Download PDF
Nuklearmedizin 2008; 47(02): 65-72
DOI: 10.1055/s-0037-1621034
Originalarbeiten
Schattauer GmbH

Routine measurement of serum calcitonin in patients with nodular thyroid disorders?

Calcitonin-Screening bei der Knotenstruma?
M. Dietlein
1   Klinik und Poliklinik für Nuklearmedizin (Direktor: Prof. Dr. H. Schicha) der Universität zu Köln
,
H. Wieler
2   Abt. Nuklearmedizin (Leitender Arzt: Prof. Dr. H. Wieler), Bundeswehrzentralkrankenhaus und Klinikum Kemperhof gGmbH, Koblenz
,
M. Schmidt
1   Klinik und Poliklinik für Nuklearmedizin (Direktor: Prof. Dr. H. Schicha) der Universität zu Köln
,
R. Schwab
3   Abt. Allgemein-, Viszeral- und Thoraxchirurgie (Leitender Arzt: Prof. Dr. H. P. Becker), Bundeswehrzentralkrankenhaus Koblenz
,
P. E. Goretzki
4   Chirurgische Klinik I (Chefarzt: Prof. Dr. P. E. Goretzki), Städtische Kliniken Neuss, Lukaskrankenhaus GmbH, Neuss
,
H. Schicha
1   Klinik und Poliklinik für Nuklearmedizin (Direktor: Prof. Dr. H. Schicha) der Universität zu Köln
› Author Affiliations
Further Information

Publication History

Eingegangen: 22 May 2007

angenommen nach Revision: 13 August 2007

Publication Date:
11 January 2018 (online)

Also available at
    Permissions and Reprints

Summary

In spite of the fact that the German Society of Endocrinology has recommended calcitonin as screening-parameter the majority of physicians in Germany do not routinely use calcitonin in patients with thyroid nodules to exclude medullary thyroid cancer (MTC). The future revision of the recommendation should describe reference values for each commercially available assay, separately for men and women (basal and after pentagastrin-stimulation), and should define sonomorphological inclusion criteria. The epidemiological database of the prevalence of MTC is controversial and the specificity of basal elevated calcitonin levels is limited up to the 5-fold of the upper reference level. If renal insufficiency, bacterial infection, and an alcohol- or druginduced stimulation of calcitonin is excluded, hypercalcitoninaemia should be confirmed by a second measurement (if necessary using another assay). Stimulation of calcitonin by use of pentagastrin is mandatory prior to the decision on thyroidectomy. A stimulated calcitonin level <100 pg/ ml justifies “wait and see”. If stimulated calcitonin levels range between 100 and 200 pg/ml or higher, the differentiation between C-cell hyperplasia and MTC remains uncertain, especially in men. The implementation of calcitonin- screening requires the definition of sonographic inclusion criteria and validation of each assay. Additional prerequisites are excellent logistic (short period between blood sampling and start of the laboratory test), knowledge of differential diagnoses, knowledge of the consumption of drugs and alcohol, availability of pentagastrin-testing and of moleculargenetic testing with full information to the patients and sufficient time before the decision on surgery is made. All this and the choice of a skilled surgeon, experienced in thyroidectomy and lymphadenectomy with a low rate of local complications are the rationale to recommend calcitonin-screening primarily in centers for thyroid disorders.

Zusammenfassung

Trotz einer Empfehlung der Deutschen Gesellschaft für Endokrinologie zugunsten des Calcitonin-Screenings wird Calcitonin mit der Frage nach einem medullären Schilddrüsenkarzinom (MTC) bei Patienten mit Schilddrüsenknoten in Deutschland mehrheitlich nicht bestimmt. Bei der Fortentwicklung der Empfehlung zum Calcitonin-Screening sollten Assay-spezifische Referenzbereiche und die Geschlechtsspezifität des Calcitonin- Spiegels (basal und nach Pentagastrin-Stimulation) berücksichtigt und sonomorphologische Einschlusskriterien definiert werden. Unabhängig hiervon besteht eine epidemiologisch unklare Datenlage zur Prävalenz des MTC und eine begrenzte Spezifität eines basal erhöhten Calcitonin-Spiegels bis etwa zum Faktor 5 des oberen Referenzbereichs. Ist eine Niereninsuffizienz, eine bakterielle Infektion sowie eine Alkohol- oder medikamentös bedingte Stimulation des Calcitonins ausgeschlossen, sollte die Hypercalcitoninämie in einer zweiten Messung (ggf. mit einem anderen Assay) bestätigt werden. Vor einer Entscheidung über eine Thyroidektomie ist der Pentagastrintest notwendig. Ein stimulierter Calcitonin-Spiegel <100 pg/ml rechtfertigt ein kontrolliertes Zuwarten. Bei stimulierten Calcitonin- Werten zwischen 100 und 200 pg/ml, ggf. >200 pg/ml ist insbesondere bei Männern die Abgrenzung einer C-Zell-Hyperplasie gegen ein MTC nicht möglich. Die Etablierung eines sinnvollen Calcitonin-Screenings verlangt die Festlegung auf geeignete sonographische Einschlusskriterien und die Verwendung eines geeigneten Assays mit Validierung der Testergebnisse an einer genügend großen Patientenzahl. Dazu ist ein kurzes Zeitfenster zwischen Blutentnahme und Verarbeitung der Blutprobe, die Kenntnis der Differenzialdiagnosen, der Medikamenten- und der Alkoholanamnese, die Verfügbarkeit des Pentagastrintests und die Veranlassung einer molekulargenetischen Untersuchung notwendig, die eine Aufklärung des Patienten mit ausreichender Bedenkzeit vor Entscheidung über eine Operation einschließt. All dies und die Auswahl eines geeigneten Operateurs mit niedriger lokaler Komplikationsrate bei Thyroidektomie mit ggf. Lymph adenektomie sprechen für die Durchführung eines Calcitonin-Screenings vornehmlich nur an Schilddrüsenzentren.

