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Value of routine measurement of serum calcitonin concentrations in patients with nodular thyroid disease: A multicenter study

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Abstract

Background: The routine measurement of serum calcitonin (CT) has been proposed for patients with nodular thyroid disease (NTD), to detect unsuspected medullary thyroid carcinoma (MTC) before surgery. Objective: To assess the prevalence of hyper-calcitoninemia and MTC in NTD patients; to compare the ability of CT measurement and fine needle aspiration cytology (FNAC) to predict MTC; to identify age groups of NTD patients who should be better candidates than others to undergo routine measurement of CT. Patients and methods: 1425 consecutive patients, referred from April 1, 2003, through March 31, 2004, to four Italian endocrine centers due to NTD, were grouped depending on age, and underwent basal and, in some cases, pentagastrin (Pg)-stimulated CT measurement, FNAC and, when indicated, surgery. Serum CT concentrations were measured by an immunoluminometric assay (ILMA). Results: Hyper-calcitoninemia was found in 23 out of 1425 patients. MTC was discovered in 9 patients, all >40 yr old and showing high CT levels. Sensitivity of basal and Pg-stimulated CT to predict MTC before surgery was 100% for both tests, whereas specificity was 95 and 93%, respectively. CT specificity reached 100% when a cutoff value of 20 pg/ml was taken. FNAC showed an overall 86% sensitivity. When >10 mm MTC nodules were considered, FNAC sensitivity approached 100%. On the contrary, a correct cytological diagnosis was obtained in only one out of five patients with <10 mm MTC nodules (microMTC); in one patient with histologically proved microMTC, FNAC even demonstrated a benign lesion. Hypercalcitoninemia or MTC were associated with chronic thyroiditis in 30 or 33% of cases, respectively. C-cell hyperplasia was found in 57% of hypercalcitoninemic patients without MTC. Conclusions: Basal CT measurement detects elevated CT values in 1.6% of NTD patients. Although CT is not a specific marker of MTC, its routine measurement represents a useful tool in the pre-operative evaluation of NTD patients, particularly those >40 yr old presenting with nodules <10 mm, even when FNAC does not show malignant features. To our knowledge, this is the first trial using ILMA to assess the ability of pre-operative CT measurement to predict MTC in a large series of NTD patients.

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References

  1. Mazzaferri EL. Management of a solitary thyroid nodule. N Engl J Med 1993, 328: 553–9.

    Article  CAS  PubMed  Google Scholar 

  2. Singer PA, Cooper DS, Daniels GH, et al. Treatment guidelines for patients with thyroid nodules and well-differentiated thyroid cancer. Arch Intern Med 1996, 156: 2165–72.

    Article  CAS  PubMed  Google Scholar 

  3. Hegedus L, Bonnema SJ, Bennedbaek FN. Management of simple nodular goiter: current status and future perspectives. Endocr Rev 2003, 24: 102–32.

    Article  PubMed  Google Scholar 

  4. Hegedus L. The thyroid nodule. N Engl J Med 2004, 351: 1764–71.

    Article  PubMed  Google Scholar 

  5. Ezzat S, Sarti DA, Cain DR, Braunstein GD. Thyroid incidentalomas: prevalence by palpation and ultrasonography. Arch Intern Med 1994, 154: 1338–40.

    Article  Google Scholar 

  6. Ross DS. Diagnostic approach to and treatment of thyroid nodules. UpToDate Clinical Reference Library 2001, 9: 3 -www.uptodate.com.

    Google Scholar 

  7. Heshmati HM, Gharib H, van Heerden JA, Sizemore GW. Advances and controversies in the diagnosis and management of medullary thyroid carcinoma. Am J Med 1997, 103: 60–9.

    Article  CAS  PubMed  Google Scholar 

  8. Murray D. The thyroid gland. In: Kovacs K, Asa S eds. Functional endocrine pathology. Vol. 1. Boston: Blackwell. 1991, 293–374.

    Google Scholar 

  9. Santoro M, Melillo RM, Carlomagno F, Vecchio G, Fusco A. RET: normal and abnormal functions. Endocrinology 2004, 145: 5448–51.

    Article  CAS  PubMed  Google Scholar 

  10. Gharib H, McConahey WM, Tiegs RD, et al. Medullary thyroid carcinoma: clinicopathologic features and long-term follow-up of 65 patients treated during 1946 through 1970. Mayo Clin Proc 1992, 67: 934–40.

    Article  CAS  PubMed  Google Scholar 

  11. Kebebew E, Ituarte PH, Siperstein AE, Duh QY, Clark OH. Medullary thyroid carcinoma: clinical characteristics, treatment, prognostic factors, and a comparison of staging systems. Cancer 2000, 88: 1139–48.

    Article  CAS  PubMed  Google Scholar 

  12. Fleming JB, Lee JE, Bouvet M, et al. Surgical strategy for the treatment of medullary thyroid carcinoma. Ann Surg 1999, 230: 697–707.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Oertel YC, Oertel JE. Thyroid cytology and histology. Baillieres Best Pract Res Clin Endocrinol Metab 2000, 14: 541–57.

