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Calcitonin as Biomarker for the Medullary Thyroid Carcinoma

  • Yoon Ju Bae
  • Michael Schaab
  • Juergen KratzschEmail author
Chapter
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 204)

Abstract

Calcitonin (CTN) is a polypeptide hormone consisting of 32 amino acids with a disulfide bridge between position 1 and 7 that is mainly produced by the C-cells of thyroid gland. The measurement of CTN concentrations in blood reflects C-cell activity and is performed in general by immunoassay methods. However, there are analytical, physiological, pharmacological, and pathological factors that can influence results of serum CTN values. Due to the influence of these factors, there is a high variability in assay-dependent cutoffs used to discriminate between MTC, C-cell hyperplasia (CCH), and the absence of the pathological impairment of C-cells. There is a lot of evidence that the measurement of serum CTN concentrations in patients with thyroid nodules can lead to an earlier diagnosis of MTC or CCH than the exclusive use of imaging procedures and/or fine-needle aspiration cytology. Basal CTN concentrations higher than 60–100 pg/mL are highly indicative for the diagnosis MTC. In the range between cutoff and 60 pg/mL CTN, both MTC and HCC may be a relevant diagnosis. PCT and CTN appear to have a comparable diagnostic capability to diagnose MTCs. However, “positive” PCT values of more than 50 pg/mL may be reached also in subclinical infections and will lead, therefore, to an overdiagnosis of the tumor. Pentagastrin- or calcium-stimulated serum CTN concentrations higher than cutoff values might improve diagnostics of MTC, but the non-availability of the first and the lacking of relevant cutoff values for the second tool favors the use of only basal values currently.

Keywords

Calcitonin Procalcitonin Immunoassay Pentagastrin stimulation Calcium stimulation Cutoff 

