Carcinoid

At a Glance

Carcinoids are rare, slowly growing subtypes of neuroendocrine tumors (NETs). They arise most commonly within the gastrointestinal (65% of cases) or respiratory (35% of cases) systems and are characterized by serotonin (5-hydroxytryptamine) production. The carcinoid syndrome occurs in about 10% of carcinoid tumors (usually in the presence of metastatic disease to the liver). It is characterized by a constellation of symptoms resulting from serotonin stimulation of various organs and peripheral tissues. Carcinoids are often discovered incidentally during endoscopic or radiographic procedures.

Carcinoid syndrome is suspected when the patient has suggestive symptoms, such as unexplained diarrhea or flushing. Other symptoms of carcinoid syndrome include tachycardia, hypotension, bronchospasm, telangiectasias, and right-sided heart failure.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Measure 5-hydroxyindoleacetic acid (5-HIAA), the end product of serotonin metabolism, in a 24-hour urine collection. Normal excretion ranges from 2 to 8 mg/day. The test is 75% sensitive and very specific (up to 100%); however, it has several limitations, including false-positive and false-negative results due to ingestion of certain drugs and foods rich in tryptophan. Some patients with carcinoid syndrome have only modest elevations of 5-HIAA (<30 mg/day), seen in other causes of increased 5-HIAA excretion, but most often values are greater than 100 mg/day.

5-HIAA testing may not be useful in foregut (bronchial, gastric) carcinoids, which often lack aromatic amino acid decarboxylase and so do not produce serotonin. Many patients with these tumors have minimal or no increase in urinary 5-HIAA excretion. Measurement of urinary serotonin may be of value in these patients, since the enzyme DOPA decarboxylase in the renal parenchyma may convert 5-hydroxytryptophan to serotonin, which is excreted.

Serum chromogranin A (CGA) is a nonspecific marker for well-differentiated neuroendocrine tumors that does not distinguish the various tumor subtypes. CGA is elevated in 90% of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). CGA concentration correlates with tumor volume, and it may be useful for staging, prognosis, and monitoring response to therapy. Plasma CGA concentrations usually parallel 5-HIAA excretion. In some cases, CGA can be more sensitive than urinary 5-HIAA. CGA is increased in other conditions, including renal insufficiency and severe malabsorption syndrome.

Blood serotonin concentration should be measured if 5-HIAA testing produces equivocal results. The mean fasting blood serotonin concentration in healthy subjects ranges from 71 to 310 ng/mL. Patients with carcinoid syndrome usually have markedly elevated values (790-4500 ng/mL). However, the specificity of this test has not been determined.

The epinephrine provocation test is useful to evaluate patients who present with flushing but have normal or minimally elevated biochemical markers. For provocation testing, the patient is placed in a supine position and an intravenous (IV) bolus of epinephrine is administered. Appearance of flushing, hypotension, and tachycardia 45-120 seconds after an injection constitutes a positive test. Test sensitivity is as high as 100%.(Table 1)