Calcitonin-Screening und Stimulationstests

Zusammenfassung

Calcitonin (hCt) ist ein vergleichsweise anspruchsvoller Parameter – sowohl hinsichtlich der Probenbehandlung als auch der Interpretation der Laborergebnisse sowie der hieraus zu ziehenden Konsequenzen. Hinsichtlich der Referenzbereiche sollten geschlechtsspezifische Unterschiede berücksichtigt werden. Die Aussagekraft des Kalzium-Stimulationstests zur Abklärung nur mäßig erhöhter hCt-Basalwerte ist derzeit umstritten; hier besteht noch weiterer Bedarf zur Optimierung bzw. Standardisierung der Durchführung und Interpretation der Ergebnisse. Sofern erwogen wird, hCt im Rahmen eines Screenings bei nodulärem Schilddrüsenbefund oder als Tumormarker in der Verlaufskontrolle behandelter medullärer Schilddrüsenkarzinom-Patienten zu bestimmen, müssen einige Rahmenbedingungen sichergestellt sein. Hierzu gehören insbesondere: optimale präanalytische und stabile laborchemische Bedingungen, Etablierung kontrollierter geschlechtsspezifischer Interventionsschwellenwerte, ein Recall-System für Patienten mit zunächst kontrollbedürftigen Werten, die Verfügbarkeit von validierten Stimulationstests im Falle fraglich pathologischer basaler hCt-Werte, Kenntnis möglicher Einflussparameter auf die Messwerte, eigene Expertise hinsichtlich der Besonderheiten des medullären Schilddrüsenkarzinoms (MTC) und die enge interdisziplinäre Kooperation zwischen Nuklearmedizin, Endokrinologie, Chirurgie und Pathologie.

Abstract

Calcitonin (hCT) is a sensitive marker for medullary thyroid cancer, but calcitonin analytics and interpretation can be challenging. Gender-specific reference ranges should be considered. The additional value of calcium stimulation tests is discussed controversially; there is still need for methodical optimization, standardization and interpretation. When hCt measurement is performed in diagnostic work-up of nodular thyroid disease or as tumor marker in MTC patients, several aspects need to be considered: optimal pre-analytical methods, stable laboratory conditions, gender-specific cut-offs for intervention, recall system for outpatients with abnormal hCT results, knowledge of confounding factors of hCT analytics and special expertise in MTC management. Moreover, interdisciplinary cooperation between nuclear medicine, endocrinology, surgery and pathology is mandatory.

Schlüsselwörter

Calcitonin - Calcitonin-Screening - Stimulationstests - Schilddrüsenknoten - medulläres Schilddrüsenkarzinom

Key words

calcitonin - calcitonin screening - stimulation tests - thyroid nodules - medullary thyroid carcinoma

