Interpretation

Metastasizing midgut carcinoid tumors usually produce blood or serum serotonin (5-hydroxytryptamine) concentrations greater than 1000 ng/mL. However, elevations above 400 ng/mL are suggestive of carcinoid tumors as the cause of carcinoid syndrome-like symptoms. Lesser increases may be nonspecific or drug-related (see Cautions).

Only a minority of patients with carcinoid tumors will have elevated serotonin levels. It is usually impossible to diagnose small carcinoid tumors (>95% of cases) without any symptoms suggestive of carcinoid syndrome by measurement of serotonin, 5-hydroxyindoleacetic acid (5-HIAA), or chromogranin A.

In patients with more advanced tumors, circulating serotonin is elevated in nearly all patients with midgut tumors, but only in approximately 50% of those with foregut carcinoids, and in no more than 20% of individuals with hindgut tumors. Foregut and hindgut tumors often have low or absent 5-hydroxytryptophan (5-HTP) decarboxylase activity and, therefore, may produce little if any serotonin. Urinary 5-HIAA is elevated in almost all carcinoid-syndrome patients with midgut tumors, in about 30% of individuals with foregut carcinoids, but almost never in hindgut tumors. Serum chromogranin A measurements are particularly suited for diagnosing hindgut tumors, being elevated in nearly all cases, even though serotonin and 5-HIAA are often normal. Chromogranin A is also elevated in 80% to 90% of patients with foregut and midgut tumors. Therefore, to achieve maximum sensitivity in the initial diagnosis of suspected carcinoid tumors, serotonin in serum/blood, 5-HIAA in urine, and serum chromogranin A should all be measured. In most cases, if none of these 3 analytes is elevated, carcinoids can be excluded as a cause of symptoms suggestive of carcinoid syndrome. For some cases, additional tests, such as urinary serotonin measurement, will be required. An example would be a non-chromogranin-secreting foregut tumor that only produces 5-HTP, rather than serotonin. In this case, circulating chromogranin, serotonin levels, and urinary 5-HIAA levels would not be elevated. However, the kidneys can convert 5-HTP to serotonin, leading to high urinary serotonin levels.

Disease progression can be monitored in patients with serotonin-producing carcinoid tumors by measurement of serotonin in blood. However, at levels above approximately 5000 ng/mL, the serotonin storage capacity of platelets becomes limiting, and there is no longer a linear relationship between tumor burden and blood serotonin levels. Urinary 5-HIAA and serum chromogranin A continue to increase in proportion to the tumor burden to much higher serotonin production levels and are, therefore, better suited for follow-up in patients with extensive disease.