg. Dec 1989;26(12):835-85. [Medline].

  4. Lubarsch O. Ueber den primaren Krebs des Ileum, nebst Bemerhunge uber das gleichzeitge Vorkommen von Krebs und Tuberculose. Virchows Arch. 1888;111:280-317.

  5. Oberndorfer S. Uber die "kleinen Dunndarm Carcinome". Verh Dtsch Ges Pathol. 1907;11:113—6.

  6. Erspamer V, Asero B. Identification of enteramine, the specific hormone of the enterochromaffin cell system, as 5-Hydroxytryptamine. Nature. 1952;169:800-1.

  7. Gosset A, Masson P. Tumeurs endocinne de l'appendice. Presse Med. 1914;22:237-40.

  8. Masson, P. Carcinoids (argentaffin-cell tumors) and nerve hyperplasia of appendicular mucosa. Am J Patholol. 1928;4:181-212.

  9. Ahlman H. Midgut carcinoid tumors. Surg Annu. 1986;18:65-93. [Medline].

  10. Papadogias D, Makras P, Kossivakis K, et al. Carcinoid syndrome and carcinoid crisis secondary to a metastatic carcinoid tumour of the lung: a therapeutic challenge. Eur J Gastroenterol Hepatol. Dec 2007;19(12):1154-9. [Medline].

  11. Bonaros N, Muller S, Bonatti J, et al. Primary ovarian carcinoid heart disease curatively treated with a two-stage procedure. Thorac Cardiovasc Surg. Oct 2007;55(7):467-9. [Medline].

  12. Chaowalit N, Connolly HM, Schaff HV, et al. Carcinoid heart disease associated with primary ovarian carcinoid tumor. Am J Cardiol. May 15 2004;93(10):1314-5. [Medline].

  13. Bhattacharyya S, Davar J, Dreyfus G, et al. Carcinoid heart disease. Circulation. Dec 11 2007;116(24):2860-5. [Medline].

  14. Cunningham JL, Janson ET, Agarwal S, Grimelius L, Stridsberg M. Tachykinins in endocrine tumors and the carcinoid syndrome. Eur J Endocrinol. Sep 2008;159(3):275-82. [Medline].

  15. Russo S, Boon JC, Kema IP, Willemse PH, den Boer JA, Korf J, et al. Patients with carcinoid syndrome exhibit symptoms of aggressive impulse dysregulation. Psychosom Med. May-Jun 2004;66(3):422-5. [Medline]. [Full Text].

  16. Quaedvlieg PF, Visser O, Lamers CB, Janssen-Heijen ML, Taal BG. Epidemiology and survival in patients with carcinoid disease in The Netherlands. An epidemiological study with 2391 patients. Ann Oncol. Sep 2001;12(9):1295-300. [Medline]. [Full Text].

  17. Berge T, Linell F. Carcinoid tumours. Frequency in a defined population during a 12-year period. Acta Pathol Microbiol Scand A. Jul 1976;84(4):322-30. [Medline].

  18. Wilson HM. Chronic subacute bowel obstruction caused by carcinoid tumour misdiagnosed as irritable bowel syndrome: a case report. Cases J. Jan 22 2009;2(1):78. [Medline].

  19. Metcalfe DD. Differential diagnosis of the patient with unexplained flushing/anaphylaxis. Allergy Asthma Proc. 2000;21(1):21-4. [Medline].

  20. Kleyn CE, Lai-Cheong JE, Bell HK. Cutaneous manifestations of internal malignancy: diagnosis and management. Am J Clin Dermatol. 2006;7(2):71-84. [Medline].

  21. Monsegu J, Algayres JP, Ciribilli JM, et al. [Tricuspid insufficiency disclosing carcinoid syndrome]. Rev Med Interne. 1994;15(9):593-6. [Medline].

  22. Shah GM, Shah RG, Veillette H, Kirkland JB, Pasieka JL, Warner RR. Biochemical assessment of niacin deficiency among carcinoid cancer patients. Am J Gastroenterol. Oct 2005;100(10):2307-14. [Medline].

  23. Banzali FM Jr, Tiwari AK, Frantz R, et al. Valvular heart disease caused by carcinoid syndrome: emphasis on the use of intraoperative transesophageal echocardiography. J Cardiothorac Vasc Anesth. Dec 2007;21(6):855-7. [Medline].