• Literatur

• 1 Borchhardt KA, Heinzl H, Gessl A et al. Calcitonin concentrations in patients with chronic kidney disease and medullary thyroid carcinoma or c-cell hyperplasia. Kidney Int 2006; 70: 2014-2020
• 2 Castagna MG, Fugazzola L, Maino F et al. Reference range of serum calcitonin in pediatric population. J Clin Endocrinol Metab 2015; 100: 1780-1784
• 3 Colombo C, Verga U, Mian C et al. Comparison of calcium and pentagastrin tests for the diagnosis and follow-up of medullary thyroid cancer. J Clin Endocrinol Metab 2012; 97: 905-913
• 4 Costante G, Meringolo D, Durante C et al. 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 2007; 92: 450-455
• 5 Doyle P, Düren C, Nerlich K et al. Potency and tolerance of calcitonin stimulation with high-dose calcium versus pentagastrin in normal adults. J Clin Endocrinol Metab 2009; 94: 2970-2974
• 6 Dralle H, Musholt TJ Schabram et al. German Association of Endocrine Surgeons practice guideline for the surgical management of malignant thyroid tumors. Langenbecks Arch Surg 2013; 398: 347-375
• 7 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: 163-168
• 8 Engelbach M, Görges 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: 1890-1894
• 9 Frank-Raue K, Machens A, Leidig-Bruckner G et al. Prevalence and clinical spectrum of nonsecretory medullary thyroid carcinoma in a series of 839 patients with sporadic medullary thyroid carcinoma. Thyroid 2013; 23: 294-300
• 10 Fugazzola L. Stimulated calcitonin cut-offs by different tests. Eur Thyroid J 2013; 2: 49-56
• 11 Giovanella L, Imperiali M, Ferrari A et al. Thyroid volume influences serum calcitonin levels in a thyroid-healthy population: results of a 3-assay, 519 subjects study. Clin Chem Lab Med 2012; 50: 895-900
• 12 Görges R. Bestimmung von Calcitonin. Nuklearmediziner 2005; 28: 4-10
• 13 Görges R, Bockisch A. Der Schilddrüsenknoten und der Stellenwert der Tumormarkerbestimmung. Nuklearmediziner 2008; 31: 228-236
• 14 Görges R, Freudenberg LS, Bockisch A. (2009) Schilddrüsenspezifische Tumormarker. Nuklearmediziner 2009; 32: 227-236
• 15 Görges R, Beindorf M, Kornely E et al. Calcitoninscreening in der Versorgungsmedizin: Auswertung von >10.000 Fällen. Nuklearmedizin 2015; 54: A61-A62
• 16 Guesgen C, Willms A, Zwad A et al. Investigation of factors potentially influencing calcitonin levels in the screening and follow-up for medullary thyroid carcinoma: a cautionary note. BMC Clin Pathol 2013; 13: 27
• 17 Guyétant S, Rousselet MC, Durigon M et al. Sex-related C cell hyperplasia in the normal human thyroid: a quantitative autopsy study. J Clin Endocrinol Metab 1997; 82: 42-47
• 18 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
• 19 Hartung-Knemeyer V, Müller S, Nagarajah J et al. Assay-Abhängigkeit der Calcitonin-Zielbereiche für „biochemisch geheilte“ Patienten mit medullärem Schilddrüsenkarzinom. Nuklearmedizin 2012; 51: 125-132
• 20 Haugen BR, Alexander EK, Bible KC et al. 2015; American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 2016; 26: 1-133
• 21 d’Herbomez M, Caron P, Bauters C et al. Reference range of serum calcitonin levels in humans: influence of calcitonin assays, sex, age, and cigarette smoking. Eur J Endocrinol 2007; 157: 749-755
• 22 Herrmann BL, Schmid KW, Görges R et al. Calcitonin screening and pentagastrin testing: predictive value for the diagnosis of medullary carcinoma in nodular thyroid disease. Eur J Endocrinol 2010; 162: 1141-1145
• 23 Iacobone M, Niccoli-Sire 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
• 24 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
• 25 Koperek O, Scheuba C, Cherenko M et al. Desmoplasia in medullary thyroid carcinoma: a reliable indicator of metastatic potential. Histopathology 2008; 52: 623-630
• 26 Kratzsch J, Petzold A, Raue F et al. Basal and stimulated calcitonin and procalcitonin by various assays in patients with and without medullary thyroid cancer. Clin Chem 2011; 57: 467-474
• 27 Lloyd RV, Douglas BR, Young WF Editor King DW. Endocrine Diseases, Atlas of nontumor pathology. Vol. 1. Washington: Armed Forces Institute of Pathology; 2002: 91-170
• 28 Lorenz K, Elwerr M, Machens A et al. Hypercalcitoninemia in thyroid conditions other than medullary thyroid carcinoma: a comparative analysis of calcium and pentagastrin stimulation of serum calcitonin. Langenbecks Arch Surg 2013; 398: 403-409