Keywords

Calcitonin - screening - thyroid nodule - medullary thyroid cancer - C-cell hyperplasia

Schlüsselwörter

Calcitonin - Screening - Schilddrüsenknoten - medulläres Schilddrüsenkarzinom - C-Zell Hyperplasie
 

  • Literatur

  • 1 Andermann P, Schlögl S, Mäder U. et al. Intra- and interobserver variability of thyroid volume measurements in healthy adults by 2D versus 3D ultrasound. Nuklearmedizin 2007; 46: 1-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Basuyau JP, Mallet E, Levroy M, Brunelle P. Reference intervals for serum calcitonin in men, women, and children. Clin Chem 2004; 50: 1828-1830.
    CrossrefPubMedGoogle Scholar
  • 3 Bennedbaek FN, Hegedüs L. Management of the solitary thyroid nodule. Results of a North American survey. J Clin Endocrinol Metab 2000; 85: 2493-2498.
    PubMedGoogle Scholar
  • 4 Bennedbaek FN, Perrild H, Hegedüs L. Diagnosis and treatment of solitary thyroid nodule. Results of a European survey. Clin Endocrinol (Oxf) 1999; 50: 357-363.
    CrossrefPubMedGoogle Scholar
  • 5 Bergholm U, Bergström R, Ekbom A. Long term follow-up of patients with medullary carcinoma of the thyroid. Cancer 1997; 79 (1) 132-138.
    CrossrefPubMedGoogle Scholar
  • 6 Bevilacqua M, Domínguez LJ, Righini V. et al. Increased gastrin and calcitonin secretion after oral calcium or peptones administration in patients with hypercalciuria: a clue to an alteration in calcium-sensing receptor activity. J Clin Endocrinol Metab 2005; 90: 1489-1494.
    CrossrefPubMedGoogle Scholar
  • 7 Bieglmayer C, Vierhapper H, Dudczak R, Niederle B. Measurement of calcitonin by immunoassay analyzers. Clin Chem Lab Med 2007; 45 (5) 662-6.
    PubMedGoogle Scholar
  • 8 Biermann M, Pixberg MK, Dörr U. et al. Impact of clinical practice guidelines on radioiodine therapy for differentiated thyroid carcinoma. Nuklearmedizin 2005; 44: 229-237.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Bonnema SJ, Bennedbaek FN, Wiersinga WM. Hegedüs L. Management of the non-toxic multi- nodular goitre: a European questionnaire study. Clin Endocrinol (Oxf) 2000; 53: 5-12.
    CrossrefPubMedGoogle Scholar
  • 10 Bonnema SJ, Bennedbaek FN, Ladenson PW, Hegedüs L. Management of the non-toxic multi-nodular goiter: a North American survey. J Clin Endocrinol Metab 2002; 87: 112-117.
    CrossrefPubMedGoogle Scholar
  • 11 Borchhardt KA, Heinzl H, Gessl A. et al. Calcito- nin concentrations in patients with chronic kidney disease and medullary thyroid carcinoma or c-cell hyperplasia. Kidney Int 2006; 70: 2014-2020.
    CrossrefPubMedGoogle Scholar
  • 12 Burgalho MJ, Santos JR, Sobrinho L. Preoperative diagnosis ofmedullary thyroid carcinoma: fine needle aspiration cytology as compared with serum calcitonin measurement. J Surg Oncol 2005; 91: 56-60.
    CrossrefPubMedGoogle Scholar
  • 13 Cooper DS, Doherty GM, Haugen BR. et al. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2006; 16 (2) 1-33.
    CrossrefPubMedGoogle Scholar
  • 14 Costante G, Meringolo D, Durante C. et al. Predictive value of serum calcitonin levels for preoperative diagnosis of medullary thyroid carcino ma in a cohort of 5817 consecutive patients with thyroid nodules. J Clin Endocrinol Metab 2007; 92: 450-455.
    CrossrefPubMedGoogle Scholar
  • 15 Diagnostic Products Cooperation (DPC) Biermann. Immulite® 2000 Calcitonin. Bad Nauheim. Los Angeles: 2004
    Google Scholar
  • 16 Dietlein M, Kobe C, Schmidt M, Schicha H. The incidentaloma of the thyroid: over-or underuse of diagnostic procedures for an epidemiologic finding?. Nuklearmedizin 2005; 44: 13-224.
    Article in Thieme ConnectGoogle Scholar
