Which specialties of doctors treat carcinoid syndrome?
Primary care doctors, including family practitioners and internists, will often first suspect the presence of the carcinoid syndrome. Consultation with both gastroenterologists and medical oncologists will soon follow. General surgeons and surgical oncologists are often involved if a primary tumor in the gastrointestinal tract is suspected, even if metastatic disease in the liver is already present.
How are carcinoid tumors and carcinoid syndrome diagnosed?
There are several aspects to the diagnosis of carcinoid tumors:
- Diagnosing the primary carcinoid tumor (the original tumor)
- Diagnosing the carcinoid syndrome
- Diagnosing local tumor metastasis (such as in the lymph nodes adjacent to the primary tumor) and distant metastasis (such as in the liver, bone, and skin)
Diagnosis of carcinoid tumors
In clinical practice, the diagnosis of carcinoid tumor is most commonly made incidentally when tests and procedures are performed for other purposes. For example, carcinoid tumors in the rectum and colon are incidentally found during colonoscopy performed for colon cancer screening, for iron deficiency anemia, or for chronic diarrhea. Carcinoid tumors of the appendix are found when appendectomies are performed for symptoms of appendicitis. Gastric carcinoid tumors are incidentally discovered when upper gastrointestinal endoscopies are performed for symptoms of ulcer, dyspepsia, abdominal pain, or anemia. If these incidentally-found carcinoid tumors are less than 1 cm in size, the prognosis is good because most of them have not metastasized, and can be cured by complete excision.
Small intestinal barium study. Finding the primary small bowel carcinoid tumors early before they become malignant and metastasize is difficult. Small bowel tumors (carcinoid tumors included) are difficult to diagnose because the traditional small intestinal
barium X-rays usually are not accurate in detecting small intestinal tumors that are not yet obstructing the intestine. Furthermore, most of the small intestine cannot be reached by either the upper endoscope or the colonoscope. Therefore, small intestinal carcinoid tumors are often diagnosed late, often after liver metastases or carcinoid syndrome has occurred.
The diagnosis of small intestinal tumors becomes easier when tumors cause small bowel obstruction either by its large size, or by causing scarring around the intestine (fibrosing mesenteritis) which leads to kinking of the small intestine (as discussed previously). Simple x-rays of the abdomen and barium small intestinal studies both can demonstrate small intestinal obstruction, and computerized axial tomography CT scan of the abdomen can demonstrate the extensive scarring of fibrosing mesenteritis. Sometimes, the carcinoid tumor is found at the time of surgery performed to relieve the small intestinal obstruction.
Capsule enteroscopy. In the past several years, capsule enteroscopy has become
widely available. Capsule enteroscopy is a novel technology in which a small capsule is swallowed that contains a camera and a source of light. Thousands of images are obtained by the capsule as it tumbles through the small intestinal, and these images are transmitted to a receiver worn around a patient’s waist. Many small intestinal diseases (ulcers, cancers, lymphomas, bleeding blood vessels, as well as carcinoid tumors) have been discovered by capsule enteroscopy. It is this author’s belief that more and more small intestinal carcinoid tumors will be discovered early as capsule enteroscopy becomes more widely used.
the primary carcinoid tumors of the small intestine or colon can be diagnosed by nuclear medicine octreotide scanning or by CAT scan of the abdomen, but more commonly, these scans are more useful in detecting metastases from carcinoid tumors. (See below.)
Diagnosis of carcinoid syndrome
One way to diagnose carcinoid tumors is by diagnosing the carcinoid syndrome first, and then by searching for the primary carcinoid tumor and its metastases. In patients with episodic attacks of flushing, diarrhea, and sometimes wheezing, the diagnosis of carcinoid syndrome can be confirmed by measuring the excretion of 5-hydroxyindolacetic acid (5-HIAA) in urine collected over a 24 hour period.
Urine for 5-HIAA. In normal, healthy individuals, a majority of the amino acid tryptophan from the diet is converted in the body to nicotinic acid. Carcinoid tumors that cause the carcinoid syndrome, convert most of the tryptophan to serotonin and 5-HIAA. Normal individuals typically excrete less than 8 mg of 5-HIAA in 24 hours. Patients with the carcinoid syndrome can excrete between 100-2000 mg of 5-HIAA in 24 hours. When the urine samples are properly collected and tests properly performed, abnormally elevated urinary 5-HIAA provide an accurate diagnosis of carcinoid syndrome and should
prompt efforts to search for the carcinoid tumors and its metastases.
