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Thyroglobulin Measurement

  • Carole Spencer
  • Ivana Petrovic
Chapter
Part of the Thyroid Function Testing book series (ENDO, volume 28)

Abstract

The thyroglobulin (Tg) gene is encoded by human chromosome 8q24.2–8q24.3 in a 8.5 kb coding sequence covering 48 exons. As illustrated in Fig. 7.1, transcription of the 330 kDa Tg monomeric protein is regulated by a number of transcription factors that include TTF-1, TTF-2, and Pax-8 [1–3]. Posttranslational processing is complex and necessitates multiple molecular chaperones to control the glycosylation, appropriate folding, dimerization, and trafficking of the mature protein to the apical membrane where thyroid peroxidase catalyses the iodination of the hormonogenic sites [1, 3–6]. Comparisons between Tg derived from papillary cancers versus normal thyroid tissue show differences in carbohydrate, iodine content, sulfation, charge, and immunological properties [7–13]. These differences likely result from defective posttranslational processing of tumor-derived Tg leading to the secretion of Tg molecules with an abnormal tertiary structure. Because Tg epitopes are conformational, any alteration in the tertiary structure of the molecule has the potential to disrupt the immunological interaction(s) with the assay reagents [7, 10, 11, 14–16]. The half-life of Tg in serum approximates 3 days and is determined by the terminal sialic acid content of the molecule [17]. Both the sialic acid and iodine content of the Tg derived from papillary tumors tend to be lower than normal, suggesting the possibility for differences in the metabolic clearance of Tg protein secreted by different tumors [8, 17–19]. An accelerated metabolic clearance of tumor-derived Tg could be the reason why serum Tg can be paradoxically low or even undetectable in some patients with a significant tumor burden [11, 12, 20–24].

Keywords

Differentiate Thyroid Cancer Subacute Thyroiditis Struma Ovarii Differentiate Thyroid Cancer Patient rhTSH Stimulation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    van de Graaf SA, Ris-Stalpers C, Pauws E, Mendive FM, Targovnik HM, de Vijlder JJ. Up to date with human thyroglobulin. J Endocrinol. 2001;170:307-321.PubMedGoogle Scholar
  2. 2.
    De Felice M, Di Lauro R. Thyroid development and its disorders: genetics and molecular mechanisms. Endocr Rev. 2004;25:722-746.PubMedGoogle Scholar
  3. 3.
    Lin JD. Thyroglobulin and human thyroid cancer. Clin Chim Acta. 2008;338:15-21.Google Scholar
  4. 4.
    Lee J, Di Jeso B, Arvan P. The cholinesterase-like domain of thyroglobulin functions as an intramolecular chaperone. J Clin Invest. 2008;118:2950-2958.PubMedGoogle Scholar
  5. 5.
    Arvan P, Kim PS, Kuliawat R, et al. Intracellular protein transport to the thyrocyte plasma membrane: potential implications for thyroid physiology. Thyroid. 1997;7:89-105.PubMedGoogle Scholar
  6. 6.
    Di Jeso B, Ulianich L, Pacifico F, et al. Folding of thyroglobulin in the calnexin/calreticulin pathway and its alteration by loss of Ca2+ from the endoplasmic reticulum. Biochem J. 2003;370:449-458.PubMedGoogle Scholar
  7. 7.
    Kim PS, Dunn AD, Dunn JT. Altered immunoreactivity of thyroglobulin in thyroid disease. J Clin Endocrinol Metab. 1988;67:161-168.PubMedGoogle Scholar
  8. 8.
    Schneider A, Ikekubo K, Kuma K. Iodine content of serum thyroglobulin in normal individuals and patients with thyroid tumors. J Clin Endocrinol Metab. 1983;57:1251-1256.PubMedGoogle Scholar
  9. 9.
    Gérard AC, Daumerie C, Mestdagh C, et al. Correlation between the loss of thyroglobulin iodination and the expression of thyroid-specific proteins involved in iodine metabolism in thyroid carcinomas. J Clin Endocrinol Metab. 2003;88:4977-4983.PubMedGoogle Scholar
  10. 10.
    de Micco C, Ruf J, Carayon P, Chrestian MA, Henry JF, Toga M. Immunohistochemical study of thyroglobulin in thyroid carcinomas with monoclonal antibodies. Cancer. 1987;59:471-476.PubMedGoogle Scholar
  11. 11.
    Schulz R, Bethauser H, Stempka L, Heilig B, Moll A, Hufner M. Evidence for immunological differences between circulating and tissue-derived thyroglobulin in men. Eur J Clin Invest. 1989;19:459-463.PubMedGoogle Scholar
  12. 12.
