Carcinoid Syndrome (cont.)
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.
Barium small intestinal study. Finding 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 barium small
intestinal x-rays are usually 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 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.
Sometimes 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 initiate
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
(acetaminophen) 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, needles 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 most often represent metastases, with liver
metastases being the most common. CT and MRI scans are not useful for detecting
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 then 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 by 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 are limited.
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.
Next: How are carcinoid tumors and carcinoid syndrome treated? »
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