  • 17 Dietlein M, Dederichs B, Kobe C. et al. Therapy for non-toxic multinodular goiter: radioiodine therapy as attractive alternative to surgery. Nuklearmedizin 2006; 45: 21-34.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Dietlein M, Wegscheider K, Vaupel R. et al. Management of multinodular goiter in Germany. Do the approaches of thyroid specialists and primary care practitioners differ? (Papillon 2005) Nuklearmedizin 2007; 46: 65-75.
    PubMedGoogle Scholar
  • 19 Dietlein M, Wegscheider K, Vaupel R. et al. Survey of management of solitary thyroid nodules in Germany?. Nuklearmedizin. 2008 47. (in press) DOI 10.3413/nukmed-0136.
    PubMedGoogle Scholar
  • 20 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 Metabol 2004; 89: 163-168.
    CrossrefPubMedGoogle Scholar
  • 21 Gibelin H, Essique D, Jones C. et al. Increased calcitonin level in thyroid nodules without medullary carcinoma. Br J Surg 2005; 92: 574-578.
    CrossrefPubMedGoogle Scholar
  • 22 Gotthardt M, Stübinger M, Pansegrau J. et al. Decrease of 99mTc-uptake in autonomous thyroid tissue in Germany since the 1970s. Nuklearmedizin 2006; 45: 122-125.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 Gotthardt M, Rubner C, Bauhofer A. et al. What is the best pre-therapeutic dosimetry for successful radioiodine therapy of multifocal autonomy?. Nuklearmedizin 2006; 45: 206-212.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Hahm JR, Lee MS, Min YK. et al. Routine measurement of serum calcitonin is useful for early detection of medullary thyroid carcinoma in patients with nodular thyroid diseases. Thyroid 2001; 11: 73-80.
    CrossrefPubMedGoogle Scholar
  • 25 Hodak S, Burman KD, Burman EM. Authors' response: Should serum calcitonin be routinely measured in patients with thyroid nodules-will the law answer before endocrinologists do?. J Clin Endocrinol Metab 2004; 89: 4769-4770.
    CrossrefGoogle Scholar
  • 26 Hölzer S, Reiners C, Mann K. et al. Patterns of care for patients with primary differentiated carcinoma of the thyroid gland in Germany during 1996. U.S. and German Thyroid Cancer Group. Cancer 2000; 89: 192-201.
    CrossrefPubMedGoogle Scholar
  • 27 Hundahl SA, Cady B, Cunningham MP. et al. Initial results from a prospective cohort study of 5583 cases of thyroid carcinoma treated in the United States during 1996. Cancer 2000; 89: 202-217.
    CrossrefPubMedGoogle Scholar
  • 28 Iacobone M, Niccoli-Sir P, Sebag F. et al. Can sporadic medullary thyroid carcinoma be biochemically predicted? Prospective analysis of 66 operated patients with elevated serum calcitonin levels. World J Surg 2002; 26: 886-890.
    CrossrefPubMedGoogle Scholar
  • 29 Karanikas G, Moameni A, 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: 515-519.
    CrossrefPubMedGoogle Scholar
  • 30 Karges W, Dralle H, Raue F. et al. Calcitonin measurement to detect medullary thyroid carcinoma in nodular goiter : German evidence-based consensus recommendation. Exp Clin Endocrinol Diabetes 2004; 112: 52-58.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 31 Machens A, Niccoli-Sire P, Hoegel J. et al. Early malignant progression of hereditary medullary thyroid cancer. N Engl J Med 2003; 349: 1517-1525.
    CrossrefPubMedGoogle Scholar
  • 32 Machens A, Schneyer U, Holzhausen H-J, Dralle H. Prospects of remission in medullary thyroid carcinoma according to basal calcitonin level. J Clin Endocrinol Metab 2005; 90: 2029-2034.
    CrossrefPubMedGoogle Scholar
  • 33 Medipan Arbeitsanleitung Calcitonin-IRMA magnum. Dahlewitz; Berlin: 2005
    Google Scholar
  • 34 Modigliani M, Cohen R, Campos J-M. et al. Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients. Clin Endocrinol (Oxf) 1998; 48 (3) 265-273.
    CrossrefPubMedGoogle Scholar