List of Abbreviations

AUC

Area under the curve

CTN

Calcitonin

CGRP

Calcitonin gene-related peptide

1,25–OH–Vitamin D3

Calcitriol

Ca

Calcium

CCH

C-cell hyperplasia

CKD

Chronic kidney disease

CV

Coefficients of variation

FNAC

Fine-needle aspiration cytology

H2RB

Histamine-2 receptor blockers

IRMA

Immunoradiometric assay

MTC

Medullary thyroid carcinoma

mRNA

Messenger ribonucleic acid

NID

Nichols Institute Diagnostics

PCTN

Procalcitonin

PG

Pentagastrin

PPV

Positive predictive value

PPI

Proton pump inhibitor

RIA

Radioimmunoassay

ROC

Receiver operating curve

RfB

Reference Institute for Bioanalytics

WHO

World Health Organization

References

  1. Ahmed SR, Ball DW (2011) Clinical review: incidentally discovered medullary thyroid cancer: diagnostic strategies and treatment. J Clin Endocrinol Metab 96:1237–1245PubMedCentralCrossRefPubMedGoogle Scholar
  2. Algeciras-Schimnich A, Preissner CM, Theobald JP, Finseth MS, Grebe SK (2009) Procalcitonin: a marker for the diagnosis and follow-up of patients with medullary thyroid carcinoma. J Clin Endocrinol Metab 94:861–868PubMedCentralCrossRefPubMedGoogle Scholar
  3. American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ et al (2009) Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 19:1167–1214Google Scholar
  4. Austin LA, Heath H 3rd (1981) Calcitonin: physiology and pathophysiology. N Engl J Med 304(5):269–278CrossRefPubMedGoogle Scholar
  5. Barbot N, Guyetant S, Beldent V, Akrass A, Cerf I, Perdrisot R, Bigorgne JC (1991) Chronic autoimmune thyroiditis and C-cell hyperplasia. Study of calcitonin secretion in 24 patients. Ann Endocrinol (Paris) 52:109–112Google Scholar
  6. Basuyau JP, Mallet E, Leroy M, Brunelle P (2004) Reference intervals for serum calcitonin in men, women, and children. Clin Chem 50:1828–1830CrossRefPubMedGoogle Scholar
  7. Becker KL, Müller B, Nylen ES et al (2002) Calcitonin gene family of peptides. Structure, molecular biology and effects. In: Bilezikian JP, Raisz LG, Rodan GA (eds) Principles of bone biology, 3rd edn. Academic Press, San Diego, pp 619–639CrossRefGoogle Scholar
  8. Becker KL, Nylén ES, White JC, Müller B, Snider RH Jr (2004) 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 89:1512–1525CrossRefPubMedGoogle Scholar
  9. Bertagna XY, Bloomgarden ZT, Rabin D, Roberts LJ, Orth DN (1980) Molecular weight forms of immunoreactive calcitonin in a patient with medullary carcinoma of the thyroid: dynamic studies with calcium, pentagastrin and somatostatin. Clin Endocrinol (Oxf) 13(2):115–123CrossRefGoogle Scholar
  10. Bieglmayer C, Scheuba C, Niederle B, Flores J, Vierhapper H (2002) Screening for medullary thyroid carcinoma: experience with different immunoassays for human calcitonin. Wien Klin Wochenschr 114:267–273PubMedGoogle Scholar
  11. Bieglmayer C, Vierhapper H, Dudczak R, Niederle B (2007) Measurement of calcitonin by immunoassay analyzers. Clin Chem Lab Med 45:662–666CrossRefPubMedGoogle Scholar
  12. Bihan H, Becker KL, Snider RH, Nylen E, Vittaz L, Lauret C et al (2003) Calcitonin precursor levels in human medullary thyroid carcinoma. Thyroid 13:819–822CrossRefPubMedGoogle Scholar
  13. Body JJ, Heath H 3rd (1984) “Nonspecific” increases in plasma immunoreactive calcitonin in healthy individuals: discrimination from medullary thyroid carcinoma by a new extraction technique. Clin Chem 30:511–514PubMedGoogle Scholar
  14. Borchhardt KA, Hörl WH, Sunder-Plassmann G (2005) Reversibility of secondary hypercalcitoninemia’ after kidney transplantation. Am J Transplant 5:757–763CrossRefGoogle Scholar
