Carcinoid Syndrome

Endocrinologically active tumors of the diffuse peripheral endocrine or paracrine system (neuroendocrine tumors) produce various amines and polypeptides with corresponding symptoms and signs, including carcinoid syndrome. Carcinoid syndrome is usually due to endocrinologically active malignant tumors that develop from neuroendocrine cells (mostly in the ileum—see Small Bowel Tumors Small-Bowel Tumors Small-bowel tumors account for 1 to 5% of gastrointestinal tumors. Small-bowel cancer accounts for an estimated 11,110 cases and about 1,700 deaths in the US annually ( 1). Diagnosis is by enteroclysis... read more ) and produce serotonin. It can, however, occur as a result of neuroendocrine tumors elsewhere in the gastrointestinal tract (particularly the appendix and rectum), pancreas, bronchi Bronchial Carcinoid Bronchial carcinoids are rare (1 to 2% of all lung cancers in adults), slow-growing neuroendocrine tumors arising from bronchial mucosa; they affect patients in their 40s to 60s. Carcinoid tumors... read more , or, rarely, the gonads. Rarely, certain highly malignant tumors (eg, oat cell carcinoma of the lung, pancreatic islet cell carcinoma Overview of Pancreatic Endocrine Tumors Pancreatic endocrine tumors arise from islet and gastrin-producing cells and often produce many hormones. Although these tumors develop most often in the pancreas, they may appear in other organs... read more , medullary thyroid carcinoma Medullary Thyroid Carcinoma There are 4 general types of thyroid cancer. Most thyroid cancers manifest as asymptomatic nodules. Rarely, lymph node, lung, or bone metastases cause the presenting symptoms of small thyroid... read more ) are responsible.

An intestinal carcinoid does not usually cause carcinoid syndrome unless hepatic metastases have occurred because metabolic products released by the tumor are rapidly destroyed by blood and liver enzymes in the portal circulation (eg, serotonin by hepatic monoamine oxidase). Hepatic metastases, however, release metabolic products via the hepatic veins directly into the systemic circulation. Metabolic products released by primary pulmonary and ovarian carcinoids bypass the portal route and may similarly induce symptoms. Rare intestinal carcinoids with only intra-abdominal spread can drain directly into the systemic circulation or the lymphatics and cause symptoms.

Serotonin, the primary hormone produced by carcinoid tumors, acts on smooth muscle to cause diarrhea, colic, and malabsorption. Histamine and bradykinin, which are produced in smaller amounts, cause flushing through their vasodilator effects.

The role of prostaglandins and various polypeptide hormones, which may be produced by paracrine cells, awaits further investigation; elevated human chorionic gonadotropin and pancreatic polypeptide levels are occasionally present with carcinoids.

Some patients develop right-sided endocardial fibrosis, leading to pulmonic stenosis Pulmonic Stenosis Pulmonic stenosis (PS) is narrowing of the pulmonary outflow tract causing obstruction of blood flow from the right ventricle to the pulmonary artery during systole. Most cases are congenital... read more and tricuspid regurgitation Tricuspid Regurgitation Tricuspid regurgitation (TR) is insufficiency of the tricuspid valve causing blood flow from the right ventricle to the right atrium during systole. The most common cause is dilation of the... read more . Lesions of the left side of the heart, which have been reported with bronchial carcinoids Bronchial Carcinoid Bronchial carcinoids are rare (1 to 2% of all lung cancers in adults), slow-growing neuroendocrine tumors arising from bronchial mucosa; they affect patients in their 40s to 60s. Carcinoid tumors... read more , are rare because serotonin is destroyed during passage through the lungs.

The most common (and often earliest) sign of carcinoid syndrome is

Flushing is often precipitated by emotional stress or the ingestion of food, hot beverages, or alcohol.

Striking skin color changes may occur, ranging from pallor or erythema to a violaceous hue.

Abdominal cramps with recurrent diarrhea occur and are often the patient’s major complaint. Malabsorption syndrome Overview of Malabsorption Malabsorption is inadequate assimilation of dietary substances due to defects in digestion, absorption, or transport. Malabsorption can affect macronutrients (eg, proteins, carbohydrates, fats)... read more may occur.

Patients with valvular lesions may have a heart murmur Cardiac Auscultation Auscultation of the heart requires excellent hearing and the ability to distinguish subtle differences in pitch and timing. Hearing-impaired health care practitioners can use amplified stethoscopes... read more . A few patients have wheezing due to bronchospasm, and some have decreased libido and erectile dysfunction Erectile Dysfunction Erectile dysfunction is the inability to attain or sustain an erection satisfactory for sexual intercourse. Most erectile dysfunction is related to vascular, neurologic, psychologic, and hormonal... read more . Pellagra Niacin Deficiency Dietary niacin deficiency (causing pellagra) is uncommon in countries with low rates of food insecurity. Clinical manifestations include the three Ds: localized pigmented rash (dermatitis);... read more develops rarely.

Carcinoids are suspected based on their symptoms and signs. Diagnosis is confirmed by demonstrating increased urinary excretion of the serotonin metabolite 5-HIAA. To avoid false-positive results, clinicians do the test after the patient has abstained from serotonin-containing foods (eg, bananas, tomatoes, plums, avocados, pineapples, eggplant, walnuts) for 3 days. Certain drugs, including guaifenesin, methocarbamol, and phenothiazines, also interfere with the test and should be stopped temporarily before testing. On the 3rd day, a 24-hour urine sample is collected for assay. Normal excretion of 5-HIAA is < 10 mg/day (< 52 micromol/day); in patients with carcinoid syndrome, excretion is usually > 50 mg/day (> 260 micromol/day).

In the past, provocative tests with calcium gluconate, catecholamines, pentagastrin, or alcohol have been used to induce flushing. Although these tests may be helpful when the diagnosis is in doubt, they are rarely used and must be done with care.

Prognosis depends on primary site, grade, and stage. Despite metastatic disease, neuroendocrine tumors are slow growing, and survival of 10 to 15 years is not unusual.

Resection of primary gastrointestinal and lung carcinoids is often curative.

For patients with hepatic metastases, surgical debulking, while not curative, may relieve symptoms and, in certain instances, prolong survival. In addition, locoregional therapies for liver metastases could include transarterial chemoembolization (TACE), bland embolization, radioembolization with yttrium-90 microspheres, or radiofrequency ablation. Other promising treatments for metastatic or recurrent disease include everolimus, a mammalian target of rapamycin (mTOR) inhibitor, and newly developed peptide receptor radionuclides.

Radiation therapy is unsuccessful, in part because of the poor tolerance of normal hepatic tissue to radiation.

No effective chemotherapeutic regimen has been established. Combination treatment that includes streptozotocin, 5-fluorouracil, and cyclophosphamide is typically used only for symptomatic patients with grade 2 (intermediate grade) metastatic disease who are unresponsive to other therapies, or have high tumor proliferation rates. However, the response duration is short.

The following is an English-language resource that may be useful. Please note that The Manual is not responsible for the content of this resource.