  • 35 Niccoli P, Wion-Barbot N, Caron P. et al. Interest of routine measurement of serum calciton. In: study in a large series of thyroidectomized patients. The French Medullary Study Group. J Clin Endocrinol Metab 1997; 82: 338-341.
    CrossrefPubMedGoogle Scholar
  • 36 Özgen AG, Hamulu F, Bayraktar F. et al. Evaluation of routine basal serum calcitonin measurement for early diagnosis of medullary thyroid carcinoma in seven hundred seventy-three patients with nodular goiter. Thyroid 1999; 9: 579-582.
    CrossrefPubMedGoogle Scholar
  • 37 Pacini F, Fontanelli M, Fugazzola L. et al. Routine measurement of serum calcitonin in nodular thyroid disease allows the preoperative diagnosis of unsuspected sporadic medullary thyroid carcinoma. J Clin Endocrinol Metab 1994; 78: 826-829.
    PubMedGoogle Scholar
  • 38 Pacini F, Schlumberger M, Dralle H. et al. European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur J. Endocrinol 2006; 154: 787-803.
    Google Scholar
  • 39 Papi G, Corsello SM, Cioni K. et al. Value of routine measurement of serum calcitonin concentrations in patients with nodular thyroid disease: a multicenter study. J Endocrinol Invest 2006; 29: 427-437.
    CrossrefPubMedGoogle Scholar
  • 40 Pinna G, Orgiana G, Riola A. et al. RET proto-oncogene in Sardinia: V804M is the most frequent mutation and may be associated with FMTC/ MEN-2 phenotype. Thyroid 2007; 17 (2) 101-104.
    CrossrefPubMedGoogle Scholar
  • 41 Reiners C, Wegscheider K, Schicha H. et al. Prevalence of thyroid disorders in the working population of Germany: ultrasonography screening in 96,278 unselected employees. Thyroid 2004; 14: 926-932.
    CrossrefPubMedGoogle Scholar
  • 42 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: 453-460.
    CrossrefPubMedGoogle Scholar
  • 43 Saller B, Görges R, Reinhardt W. et al. Sensitive calcitonin measurement by two-site immunome- tric assays: implications for calcitonin-screening in nodular thyroid disease. Clin Lab 2002; 48: 191-200.
    PubMedGoogle Scholar
  • 44 Scantibodies Laboratories. Calcitonin Assay. Santee; CA / USA: 2007
    Google Scholar
  • 45 Schrabram J, Wahl RA. Welche Relevanz haben leicht erhöhte, nicht hereditär bedingte Kalzito- ninkonzentrationen vor Schilddrüsenoperationen. Viszeralchirurgie 2001; 36: 391-395.
    Article in Thieme ConnectGoogle Scholar
  • 46 Schütz M, Beheshti M, Oezer S. et al. Calcitonin measurements for early detection of medullary thyroid carcinoma or its premalignant conditions in Hashimoto's thyroiditis. Anticancer Res 2006; 26: 723-727.
    Google Scholar
  • 47 Schwab R, Wieler H, Birtel S. et al. Confronting the practice of surgery on differentiated thyroid cancer with current guidelines in Germany. [German] Nuklearmedizin 2005; 44: 185-191.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 48 Vantyghem MC, Danel T, Marcelli-Tourvieille S. et al. Calcitonin levels do not decrease with weaning in chronic alcoholism. Thyroid 2007; 17 (3) 213-217.
    CrossrefPubMedGoogle Scholar
  • 49 Vierhapper H, Raber W, Bieglmayer C. et al. Routine measurement of plasma calcitonin in nodular thyroid diseases. J Clin Endocrinol Metab 1997; 82: 1589-1593.
    CrossrefPubMedGoogle Scholar
  • 50 Vierhapper H, Bieglmayer C, Heinze G, Baumgartner-Parzer S. Frequency of RET proto-oncogene mutations in patients with normal and with moderately elevated pentagastrin-stimulated serum concentrations of calcitonin. Thyroid 2004; 14: 580-583.
    CrossrefPubMedGoogle Scholar
  • 51 Vierhapper H, Niederle B, Bieglmayer C. et al. Early diagnosis and curative therapy of medullary thyroid carcinoma by routine measurement of serum calcitonin in patients with thyroid disorders. Thyroid 2005; 15 (11) 1267-1272.
    CrossrefPubMedGoogle Scholar