    Shimizu K, Nakamura K, Kobatake S, et al. The clinical utility of Lens culinaris agglutinin-reactive thyroglobulin ratio in serum for distinguishing benign from malignant conditions of the thyroid. Clin Chim Acta. 2007;379:101-104.PubMedGoogle Scholar
  13. 13.
    Emoto N, Kunii YK, Ashizawa M, et al. Reduced sulfation of chondroitin sulfate in thyroglobulin derived from human papillary thyroid carcinomas. Cancer Sci. 2007;98:1577-1581.PubMedGoogle Scholar
  14. 14.
    McLachlan SM, Rapoport B. Why measure thyroglobulin autoantibodies rather than thyroid peroxidase autoantibodies. Thyroid. 2004;14:510-520.PubMedGoogle Scholar
  15. 15.
    Prentice L, Kiso Y, Fukuma N, et al. Monoclonal thyroglobulin autoantibodies: variable region analysis and epitope recognition. J Clin Endocrinol Metab. 1995;80:977-986.PubMedGoogle Scholar
  16. 16.
    Spencer CA, Bergoglio LM, Kazarosyan M, Fatemi S, LoPresti JS. Clinical impact of thyroglobulin (Tg) and Tg autoantibody method differences on the management of patients with differentiated thyroid carcinomas. J Clin Endocrinol Metab. 2005;90:5566-5575.PubMedGoogle Scholar
  17. 17.
    Morell AG, Gregoriadis G, Scheinberg IH, Hickman J, Ashwell G. The role of sialic acid in determining the survival of glycoproteins in the circulation. J Biol Chem. 1971;246:1461-1467.PubMedGoogle Scholar
  18. 18.
    Sinadinovic J, Cvejic D, Savin S, Jancic-Zuguricas M, Micic JV. Altered terminal glycosylation of thyroglobulin in papillary thyroid carcinoma. Exp Clin Endocrinol. 1992;100:124-128.PubMedGoogle Scholar
  19. 19.
    Bastiani P, Papandreou MJ, Blanck O, Fenouillet E, Thibault V, Miquelis R. On the relationship between completion of N-acetyllactosamine oligosaccharide units and iodine content of thyroglobulin: a reinvestigation. Endocrinology. 1995;136:4204-4209.PubMedGoogle Scholar
  20. 20.
    Feldt-Rasmussen U. Serum thyroglobulin and thyroglobulin autoantibodies in thyroid diseases. Pathogenic and diagnostic aspects. Allergy. 1983;38:369-387.PubMedGoogle Scholar
  21. 21.
    Jeevanram RK, Shah DH, Sharma SM, Ganatra RD. Disappearance rate of endogenously radioiodinated thyroglobulin and thyroxine after radioiodine treatment. Cancer. 1982;49:2281-2284.PubMedGoogle Scholar
  22. 22.
    Hocevar M, Auersperg M, Stanovnik L. The dynamics of serum thyroglobulin elimination from the body after thyroid surgery. Eur J Surg Oncol. 1997;23:208-210.PubMedGoogle Scholar
  23. 23.
    Ikekubo K, Pervos R, Schneider AB. Clearance of normal and tumor-related thyroglobulin from the circulation of rats: role of the terminal sialic acid residues. Metabolism. 1980;29:673-681.PubMedGoogle Scholar
  24. 24.
    Magro G, Perissinotto D, Schiappacassi M, et al. Proteomic and postproteomic characterization of keratan sulfate-glycanated isoforms of thyroglobulin and transferrin uniquely elaborated by papillary thyroid carcinomas. Am J Pathol. 2003;163:183-196.PubMedGoogle Scholar
  25. 25.
    Cole TG, Johnson D, Eveland BJ, Nahm MH. Cost-effective method for detection of “hook effect” in tumor marker immunometric assays. Clin Chem. 1993;39:695-696.PubMedGoogle Scholar
  26. 26.
    Spencer CA, Takeuchi M, Kazarosyan M. Current status and performance goals for serum thyroglobulin assays. Clin Chem. 1996;42:164-173.PubMedGoogle Scholar
  27. 27.
    Schofl C, Schofl-Siegert B, Karstens JH, et al. Falsely low serum prolactin in two cases of invasive macroprolactinoma. Pituitary. 2002;5:261-265.PubMedGoogle Scholar
  28. 28.
    Morgenthaler NG, Froehlich J, Rendl J, et al. Technical evaluation of a new immunoradiometric and a new immunoluminometric assay for thyroglobulin. Clin Chem. 2002;48:1077-1083.PubMedGoogle Scholar
  29. 29.
    Feldt-Rasmussen U, Schlumberger M. European interlaboratory comparison of serum thyroglobulin measurement. J Endocrinol Invest. 1988;11:175-181.PubMedGoogle Scholar
  30. 30.