  15. Boschin IM, Torresan F, Toniato A, Zane M, Ide EC, Pennelli G et al (2014) Incidental medullary thyroid microcarcinoma revealed by mild increase of preoperative serum calcitonin levels: therapeutic implications. Endocrine 45:448–453CrossRefPubMedGoogle Scholar
  16. Bringhurst FR, Demay MB, Kronenberg HM (2011) Hormones and disorders of mineral metabolism. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM (eds) Williams textbook of endocrinology. Elsevier Saunders, Philadelphia, pp 1250–1252Google Scholar
  17. Bucht E, Tørring O, Sjöberg HE (1985) Gel chromatography of immunoextracted plasma calcitonin in response to the calcium clamp in healthy males. Acta Endocrinol (Copenh) 110:421–428Google Scholar
  18. Camacho CP, Lindsey SC, Kasamatsu TS, Machado AL, Martins JR, Biscolla RP et al (2014) Development and application of a novel sensitive immunometric assay for calcitonin in a large cohort of patients with medullary and differentiated thyroid cancer, thyroid nodules, and autoimmune thyroid diseases. Eur Thyroid J 3:117–124PubMedCentralCrossRefPubMedGoogle Scholar
  19. Care AD (1992) The regulation of the secretion of calcitonin. Bone Miner 16:182–185CrossRefPubMedGoogle Scholar
  20. Chambers TJ, Moore A (1983) The sensitivity of isolated osteoclasts to morphological transformation by calcitonin. J Clin Endocrinol Metab 57:819–824CrossRefPubMedGoogle Scholar
  21. Chambers TJ, McSheehy PM, Thomson BM, Fuller K (1985) The effect of calcium-regulating hormones and prostaglandins on bone resorption by osteoclasts disaggregated from neonatal rabbit bones. Endocrinology 116:234–239CrossRefPubMedGoogle Scholar
  22. Chambon G, Alovisetti C, Idoux-Louche C, Reynaud C, Rodier M, Guedj AM et al (2011) The use of preoperative routine measurement of basal serum thyrocalcitonin in candidates for thyroidectomy due to nodular thyroid disorders: results from 2733 consecutive patients. J Clin Endocrinol Metab 96:75–81CrossRefPubMedGoogle Scholar
  23. Chan T, Gu F (2011) Early diagnosis of sepsis using serum biomarkers. Expert Rev Mol Diagn 11:487–496CrossRefPubMedGoogle Scholar
  24. Cohen R, Campos JM, Salaün C, Heshmati HM, Kraimps JL, Proye C et al (2000) Preoperative calcitonin levels are predictive of tumor size and postoperative calcitonin normalization in medullary thyroid carcinoma. Groupe d’Etudes des Tumeurs a Calcitonine (GETC). J Clin Endocrinol Metab 85:919–922CrossRefPubMedGoogle Scholar
  25. Colombo C, Verga U, Mian C, Ferrero S, Perrino M, Vicentini L et al (2012) Comparison of calcium and pentagastrin tests for the diagnosis and follow-up of medullary thyroid cancer. J Clin Endocrinol Metab 97:905–913CrossRefPubMedGoogle Scholar
  26. Copp DH, Cameron EC, Cheney BA, Davidson AG, Henze KG (1962) Evidence for calcitonin-a new hormone from the parathyroid that lowers blood calcium. Endocrinology 70:638–649CrossRefPubMedGoogle Scholar
  27. Costante G, Meringolo D, Durante C, Bianchi D, Nocera M, Tumino S et al (2007) Predictive value of serum calcitonin levels for preoperative diagnosis of medullary thyroid carcinoma in a cohort of 5817 consecutive patients with thyroid nodules. J Clin Endocrinol Metab 92:450–455CrossRefPubMedGoogle Scholar
  28. Costante G, Durante C, Francis Z, Schlumberger M, Filetti S (2009) Determination of calcitonin levels in C-cell disease: clinical interest and potential pitfalls. Nat Clin Pract Endocrinol Metab 5:35–44CrossRefPubMedGoogle Scholar
  29. Cooper CW, Hirsch PF, Toverud SU, Munson PL (1967) An improved method for the biological assay of thyrocalcitonin. Endocrinology 81:610–616CrossRefPubMedGoogle Scholar
