Download PDF
Horm Metab Res
DOI: 10.1055/a-2794-3447
Original Article: Endocrine Care

Procalcitonin as a Tumour Marker in Medullary Thyroid Carcinoma: A Comparative Study with Calcitonin and Carcinoembryonic Antigen

Authors

  • Stylianos Kopanos

    1   Academic Department of Endocrinology, Diabetes and Infectiology, Klinikum Bielefeld, Klinikum Bielefeld gemGmbH, Bielefeld, Germany (Ringgold ID: RIN14970)

  • Ahmed Hossam Khalil

    2   Internal Medicine & Gastroenterology, Independent Consultant, Marl, Germany

  • Sandra Nicole Scheel

    3   Academic Department of Endocrinology, Diabetes and Infectiology, Klinikum Bielefeld, Medical School and University Medical Centre East Westphalia-Lippe Bielefeld University, Germany, Klinikum Bielefeld gemGmbH, Bielefeld, Germany (Ringgold ID: RIN14970)

  • Michael Wehmeier

    4   Institute of Medical Laboratory Diagnostics, Microbiology and Transfusion Medicine, University Medical Center OWL, Bielefeld, Germany, Klinikum Bielefeld Mitte, Bielefeld, Germany (Ringgold ID: RIN91788)

  • Joachim Feldkamp

    5   Academic Department of Endocrinology, Diabetes and Infectiology, Klinikum Bielefeld, Klinikum Bielefeld, Bielefeld, Germany

This research received no specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Further Information
Also available at
   Permissions and Reprints

Abstract

Medullary thyroid carcinoma is a rare neuroendocrine tumor of parafollicular C-cells. Calcitonin is the primary tumor marker but presents several limitations, including assay variability and false positives in renal dysfunction, proton pump inhibitor use and smoking. Procalcitonin may offer advantages in stability and specificity. To evaluate the diagnostic performance of procalcitonin compared to calcitonin and carcinoembryonic antigen in patients with medullary thyroid carcinoma, we conducted a retrospective study of 60 patients with histologically confirmed medullary thyroid carcinoma at a single endocrine center. Calcitonin, procalcitonin, and carcinoembryonic antigen levels were analyzed pre- and postoperatively over a 4-year period (2015–2019). Statistical analyses included Spearman’s correlation and receiver operating characteristic curve analysis. Subgroup analyses examined the effects of renal dysfunction, proton pump inhibitors, and smoking. Calcitonin and procalcitonin showed a strong correlation (r=0.874 and p<0.001). Procalcitonin maintained high specificity and sensitivity (area under the curve>0.95 across all years) and remained unaffected by the proton pump inhibitor use or renal impairment. Carcinoembryonic antigen correlated with tumor progression but lacked sufficient specificity alone. The combined use of calcitonin and procalcitonin improved diagnostic accuracy. In all patients with detectable tumor burden, procalcitonin was positive. False-positive calcitonin results were observed in patients without evidence of active diseases but with renal dysfunction or proton pump inhibitor use; procalcitonin remained negative in these cases. Procalcitonin is a reliable tumor marker for medullary thyroid carcinoma, especially in postoperative surveillance. Its stability and independence from common confounders make it a valuable complement to calcitonin. The combined assessment of calcitonin and procalcitonin enhances diagnostic performance and should be considered in routine clinical practice.