    Schaadt B, Feldt-Rasmussen U, Rasmussen B, et al. Assessment of the influence of thyroglobulin (Tg) autoantibodies and other interfering factors on the use of serum Tg as tumor marker in differentiated thyroid carcinoma. Thyroid. 1995;5:165-170.PubMedGoogle Scholar
  31. 31.
    Kato R, Maruyama M, Sekino T, Kasuga Y. A new assay for thyroglobulin concentration in serum using monoclonal antibodies against synthetic peptides. Clin Chim Acta. 2000;298:69-84.PubMedGoogle Scholar
  32. 32.
    Weightman DR, Mallick UK, Fenwick JD, et al. Discordant serum thyroglobulin results generated by two classes of assay in patients with thyroid carcinoma: correlation with clinical outcome after 3 years of follow-up. Cancer. 2003;98:41-47.PubMedGoogle Scholar
  33. 33.
    Schneider AB, Pervos R. Radioimmunoassay of human thyroglobulin: effect of antithyroglobulin autoantibodies. J Clin Endocrinol Metab. 1978;47:126-137.PubMedGoogle Scholar
  34. 34.
    Feldt-Rasmussen U, Profilis C, Colinet E, et al. Human thyroglobulin reference material (CRM 457) 1st part: assessment of homogeneity, stability and immunoreactivity. Ann Biol Clin (Paris). 1996;54:337-342.Google Scholar
  35. 35.
    Iervasi A, Iervasi G, Carpi A, Zucchelli GC. Serum thyroglobulin measurement: clinical background and main methodological aspects with clinical impact. Biomed Pharmacother. 2006;60:414-424.PubMedGoogle Scholar
  36. 36.
    Jensen E, Petersen PH, Blaabjerg O, Hegedus L. Biological variation of thyroid autoantibodies and thyroglobulin. Clin Chem Lab Med. 2007;45:1058-1064.PubMedGoogle Scholar
  37. 37.
    Feldt-Rasmussen U, Petersen PH, Blaabjerg O, Horder M. Long-term variability in serum thyroglobulin and thyroid related hormones in healthy subjects. Acta Endocrinol (Copenhagen). 1980;95:328-334.Google Scholar
  38. 38.
    Ferrari L, Biancolini D, Seregni E, et al. Critical aspects of immunoradiometric thyroglobulin assays. Tumori. 2003;89:537-539.PubMedGoogle Scholar
  39. 39.
    Schlumberger M, Hitzel A, Toubert ME, et al. Comparison of seven serum thyroglobulin assays in the follow-up of papillary and follicular thyroid cancer patients. J Clin Endocrinol Metab. 2007;92:2487-2495.PubMedGoogle Scholar
  40. 40.
    Ross HA, Netea-Maier RT, Schakenraad E, Bravenboer B, Hermus AR, Sweep FC. Assay bias may invalidate decision limits and affect comparability of serum thyroglobulin assay methods: an approach to reduce interpretation differences. Clin Chim Acta. 2008;394:104-109.PubMedGoogle Scholar
  41. 41.
    Baloch Z, Carayon P, Conte-Devolx B, et al. Laboratory medicine practice guidelines: laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid. 2003;13:57-67.Google Scholar
  42. 42.
    Spencer CA, Lopresti JS. Measuring thyroglobulin and thyroglobulin autoantibody in patients with differentiated thyroid cancer. Nat Clin Pract Endocrinol Metab. 2008;4:223-233.PubMedGoogle Scholar
  43. 43.
    Haugen BR, Ladenson PW, Cooper DS, et al. A comparison of recombinant human thyrotropin and thyroid hormone withdrawal for the detection of thyroid remnant or cancer. J Clin Endocrinol Metab. 1999;84:3877-3885.PubMedGoogle Scholar
  44. 44.
    Mazzaferri EL, Robbins RJ, Spencer CA, et al. A consensus report of the role of serum thyroglobulin as a monitoring method for low-risk patients with papillary thyroid carcinoma. J Clin Endocrinol Metab. 2003;88:1433-1441.PubMedGoogle Scholar
  45. 45.
    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.PubMedGoogle Scholar
  46. 46.
    Cooper DS, Doherty GM, Haugen BR, et al. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. The American Thyroid Association Guidelines Taskforce. Thyroid. 2006;16:109-142.Google Scholar
  47. 47.
    Giovanella L, Ceriani L, Ghelfo A, et al. Thyroglobulin assay during thyroxine treatment in low-risk differentiated thyroid cancer management: comparison with recombinant human thyrotropin-stimulated assay and imaging procedures. Clin Chem Lab Med. 2006;44:648-652.PubMedGoogle Scholar
  48. 48.
