Kalzitonin ist ein vergleichsweise sensitiver, spezifischer und reliabler Tumormarker, der bei der Primärdiagnostik und Nachsorge des C-Zellkarzinoms sowie der neoplastischen C-Zell-Hyperplasie einen zentralen Stellenwert besitzt. Wesentlich seltener wird Kalzitonin auch bei anderen Tumorarten nachgewiesen. Zur Messung sollten immunometrische Two-Site-Assays mit einer funktionellen Sensitivität um 1-2 pg/ml verwendet werden. Assays mit weitgehend selektiver Erfassung der monomeren Kalzitoninform bieten den Vorteil einer höheren Spezifität bezüglich des Erkennens von C-Zellkarzinomen. Unter diesen Voraussetzungen besitzen bereits Messungen des basalen Kalzitonins eine hohe diagnostische Aussagekraft. Die Durchführung eines Pentagastrintests kann die diagnostische Sensitivität und Spezifität der Kalzitoninbestimmung steigern, aber falsch positive Ergebnisse sind auch hierbei insbesondere bei C-Zellhyperplasie und Niereninsuffizienz von klinischer Relevanz. Bezüglich des Screenings der Familienmitglieder von Patienten mit C-Zellkarzinom hat die molekulargenetische Diagnostik in den letzten Jahren den Pentagastrintest weitgehend abgelöst. Als neues Einsatzgebiet rückt derzeit das Kalzitoninscreening bei Struma nodosa stärker in den Blickpunkt. Zwar können hierdurch nur bis 10 % der (ohnehin seltenen) Schilddrüsenmalignome erfasst werden, und bei den empfohlenen Interventionsschwellenwerten wird ein nicht unerheblicher Anteil unnötiger Schilddrüsenoperationen verursacht, aber die Chance kurativer Interventionen durch Erfassung früher Tumorstadien steigt.
Abstract
Calcitonin in serum is a comparatively highly sensitive, specific and reliable tumor marker of central relevance for the diagnosis and follow-up of medullary thyroidal C-cell carcinoma (MTC) and neoplastic C-cell hyperplasia (CCH). It is seen considerably less often in other tumor entities. For determination we recommend immunometric two-site assays of approximately 1-2 pg/ml sensitivity. Higher MTC specificity is achieved by assays focussing on a largely selective determination of monomeric calcitonin. If this is realized, basal calcitonin levels are already greatly relevant for MTC or CCH diagnosis. The diagnostic sensitivity and specificity of calcitonin determination may be further enhanced by means of pentagastrin test, but even then false positive results are clinically relevant especially in benign CCH and renal insufficiency. In family screening in case of MTC patients, moleculargenetic techniques have become the procedure of choice and have now largely replaced the pentagastrin test. Calcitonin screening in adenomatous goitre (struma nodosa) is making headway. Although this accounts for only 10 % of thyroidal malignomas (which are in fact rare), and the recommanded levels of intervention will result in many unnecessary surgical operations, early tumor staging definitely increases the chances for curative intervention.
1
Barbot N, Calmettes C, Schuffenecker I, Saint-Andre J P, Franc B, Rohmer V, Jallet P, Bigorgne J C.
Pentagastrin stimulation test and early diagnosis of medullary thyroid carcinoma using an immunoradiometric assay of calcitonin: comparison with genetic screening in hereditary medullary thyroid carcinoma.
J Clin Endocrinol Metab.
1994;
78
114-120
2
Becker K L, Nash D, Silva O L, Snider R H, Moore C F.
Increased serum and urinary calcitonin levels in patients with pulmonary disease.
Chest.
1981;
79
211-216
3
Bockhorn M, Frilling A, Rewerk S, Liedke M, Dirsch O, Schmid K W, Broelsch C E.
Lack of elevated serum carcinoembryonic antigen and calcitonin in medullary thyroid carcinoma.
Thyroid.
2004;
14
468-470
4
Body J J, Chanoine J P, Dumon J C, Delange F.
Circulating calcitonin levels in healthy children and subjects with congenital hypothyroidism from birth to adolescence.
J Clin Endocrinol Metab.