  24. Kulke MH, Freed E, Chiang DY, Philips J, Zahrieh D, Glickman JN, et al. High-resolution analysis of genetic alterations in small bowel carcinoid tumors reveals areas of recurrent amplification and loss. Genes Chromosomes Cancer. Jul 2008;47(7):591-603. [Medline].

  25. Granerus G, Lindell SE, Waldenstrom J, et al. Histamine metabolism in carcinoidosis. Lancet. Jun 4 1966;1(7449):1267-8. [Medline].

  26. Campana D, Nori F, Piscitelli L, Morselli-Labate AM, Pezzilli R, Corinaldesi R, et al. Chromogranin A: is it a useful marker of neuroendocrine tumors?. J Clin Oncol. May 20 2007;25(15):1967-73. [Medline].

  27. Bhattacharyya S, Toumpanakis C, Caplin ME, Davar J. Usefulness of N-terminal pro-brain natriuretic peptide as a biomarker of the presence of carcinoid heart disease. Am J Cardiol. Oct 1 2008;102(7):938-42. [Medline].

  28. Sinzinger H, Renner F, Granegger S. Unsuccessful iodine-131 MIBG imaging of carcinoid tumors and apudomas. J Nucl Med. Jul 1986;27(7):1221-2. [Medline].

  29. Garg S, Bourantas CV, Nair RK, Alamgir F. Carcinoid syndrome diagnosed by echocardiography. Int J Cardiol. Feb 11 2009;[Medline].

  30. Bastarrika G, Cao MG, Cano D, et al. Magnetic resonance imaging diagnosis of carcinoid heart disease. J Comput Assist Tomogr. Nov-Dec 2005;29(6):756-9. [Medline].

  31. Sinha V, Dyer P, Shuvro RC, Geh JI, Karandikar S. Case of carcinoid crisis following a fine-needle biopsy of hepatic metastasis. Eur J Gastroenterol Hepatol. Jan 2009;21(1):101-3. [Medline].

  32. Joensuu H, Kumpulainen E, Grohn P. Treatment of metastatic carcinoid tumour with recombinant interferon alfa. Eur J Cancer. 1992;28A(10):1650-3. [Medline].

  33. Hodul P, Malafa M, Choi J, et al. The role of cytoreductive hepatic surgery as an adjunct to the management of metastatic neuroendocrine carcinomas. Cancer Control. Jan 2006;13(1):61-71. [Medline].

  34. Eller R, Frazee R, Roberts J. Gastrointestinal carcinoid tumors. Am Surg. Jul 1991;57(7):434-7. [Medline].

  35. Farndon JR. The carcinoid syndrome: methods of treatment and recent experience with hepatic artery ligation and infusion. Clin Oncol. Dec 1977;3(4):365-75. [Medline].

  36. Codd JE, Drozda J, Merjavy J. Palliation of carcinoid heart disease. Arch Surg. Sep 1987;122(9):1076-7. [Medline].

  37. Bhattacharyya S, Davar J, Dreyfus G, Caplin ME. Carcinoid heart disease. Circulation. Dec 11 2007;116(24):2860-5. [Medline].

  38. Chambers AJ, Pasieka JL, Dixon E, Rorstad O. The palliative benefit of aggressive surgical intervention for both hepatic and mesenteric metastases from neuroendocrine tumors. Surgery. Oct 2008;144(4):645-51; discussion 651-3. [Medline].

  39. Bernheim AM, Connolly HM, Rubin J, Møller JE, Scott CG, Nagorney DM, et al. Role of hepatic resection for patients with carcinoid heart disease. Mayo Clin Proc. Feb 2008;83(2):143-50. [Medline].

  40. Gregor M. Therapeutic principles in the management of metastasising carcinoid tumors: drugs for symptomatic treatment. Digestion. 1994;55 Suppl 3:60-3. [Medline].

  41. Kleyn CE, Lai-Cheong JE, Bell HK. Cutaneous manifestations of internal malignancy: diagnosis and management. Am J Clin Dermatol. 2006;7(2):71-84. [Medline].