    Giovanella L, Ceriani L, Suriano S, Ghelfo A, Maffioli M. Thyroglobulin measurement before rhTSH-aided 131-I ablation in detecting metastases from differentiated thyroid carcinoma. Clin Endocrinol (Oxford). 2008;68:659-663.Google Scholar
  49. 49.
    Baudin E, Do Cao C, Cailleux AF, Leboulleux S, Travagli JP, Schlumberger M. Positive predictive value of serum thyroglobulin levels, measured during the first year of follow-up after thyroid hormone withdrawal, in thyroid cancer patients. J Clin Endocrinol Metab. 2003;88:1107-1111.PubMedGoogle Scholar
  50. 50.
    Schaap J, Eustatia-Rutten CF, Stokkel M, et al. Does radioiodine therapy have disadvantageous effects in non-iodine accumulating differentiated thyroid carcinoma. Clin Endocrinol (Oxford). 2002;57:117-124.Google Scholar
  51. 51.
    Iervasi A, Iervasi G, Ferdeghini M, et al. Clinical relevance of highly sensitive Tg assay in monitoring patients treated for differentiated thyroid cancer. Clin Endocrinol (Oxford). 2007;67:434-441.Google Scholar
  52. 52.
    Tuttle RM, Leboeuf R. Follow up approaches in thyroid cancer: a risk adapted paradigm. Endocrinol Metab Clin North Am. 2008;37:419-435.PubMedGoogle Scholar
  53. 53.
    Huang SH, Wang PW, Huang YE, et al. Sequential follow-up of serum thyroglobulin and whole body scan in thyroid cancer patients without initial metastasis. Thyroid. 2006;16:1273-1278.PubMedGoogle Scholar
  54. 54.
    Pacini F, Agate L, Elisei R, et al. Outcome of differentiated thyroid cancer with detectable serum Tg and negative diagnostic 131-I whole body scan: comparison of patients treated with high 131-I activities versus untreated patients. J Clin Endocrinol Metab. 2001;86:4092-4097.PubMedGoogle Scholar
  55. 55.
    Valadão MM, Rosário PW, Borges MA, et al. Positive predictive value of detectable stimulated tg during the first year after therapy of thyroid cancer and the value of comparison with Tg-ablation and Tg measured after 24 months. Thyroid. 2006;16:1145-1149.PubMedGoogle Scholar
  56. 56.
    Rosario P, Borges M, Reis J, Alves MF. Effect of suppressive therapy with levothyroxine on the reduction of serum thyroglobulin after total thyroidectomy. Thyroid. 2006;16:199-200.PubMedGoogle Scholar
  57. 57.
    Zophel K, Wunderlich G, Smith BR. Serum thyroglobulin measurements with a high sensitivity enzyme-linked immunosorbent assay: is there a clinical benefit in patients with differentiated thyroid carcinoma? Thyroid. 2003;13:861-865.PubMedGoogle Scholar
  58. 58.
    Van Herle AJ, Uller RP, Matthews NI, Brown J. Radioimmunoassay for measurement of thyroglobulin in human serum. J Clin Invest. 1973;52:1320-1327.PubMedGoogle Scholar
  59. 59.
    Spencer CA, LoPresti JS, Patel A, et al. Applications of a new chemiluminometric thyrotropin assay to subnormal measurement. J Clin Endocrinol Metab. 1990;70:453-460.PubMedGoogle Scholar
  60. 60.
    Mazzaferri EL. Will highly sensitive thyroglobulin assays change the management of thyroid cancer? Clin Endocrinol (Oxford). 2007;67:321-323.Google Scholar
  61. 61.
    Smallridge RC, Meek SE, Morgan MA, et al. Monitoring thyroglobulin in a sensitive immunoassay has comparable sensitivity to recombinant human tsh-stimulated thyroglobulin in follow-up of thyroid cancer patients. J Clin Endocrinol Metab. 2007;92:82-87.PubMedGoogle Scholar
  62. 62.
    Rosario PW, Purisch S. Does a highly sensitive thyroglobulin (Tg) assay change the clinical management of low-risk patients with thyroid cancer with Tg on T4 < 1 ng/ml determined by traditional assays? Clin Endocrinol (Oxford). 2008;68:338-342.Google Scholar
  63. 63.
    Rodbard D. Statistical estimation of the minimal detectable concentration (“sensitivity”) for radioligand assays. Anal Biochem. 1978;90:1-12.PubMedGoogle Scholar
  64. 64.
    Després N, Grant AM. Antibody interference in thyroid assays: a potential for clinical misinformation. Clin Chem. 1998;44:440-454.PubMedGoogle Scholar
  65. 65.
    Kricka LJ. Human anti-animal antibody interferences in immunological assays. Clin Chem. 1999;45:942-956.PubMedGoogle Scholar
  66. 66.