  30. Daniels GH (2011) Screening for medullary thyroid carcinoma with serum calcitonin measurements in patients with thyroid nodules in the United States and Canada. Thyroid 21:1199–1207CrossRefPubMedGoogle Scholar
  31. Davey RA, Findlay DM (2013) Calcitonin: physiology or fantasy? J Bone Miner Res 28:973–979CrossRefPubMedGoogle Scholar
  32. Deftos LJ (1971) Immunoassay for human calcitonin. I. Method. Metabolism 20:1122–1128CrossRefPubMedGoogle Scholar
  33. Deftos LJ, Lee MR, Potts JT Jr (1968) A radioimmunoassay for thyrocalcitonin. Proc Natl Acad Sci USA 60:293–299PubMedCentralCrossRefPubMedGoogle Scholar
  34. Deftos LJ, Roos BA, Bronzert D, Parthemore JG (1975) Immunochemical heterogeneity of calcitonin in plasma. J Clin Endocrinol Metab 40:409–412CrossRefPubMedGoogle Scholar
  35. d’Herbomez M, Leclerc L, Vantyghem MC, Fourrier F, Proye C, Wemeau JL (2001) Clinical evaluation of a new sensitive calcitonin assay: study of specificity. Clin Chim Acta 311:149–155CrossRefPubMedGoogle Scholar
  36. d’Herbomez M, Caron P, Bauters C, Do Cao C, Schlienger JL, Sapin R, Baldet L, Carnaille B, Wémeau JL, French Group GTE (Groupe des Tumeurs Endocrines) (2007) Reference range of serum calcitonin levels in humans: influence of calcitonin assays, sex, age, and cigarette smoking. Eur J Endocrinol 157:749–755Google Scholar
  37. Elisei R, Bottici V, Luchetti F, Di Coscio G, Romei C, Grasso L et al (2004) 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 89:163–168CrossRefPubMedGoogle Scholar
  38. Engelbach M, Heerdt S, Görges R, Kunt T, Pfützner A, Forst T et al (1998) Is there an ectopic secretion of monomeric calcitonin in the human being? Langenbecks Arch Surg 83:456–459CrossRefGoogle Scholar
  39. Engelbach M, Görges R, Forst T, Pfützner A, Dawood R, Heerdt S et al (2000) Improved diagnostic methods in the follow-up of medullary thyroid carcinoma by highly specific calcitonin measurements. J Clin Endocrinol Metab 85:1890–1894PubMedGoogle Scholar
  40. Erdogan MF, Güllü S, Başkal N, Uysal AR, Kamel N, Erdoğan G (1997) Omeprazole calcitonin stimulation test for the diagnosis follow-up and family screening in medullary thyroid carcinoma. J Clin Endocrinol Metab 82:897–899CrossRefPubMedGoogle Scholar
  41. Erdogan MF, Gursoy A, Kulaksizoglu M (2006) Long-term effects of elevated gastrin levels on calcitonin secretion. J Endocrinol Invest 29:771–775CrossRefPubMedGoogle Scholar
  42. Escalada J, Teruel JL, Pavón I, Vila T, Navarro J, Varela C (1993) Normal calcitonin response to pentagastrin stimulation in patients with chronic renal failure. Acta Endocrinol (Copenh) 129:39–41Google Scholar
  43. Friedmann PA, Gesek FA (1995) Cellular calcium transport in renal epithelia: measurement, mechanisms and regulation. Physiol Rev 75:429–471Google Scholar
  44. Freston JW (1994) Omeprazole, hypergastrinemia, and gastric carcinoid tumors. Ann Intern Med 121:232–233CrossRefPubMedGoogle Scholar
  45. Fugazzola L (2013) Stimulated calcitonin cut-offs by different tests. Eur Thyroid J 2:49–56PubMedCentralPubMedGoogle Scholar
  46. Garancini S, Ballada L, Roncari G, Gastaldi L (1983) Calcitonin in chronic renal failure. Nephron 34:224–227CrossRefPubMedGoogle Scholar
  47. Garrett JE, Tamir H, Kifor O, Simin RT, Rogers KV, Mithal A et al (1995) Calcitonin-secreting cells of the thyroid express an extracellular calcitonin receptor gene. Endocrinology 136:5202–5211PubMedGoogle Scholar
  48. Gharib H, Papini E, Paschke R, Duick DS, Valcavi R, Hegedüs L et al; AACE/AME/ETA Task Force on Thyroid Nodules. American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules (2010) Endocr Pract 16 Suppl 1:1–43Google Scholar