• 29 Machens A, Hoffmann F, Sekulla C et al. Importance of gender-specific calcitonin thresholds in screening for occult sporadic medullary thyroid cancer. Endocr Relat Cancer 2009; 16: 1291-1298
• 30 Martinetti A, Seregni E, Ferrari L et al. Evaluation of circulating calcitonin: analytical aspects. Tumori 2003; 89: 566-568
• 31 Mian C, Perrino M, Colombo C et al. Refining calcium test for the diagnosis of medullary thyroid cancer: cutoffs, procedures, and safety. J Clin Endocrinol Metab 2014; 99: 1656-1664
• 32 Modigliani E, Cohen R, Campos JM et al. Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients. The GETC Study Group. Groupe d’étude des tumeurs à calcitonine. Clin Endocrinol (Oxf) 1998; 48: 265-273
• 33 Pacini F, Fontanelli M, Fugazzola L et al. Routine measurement of serum calcitonin in nodular thyroid diseases allows the preoperative diagnosis of unsuspected sporadic medullary thyroid carcinoma. J Clin Endocrinol Metab 1994; 78: 826-829
• 34 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
• 35 Paschke R, Hegedüs L, Alexander E et al. Thyroid nodule guidelines: agreement, disagreement and need for future research. Nat Rev Endocrinol 2011; 7: 354-361
• 36 Perros P, Boelaert K, Colley S et al. British Thyroid Association. Guidelines for the management of thyroid cancer. Clin Endocrinol 2014; 81 (Suppl. 01) 1-122
• 37 Rosario PW, Calsolari MR. Influence of chronic autoimmune thyroiditis and papillary thyroid cancer on serum calcitonin levels. Thyroid 2013; 23: 671-674
• 38 Rink T, Truong PN, Schroth HJ et al. Calculation and validation of a plasma calcitonin limit for early detection of medullary thyroid carcinoma in nodular thyroid disease. Thyroid 2009; 19: 327-332
• 39 Saller B, Görges R, Reinhardt W et al. Sensitive calcitonin measurement by two-site immunometric assays: implications for calcitonin screening in nodular thyroid disease. Clin Lab 2002; 48: 191-200
• 40 Saller B, Moeller L, Görges R et al. Role of conventional ultrasound and color Doppler sonography in the diagnosis of medullary thyroid carcinoma. Exp Clin Endocrinol Diabetes 2002; 110: 403-407
• 41 Schmid KW. Histopathology of C Cells and Medullary Thyroid Carcinoma. Recent Results Cancer Res 2015; 204: 41-60
• 42 Sheu SY, Görges R, Schmid KW. Hyperplasien der Schilddrüse. Pathologe 2003; 24: 348-356
• 43 Schneider C, Kobe C, Schmidt M et al. Calcitonin screening in patients with thyroid nodules. Diagnostic value Nuklearmedizin 2012; 51: 228-233
• 44 Schneider R, Waldmann J, Swaid Z et al. Calcitonin-secreting pancreatic endocrine tumors: systematic analysis of a rare tumor entity. Pancreas 2011; 40: 213-221
• 45 Schuetz 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
• 46 Shan CX, Zhang W, Jiang DZ et al. Routine central neck dissection in differentiated thyroid carcinoma: a systematic review and meta-analysis. Laryngoscope 2012; 122: 797-804
• 47 Thiem U, Marculescu R, Cejka D et al. Low-dose calcium versus pentagastrin for stimulation of calcitonin in chronic hemodialysis patients: a pilot study. J Clin Endocrinol Metab 2014; 99: 4704-4711
• 48 Tiedje V, Ting S, Dralle H et al. Das medulläre Schilddrüsenkarzinom. Internist 2015; 56: 1019-1031
• 49 Trimboli P, Treglia G, Guidobaldi L et al. Detection rate of FNA cytology in medullary thyroid carcinoma: a meta-analysis. Clin Endocrinol (Oxf) 2015; 82: 280-285
• 50 Ubl P, Gincu T, Keilani M et al. Comparison of side effects of pentagastrin test and calcium stimulation test in patients with increased basal calcitonin concentration: the gender-specific differences. Endocrine 2014; 46: 549-553
• 51 Verburg FA, Reiners C, Grelle I et al. Calcium stimulated calcitonin measurement: a procedural proposal. Exp Clin Endocrinol Diabetes 2013; 121: 318-320
• 52 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: 1267-1272
• 53 Vitale G, Ciccarelli A, Caraglia M et al. Comparison of two provocative tests for calcitonin in medullary thyroid carcinoma: omeprazole vs pentagastrin. Clin Chem 2002; 48: 1505-1510
• 54 Wells Jr SA, Asa SL, Dralle H et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid 2015; 25: 567-610
• 55 Woliński K, Rewaj-Łosyk M, Ruchała M. Sonographic features of medullary thyroid carcinomas – a systematic review and meta-analysis. Endokrynol Pol 2014; 65: 314-318