Der Nuklearmediziner 2016; 39(02): 104-110
DOI: 10.1055/s-0042-101887
Immunologische In-Vitro-Diagnostik
© Georg Thieme Verlag KG Stuttgart · New York

Thyreoglobulin – mehr als ein Nachsorgeparameter?

Thyroglobulin – More than a Parameter of Follow-up?
M. Zimny
1   ÜBaG Nuklearmedizin Hanau – Offenbach – Frankfurt – Gießen, Hanau
› Author Affiliations
Further Information

Publication History

Publication Date:
15 June 2016 (online)

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.

 
  • 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; DOI: 10.1186/s12937-015-0116-y.
  • 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; DOI: 10.1093/jnci/dju097.
  • 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