  49. Gibelin H, Essique D, Jones C, Levillain P, Maréchaud R, Kraimps JL (2005) Increased calcitonin level in thyroid nodules without medullary carcinoma. Br J Surg 92:574–578CrossRefPubMedGoogle Scholar
  50. Giovanella L (2012) Serum procalcitonin and calcitonin normal values before and after calcium gluconate infusion. Exp Clin Endocrinol Diabetes 120:169–170CrossRefPubMedGoogle Scholar
  51. Goltzman D, Tischler AS (1978) Characterization of the immunochemical forms of calcitonin released by a medullary thyroid carcinoma in tissue culture. J Clin Invest 61:449–458PubMedCentralCrossRefPubMedGoogle Scholar
  52. Grauer A, Raue F, Ziegler R (1998) Clinical usefulness of a new chemiluminescent two-site immunoassay for human calcitonin. Exp Clin Endocrinol Diabetes 106:353–359CrossRefPubMedGoogle Scholar
  53. Guesgen C, Willms A, Zwad A, Waldeck S, Wieler H, Schwab R (2013) Investigation of factors potentially influencing calcitonin levels in the screening and follow-up for medullary thyroid carcinoma: a cautionary note. BMC Clin Pathol 13:27Google Scholar
  54. Hahm JR, Lee MS, Min YK, Lee MK, Kim KW, Nam SJ et al (2001) Routine measurement of serum calcitonin is useful for early detection of medullary thyroid carcinoma in patients with nodular thyroid diseases. Thyroid 11:73–80CrossRefPubMedGoogle Scholar
  55. Heath H 3rd, Sizemore GW (1977) Plasma calcitonin in normal man. Differences between men and women. J Clin Invest 60:1135–1140PubMedCentralCrossRefPubMedGoogle Scholar
  56. Heath H 3rd, Sizemore GW (1979) Immunochemical heterogeneity of calcitonin in tumor, tumor venous effluent, and peripheral blood of patients with medullary thyroid carcinoma. J Lab Clin Med 93:390–401PubMedGoogle Scholar
  57. Hirsch PF, Lester GE, Talmage RV (2001) Calcitonin, an enigmatic hormone does it have a function? J Musculoskelet Neuronal Interact 1:299–305PubMedGoogle Scholar
  58. Hirsch PF, Voelkel EF, Munson PL (1964) Thyrocalcitonin: Hypocalcemic hypophospatemic principle of the thyroid gland. Science 146:412–413 Google Scholar
  59. Hurley DL, Tiegs RD, Wahner HW, Heath H 3rd (1987) Axial and appendicular bone mineral density in patients with long-term deficiency or excess of calcitonin. N Engl J Med 317:537–541CrossRefPubMedGoogle Scholar
  60. Kaczka K, Mikosiński S, Fendler W, Celnik A, Pomorski L (2012) Calcitonin and procalcitonin in patients with medullary thyroid cancer or bacterial infection. Adv Clin Exp Med 21:169–178PubMedGoogle Scholar
  61. Kanis JA, Adams ND, Cecchettin M, Luizetto G, Gaspar S, Heynen G (1979) Ethanol induced secretion of calcitonin in chronic renal disease. Clin Endocrinol (Oxf) 10:155–161CrossRefGoogle Scholar
  62. Kapoor D, Jones TH (2005) Smoking and hormones in health and endocrine disorders. Eur J Endocrinol 152:491–499CrossRefPubMedGoogle Scholar
  63. Karges W, Dralle H, Raue F, Mann K, Reiners C, Grussendorf M et al; German Society for Endocrinology (DGE)—Thyroid Section (2004) Calcitonin measurement to detect medullary thyroid carcinoma in nodular goiter: German evidence-based consensus recommendation. Exp Clin Endocrinol Diabetes 112:52–58Google Scholar
  64. Kim HK, Bae WK, Choi YD, Shim HJ, Yoon JH, Kang HC (2014) Serum calcitonin may falsely estimate tumor burden in chronic hypercalcemia: a case of prostatic and multiple bone metastases from medullary thyroid cancer. Thyroid 24:599–603CrossRefPubMedGoogle Scholar
  65. Klinkenberg-Knol EC, Festen HP, Jansen JB, Lamers CB, Nelis F, Snel P et al (1994) Long-term treatment with omeprazole for refractory reflux esophagitis: efficacy and safety. Ann Intern Med 121:161–167CrossRefPubMedGoogle Scholar
