Calcitonin precursor levels in human medullary thyroid carcinoma

Thyroid. 2003 Aug;13(8):819-22. doi: 10.1089/105072503768499716.


Design: The hormonal serum marker for the presence and course of patients with medullary thyroid cancer (MTC) is the mature calcitonin (CT) peptide. Other CALC-1 gene products such as the 116-amino acid polypeptide prohormone, procalcitonin, as well as its component calcitonin precursors (CTpr) may also be increased in their sera. We performed a study to evaluate the clinical utility of serum levels CTpr in these patients.

Methods: Twenty-one patients with MTC (9 males, 12 females; 23-76 years of age) were evaluated. The diagnosis was confirmed by histologic examination, except for 2 (a proven RET mutation plus an abnormal pentagastrin-stimulated CT level). Nine patients had postoperative hypercalcitoninemia and 3 of these died. The specific assay for mature CT was a commercial immunoradiometric assay (hCT-IRMA); the immunoluminometric assay for CTpr (B.R.A.H.M.S Diagnostica, Berlin, Germany) detects intact procalcitonin and the free CT:CT carboxypeptide-1.

Results: All patients had detectable serum CTpr. These levels considerably exceeded those of mature CT, averaging 7.6-fold greater. CTpr levels correlated positively with mature CT (r = 0.61; p < 0.001). After pentagastrin administration, there was a parallelism of response between the two assays. Whenever there were known metastases, CTpr increased markedly.

Conclusion: This study demonstrates the universal presence of CTpr in the blood of patients with MTC. The measurement of these peptides may offer a new dimension to the clinical evaluation of this malignancy.

MeSH terms

  • Biomarkers, Tumor / blood
  • Calcitonin / blood*
  • Calcitonin Gene-Related Peptide
  • Humans
  • Oncogene Proteins / genetics
  • Prognosis
  • Protein Precursors / blood*
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases / genetics
  • Reference Values
  • Retrospective Studies
  • Thyroid Neoplasms / blood*
  • Thyroid Neoplasms / diagnosis*
  • Thyroid Neoplasms / genetics


  • Biomarkers, Tumor
  • CALCA protein, human
  • Oncogene Proteins
  • Protein Precursors
  • Calcitonin
  • Proto-Oncogene Proteins c-ret
  • RET protein, human
  • Receptor Protein-Tyrosine Kinases
  • Calcitonin Gene-Related Peptide