    Article  CAS  PubMed  Google Scholar 

  14. Ravetto C, Colombo L, Dottorini ME. Usefulness of fine-needle aspiration in the diagnosis of thyroid carcinoma: a retrospective study in 37,895 patients. Cancer 2000, 90: 357–63.

    Article  CAS  PubMed  Google Scholar 

  15. Tashjian Jr AH, Howland BG, Melvin KEW, Hill CS Jr. Immunoassay of human calcitonin. Clinical measurement, relation to serum calcium and studies in patients with medullary thyroid carcinoma. N Engl J Med 1970, 283: 890–5.

    CAS  Google Scholar 

  16. Pacini F, Basolo F, Elisei R, Fugazzola L, Cola A, Pinchera A. Medullary thyroid cancer. An immunohistochemical and humoral study using six separate antigens. Am J Clin Pathol 1991, 95: 300–8.

    CAS  Google Scholar 

  17. Elisei R, Bottici V, Luchetti F, et al. Impact of routine measurement of serum calcitonin on the diagnosis and outcome of medullary thyroid cancer: experience in 10,864 patients with nodular thyroid disorders. J Clin Endocrinol Metab 2004, 89: 163–8.

    Article  CAS  PubMed  Google Scholar 

  18. Karanikas G, Abbas M, Poetzi C, et al. Frequency and relevance of elevated calcitonin levels in patients with neoplastic and nonneoplastic thyroid disease and in healthy subjects. J Clin Endocrinol Metab 2004, 89: 515–9.

    Article  CAS  PubMed  Google Scholar 

  19. Kotzmann H, Schmidt A, Scheuba C, et al. Basal calcitonin levels and the response to pentagastrin stimulation in patients after kidney transplantation or on chronic hemodialysis as indicators of medullary carcinoma. Thyroid 1999, 9: 943–7.

    Article  CAS  PubMed  Google Scholar 

  20. Santeusanio G, Iafrate E, Partenzi A, Mauriello A, Autelitano F, Spagnoli L. A critical reassessment of the concept of C-cell hyperplasia of the thyroid. Appl Immunohistochem 1997, 5: 160–72.

    Article  Google Scholar 

  21. Gibson WG, Peng TC, Croker BP. Age-associated C-cell hyperplasia in the human thyroid. Am J Pathol 1982, 106: 388–93.

    CAS  PubMed Central  PubMed  Google Scholar 

  22. Hodak SP, Burman KD. The calcitonin conundrum-Is ittime for routine measurement of serum calcitonin in patients with thyroid nodules? J Clin Endocrinol Metab 2004, 89: 511–4.

    Article  CAS  PubMed  Google Scholar 

  23. Deftos LJ. Should serum calcitonin be routinely measured in patients with thyroid nodules-Will the law answer before endocrinologists do? J Clin Endocrinol Metab 2004, 89: 4768–9.

    Article  CAS  PubMed  Google Scholar 

  24. Castro R, Gharib H. Continuing controversy in the management of thyroid nodules. Ann Intern Med 2005, 42: 926–31.

    Article  Google Scholar 

  25. Rosai J, Carcangiu ML, DeLellis RA. Tumors of the thyroid gland. 3rd series. Fascicle 5. AFIP. Washington DC: Armed Forces Institute of Pathology. 1990, 223–9.

    Google Scholar 

  26. Shah JP, Kian K, Forastiere A, et al. American Joint Committee on Cancer. Cancer staging manual. 6th ed. New York: Springer-Verlag. 2002, 77–87.

    Google Scholar 

  27. Papi G, Corrado S, Pomponi MG, Carapezzi C, Cesinaro A, LiVolsi VA. Concurrent lymph node metastases of medullary and papillary thyroid carcinoma in a case with RET oncogene germline mutation. Endocr Pathol 2003, 14: 269–76.

    Article  CAS  PubMed  Google Scholar 

  28. Pacini F, Fontanelli M, Fugazzola L, et al. Routine measurement of serum calcitonin in nodularthyroid diseases allows the preoperative diagnosis of unsuspected sporadic medullary thyroid carcinoma. J Clin Endocrinol Metab 1994, 78: 826–9.

    CAS  PubMed  Google Scholar 

  29. Rieu M, Lame MC, Richard A, et al. Prevalence of sporadic medullary thyroid carcinoma: the importance of routine measurement of serum calcitonin in the diagnostic evaluation of thyroid nodules. Clin Endocrinol (Oxf) 1995, 42: 453–60.

    Article  CAS  Google Scholar 

  30. Niccoli P, Wion-Barbot N, Caron P, et al. Interest of routine measurement of serum calcitonin: study in a large series of thyroidectomized patients. The French Medullary Study Group. J Clin Endocrinol Metab 1997, 82: 338–41.