  66. Kotzmann H, Schmidt A, Scheuba C, Kaserer K, Watschinger B, Söregi G et al (1999) Basal calcitonin levels and the response to pentagastrin stimulation in patients after kidney transplantation or on chronic hemodialysis as indicators of medullary carcinoma. Thyroid 9:943–947CrossRefPubMedGoogle Scholar
  67. Kratzsch J, Petzold A, Raue F, Reinhardt W, Bröcker-Preuss M, Görges R et al (2011) Basal and stimulated calcitonin and procalcitonin by various assays in patients with and without medullary thyroid cancer. Clin Chem 57:467–474CrossRefPubMedGoogle Scholar
  68. Leboeuf R, Langlois M, Martin M, Ahnadi CE, Fink GD (2006) “Hook effect” in calcitonin immunoradiometric assay in patients with metastatic medullary thyroid carcinoma: case report and review of the literature. J Clin Endocrinol Metab 91:361–364CrossRefPubMedGoogle Scholar
  69. Lee JC, Parthemore JG, Deftos LJ (1977) Immunochemical heterogeneity of calcitonin in renal failure. J Clin Endocrinol Metab 45:528–533CrossRefPubMedGoogle Scholar
  70. Machens A, Hauptmann S, Dralle H (2008) Medullary thyroid cancer responsiveness to pentagastrin stimulation: an early surrogate parameter of tumor dissemination? J Clin Endocrinol Metab 93:2234–2238CrossRefPubMedGoogle Scholar
  71. Machens A, Lorenz K, Dralle H (2014) Utility of serum procalcitonin for screening and risk stratification of medullary thyroid cancer. J Clin Endocrinol Metab 99:2986–2994CrossRefPubMedGoogle Scholar
  72. Martínez ME, Miguel JL, Gómez P, Selgas R, Salinas M, Gentil M et al (1983) Plasma calcitonin concentration in patients treated with chronic dialysis: differences between hemodialysis and CAPD. Clin Nephrol 19:250–253PubMedGoogle Scholar
  73. MacIntyre I, Girgis SI, Hillyard CJ (1984) Essential steps in the measurement of normal circulating levels of calcitonin. Biomed Pharmacother 38:230–234PubMedGoogle Scholar
  74. Marx SJ, Woodward CJ, Aurbach GD (1972) Calcitonin receptors of kidney and bone. Science 178:999–1001CrossRefPubMedGoogle Scholar
  75. Mian C, Perrino M, Colombo C, Cavedon E, Pennelli G, Ferrero S et al (2014) Refining calcium test for the diagnosis of medullary thyroid cancer: cutoffs, procedures, and safety. J Clin Endocrinol Metab 99:1656–1664CrossRefPubMedGoogle Scholar
  76. Milone F, Ramundo V, Chiofalo MG, Severino R, Paciolla I, Pezzullo L et al (2010) Predictive value of pentagastrin test for preoperative differential diagnosis between C-cell hyperplasia and medullary thyroid carcinoma in patients with moderately elevated basal calcitonin levels. Clin Endocrinol (Oxf) 73:85–88Google Scholar
  77. Morimoto S, Okada Y, Onishi T, Takai S, Miyauchi A, Lee S et al (1981) Heterogeneity of plasma and urinary immunoreactive calcitonin in patients with medullary carcinoma of the thyroid. Endocrinol Jpn 28:583–594CrossRefPubMedGoogle Scholar
  78. Motté P, Vauzelle P, Gardet P, Ghillani P, Caillou B, Parmentier C et al (1988) Construction and clinical validation of a sensitive and specific assay for serum mature calcitonin using monoclonal anti-peptide antibodies. Clin Chim Acta 174:35–54CrossRefPubMedGoogle Scholar
  79. Mulder H, Silberbusch J, Hackeng WH, Koorevaar G, den Ottolander GJ (1982) Enhanced calcitonin release in chronic renal failure depending on the absence of severe secondary hyperparathyroidism. Nephron. 31:123–128CrossRefPubMedGoogle Scholar
  80. Mulder H, Hackeng WH, vd Lely AJ, Siersema-Smallegange M (1990) Change of serum calcitonin in patients receiving glucocorticoids: an acute phase study. Neth J Med 36:288–290Google Scholar
