Thyreoglobulin – mehr als ein Nachsorgeparameter?

M. Zimny

doi:10.1055/s-0042-101887

Der Nuklearmediziner, Inhaltsverzeichnis

Der Nuklearmediziner 2016; 39(02): 104-110
DOI: 10.1055/s-0042-101887

Immunologische In-Vitro-Diagnostik

Thyreoglobulin – mehr als ein Nachsorgeparameter?

Thyroglobulin – More than a Parameter of Follow-up?

M. Zimny

¹ÜBaG Nuklearmedizin Hanau – Offenbach – Frankfurt – Gießen, Hanau

› Institutsangaben

Abstract

Zusammenfassung

Thyreoglobulin ist das vorherrschende Protein der Schilddrüse und essenzieller Bestandteil der Schilddrüsenhormonsynthese. Während mit unempfindlichen historischen Bestimmungsmethoden Thyreoglobulin nur selten im Serum von Patienten nachgewiesen werden konnte, erlauben aktuelle, hochsensitive Bestimmungsmethoden den Nachweis schon geringster Thyreoglobulinkonzentrationen im Serum. Diese Übersicht gibt einen Überblick über die Entwicklung der aktuellen Bestimmungsmethoden und deren Limitationen. Zudem wird neben der etablierten klinischen Anwendung in der Nachsorge des differenzierten, nicht-medullären Schilddrüsenkarzinoms die Rolle des Thyreoglobulins bei der Einschätzung von Schilddrüsenknoten, der Abklärung einer ätiologisch unklaren Hyperthyreose, der kongenitalen Hypothyreose, als Monitoring-Parameter von Krankheitsbildern mit erhöhter Schilddrüsenfollikeldestruktion und als Biomarker der Iodversorgung betrachtet.

Abstract

Thyroglobulin is the predominant protein of the thyroid and an essential molecule for the synthesis of thyroid hormones. Historically, using insensitive tests, thyroglobulin was only occasionally found in the sera of patients with thyroid disorders. Nowadays, highly sensitive assays enable the detection of minuscule amounts of thyroglobulin in patient’s sera. This review elucidates the development and limitations of current Tg-assays. Aside from the established clinical use of thyroglobulin as the most relevant parameter for the follow-up of non-medullary differentiated thyroid cancer the role of thyroglobulin for the assessment of thyroid nodules, hyperthyroidism of unclear etiology, or congenital hypothyroidism as well as monitoring parameter in thyroid disorders accompanied by increased destruction of thyroid follicles and as a biomarker of the iodine nutrition status is discussed.

Schlüsselwörter

Thyreoglobulin - differenziertes Schilddrüsenkarzinom - Hyperthyreose - Hypothyreose - Schilddrüsenfollikeldestruktion - Iodversorgung

Key words

thyroglobulin - differentiated thyroid carcinoma - hyperthyroidism - hypothyroidism - destruction of thyroid follicles - iodine status