1993;
77
565-567
5
Borges M F, Abelin N M, Menezes F O, Dahia P L, Toledo S P.
Calcitonin deficiency in early stages of chronic autoimmune thyroiditis.
Clin Endocrinol (Oxf).
1998;
49
69-75
6
Brauckhoff M, Gimm O, Brauckhoff K, Ukkat J, Thomusch O, Dralle H.
Calcitonin kinetics in the early postoperative period of medullary thyroid carcinoma.
Langenbecks Arch Surg.
2001;
386
434-439
11
Dietlein M, Moka D, Schmidt M, Theissen P, Schicha H.
Prävention, Screening and Therapie gutartiger Schilddrüsenerkrankungen unter dem Aspekt von Kosten und Nutzen.
Nuklearmedizin.
2003;
42
181-189
13
Engelbach M, Görges R, Forst T, Pfutzner A, Dawood R, Heerdt S, Kunt T, Bockisch A, Beyer J.
Improved diagnostic methods in the follow-up of medullary thyroid carcinoma by highly specific calcitonin measurements.
J Clin Endocrinol Metab.
2000;
85
1890-1894
14
Engelbach M, Heerdt S, Gorges R, Kunt T, Pfutzner A, Forst T, Diefenbach K, Walgenbach S, Beyer J.
Is there an ectopic secretion of monomeric calcitonin in the human being?.
Langenbecks Arch Surg.
1998;
383
456-459
15
Erdogan M F, Gullu S, Baskal N, Uysal A R, Kamel N, Erdogan G.
Omeprazole: calcitonin stimulation test for the diagnosis follow-up and family screening in medullary thyroid carcinoma.
J Clin Endocrinol Metab.
1997;
82
897-899
16
Franc S, Niccoli-Sire P, Cohen R, Bardet S, Maes B, Murat A, Krivitzky A, Modigliani E.. French Medullary Study Group (GETC) .
Complete surgical lymph node resection does not prevent authentic recurrences of medullary thyroid carcinoma.
Clin Endocrinol (Oxf).
2001;
55
403-409
18
Gimm O, Ukkat J, Dralle H.
Determinative factors of biochemical cure after primary and reoperative surgery for sporadic medullary thyroid carcinoma.
World J Surg.
1998;
22
562-567
19 Görges R. The changing epidemiology of thyroid cancer. In: Biersack HJ, Grünwald F (eds). Thyroid cancer. Springer, Berlin, Heidelberg 2001
20
Grauer A, Raue F, Ziegler R.
Clinical usefulness of a new chemiluminescent two-site immunoassay for human calcitonin.
Exp Clin Endocrinol Diabetes.
1998;
106
353-359
21
Guyetant S, Wion-Barbot N, Rousselet M C, Franc B, Bigorgne J C, Saint-Andre J P.
C-cell hyperplasia associated with chronic lymphocytic thyroiditis: a retrospective quantitative study of 112 cases.
Hum Pathol.
1994;
25
514-521
24
Hernandez G, Simo R, Oriola J, Mesa J.
False-positive results of basal and pentagastrin-stimulated calcitonin in non-gene carriers of multiple endocrine neoplasia type 2 A.
Thyroid.
1997;
7
51-54
26
Kebebew E, Ituarte P H, Siperstein A E, Duh Q Y, Clark O H.
Related Articles, Links Abstract Medullary thyroid carcinoma: clinical characteristics, treatment, prognostic factors, and a comparison of staging systems.
Cancer.
2000;
88
1139-1148
27
Kotzmann H, Schmidt A, Scheuba C, Kaserer K, Watschinger B, Soregi G, Niederle B, Vierhapper H.
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
943-947
28
Lind L, Bucht E, Ljunghall S.
Pronounced elevation in circulating calcitonin in critical care patients is related to the severity of illness and survival.
Intensive Care Med.
1995;
21
63-66
29
Lissak B, Baudin E, Cohen R, Barbot N, Meyrier A, Niccoli P, Bouyge N, Modigliani E.
Pentagastrin testing in patients with renal insufficiency: normal responsivity of mature calcitonin.
Thyroid.
