Procalcitonin (PCT) has been suggested as a tumor marker in patients with medullary thyroid carcinoma (MTC). Clinical application data in long term follow-up are missing.
210 serum samples of 169 consecutive patients with MTC (92 sporadic, 77 hereditary, 158 postoperative follow-up, 11 preoperative) were collected between 2018 and 2020. Postoperative patients were stratified into three groups according to their disease status at the end of follow-up: cured (n=51, calcitonin (CT) levels < limit of quantitation), minimal residual disease (n=55, detectable CT and no metastases provable by imaging methods), metastatic disease (n=52). In five patients CT and PCT were measured while on therapy with tyrosine kinase inhibitors (TKI). CT was analyzed by the Roche ECLIA, PCT by three assays from Roche, PES, Abbott.
The mean ± SD values seen with the three PCT assays in the MTC response groups, cured: <0.06, 0.016 ± 0.007, 0.014 ± 0.007 ng/mL, minimal residual disease: 0.511 ± 0.800, 0.389 ± 0.687, 0.341 ± 0.614 ng/mL, metastatic disease 109 ± 202, 60.4 ± 110, 63.3 ± 115 ng/mL correlate well with the CT results in these groups: cured <1.0 pg/mL, minimal residual disease 91.3 ± 121.5 pg/mL, metastatic disease 14,489 ± 30,772 pg/mL. There was a significant correlation (p<0.001) between the three PCT assays (Roche/PES r=0.970, Roche/Abbott r=0.976, Abbott/PES r=0.995). In the course of treatment with TKI both CT and PCT reflected clinical state. Preoperative PCT in hereditary MTC has the same diagnostic validity than CT.
PCT measured with three different immunoassays is as good as the standard tumor marker CT in the follow-up of MTC but has a superior analytical stability.
Research funding: None declared.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: The study was approved by the Ethics Committee of the University of Heidelberg (S-003/2015).
1. Kratzsch, J, Petzold, A, Raue, F, Reinhardt, W, Brocker-Preuss, M, Gorges, R, et al.. Basal and stimulated calcitonin and procalcitonin by various assays in patients with and without medullary thyroid cancer. Clin Chem 2011;57:467–74. https://doi.org/10.1373/clinchem.2010.151688.Search in Google Scholar PubMed
2. Kahaly, GJ, Algeciras-Schimnich, A, Davis, TE, Diana, T, Feldkamp, J, Karger, S, et al.. United States and European multicenter prospective study for the analytical performance and clinical validation of a novel sensitive fully automated immunoassay for calcitonin. Clin Chem 2017;63:1489–96. https://doi.org/10.1373/clinchem.2016.270009.Search in Google Scholar PubMed
3. Karagiannis, AK, Girio-Fragkoulakis, C, Nakouti, T. Procalcitonin: a new biomarker for medullary thyroid cancer? a systematic review. Anticancer Res 2016;36:3803–10.Search in Google Scholar
4. Algeciras-Schimnich, A, Preissner, CM, Theobald, JP, Finseth, MS, Grebe, SK. Procalcitonin: a marker for the diagnosis and follow-up of patients with medullary thyroid carcinoma. J Clin Endocrinol Metab 2009;94:861–8. https://doi.org/10.1210/jc.2008-1862.Search in Google Scholar PubMed PubMed Central
5. Machens, A, Lorenz, K, Dralle, H. Utility of serum procalcitonin for screening and risk stratification of medullary thyroid cancer. J Clin Endocrinol Metab 2014;99:2986–94. https://doi.org/10.1210/jc.2014-1278.Search in Google Scholar PubMed
6. Walter, MA, Meier, C, Radimerski, T, Iten, F, Kranzlin, M, Muller-Brand, J, et al.. Procalcitonin levels predict clinical course and progression-free survival in patients with medullary thyroid cancer. Cancer 2010;116:31–40. https://doi.org/10.1002/cncr.24738.Search in Google Scholar PubMed
7. Giovanella, L, Imperiali, M, Piccardo, A, Taborelli, M, Verburg, FA, Daurizio, F, et al.. Procalcitonin measurement to screen medullary thyroid carcinoma: a prospective evaluation in a series of 2705 patients with thyroid nodules. Eur J Clin Invest 2018;48:e12934. https://doi.org/10.1111/eci.12934.Search in Google Scholar PubMed PubMed Central
9. Novotny, AR, Luppa, P, Rosenberg, R, Schneider, H, Maak, M, Bartels, H, et al.. Procalcitonin can be used for monitoring sepsis in patients with medullary thyroid carcinoma. Thyroid 2009;19:1287–9. https://doi.org/10.1089/thy.2009.0093.Search in Google Scholar PubMed
10. Wells, SAJr, Asa, SL, Dralle, H, Elisei, R, Evans, DB, Gagel, RF, et al.. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid 2015;25:567–610. https://doi.org/10.1089/thy.2014.0335.Search in Google Scholar PubMed PubMed Central
11. Raue, F, Bruckner, T, Frank-Raue, K. Long-term outcomes and aggressiveness of hereditary medullary thyroid carcinoma: 40 Years of experience at one center. J Clin Endocrinol Metab 2019;104:4264–72. https://doi.org/10.1210/jc.2019-00516.Search in Google Scholar PubMed