    Choi WW, Srivatsa S, Ritchie JC. Aberrant thyroid testing results in a clinically euthyroid patient who had received a tumor vaccine. Clin Chem. 2005;51:673-675.PubMedGoogle Scholar
  67. 67.
    Ismail AAA, Walker PL, Cawood ML, Barth JH. Interference in immunoassay is an underestimated problem. Ann Clin Biochem. 2002;39:366-373.PubMedGoogle Scholar
  68. 68.
    Preissner CM, O'Kane DJ, Singh RJ, Morris JC, Grebe SK. Phantoms in the assay tube: heterophile antibody interferences in serum thyroglobulin assays. J Clin Endocrinol Metab. 2003;88:3069-3074.PubMedGoogle Scholar
  69. 69.
    Massart C, Corcuff JB, Bordenave L. False-positive results corrected by the use of heterophilic antibody-blocking reagent in thyroglobulin immunoassays. Clin Chim Acta. 2008;388:211-213.PubMedGoogle Scholar
  70. 70.
    Boscato LM, Stuart MC. Incidence and specificity of interference in two-site immunoassays. Clin Chem. 1986;32:1491-1495.PubMedGoogle Scholar
  71. 71.
    Tan MJ, Tan F, Hawkins R, Mukherjee JJ. A hyperthyroid patient with measurable thyroid-stimulating hormone concentration—a trap for the unwary. Ann Acad Med Singapore. 2006;35:500-503.PubMedGoogle Scholar
  72. 72.
    Giovanella L, Ghelfo A. Undetectable serum thyroglobulin due to negative interference of heterophile antibodies in relapsing thyroid carcinoma. Clin Chem. 2007;53:1871-1872.PubMedGoogle Scholar
  73. 73.
    Levinson SS, Miller JJ. Towards a better understanding of heterophile (and the like) antibody interference with modern immunoassays. Clin Chim Acta. 2002;325:1-15.PubMedGoogle Scholar
  74. 74.
    Rotmensch S, Cole LA. False diagnosis and needless therapy of presumed malignant disease in women with false-positive human chorionic gonadotropin concentrations. Lancet. 2000;355:712-715.PubMedGoogle Scholar
  75. 75.
    Spencer CA, Takeuchi M, Kazarosyan M, et al. Serum thyroglobulin autoantibodies: prevalence, influence on serum thyroglobulin measurement and prognostic significance in patients with differentiated thyroid carcinoma. J Clin Endocrinol Metab. 1998;83:1121-1127.PubMedGoogle Scholar
  76. 76.
    Benvenga S, Burek CL, Talor M, Rose NR, Trimarchi F. Heterogeneity of the thyroglobulin epitopes associated with circulating thyroid hormone autoantibodies in hashimoto's thyroiditis and non-autoimmune thyroid diseases. J Endocrinol Invest. 2002;25:977-982.PubMedGoogle Scholar
  77. 77.
    Pinchera A, Mariotti S, Vitti P, et al. Interference of serum thyroglobulin in the radioassay for serum antithyroglobulin antibodies. J Clin Endocrinol Metab. 1977;45:1077-1088.PubMedGoogle Scholar
  78. 78.
    Feldt-Rasmussen U, Høier-Madsen M, Hansen HS, Blichert-Toft M. Comparison between homogeneous phase radioassay and enzyme-linked immunosorbent assay for measurement of antithyroglobulin antibody content in serum. Acta Pathol Microbiol Immunol Scand. 1986;94:33-38.Google Scholar
  79. 79.
    Feldt-Rasmussen U. Serum thyroglobulin and thyroglobulin autoantibodies in thyroid diseases. pathogenetic and diagnostic aspects. Allergy. 1983;38:369-387.PubMedGoogle Scholar
  80. 80.
    Görges R, Maniecki M, Jentzen W, et al. Development and clinical impact of thyroglobulin antibodies in patients with differentiated thyroid carcinoma during the first 3 years after thyroidectomy. Eur J Endocrinol. 2005;153:49-55.PubMedGoogle Scholar
  81. 81.
    Sapin R, Gasser F, Chambron J. Recovery determination in 600 sera analyzed for thyroglobulin with a recently commercialized IRMA kit. Clin Chem. 1992;38:1920-1921.PubMedGoogle Scholar
  82. 82.
    Okosieme OE, Evans C, Moss L, Parkes AB, Premawardhana LD, Lazarus JH. Thyroglobulin antibodies in serum of patients with differentiated thyroid cancer: relationship between epitope specificities and thyroglobulin recovery. Clin Chem. 2005;51:729-734.PubMedGoogle Scholar
  83. 83.
    Ratcliffe JG, Ayoub LA, Pearson D. The measurement of serum thyroglobulin in the presence of thyroglobulin antibodies. Clin Endocrinol (Oxford). 1981;15:507-518.Google Scholar
  84. 84.
