Interpretation of Unexpectedly High Levels of Endocrine Tumor Markers.

OBJECTIVE: Endocrine tumor markers (ETMs) are important and indispensable tools in the diagnosis and follow-up of endocrine tumors. Unexpectedly high level of ETM (UHLETM) is often encountered in clinical practice. The objectives of this article are to discuss the approach to UHLETMs and describe the most common UHLETMs.

METHODS: Literature review and personal experience with UHLETMs.

RESULTS: A UHLETM is defined as an ETM level much higher than what an endocrinologist would expect based on the patient's clinical information, other biochemical test results, and imaging findings. Most UHLETMs are false positive, in that they do not indicate the existence or growth of an endocrine tumor. The key issue, however, is how to convincingly prove that a UHLETM is false positive. The most important question to help resolve UHLETMs is whether the UHLETMs are due to false or true results. Some UHLETMs are due to interpretation errors, laboratory errors, or spurious test results, while the true levels of the ETMs are normal or unchanged from previous results. Other UHLETMs are due to nontumor conditions or medications, and the true levels of the ETMs are indeed very high. When it is not straightforward to assess whether certain UHLETMs are due to false or true results, they may be due to novel conditions.

CONCLUSION: UHLETMs provide endocrinologists great opportunities to learn the basic biology and measurement of ETMs. Unresolved UHLETMs are exciting clinical research opportunities which may lead to discovery of new diseases and new mechanisms of measurement interference.

ABBREVIATIONS: 5-HIAAA = 5-hydroxyindoleacetic acid; 5-HTP = 5-hydroxytryptophan; CGA = chromogranin A; ETM = endocrine tumor marker; MTC = medullary thyroid carcinoma; UHLETM = unexpectedly high level of endocrine tumor marker.