  81. Niccoli P, Brunet P, Roubicek C, Roux F, Baudin E, Lejeune PJ et al (1995) Abnormal calcitonin basal levels and pentagastrin response in patients with chronic renal failure on maintenance hemodialysis. Eur J Endocrinol 132:75–81CrossRefPubMedGoogle Scholar
  82. Pacini F, Fontanelli M, Fugazzola L, Elisei R, Romei C, Di Coscio G et al (1994) Routine measurement of serum calcitonin in nodular thyroid diseases allows the preoperative diagnosis of unsuspected sporadic medullary thyroid carcinoma. J Clin Endocrinol Metab 78:826–829PubMedGoogle Scholar
  83. Pacini F, Schlumberger M, Dralle H, Elisei R, Smit JW, Wiersinga W; European Thyroid Cancer Taskforce (2006) European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur J Endocrinol 154:787–803 (Erratum in: Eur J Endocrinol 155:385)Google Scholar
  84. Papapetrou PD, Polymeris A, Karga H, Vaiopoulos G (2006) Heterophilic antibodies causing falsely high serum calcitonin values. J Endocrinol Invest 29:919–923CrossRefPubMedGoogle Scholar
  85. Polymeris A, Papapetrou PD, Papandroulaki F, Thanou S (2011) Hyperinsulinemia during oral glucose tolerance test and high normal serum cortisol are associated with increased secretion of calcitonin in normal subjects. Hormones (Athens) 10:304–312CrossRefGoogle Scholar
  86. Parthemore JG, Bronzert D, Roberts G, Deftos LJ (1974) A short calcium infusion in the diagnosis of medullary thyroid carcinoma. J Clin Endocrinol Metab 39:108–111CrossRefPubMedGoogle Scholar
  87. Pina G, Dubois S, Murat A, Berger N, Niccoli P, Peix JL et al.; Groupe de Tumeurs Endocrines (2013) Is basal ultrasensitive measurement of calcitonin capable of substituting for the pentagastrin-stimulation test? Clin Endocrinol (Oxf) 78:358–364. RfB4/2014:http://www.dgkl.rfb.de/cgi/displayAnaStats?rv_type=TM&rvTypeForDetails=TM&year=2014&rv_num=4&analyte=all&searchType=rv_type&anaV=19). Assessed on 24 Mar 2014
  88. Rink T, Truong PN, Schroth HJ, Diener J, Zimny M, Grünwald F (2009) Calculation and validation of a plasma calcitonin limit for early detection of medullary thyroid carcinoma in nodular thyroid disease. Thyroid 19:327–332CrossRefPubMedGoogle Scholar
  89. Roche cobas, calcitonin product characteristic. http://www.cobas.com/home/product/clinical-and-immunochemistry-testing/elecsys-calcitonin.html. Assessed on 24 Mar 2015
  90. Saller B, Görges R, Reinhardt W, Haupt K, Janssen OE, Mann K (2002) Sensitive calcitonin measurement by two-site immunometric assays: implications for calcitonin screening in nodular thyroid disease. Clin Lab 48:191–200PubMedGoogle Scholar
  91. Scheuba C, Kaserer K, Weinhäusl A, Pandev R, Kaider A, Passler C et al (1999) Is medullary thyroid cancer predictable? A prospective study of 86 patients with abnormal pentagastrin tests. Surgery 126:1089–1095CrossRefPubMedGoogle Scholar
  92. Schifter S (1993) A new highly sensitive radioimmunoassay for human calcitonin useful for physiological studies. Clin Chim Acta 215:99–109CrossRefPubMedGoogle Scholar
  93. Singer FR, Habener JF (1974) Multiple immunoreactive forms of calcitonin in human plasma. Biochem Biophys Res Commun 61:710–716CrossRefPubMedGoogle Scholar
  94. Sizemore GW, Hpeath H 3rd, Larson JM (1975) Immunochemical heterogeneity of calcitonin in plasma of patients with medullary thryoid carcinoma. J Clin Invest 55:1111–1118PubMedCentralCrossRefPubMedGoogle Scholar
  95. Snider RH, Silva OL, Moor CF, Becker KL (1977) Clin Chim Acta. Immunochemical heterogeneity of calcitonin in man: effect on radioimmunoassay 76:1–14Google Scholar