    Hollowell JG, Staehling NW, Hannon WH, et al. Serum thyrotropin, thyroxine, and thyroid antibodies in the United States population (1988 to 1994): NHANES III. J Clin Endocrinol Metab. 2002;87:489-499.Google Scholar
  85. 85.
    Chung JK, Park YJ, Kim TY, et al. Clinical significance of elevated level of serum antithyroglobulin antibody in patients with differentiated thyroid cancer after thyroid ablation. Clin Endocrinol (Oxford). 2002;57:215-221.Google Scholar
  86. 86.
    Pacini F, Mariotti S, Formica N, et al. Thyroid autoantibodies in thyroid cancer: incidence and relationship with tumour outcome. Acta Endocrinol (Copenhagen). 1988;119:373-380.Google Scholar
  87. 87.
    Cubero JM, Rodríguez-Espinosa J, Gelpi C, Estorch M, Corcoy R. Thyroglobulin autoantibody levels below the cut-off for positivity can interfere with thyroglobulin measurement. Thyroid. 2003;13:659-661.PubMedGoogle Scholar
  88. 88.
    Küçük ON, Aras G, Kulak HA, et al. Clinical importance of anti-thyroglobulin auto-antibodies in patients with differentiated thyroid carcinoma: comparison with 99mTc-MIBI scans. Nucl Med Commun. 2006;27:873-876.PubMedGoogle Scholar
  89. 89.
    Chiovato L, Latrofa F, Braverman LE, et al. Disappearance of humoral thyroid autoimmunity after complete removal of thyroid antigens. Ann Intern Med. 2003;139:346-351.PubMedGoogle Scholar
  90. 90.
    Thomas D, Liakos V, Vassiliou E, Hatzimarkou F, Tsatsoulis A, Kaldrimides P. Possible reasons for different pattern disappearance of thyroglobulin and thyroid peroxidase autoantibodies in patients with differentiated thyroid carcinoma following total thyroidectomy and iodine-131 ablation. J Endocrinol Invest. 2007;30:173-180.PubMedGoogle Scholar
  91. 91.
    Rubello D, Casara D, Girelli ME, Piccolo M, Busnardo B. Clinical meaning of circulating antithyroglobulin antibodies in differentiated thyroid cancer: a prospective study. J Nucl Med. 1992;33:1478-1480.PubMedGoogle Scholar
  92. 92.
    Sapin R, d'Herbomez M, Gasser F, Meyer L, Schlienger JL. Increased sensitivity of a new assay for anti-thyroglobulin antibody detection in patients with autoimmune thyroid disease. Clin Biochem. 2003;36:611-616.PubMedGoogle Scholar
  93. 93.
    Sellitti DF, Akamizu T, Doi SQ, et al. Renal expression of two ‘thyroid-specific’ genes: thyrotropin receptor and thyroglobulin. Exp Nephrol. 2000;8:235-243.PubMedGoogle Scholar
  94. 94.
    Barzon L, Boscaro M, Pacenti M, Taccaliti A, Palu G. Evaluation of circulating thyroid-specific transcripts as markers of thyroid cancer relapse. Int J Cancer. 2004;110:914-920.PubMedGoogle Scholar
  95. 95.
    Eszlinger M, Neumann S, Otto L, Paschke R. Thyroglobulin mRNA quantification in the peripheral blood is not a reliable marker for the follow-up of patients with differentiated thyroid cancer. Eur J Endocrinol. 2002;147:575-582.PubMedGoogle Scholar
  96. 96.
    Grammatopoulos D, Elliott Y, Smith SC, et al. Measurement of thyroglobulin mRNA in peripheral blood as an adjunctive test for monitoring thyroid cancer. Mol Pathol. 2003;56:162-166.PubMedGoogle Scholar
  97. 97.
    Elisei R, Vivaldi A, Agate L, et al. Low specificity of blood thyroglobulin messenger ribonucleic acid assay prevents its use in the follow-up of differentiated thyroid cancer patients. J Clin Endocrinol Metab. 2004;89:33-39.PubMedGoogle Scholar
  98. 98.
    Kaufmann S, Schmutzler C, Schomburg L, et al. Real time RT-PCR analysis of thyroglobulin mRNA in peripheral blood in patients with congenital athyreosis and with differentiated thyroid carcinoma after stimulation with recombinant human thyrotropin. Endocr Regul. 2004;38:41-49.PubMedGoogle Scholar
  99. 99.
    Ringel MD. Editorial: molecular detection of thyroid cancer: differentiating “signal” and “noise” in clinical assays. J Clin Endocrinol Metab. 2004;89:29-32.PubMedGoogle Scholar
  100. 100.