12. Lindsey, SC, Ganly, I, Palmer, F, Tuttle, RM. Response to initial therapy predicts clinical outcomes in medullary thyroid cancer. Thyroid 2015;25:242–9. https://doi.org/10.1089/thy.2014.0277.Search in Google Scholar PubMed
13. Opsahl, EM, Akslen, LA, Schlichting, E, Aas, T, Brauckhoff, K, Hagen, AI, et al.. Trends in diagnostics, surgical treatment, and prognostic factors for outcomes in medullary thyroid carcinoma in Norway: a nationwide population-based study. Eur Thyroid J 2019;8:31–40. https://doi.org/10.1159/000493977.Search in Google Scholar PubMed PubMed Central
14. Wolinski, K, Kaznowski, J, Klimowicz, A, Maciejewski, A, Lapinska-Cwojdzinska, D, Gurgul, E, et al.. Diagnostic value of selected biochemical markers in the detection of recurrence of medullary thyroid cancer - comparison of calcitonin, procalcitonin, chromogranin A, and carcinoembryonic antigen. Endokrynol Pol 2017;68:434–7. https://doi.org/10.5603/EP.a2017.0038.Search in Google Scholar PubMed
15. Giovanella, L, Fontana, M, Keller, F, Verburg, FA, Ceriani, L. Clinical performance of calcitonin and procalcitonin Elecsys® immunoassays in patients with medullary thyroid carcinoma. Clin Chem Lab Med 2021;59:743–7.10.1515/cclm-2020-1424Search in Google Scholar PubMed
17. Machens, A, Lorenz, K, Dralle, H. Prediction of biochemical cure in patients with medullary thyroid cancer. Br J Surg 2020;107:695–704. https://doi.org/10.1002/bjs.11444.Search in Google Scholar PubMed
18. Jung, KY, Kim, SM, Yoo, WS, Kim, BW, Lee, YS, Kim, KW, et al.. Postoperative biochemical remission of serum calcitonin is the best predictive factor for recurrence-free survival of medullary thyroid cancer: a large-scale retrospective analysis over 30 years. Clin Endocrinol 2016;84:587–97. https://doi.org/10.1111/cen.12852.Search in Google Scholar PubMed
19. Giovanella, L, Giordani, I, Imperiali, M, Orlandi, F, Trimboli, P. Measuring procalcitonin to overcome heterophilic-antibody-induced spurious hypercalcitoninemia. Clin Chem Lab Med 2018;56:e191–e3. https://doi.org/10.1515/cclm-2017-0993.Search in Google Scholar PubMed
20. Giovanella, L, Maffioli, M, Suriano, S, Dorizzi, RM. Elevated calcitonin and procalcitonin levels in nonmedullary benign and malignant thyroid nodules. Clin Endocrinol 2010;72:852–3. https://doi.org/10.1111/j.1365-2265.2009.03733.x.Search in Google Scholar PubMed
21. Lim, SK, Guechot, J, Vaubourdolle, M. Negative predictive value of procalcitonin in medullary thyroid carcinoma. Ann Biol Clin 2016;74:213–8. https://doi.org/10.1684/abc.2015.1115.Search in Google Scholar PubMed
22. Brutsaert, EF, Gersten, AJ, Tassler, AB, Surks, MI. Medullary thyroid cancer with undetectable serum calcitonin. J Clin Endocrinol Metab 2015;100:337–41. https://doi.org/10.1210/jc.2014-3095.Search in Google Scholar
24. El Ayadi, A, Herndon, DN, Finnerty, CC. 21 - biomarkers in burn patient care. In: Herndon, DN, editor. Total burn care. Amsterdam: Elesevier; 2018:232–5 pp.10.1016/B978-0-323-47661-4.00021-6Search in Google Scholar
25. Whang, KT, Steinwald, PM, White, JC, Nylen, ES, Snider, RH, Simon, GL, et al.. Serum calcitonin precursors in sepsis and systemic inflammation. J Clin Endocrinol Metab 1998;83:3296–301. https://doi.org/10.1210/jcem.83.9.5129.Search in Google Scholar
26. Assicot, M, Gendrel, D, Carsin, H, Raymond, J, Guilbaud, J, Bohuon, C. High serum procalcitonin concentrations in patients with sepsis and infection. Lancet 1993;341:515–8. https://doi.org/10.1016/0140-6736(93)90277-n.Search in Google Scholar
27. Becker, KL, Nylen, ES, White, JC, Muller, B, Snider, RHJr. Clinical review 167: procalcitonin and the calcitonin gene family of peptides in inflammation, infection, and sepsis: a journey from calcitonin back to its precursors. J Clin Endocrinol Metab 2004;89:1512–25. https://doi.org/10.1210/jc.2002-021444.Search in Google Scholar PubMed
29. Waterston, J, Chang, EP, Dombalagian, M, Messick, K, Messick, W, Seaver, LC, et al.. Evaluation of the ARCHITECT BRAHMS PCT (procalcitonin) assay. Clin Chem 2016;62(A-310 Suppl).Search in Google Scholar
30. Lippi, G, Salvagno, GL, Gelati, M, Pucci, M, Lo Cascio, C, Demonte, D, et al.. Two-center comparison of 10 fully-automated commercial procalcitonin (PCT) immunoassays. Clin Chem Lab Med 2019;58:77–84. https://doi.org/10.1515/cclm-2019-0888.Search in Google Scholar PubMed
The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2021-0428).
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