Volltext

Referenzen

Literatur
1 Ashcraft MW, Van Herle AJ. The comparative value of serum thyroglobulin measurements and iodine 131 total body scans in the follow-up study of patients with treated differentiated thyroid cancer. Am J Med 1981; 71: 806-814
2 Assem ESK. Thyroglobulin in the serum of parturient women and newborn infants. Lancet 1964; 283: 139-141
3 Bayer MF, Kriss JP. Immunoradiometric assay for serum thyroglobulin: semiquantitative measurement of thyroglobulin in antithyroglobulin-positive sera. J Clin Endocrinol Metab 1979; 49: 557-564
4 Beltrão CB, Juliano AG, Chammas MC et al. Etiology of congenital hypothyroidism using thyroglobulin and ultrasound combination. Endocr J 2010; 57: 587-593
5 Czernichow P, Schlumberger M, Pomarede R et al. Plasma thyroglobulin measurements help determine the type of thyroid defect in congenital hypothyroidism. J Clin Endocrinol Metab 1983; 56: 242-245
6 Di Jeso B, Arvan P. Thyroglobulin from Molecular and Cellular Biology to Clinical Endocrinology. Endocr Rev 2015; DOI: http://dx.doi.org/10.1210/er2015-1090
7 Dilli D, Oğuz SS, Andiran N et al. Serum thyroid hormone levels in preterm infants born before 33 weeks of gestation and association of transient hypothyroxinemia with postnatal characteristics. J Pediatr Endocrinol Metab 2010; 23: 899-912
8 Dumont J, Opitz R, Christophe D et al. Ontogeny, Anatomy, Metabolism and Physiology of the Thyroid. In: www.thyroidmanager.org Endocrine Education, South Dartmouth MA 2015
9 Eustatia-Rutten CFA, Smit JWA, Romijn JA et al. Diagnostic value of serum thyroglobulin measurements in the follow-up of differentiated thyroid carcinoma, a structured meta-analysis. Clin Endocrinol (Oxf) 2004; 61: 61-74
10 Feldt-Rasmussen U, Rasmussen AK. Serum thyroglobulin (Tg) in presence of thyroglobulin autoantibodies (TgAb). Clinical and methodological relevance of the interaction between Tg and TgAb in vitro and in vivo. J Endocrinol Invest 1985; 8: 571-576
11 Feldt-Rasmussen U, Schlumberger M. European interlaboratory comparison of serum thyroglobulin measurement. J Endocrinol Invest 1988; 11: 175-181
12 Giovanella L, Bongiovanni M, Trimboli P. Diagnostic value of thyroglobulin assay in cervical lymph node fine-needle aspirations for metastatic differentiated thyroid cancer. Curr Opin Oncol 2013; 25: 6-13
13 Giovanella L, Clark PM, Chiovato L et al. Thyroglobulin measurement using highly sensitive assays in patients with differentiated thyroid cancer: a clinical position paper. Eur J Endocrinol 2014; 171: R33-R46
14 Han JM, Kim WB, Yim JH et al. Long-term clinical outcome of differentiated thyroid cancer patients with undetectable stimulated thyroglobulin level one year after initial treatment. Thyroid 2012; 22: 784-790
15 Haugen BR, Alexander EK, Bible KC et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 2016; 26: 1-133
16 Heemstra KA, Liu YY, Stokkel M et al. Serum thyroglobulin concentrations predict disease-free remission and death in differentiated thyroid carcinoma. Clin Endocrinol (Oxf) 2007; 66: 58-64
17 Hektoen L, Carlson AJ, Schulhof K. The precipitin reaction of thyroglobulin: presence of thyroglobulin in the thyroid lymph of goitrous dogs. J Am Med Assoc 1923; 81: 86-88
18 Herle AJ, Uller RP. Elevated serum thyroglobulin. A marker of metastases in differentiated thyroid carcinomas. J Clin Invest 1975; 56: 272-277
19 Hoofnagle AN, Becker JO, Wener MH et al. Quantification of thyroglobulin, a low-abundance serum protein, by immunoaffinity peptide enrichment and tandem mass spectrometry. Clin Chem 2008; 54: 1796-1804