1998;
8
265-268
30
Marsh D J, McDowall D, Hyland V J, Andrew S D, Schnitzler M, Gaskin E L, Nevell D F, Diamond T, Delbridge L, Clifton-Bligh P, Robinson B G.
The identification of false positive responses to the pentagastrin stimulation test in RET mutation negative members of MEN 2 A families.
Clin Endocrinol (Oxf).
1996;
44
213-220
31
Marrinan M, Skrabanek P, Moriarty M, McPartlin J, Powell D.
Hypercalcitoninaemia in medullary carcinoma of the thyroid and other malignancies: value of calcitonin as tumour marker.
Horm Metab Res.
1982;
14
213-215
32
Martinetti A, Seregni E, Ferrari L, Pallotti F, Aliberti G, Coliva A, Fracassi S, Bombardieri E.
Evaluation of circulating calcitonin: analytical aspects.
Tumori.
2003;
89
566-568
33
Mendelsohn G, Wells Jr S A, Baylin S B.
Relationship of tissue carcinoembryonic antigen and calcitonin to tumor virulence in medullary thyroid carcinoma. An immunohistochemical study in early, localized, and virulent disseminated stages of disease.
Cancer.
1984;
54
657-662
34
Modigliani E, Cohen R, Campos J M,. et al .
Prognostic factors for survival and biochemical cure in medullary thyroid carcinoma: results in 899 patients. The GETC Study Group.
Clin Endocrinol (Oxf).
1998;
48
265-273
35
Niccoli P, Brunet P, Roubicek C, Roux F, Baudin E, Lejeune P J, Berland Y, Conte-Devolx B.
Abnormal calcitonin basal levels and pentagastrin response in patients with chronic renal failure on maintenance hemodialysis.
Eur J Endocrinol.
1995;
132
75-81
38
Poppe K, Verbruggen L A, Velkeniers B, Finne E, Body J J, Vanhaelst L.
Calcitonin reserve in different stages of atrophic autoimmune thyroiditis.
Thyroid.
1999;
9
1211-1214
39
Raue F. German MTC/MEN Study Group .
German medullary thyroid carcinoma/multiple endocrine neoplasia registry.
Langenbecks Arch Surg.
1998;
383
334-336
40
Redding A H, Levine S N, Fowler M R.
Normal preoperative calcitonin levels do not always exclude medullary thyroid carcinoma in patients with large palpable thyroid masses.
Thyroid.
2000;
10
919-922
42
Sagulin G B, Bucht E, Gilljam H, Sjoberg H, Roomans G M.
Plasma calcitonin levels in patients with cystic fibrosis.
Res Commun Chem Pathol Pharmacol.
1990;
69
325-334
43
Saller B, Görges R, Reinhardt W, Haupt K, Janssen O E, Mann K.
Sensitive calcitonin measurement by two-site immunometric assays: implications for calcitonin screening in nodular thyroid disease.
Clin Lab.
2002;
48
191-200
44
Saller B, Moeller L, Görges R, Janssen O E, Mann K.
Role of conventional ultrasound and color Doppler sonography in the diagnosis of medullary thyroid carcinoma.
Exp Clin Endocrinol Diabetes.
2002;
110
403-407
47
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
356-360
48
Ukkat J, Gimm O, Brauckhoff M, Bilkenroth U, Dralle H.
Single center experience in primary surgery for medullary thyroid carcinoma.
World J Surg.
2004;
28
1271-1274
49
Vitale G, Ciccarelli A, Caraglia M, Galderisi M, Rossi R, Del Prete S, Abbruzzese A, Lupoli G.
Comparison of two provocative tests for calcitonin in medullary thyroid carcinoma: omeprazole vs pentagastrin.
Clin Chem.
2002;
48
1505-1510
50
Zaidi M, Inzerillo A M, Moonga B S, Bevis P J, Huang C L.
Forty years of calcitonin - where are we now? A tribute to the work of Iain Macintyre, FRS.
Bone.
2002;
30
655-663
51
Zwermann O, Piepkorn B, Engelbach M, Beyer J, Kann P.
Abnormal pentagastrin response in a patient with pseudohypoparathyroidism.
Exp Clin Endocrinol Diabetes.
2002;
110
86-91
