Carcinoid Tumor

I. What every physician needs to know.

Carcinoid tumors are rare, slow-growing tumors that originate in the cells of the neuroendocrine system. They are generally asymptomatic. Carcinoid tumors occur most commonly in the gastrointestinal (GI) tract, lungs and bronchi. Carcinoid tumors derive from different embryonic divisions of the gut: foregut tumors originate in the lungs, bronchi or stomach; midgut tumors in the small intestine, appendix or proximal large bowel; and hindgut tumors in the distal colon or rectum.

Carcinoid tumors secrete several bioactive compounds including serotonin and bradykinin and the secretory pattern varies on location. Foregut tumors secrete low levels of serotonin, being deficient in the enzyme needed to convert 5-hydroxytryptophan to serotonin. Midgut tumors secrete high levels of serotonin whereas most hindgut tumors do not secrete 5-hydroxytryptophan or serotonin. These differences in secretory patterns are responsible for the different clinical manifestations and biochemical characteristics of these tumors.

About 5% of patients develop metastatic disease or carcinoid syndrome if there are metastases to the liver or if the primary tumor is not in the GI tract. Carcinoid syndrome is classically described as flushing, diarrhea and valvular heart disease,and results from bioactive secretions of functional tumors.

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Diarrhea and cardiac complications are probably caused by serotonin itself, but the cutaneous flushing is thought to be produced by one of the kinins.

II. Diagnostic Confirmation: Are you sure your patient has carcinoid tumor?

Carcinoid tumor can be difficult to diagnose, as it is often asymptomatic. Many carcinoid tumors are found incidentally during surgeries for other reasons. Diagnosis of carcinoid syndrome is based on consistent symptoms plus objective evidence e.g. carcinoid tumor on histology, elevated biologic markers e.g. 5-hydroxyindoleacetic acid (5-HIAA) or plasma chromogranin A.

A. History Part I: Pattern Recognition:

Symptoms vary by tumor site.

Pulmonary carcinoids

Symptoms related to bronchial obstruction by tumor may include recurrent pneumonia for years, cough, hemoptysis, chest pain, symptoms of Cushing’s syndrome with ectopic adrenocorticotropic hormone (ACTH) secretion, and symptoms of acromegaly with ectopic secretion of growth-hormone releasing factor. Carcinoid syndrome as described above is not common as pulmonary carcinoids are usually non-secretory.

Gastric carcinoid tumors

Symptoms may include abdominal pain, diarrhea and GI bleeding in patients with Zollinger-Ellison syndrome. Histamine-mediated atypical carcinoid syndrome occurs in patients with sporadic gastric carcinoids, with flushing being the primary symptom.

Tumors of the small intestine

Symptoms may include abdominal pain and obstruction. With appendiceal tumors, less than ten percent of patients are symptomatic. Appendicitis may be the presenting symptom with appendiceal tumors.

Carcinoid heart disease may present with symptoms of right heart failure. There may be pulmonary stenosis or tricuspid incompetence.

B. History Part 2: Prevalence:

Carcinoid tumors occur in 8.4 per 100,000 people.

C. History Part 3: Competing diagnoses that can mimic carcinoid tumor.

  • Pheochromocytoma

  • Thyroid disease

  • Asthma

  • Congestive heart failure (CHF)

  • Any cause of diarrhea

  • Toxic ingestions

For cardiac symptoms, rule out endocarditis, dilated cardiomyopathy, ischemic heart disease and rheumatic heart disease.

D. Physical Examination Findings.

Carcinoid tumors are generally found incidentally during surgery for other conditions. Wheezes may occur with pulmonary carcinoid. Hepatomegaly can be seen with liver metastases. Flushing and telangiectasia can be seen with carcinoid syndrome.

E. What diagnostic tests should be performed?

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

A twenty-four hour urine test for 5-HIAA is recommended. This is the end product of serotonin. The test has a 75% sensitivity but high specificity. False positive results may be induced by the ingestion of certain drugs and tryptophan/serotonin-rich foods. This is the most useful initial diagnostic test. In non-secretory tumors such as those from the foregut and hindgut, the urine 5-HIAA may return negative (unless with liver metastasis), and is diagnosed from imaging studies.

Plasma chromogranin A (plasma chromogranin B and C are less sensitive indicators of neuroendocrine tumors as compared to chromogranin A) can also be used.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

  • Contrast enhanced computed tomography (CT). For GI tract tumors: spiral, contrast-enhanced triple-phase CT of the abdomen and pelvis.