    Verburg FA, Lips CJ, Lentjes EG, de Klerk JM. Detection of circulating Tg-mRNA in the follow-up of papillary and follicular thyroid cancer: how useful is it? Br J Cancer. 2004;91:200-204.PubMedGoogle Scholar
  101. 101.
    Amakawa M, Kato R, Kameko F, Maruyama M,Tajiri J. Thyroglobulin mRNA expression in peripheral blood lymphocytes of healthy subjects and patients with thyroid disease. Clin Chim Acta. 2008;390:97-103.PubMedGoogle Scholar
  102. 102.
    Tallini G, Ghossein RA, Emanuel J, et al. Detection of thyroglobulin, thyroid peroxidase, and RET/PTC1 mRNA transcripts in the peripheral blood of patients with thyroid disease. J Clin Oncol. 1998;16:1158-1166.PubMedGoogle Scholar
  103. 103.
    Ringel MD, Balducci-Silano PL, Anderson JS, et al. Quantitative reverse transcription-polymerase chain reaction of circulating thyroglobulin messenger ribonucleic acid for monitoring patients with thyroid carcinoma. J Clin Endocrinol Metab. 1999;84:4037-4042.PubMedGoogle Scholar
  104. 104.
    Bellantone R, Lombardi CP, Bossola M, et al. Validity of thyroglobulin mRNA assay in peripheral blood of postoperative thyroid carcinoma patients in predicting tumor recurrences varies according to the histologic type: results of a prospective study. Cancer. 2001;92:2273-2279.PubMedGoogle Scholar
  105. 105.
    Chinnappa P, Taguba L, Arciaga R, et al. Detection of thyrotropin-receptor messenger ribonucleic acid (mRNA) and thyroglobulin mRNA transcripts in peripheral blood of patients with thyroid disease: sensitive and specific markers for thyroid cancer. J Clin Endocrinol Metab. 2004;89:3705-3709.PubMedGoogle Scholar
  106. 106.
    Lombardi CP, Bossola M, Princi P, et al. Circulating thyroglobulin mRNA does not predict early and midterm recurrences in patients undergoing thyroidectomy for cancer. Am J Surg. 2008;196:326-332.PubMedGoogle Scholar
  107. 107.
    Takano T, Miyauchi A, Yoshida H, Hasegawa Y, Kuma K, Amino N. Quantitative measurement of thyroglobulin mRNA in peripheral blood of patients after total thyroidectomy. Br J Cancer. 2001;85:102-106.PubMedGoogle Scholar
  108. 108.
    Span PN, Sleegers MJ, van den Broek WJ, et al. Quantitative detection of peripheral thyroglobulin mRNA has limited clinical value in the follow-up of thyroid cancer patients. Ann Clin Biochem. 2003;40:94-99.PubMedGoogle Scholar
  109. 109.
    Bojunga J, Röddiger S, Stanisch M, et al. Molecular detection of thyroglobulin mRNA transcripts in peripheral blood of patients with thyroid disease by RT-PCR. Br J Cancer. 2000;82:1650-1655.PubMedGoogle Scholar
  110. 110.
    Savagner F, Rodien P, Reynier P, Rohmer V, Bigorgne JC, Malthiery Y. Analysis of Tg transcripts by real-time RT-PCR in the blood of thyroid cancer patients. J Clin Endocrinol Metab. 2002;87:635-639.PubMedGoogle Scholar
  111. 111.
    Fugazzola L, Persani L, Mannavola D, et al. Recombinant human TSH testing is a valuable tool for differential diagnosis of congenital hypothyroidism during L-thyroxine replacement. Clin Endocrinol (Oxford). 2003;59:230-236.Google Scholar
  112. 112.
    Rubio IG, Silva MN, Knobel M, et al. Peripheral blood levels of thyroglobulin mRNA and serum thyroglobulin concentrations after radioiodine ablation of multinodular goiter with or without pre-treatment with recombinant human thyrotropin. J Endocrinol Invest. 2007;30:535-540.PubMedGoogle Scholar
  113. 113.
    Jahagirdar VR, Strouhal P, Holder G, Gama R, Singh BM. Thyrotoxicosis factitia masquerading as recurrent Graves' disease: endogenous antibody immunoassay interference, a pitfall for the unwary. Ann Clin Biochem. 2008;45:325-327.PubMedGoogle Scholar
  114. 114.
    Mariotti S, Barbesino G, Caturegli P, et al. Assay of thyroglobulin in serum with thyroglobulin autoantibodies: an unobtainable goal? J Clin Endocrinol Metab. 1995;80:468-472.PubMedGoogle Scholar
  115. 115.
    Marquet PY, Daver A, Sapin R, et al. Highly sensitive immunoradiometric assay for serum thyroglobulin with minimal interference from autoantibodies. Clin Chem. 1996;42:258-262.PubMedGoogle Scholar
  116. 116.