  42. Ramage JK, Davies AH, Ardill J, et al. Guidelines for the management of gastroenteropancreatic neuroendocrine (includingcarcinoid) tumours. Gut. Jun 2005;54 Suppl 4:iv:1-16. [Medline].

  43. Patients, Caregivers, and Friends. The Carcinoid Foundation. Available at www.carcinoid.org/index.shtml. Accessed September 27, 2009.

  44. Jabbour-Khoury S, Dabbous A, al-Jazzar M, et al. Anesthetic management of a patient having a carcinoid syndrome. Middle East J Anesthesiol. Oct 2003;17(3):435-47. [Medline].

  45. Anderson AS, Krauss D, Lang R. Cardiovascular complications of malignant carcinoid disease. Am Heart J. Oct 1997;134(4):693-702. [Medline].

  46. Anthony LB, Martin W, Delbeke D, et al. Somatostatin receptor imaging: predictive and prognostic considerations. Digestion. 1996;57 Suppl 1:50-3. [Medline].

  47. Bhattacharyya S, Toumpanakis C, Caplin ME, et al. Analysis of 150 patients with carcinoid syndrome seen in a single year at one institution in the first decade of the twenty-first century. Am J Cardiol. Feb 1 2008;101(3):378-81. [Medline].

  48. Bourgault C, Bergeron S, Bogaty P, et al. A most unusual acute coronary syndrome. Can J Cardiol. Apr 2006;22(5):429-32. [Medline].

  49. de Diego C, Marcos Alberca P, Cabrera JA, et al. Pathognomonic echocardiographic features of carcinoid syndrome. Clin Cardiol. Mar 2006;29(3):134. [Medline].

  50. [Guideline] de Herder WW, O'Toole D, Rindi G. ENETS Consensus Guidelinesfor the Diagnosis and Treatment of Neuroendocrine Gastrointestinal TumorsPart 2 – Midgut and Hindgut Tumors. Neuroendocrinology. 2008;87.

  51. Di Lucca J, Mahé E, Saiag P. [Severe acrocyanosis in carcinoid syndrome]. Ann Dermatol Venereol. Nov 2007;134(11):895-6. [Medline].

  52. Farling PA, Durairaju AK. Remifentanil and anaesthesia for carcinoid syndrome. Br J Anaesth. Jun 2004;92(6):893-5. [Medline].

  53. Feldman JM. Histaminuria from histamine-rich foods. Arch Intern Med. Nov 1983;143(11):2099-102. [Medline].

  54. Frilling A, Rogiers X, Knofel WT, et al. Liver transplantation for metastatic carcinoid tumors. Digestion. 1994;55 Suppl 3:104-6. [Medline].

  55. González O, Alberca MT, Santonja C. Echocardiographic diagnosis of carcinoid disease: exceptional evolution after ovarian tumor resection without cardiac surgery. Eur J Echocardiogr. Dec 2007;8(6):497-500. [Medline].

  56. Hodgson HJ. Controlling the carcinoid syndrome. BMJ. Nov 12 1988;297(6658):1213-4. [Medline].

  57. Jaber WA, Klarich KW. Images in cardiovascular medicine. Carcinoid heart disease. Circulation. Feb 21 2006;113(7):e160-1. [Medline].

  58. Jagernauth S, Patel A, Baig K, et al. Fungal endocarditis of the eustachian valve in carcinoid heart disease: a case report. J Heart Valve Dis. Nov 2007;16(6):631-3. [Medline].

  59. Lee KJ, Connolly HM, Pellikka PA. Carcinoid pulmonary valvulopathy evaluated by real-time 3-dimensional transthoracic echocardiography. J Am Soc Echocardiogr. Apr 2008;21(4):407.e1-2. [Medline].

  60. Majeed F, Porter TR, Tarantolo S, et al. Carcinoid crisis and reversible right ventricular dysfunction after embolization in untreated carcinoid syndrome. Eur J Echocardiogr. Oct 2007;8(5):386-9. [Medline].

  61. Mansencal N, Mitry E, Forissier JF, et al. Assessment of patent foramen ovale in carcinoid heart disease. Am Heart J. May 2006;151(5):1129.e1-6. [Medline].

  62. Maton PN. The carcinoid syndrome. JAMA. Sep 16 1988;260(11):1602-5. [Medline].

  63. Merino J, Zuluaga A, Gutierrez-Tejero F, et al. Pure testicular carcinoid associated with intratubular germ cell neoplasia. J Clin Pathol. Dec 2005;58(12):1331-3. [Medline].