    Article  CAS  Google Scholar 

  31. Vierhapper H, Raber W, Bieglmayer C, Kaserer K, Weinhausl A, Niederle B. Routine measurement of plasma calcitonin in nodularthyroid diseases. J Clin Endocrinol Metab 1997, 82: 1589–93.

    Article  CAS  PubMed  Google Scholar 

  32. Eng C. The RET proto-oncongene in multiple endocrine neoplasia type 2 and Hirschsprung’s disease. N Engl J Med 1996, 335: 943–51.

    Article  CAS  PubMed  Google Scholar 

  33. Komminoth P. The RET proto-oncogene in medullary and papillary thyroid carcinoma. Virchows Arch 1997, 431: 1–9.

    Article  CAS  PubMed  Google Scholar 

  34. Tommasi M, Brocchi A, Cappellini A, Raspanti S, Mannelli M. False serum calcitonin high levels using a non-competitive two-site IRMA. J Endocrinol Invest 2001, 24: 356–60.

    CAS  PubMed  Google Scholar 

  35. Bieglmayer C, Niederle B, Vierhapper H. Interference causes false high calcitonin levels with a commercial assay. J Endocrinol Invest 2002, 25: 197.

    CAS  PubMed  Google Scholar 

  36. Engelbach M, Gorges R, Forst T, et al. Improved diagnostic methods in the follow-up of medullary thyroid carcinoma by highly specific calcitonin measurements. J Clin Endocrinol Metab 2000, 85: 1890–4.

    CAS  PubMed  Google Scholar 

  37. Sheuba C, Kaserer K, Weinhausl A, et al. Is medullary thyroid cancer predictable? A prospective study of 86 patients with abnormal pentagastrin tests. Surgery 1999, 126: 1089–95.

    Article  Google Scholar 

  38. Rosai J. Surgical Pathology. New York: Mosby. 9th ed. 2004, 557.

    Google Scholar 

  39. Perry A, Molberg K, Albores-Saavedra J. Physiologic versus neoplastic C-cell hyperplasia of the thyroid: separation of distinct histologic and biologic entities. Cancer 1996, 77: 750–6.

    Article  CAS  PubMed  Google Scholar 

  40. Guyetant S, Wion-Barbot N, Rousselet MC, Franc B, Bigorgne JC, Saint-Andre JP. C-cell hyperplasia associated with chronic lymphocytic thyroiditis: a retrospective quantitative study of 112 cases. Hum Pathol 1994, 25: 514–21.

    Article  CAS  PubMed  Google Scholar 

  41. Barbot N, Guyetant S, Beldent V, et al. Chronic autoimmune thyroiditis and C-cell hyperplasia. Study of calcitonin secretion in 24 patients. Ann Endocrinol (Paris) 1991, 52: 109–12.

    CAS  Google Scholar 

  42. Biddinger PW, Brennan MF, Rosen PP. Symptomatic C-cell hyperplasia associated with chronic lymphocytic thyroiditis. Am J Surg Pathol 1991, 15: 599–604.

    Article  CAS  PubMed  Google Scholar 

  43. Holm LE, Blomgren H, Lowhagen T. Cancer risks in chronic lymphocytic thyroiditis. N Engl J Med 1985, 312: 601–4.

    Article  CAS  PubMed  Google Scholar 

  44. Taruscio D, Cerbo M. Rare diseases: general principle, specific problems, and health interventions. Ann Ist Super Sanita 1999, 35: 237–44.

    CAS  PubMed  Google Scholar 

Download references

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Authors and Affiliations

  1. Department of Internal Medicine, University of Modena and Reggio Emilia, Rome

    G. Papi MD (Chair of Endocrinology), K. Cioni (Chair of Endocrinology) & C. Carani (Chair of Endocrinology)

  2. Department of Internal Medicine, Catholic University of Rome, Rome

    S. M. Corsello (Chair of Endocrinology) & A. Pontecorvi (Chair of Endocrinology)

  3. Department of Internal Medicine, AUSL Modena, Catholic University of Rome, Rome

    A. M. Pizzini, C. Carapezzi & A. Baldini

  4. Section of Pathology, Catholic University of Rome, Rome

    G. Fadda

  5. Institute of Endocrinology, University of Milan, Milan, Italy

    E. Roti

  6. Section of Pathology, Department of Forensic and Morphologic Sciences, University of Modena and Reggio Emilia, Rome

    S. Corrado

  7. Laboratory of Endocrinology, University of Modena and Reggio Emilia, Rome

    C. Carani (Chair of Endocrinology)

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  1. G. Papi MD
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Correspondence to G. Papi MD.

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Papi, G., Corsello, S.M., Cioni, K. et al. Value of routine measurement of serum calcitonin concentrations in patients with nodular thyroid disease: A multicenter study. J Endocrinol Invest 29, 427–437 (2006). https://doi.org/10.1007/BF03344126

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