20 Katagiri R, Asakura K, Uechi K et al. Adequacy of iodine intake in three different Japanese adult dietary patterns: a nationwide study. Nutr J 2015;
21 Kim MJ, Kim E-K, Kim BM et al. Thyroglobulin measurement in fine-needle aspirate washouts: the criteria for neck node dissection for patients with thyroid cancer. Clin Endocrinol (Oxf) 2009; 70: 145-151
22 Lee EK, Chung K-W, Min HS et al. Preoperative serum thyroglobulin as a useful predictive marker to differentiate follicular thyroid cancer from benign nodules in indeterminate nodules. J Korean Med Sci 2012; 27: 1014-1018
23 Lemb J, Hüfner M, Meller B et al. How reliable is secondary risk stratification with stimulated thyroglobulin in patients with differentiated thyroid carcinoma? Results from a retrospective study. Nuklearmedizin 2013; 52: 88-96
24 Lemish I, Bennett F, Martin C et al. A sensitive human thyroglobulin RIA to define clearly the presence or absence of functioning thyroid tissue. J Nucl Med 1984; 25: 49-55
25 Lerman J. Iodine components of the blood. Circulating thyroglobulin in normal persons and in persons with thyroid disease. J Clin Invest 1940; 19: 555-560
26 Lo Gerfo P, Colacchio D, Stillman T et al. Serum thyroglobulin and recurrent thyroid cancer. Lancet 1977; 309: 881-882
27 Madeddu G, Casu AR, Costanza C et al. Serum thyroglobulin levels in the diagnosis and follow-up of subacute “painful” thyroiditis. A sequential study. Arch Intern Med 1985; 145: 243-247
28 Mariotti S, Martino E, Cupini C et al. Low serum thyroglobulin as a clue to the diagnosis of thyrotoxicosis factitia. N Engl J Med 1982; 307: 410-412
29 Ma ZF, Skeaff SA. Thyroglobulin as a biomarker of iodine deficiency: a review. Thyroid 2014; 24: 1195-1209
30 Medeiros-Neto G, Targovnik HM, Vassart G. Defective thyroglobulin synthesis and secretion causing goiter and hypothyroidism. Endocr Rev 1993; 14: 165-183
31 Murray JR, Williams GR, Harrington KJ et al. Rising thyroglobulin tumour marker during pregnancy in a thyroid cancer patient: no cause for alarm?. Clin Endocrinol (Oxf) 2012; 77: 155-157
32 Nishihara E, Ohye H, Amino N et al. Clinical characteristics of 852 patients with subacute thyroiditis before treatment. Intern Med 2008; 47: 725-729
33 Owen CA, McConahey WM. An unusual iodinated protein of the serum in hashimoto's thyroiditis. J Clin Endocrinol Metab 1956; 16: 1570-1579
34 Pacini F, Fugazzola L, Lippi F et al. Detection of thyroglobulin in fine needle aspirates of nonthyroidal neck masses: a clue to the diagnosis of metastatic differentiated thyroid cancer. J Clin Endocrinol Metab 1992; 74: 1401-1404
35 Pacini F, Pinchera A. Serum and tissue thyroglobulin measurement: clinical applications in thyroid disease. Biochimie 1999; 81: 463-467
36 Pelttari H, Välimäki MJ, Löyttyniemi E et al. Post-ablative serum thyroglobulin is an independent predictor of recurrence in low-risk differentiated thyroid carcinoma: a 16-year follow-up study. Eur J Endocrinol 2010; 163: 757-763
37 Pitt-Rivers R. The Thyroid Hormones: Historical Aspects. In Hormonal proteins and Peptides. Editor Li CH. Vol. 6. Academic Press; New York: 1978
38 Preissner CM, O’Kane DJ, Singh RJ et al. Phantoms in the assay tube: heterophile antibody interferences in serum thyroglobulin assays. J Clin Endocrinol Metab 2003; 88: 3069-3074
39 Rinaldi S, Plummer M, Biessy C et al. Thyroid-stimulating hormone, thyroglobulin, and thyroid hormones and risk of differentiated thyroid carcinoma: the EPIC study. J Natl Cancer Inst 2014;
40 Rink T, Dembowski W, Schroth HJ et al. Stellenwert des Serum-Thyreoglobulinspiegels bei der Diagnostik benigner und maligner Schilddrüsenerkrankungen. Nuklearmedizin 2000; 39: 133-138
