Calcitonin may not be the only biomarker for medullary thyroid carcinoma (MTC), according to a study recently published in the European Journal of Endocrinology.

This literature review referenced 110 different publications that aimed to evaluate potential biomarkers for MTC other than calcitonin. The authors noted that although markedly elevated calcitonin levels can almost always confirm a diagnosis of MTC, mild elevations of this hormone do not have a clear clinical significance and require further workup. This realization supports the need to identify other serum markers that may aid in the diagnosis and prognosis of MTC.

“At present, data does not seem solid enough yet to establish effective flowcharts in evaluating a thyroid nodule for MTC, involving alternative serum markers, particularly in cases of moderately high CT levels, with the aim to identify the rare MTC cases correctly, possibly in an early stage,” the authors wrote. 

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Procalcitonin has been proposed in previous publications as a diagnostic tool for MTC. As the precursor of calcitonin itself, a rise in plasma levels correlates with a pathologic process in the C cells of the thyroid. However, many other entities also increase procalcitonin in blood. Due to its lower specificity, procalcitonin can not replace calcitonin in the diagnosis of MTC but could complement it.

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Another proposed marker is the carcinoembryonic antigen (CEA), an already established tumor marker for many other gastrointestinal cancers. This adhesion glycoprotein can increase up to 70% in patients with MTC. Although not specific, CEA might play a role in preoperative tumor size prognosis, as higher levels correlate with greater-sized tumors in MTC.

Another glycoprotein, called chromogranin A, has showcased a sensitivity for MTC of 24% to 50%. Similarly to the other markers, it is not specific and can levels also increase in other neoplasms.

On the other hand, neuron-specific enolase has also been proposed as a diagnostic marker for MTC, exhibiting a sensitivity of 38% to 70% and a specificity of 30% to 85% for neuroendocrine tumors. Regardless, not all MTC is positive for this cytosolic protein.

Finally, some newly proposed markers for MTC include calcitonin gene-related peptide, pro-gastrin-releasing peptide, micro RNAs, and even catecholamines, serotonin, histamine, and adrenocorticotropic hormones. Although some of these show promising results as potential guides in managing MTC, further research is needed to identify a clear clinical significance.


Censi S, Manso J, Mian C. Other markers of medullary thyroid cancer, not only calcitonin. Eur J Endocrinol. Published online January 18, 2023. doi:10.1093/ejendo/lvac009