Keywords

Medullary thyroid carcinoma - procalcitonin - cancer - calcitonin - tumor marker

Supplementary Material



Publication History

Received: 19 November 2025

Accepted after revision: 21 January 2026

Article published online:
05 February 2026

© 2026. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

  • References

  • 1 Zarkesh M, Arab N, Tavangar SM. et al. Utilizing the circulating tumor markers in diagnosis and management of medullary thyroid cancer. Pathol Res Pract 2022; 229: 153694
    Search in Google Scholar
  • 2 Woliński K, Kaznowski J, Klimowicz A. 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: 434-437
    Search in Google Scholar
  • 3 Wells SA, Asa SL, Dralle H. et al. Revised American thyroid association guidelines for the management of medullary thyroid carcinoma. Thyroid 2015; 25: 567-610
    Search in Google Scholar
  • 4 Trimboli P, Crescenzi A, Saggiorato E. et al. Novel acquisitions in the diagnosis of medullary thyroid carcinoma. Minerva Endocrinol 2017; 42: 238-247
    Search in Google Scholar
  • 5 Rosario PW, Mourão GF. Diagnostic Utility of Procalcitonin for Sporadic Medullary Thyroid Carcinoma in Patients with Nodular Disease and Mild or Moderate Hypercalcitoninemia. Horm Metab Res 2022; 54: 220-223
    Search in Google Scholar
  • 6 Raue F, Frank-Raue K. Long-term follow-up in medullary thyroid carcinoma. Recent Results Cancer Res 2015; 204: 207-225
    Search in Google Scholar
  • 7 Ordoulidis SEM, Siampanopoulou M. Clarification on the role of thyroid scintigraphy in the era of TIRADS: a response to Trimboli et al. (2024). Endocrine 2024; 86: 1188-9
    Search in Google Scholar
  • 8 Leimbach RD, Hoang TD, Shakir MKM. Diagnostic Challenges of Medullary Thyroid Carcinoma. Oncol Switz 2021; 99: 422-432
    Search in Google Scholar
  • 9 Giovanella L, Verburg FA, Imperiali M. et al. Comparison of serum calcitonin and procalcitonin in detecting medullary thyroid carcinoma among patients with thyroid nodules. Clin Chem Lab Med 2013; 51: 1477-1481
    Search in Google Scholar
  • 10 Lim SK, Guéchot J, Vaubourdolle M. Negative predictive value of procalcitonin in medullary thyroid carcinoma. Ann Biol Clin (Paris) 2016; 72: 213-218
    Search in Google Scholar
  • 11 Giovanella L, Fontana M, Keller F. et al. Clinical performance of calcitonin and procalcitonin Elecsys®immunoassays in patients with medullary thyroid carcinoma. Clin Chem Lab Med 2021; 59: 743-747
    Search in Google Scholar
  • 12 Jin LX, Moley JF. Surgery for lymph node metastases of medullary thyroid carcinoma: A review. Cancer 2016; 122: 358-366
    Search in Google Scholar
  • 13 Machens A, Dralle H. Surgical Treatment of Medullary Thyroid Cancer. Recent Results Cancer Res 2025; 223: 247-266
    Search in Google Scholar
  • 14 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
    Search in Google Scholar
  • 15 Kratzsch J, Willenberg A, Frank-Raue K. et al Procalcitonin measured by three different assays is an excellent tumor marker for the follow-up of patients with medullary thyroid carcinoma. Clin Chem Lab Med 2021; 59: 1861-1868
    Search in Google Scholar
  • 16 Trimboli P, Lauretta R, Barnabei A. et al. Procalcitonin as a postoperative marker in the follow-up of patients affected by medullary thyroid carcinoma. Int J Biol Markers 2018; 33: 156-160
    Search in Google Scholar
  • 17 Censi S, Stefano MD, Repaci A. et al. Basal and Calcium-Stimulated Procalcitonin for the Diagnosis of Medullary Thyroid Cancers: Lights and Shadows. Front Endocrinol 2021; 12: 754565
    Search in Google Scholar
  • 18 Bihan H, Becker KL, Snider RH. et al. Calcitonin precursor levels in human medullary thyroid carcinoma. Thyroid 2003; 13: 819-822
    Search in Google Scholar
  • 19 Algeciras-Schimnich A, Carol MP, Theobald JP. et al. Procalcitonin: A marker for the diagnosis and follow-up of patients with medullary thyroid carcinoma. J Clin Endocrinol Metab 2009; 94: 861-868
    Search in Google Scholar
  • 20 Chaftari AM, Hachem R, Reitzel R. et al. Role of procalcitonin and interleukin-6 in predicting cancer, and its progression independent of infection. PLoS ONE 2015; 10: e0130999
    Search in Google Scholar
  • 21 Bae YJ, Schaab M, Kratzsch J. Calcitonin as biomarker for the medullary thyroid carcinoma. Recent Results Cancer Res 2015; 204: 117-137
    Search in Google Scholar
  • 22 Gambardella C, Offi C, Patrone R. et al. Calcitonin negative Medullary Thyroid Carcinoma: A challenging diagnosis or a medical dilemma?. BMC Endocr Disord 2019; 19: 45
    Search in Google Scholar
  • 23 Giovanella L, Garo ML, Ceriani L. et al. Procalcitonin as an Alternative Tumor Marker of Medullary Thyroid Carcinoma. J Clin Endocrinol Metab 2021; 106: 3634-3643
    Search in Google Scholar
  • 24 Censi S, Manso J, Mian C. Other markers of medullary thyroid cancer, not only calcitonin. Eur J Endocrinol 2023; 188: R1-R13
    Search in Google Scholar