  96. Steinbach G, Rau B, Debard AL, Javourez JF, Bienvenu J, Ponzio A et al (2004) Multicenter evaluation of a new immunoassay for procalcitonin measurement on the Kryptor System. Clin Chem Lab Med 42:440–449CrossRefPubMedGoogle Scholar
  97. Tate J, Ward G (2004) Interferences in immunoassay. Clin Biochem Rev 25:105–120PubMedCentralPubMedGoogle Scholar
  98. Thiem U, Marculescu R, Cejka D, Gessl A, Borchhardt K (2014) Low-dose calcium versus pentagastrin for stimulation of calcitonin in chronic hemodialysis patients: a pilot study. J Clin Endocrinol Metab 99:4704–4711CrossRefPubMedGoogle Scholar
  99. Tobler PH, Tschopp FA, Dambacher MA, Born W, Fischer JA (1983) Identification and characterization of calcitonin forms in plasma and urine of normal subjects and medullary carcinoma patients. J Clin Endocrinol Metab 57:749–754CrossRefPubMedGoogle Scholar
  100. Toledo SP, Lourenço DM Jr, Santos MA, Tavares MR, Toledo RA, Correia-Deur JE (2009) Hypercalcitoninemia is not pathognomonic of medullary thyroid carcinoma. Clinics (Sao Paulo) 64:699–706CrossRefGoogle Scholar
  101. Tommasi M, Raspanti S (2007a) Hook effect in calcitonin immunoradiometric assay. Clin Chem Lab Med 45:1073–1074CrossRefPubMedGoogle Scholar
  102. Tommasi M, Raspanti S (2007b) Comparison of calcitonin determinations by polyclonal and monoclonal IRMAs. Clin Chem 53:798–799CrossRefPubMedGoogle Scholar
  103. Uhrova J, Brodska H, Vanickova Z, Benakova H, Zima T (2011) Procalcitonin interference in an immunometric calcitonin assay. Scand J Clin Lab Invest 71:157–162PubMedGoogle Scholar
  104. Uwaifo GI, Remaley AT, Stene M, Reynolds JC, Yen PM, Snider RH et al (2001) A case of spurious hypercalcitoninemia: a cautionary tale on the use of plasma calcitonin assays in the screening of patients with thyroid nodules for neoplasia. J Endocrinol Invest 24:361–369CrossRefPubMedGoogle Scholar
  105. Vantyghem MC, Danel T, Marcelli-Tourvieille S, Moriau J, Leclerc L, Cardot-Bauters C et al (2007) Calcitonin levels do not decrease with weaning in chronic alcoholism. Thyroid 17:213–217CrossRefPubMedGoogle Scholar
  106. Vieira AE, Mello MP, Elias LL, Lau IF, Maciel LM, Moreira AC, Castro M (2002) Molecular and biochemical screening for the diagnosis and management of medullary thyroid carcinoma in multiple endocrine neoplasia type 2A. Horm Metab Res 34:202–206CrossRefPubMedGoogle Scholar
  107. Vitale G, Ciccarelli A, Caraglia M, Galderisi M, Rossi R, Del Prete S et al (2002) Comparison of two provocative tests for calcitonin in medullary thyroid carcinoma: omeprazole vs pentagastrin. Clin Chem 48:1505–1510PubMedGoogle Scholar
  108. Voelkel EF, Tashjian AH Jr (1971) Measurement of thyrocalcitonin-like activity in urine of patients with medullary carcinoma. J Clin Endocrinol Metab 32:102–109CrossRefPubMedGoogle Scholar
  109. Walter MA, Meier C, Radimerski T, Iten F, Kränzlin M, Müller-Brand J et al (2010) Procalcitonin levels predict clinical course and progression-free survival in patients with medullary thyroid cancer. Cancer 116:31–40PubMedGoogle Scholar
  110. Zaidi M, Moonga BS, Abe E (2002) Calcitonin and bone formation: a knockout full of suprises. J Clin Invest 110:1769–1771Google Scholar
  111. Zayed AA, Alzubaidi M, Atallah S, Momani MS, Al-Delaimy WK (2013) Should food intake and circadian rhythm be considered when measuring serum calcitonin level? Endocr Pract 19:620–626CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Yoon Ju Bae
    • 1
  • Michael Schaab
    • 1
  • Juergen Kratzsch
    • 1
    Email author
  1. 1.Institut für Laboratoriumsmedizin, Klinische Chemie und Molekulare DiagnostikUniversität LeipzigLeipzigGermany

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