41 Robbins J. Thyroglobulin in serum after I131 Therapy I. Salting out. J Biol Chem 1954; 208: 377-386
42 Robbins J, Petermann ML, Rall JE. Thyroglobulin in serum after I131 therapy. II. Sedimentation in the ultracentrifuge. J Biol Chem 1954; 208: 387-393
43 Robbins J, Rall JE, Becker DV et al. The nature of the serum iodine after large doses of I131. J Clin Endocrinol Metab 1952; 12: 856-874
44 Sands NB, Karls S, Amir A et al. McGill Thyroid Nodule Score (MTNS): “rating the risk,” a novel predictive scheme for cancer risk determination. J Otolaryngol Head Neck Surg 2011; 40 (Suppl. 01) S1-S13
45 Sava L, Tomaselli L, Runello F et al. Serum thyroglobulin levels are elevated in newborns from iodine-deficient areas. J Clin Endocrinol Metab 1986; 62: 429-432
46 Scheffler P, Forest VI, Leboeuf R et al. Serum thyroglobulin improves the sensitivity of the McGill Thyroid Nodule Score for well-differentiated thyroid cancer. Thyroid 2014; 24: 852-857
47 Schenke S, Klett R, Braun S et al. Thyroiditis de Quervain. Are there predictive factors for long-term hormone-replacement?. Nuklearmedizin 2013; 52: 137-140
48 Spencer C, Fatemi S. Thyroglobulin antibody (TgAb) methods – Strengths, pitfalls and clinical utility for monitoring TgAb-positive patients with differentiated thyroid cancer. Best Pract Res Clin Endocrinol Metab 2013; 27: 701-712
49 Spencer C, LoPresti J, Fatemi S. How sensitive (second-generation) thyroglobulin measurement is changing paradigms for monitoring patients with differentiated thyroid cancer, in the absence or presence of thyroglobulin autoantibodies. Curr Opin Endocrinol Diabetes Obes 2014; 21: 394-404
50 Spencer CA, Takeuchi M, Kazarosyan M. Current status and performance goals for serum thyroglobulin assays. Clin Chem 1996; 42: 164-173
51 Staudt J, Happel C, Middendorp M et al. Nachsorge in der Schwangerschaft: hTg-Verlauf. Nuklearmedizin 2010; 49: N38-N40
52 Stemmermann GN. Serum protein changes in subacute thyroiditis. J Am Med Assoc 1956; 162: 31-32
53 Trimboli P, Treglia G, Giovanella L. Preoperative measurement of serum thyroglobulin to predict malignancy in thyroid nodules: a systematic review. Horm Metab Res 2015; 47: 247-252
54 Van Herle AJ, Uller RP, Matthews NI et al. Radioimmunoassay for measurement of thyroglobulin in human serum. J Clin Invest 1973; 52: 1320-1327
55 Van Herle AJ, Vassart G, Dumont JE. Control of thyroglobulin synthesis and secretion. (First of two parts). N Engl J Med 1979; 301: 239-249
56 Vejbjerg P, Knudsen N, Perrild H et al. Thyroglobulin as a marker of iodine nutrition status in the general population. Eur J Endocrinol 2009; 161: 475-481
57 Verburg FA, Wäschle K, Reiners C et al. Heterophile antibodies rarely influence the measurement of thyroglobulin and thyroglobulin antibodies in differentiated thyroid cancer patients. Horm Metab Res 2010; 42: 736-739
58 Wong H, Wong KP, Yau T et al. Is there a role for unstimulated thyroglobulin velocity in predicting recurrence in papillary thyroid carcinoma patients with detectable thyroglobulin after radioiodine ablation?. Ann Surg Oncol 2012; 19: 3479-3485
59 Zimmermann MB, Aeberli I, Andersson M et al. Thyroglobulin is a sensitive measure of both deficient and excess iodine intakes in children and indicates no adverse effects on thyroid function in the UIC range of 100-299 μg/L: a UNICEF/ICCIDD study group report. J Clin Endocrinol Metab 2013; 98: 1271-1280
60 Zimny M, Selkinski I, Blasius S et al. Risk of malignancy in follicular thyroid neoplasm: predictive value of thyrotropin. Nuklearmedizin 2012; 51: 119-124