  64. Mignon M. Natural history of neuroendocrine enteropancreatic tumors. Digestion. 2000;62 Suppl 1:51-8. [Medline].

  65. [Best Evidence] Moller JE, Pellikka PA, Bernheim AM, et al. Prognosis of carcinoid heart disease: analysis of 200 cases over two decades. Circulation. Nov 22 2005;112(21):3320-7. [Medline].

  66. Mollet NR, Dymarkowski S, Bogaert J. MRI and CT revealing carcinoid heart disease. Eur Radiol. Dec 2003;13 Suppl 4:L14-8. [Medline].

  67. Park SB, Kim JK, Cho KS. Imaging findings of a primary bilateral testicular carcinoid tumor associated with carcinoid syndrome. J Ultrasound Med. Mar 2006;25(3):413-6. [Medline].

  68. Robertson RG, Geiger WJ, Davis NB. Carcinoid tumors. Am Fam Physician. 2006;74(3):429-34. [Full Text].

  69. Rorstad O. Prognostic indicators for carcinoid neuroendocrine tumors of the gastrointestinal tract. J Surg Oncol. Mar 1 2005;89(3):151-60. [Medline].

  70. Rosenberg JM, Welch JP. Ileal tumor causing carcinoid syndrome without hepatic metastases. Arch Surg. Apr 1984;119(4):485. [Medline].

  71. Shapiro RS, Shafir M, Sung M, et al. Cryotherapy of metastatic carcinoid tumors. Abdom Imaging. May-Jun 1998;23(3):314-7. [Medline].

  72. Somak R, Shramana M, Vijay S, et al. Primary carcinoid tumor of the ovary: a case report. Arch Gynecol Obstet. Jan 2008;277(1):79-82. [Medline].

  73. Stella M, Decian F, Mithieux F, et al. Ileal carcinoid with liver metastasis presenting after ten years with abdominal mass and right heart failure: report of a case. Tumori. Jan-Feb 2006;92(1):83-5. [Medline].

  74. van der Horst-Schrivers AN, Wymenga AN, Links TP, et al. Complications of midgut carcinoid tumors and carcinoid syndrome. Neuroendocrinology. 2004;80 Suppl 1:28-32. [Medline].

  75. Yeo CJ, Couse NF, Zinner MJ. Serotonin and substance P stimulate intestinal secretion in the isolated perfused ileum. Surgery. Jan 1989;105(1):86-92. [Medline].

  76. Zeitlin IJ. Kinin release in the carcinoid syndrome. Lancet. Nov 1971;2(7732):1040. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

malignant carcinoid syndrome, malignant carcinoid tumor, carcinoid tumors, cancer metastases, cancer metastasis, serotonin excess, neuroendocrine tumors, intestinal tumors, gastroenteropancreatic tumors, facial flushing, diarrhea, asthma

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Luigi Santacroce, MD, Assistant Professor, Medical School, State University at Bari, Italy
Disclosure: Nothing to disclose.

Coauthor(s)

Laura Diomede, University of Bari School of Medicine, Italy
Disclosure: Nothing to disclose.

Lodovico Balducci, MD, Professor of Oncology and Medicine, University of South Florida College of Medicine; Division Chief, Senior Adult Oncology Program, H Lee Moffitt Cancer Center and Research Institute
Disclosure: Nothing to disclose.

Medical Editor

Sanjiv S Agarwala, MD, Chief of Oncology and Hematology, St Luke's Cancer Center, St Luke's Hospital and Health Network; Associate Professor of Cancer Biology, University of Pennsylvania
Sanjiv S Agarwala, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Head and Neck Surgery, Eastern Cooperative Oncology Group, and European Society for Medical Oncology
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD, Clinical Professor of Medicine, Division of Hematology/Medical Oncology, Department of Internal Medicine, University of Arizona College of Medicine at Tucson; Consulting Staff, Arizona Cancer Center
Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research
Disclosure: GlobeImmune Salary Consulting; Amplimed Consulting fee Consulting; FibroGen Consulting fee Consulting

RELATED EMEDICINE ARTICLES
 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.