Certain foods and medications can interfere with the accuracy of measurements of 5-HIAA in the urine by either falsely increasing or decreasing the 5-HIAA values. These medications and foods should be avoided for 2 days before and the day of urine collection.
Foods that falsely elevate 5-HIAA values include avocados, pineapples, bananas, kiwi, plums, egg plant, walnuts, hickory nuts, and pecans. Medications that falsely elevate 5-HIAA values include
(Tylenol), Robitussin, Phenobarbital, Ephedrine, Nicotine, fluorouracil (Carac, Efudex, Fluoroplex) , and mesalamine (Asacol, Pentasa, and Colazal).
Medications that can falsely lower 5-HIAA values include aspirin, heparin, alcohol, methyldopa, imipramine, isoniazid, levodopa, phenothiazines, and MAO inhibitors.
Chromogranin A. Chromogranin A is a protein produced by carcinoid tumors. It is not as widely used as urinary 5-HIAA for diagnosing the carcinoid syndrome, but it is used by doctors for predicting prognosis. Thus, the blood levels of chromogranin A correlates with the amount of tumor in the body (also known as the tumor burden). Patients with very high chromogranin A levels have worse survival than those with lower levels.
Diagnosing carcinoid tumor metastasis
CT and MRI scans. CT and MRI (magnetic resonance imaging) scans are commonly used in the evaluation of abdominal pain, weight loss, abnormal liver tests, and other symptoms. When liver tumors or abnormal lymph nodes are found on these scans, a needle can be inserted into the tumors or nodes to obtain tissue for diagnosis. If adequate amounts of tissue are obtained, an experienced pathologist can diagnose carcinoid tumors by examining the tissue under a microscope. Unfortunately, tumors found by CT and MRI scans often represent metastases, with liver metastases being the most common. CT and MRI scans are not useful for detecting the primary carcinoid tumors in the small intestine or the colon when they are still small and resectable.
Indium 111 octreotide scans. Carcinoid tumor cells, like all other cells, have membranes that surround their contents. The cells of approximately 90% of carcinoid tumors have membranes covered with receptors for a hormone called somatostatin. Somatostatin binds to these receptors. Octreotide is a chemical made to resemble somatostatin, and therefore also binds to the receptors. When radioactive indium 111-labeled octreotide is injected into a patient’s vein, the radioactive octreotide will bind to the membrane of carcinoid tumors. When the patient is placed under a nuclear camera, the carcinoid tumors will appear as bright spots on the scan. This octreotide scan is very accurate (more accurate than CT and MRI scans) in detecting liver and other metastases of carcinoid tumors and is also more accurate than CT scans and MRI scans for detecting primary carcinoid tumors. Patients who have carcinoid tumors that appear on octreotide scans also are more likely to respond to treatment with octreotide. (See below.) Sometimes, additional carcinoid tumors are found in the liver and lymph nodes with the octreotide scan that are not seen
on CT scan.
Indium111-octreotide scans have limitations. The rate of detection of primary carcinoid tumors by the octreotide scan is still only 60%. Scans usually cannot detect primary carcinoid tumors smaller than 1 cm. Scans also cannot detect carcinoid tumors that do not have somatostatin receptors or have receptors that do not bind octreotide. There are two other nuclear scans (PET scans and radioactive MIBG scan) that can be used in conjunction with the octreotide scan that may improve accuracy, but experience with these two scans
In practice, CT, MRI, and octreotide scans often are used in combination to detect carcinoid tumors, often with accuracy rates approaching 90%. Accurately identifying all of the sites of the carcinoid tumor has important implications for treatment. For example, if only liver metastases are found, the patient potentially can be treated by surgical resection of both the primary tumor and the liver metastasis. If carcinoid tumor metastases are found in the liver as well as other organs, then the patient will not be a good surgical candidate.
Bone scan. In approximately 10% of patients with carcinoid tumors the tumor metastasizes to the bones and can cause bone pain. Bone scans using radioactive phosphate are accurate for detecting these bony metastases.
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