  • Magnetic resonance imaging (MRI) is the most sensitive method for detection of liver metastases.

  • Somatostatin-receptor-scintigraphy (SRS, octreoscan): Many carcinoid tumors express high levels of somatostatin receptors and can therefore be imaged with a radiolabeled form of the somatostatin analog octreotide using SRS. This is the preferred imaging test.

  • Bronchoscopy for bronchial carcinoid

  • Echocardiogram

  • Endoscopic ultrasound

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

Blood serotonin test.

III. Default Management.

A. Immediate management.

Management of acute carcinoid syndrome can be life-threatening due to the release of vasoactive substances from the tumor. This can be spontaneous or secondary to surgery, chemotherapy or hepatic artery embolization. It manifests as cardiovascular collapse (hypo or hypertension) tachycardia, and a change in mental status.

Treatment differs from those for other causes of shock in that catecholamines and calcium should not be used since they trigger the release of large amounts of bioactive chemicals from the tumor. In addition, shock in this situation is refractory to fluid. The mainstay of treatment is the infusion of octreotide and plasma. This can be prevented by giving octreotide prior to manipulating the tumor.

B. Physical Examination Tips to Guide Management.


C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

Tumor markers and CT/MRI should be carried out every 3 months in the first year after diagnosis. After this, in patients with stable disease check tumor markers every 4-6 months and annual OctreoScan (and if surgery, radiation or treatment change considered) Long term in patients post surgery, take a history and do a physical examination and tumor markers every 6 months for years 1-3 and annually thereafter. Perform imaging only as indicated (ie if tumor markers positive). OctreoScan or CT is preferred. In symptomatic patients will need to follow more closely and will depend on the aggressiveness of the disease, but at least every 3 months in the first year and every 4-6 months after this with tumor markers and imaging as appropriate.

D. Long-term management.

Treatment decisions are complex and related to the location of the tumor and whether metastases are present. Patients should be referred to subspecialists who are familiar with the management of carcinoid tumor. Localized carcinoid tumors should be treated with surgery. Other treatment options for metastatic disease or treatment of carcinoid syndrome include somatostatin analogs (octreotide and lanreotide), interferon and chemotherapy.

Ninety percent of patients with carcinoid syndrome have metastatic disease typically to the liver. Patients need to control symptoms by avoiding alcohol and specific forms of activity that involve pressure to the right upper quadrant. Can be treated with long acting somatostatin analogues, hepatic artery embolization and chemotherapy.

Diarrhea can be managed with codeine and cholestyramine. Asthma can be managed with bronchodilators. Flushing by avoidance of alcohol and certain foods that trigger symptoms such as coffee, cheese, chocolate.

Cardiac complications can be treated with diuretics, valve replacement and long-acting somatostatin analogs.

E. Common Pitfalls and Side-Effects of Management


IV. Management with Co-Morbidities

Peri-operative management of carcinoid:

Somatostatin analogs may reduce the risk of carcinoid crisis

Patients who are well-controlled with long-acting analogs can be treated with another dose 2 hours preoperatively

For emergency surgery give IV or SQ bolus of somatostatin analog

There is some evidence that intra-operative octreotide may reduce the risk of complications (hypotension, bronchospasm)

V. Transitions of Care

A. Sign-out considerations While Hospitalized.


B. Anticipated Length of Stay.


C. When is the Patient Ready for Discharge?


D. Arranging for Clinic Follow-up

1. When should clinic follow up be arranged and with whom?

Patients need to be referred for subspecialty management. (Gastroenterology, Oncology, Pulmonary etc.)

VI. What's the evidence?

Kulke, MH, Maher, RJ. “Carcinoid tumors”. NEJM. vol. 340. 1999. pp. 858-68.

Schriner, Yao, JC, Ajani, JA. “Carcinoid – a comprehensive review”. Acta Oncol. vol. 42. 2003. pp. 672-92.

Maroun, J, Kocha, W, Kvals, J. “Guidelines for the diagnosis and management of carcinoid tumors Part 1 : The gastrointestinal tract. A statement from a Canadian national expert group”. Curr Oncology. vol. 13. 2006. pp. 67-79.

Robertson, R. “Carcinoid tumors”. Am Fam Physiian. vol. 74. 2006. pp. 429-434.

Adarwa, G. “Carcinoid tumors what should increase our suspicion”. Cleve Clin J Med. vol. 75. 2008. pp. 849