    Weigle WO, High GJ. The behaviour of autologous thyroglobulin in the circulation of rabbits immunized with either heterologous or altered homologous thyroglobulin. J Immunol. 1967;98:1105-1114.PubMedGoogle Scholar
  117. 117.
    Feldt-Rasmussen U, Petersen PH, Date J, Madse CM. Sequential changes in serum thyroglobulin (Tg) and its autoantibodies (TgAb) following subtotal thyroidectomy of patients with preoperatively detectable TgAb. Clin Endocrinol (Oxford). 1980;12:29-38.Google Scholar
  118. 118.
    Hjiyiannakis P, Mundy J, Harmer C. Thyroglobulin antibodies in differentiated thyroid cancer. Clin Oncol. 1999;11:240-244.Google Scholar
  119. 119.
    Clark PM, Beckett G. Can we measure serum thyroglobulin? Ann Clin Biochem. 2002;39:196-202.PubMedGoogle Scholar
  120. 120.
    Black EG, Hoffenberg R. Should one measure serum thyroglobulin in the presence of anti-thyroglobulin antibodies? Clin Endocrinol (Oxford). 1983;19:597-601.Google Scholar
  121. 121.
    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.PubMedGoogle Scholar
  122. 122.
    Uller RP, Van Herle AJ. Effect of therapy on serum thyroglobulin levels in patients with Graves' disease. J Clin Endocrinol Metab. 1978;46:747-755.PubMedGoogle Scholar
  123. 123.
    Fenzi GF, Ceccarelli C, Macchia E, et al. Reciprocal changes of serum thyroglobulin and TSH in residents of a moderate endemic goitre area. Clin Endocrinol (Oxford). 1985;23:115-122.Google Scholar
  124. 124.
    Pardo V, Rubio IG, Knobel M, et al. Phenotypic variation among four family members with congenital hypothyroidism caused by two distinct thyroglobulin gene mutations. Thyroid. 2008;18:783-786.PubMedGoogle Scholar
  125. 125.
    Ericsson UB, Tegler L, Lennquist S, Borup Christensen S, Stahl E, Thorell JI. Serum thyroglobulin in differentiated thyroid carcinoma. Acta Chir Scand. 1984;150:367-375.PubMedGoogle Scholar
  126. 126.
    Berghout A, Wiersinga WM, Smits NJ, Touber JL. Interrelationships between age, thyroid volume, thyroid nodularity, and thyroid function in patients with sporadic nontoxic goiter. Am J Med. 1990;89:602-608.PubMedGoogle Scholar
  127. 127.
    Bachelot A, Cailleux AF, Klain M, et al. Relationship between tumor burden and serum thyroglobulin level in patients with papillary and follicular thyroid carcinoma. Thyroid. 2002;12:707-711.PubMedGoogle Scholar
  128. 128.
    Pacini F, Molinaro E, Castagna MG, et al. Recombinant human thyrotropin-stimulated serum thyroglobulin combined with neck ultrasonography has the highest sensitivity in monitoring differentiated thyroid carcinoma. J Clin Endocrinol Metab. 2003;88:3668-3673.PubMedGoogle Scholar
  129. 129.
    Feldt-Rasmussen U, Petersen PH, Date J, Madsen CM. Serum thyroglobulin in patients undergoing subtotal thyroidectomy for toxic and nontoxic goiter. J Endorinol Invest. 1982;5:161-164.Google Scholar
  130. 130.
    Luboshitzky R, Lavi I, Ishay A. Serum thyroglobulin levels after fine-needle aspiration of thyroid nodules. Endocr Pract. 2006;12:264-269.PubMedGoogle Scholar
  131. 131.
    Feldt-Rasmussen U, Bech K, Date J, Johansen K. A prospective study of the differential changes in serum thyroglobulin and its autoantibodies during propylthiouracil or radioiodine therapy of patients with Graves' disease. Acta Endocrinol (Copenhagen). 1982;99:379-385.Google Scholar
  132. 132.
    Smallridge RC, De Keyser FM, Van Herle AJ, Butkus NE, Wartofsky L. Thyroid iodine content and serum thyroglobulin: cues to the natural history of destruction-induced thyroiditis. J Clin Endocrinol Metab. 1986;62:1213-1219.PubMedGoogle Scholar
  133. 133.
    Duick DS, Stein RB, Warren DW, Nicoloff JT. The significance of partial suppressibility of serum thyroxine by triidothyronine administration in euthyroid man. J Clin Endocrinol Metab. 1975;41:229-234.PubMedGoogle Scholar
  134. 134.
    Gardner DF, Rothman J, Utiger RD. Serum thyroglobulin in normal subjects and patients with hyperthyroidism due to Graves' disease: effects of T3, iodide, 131I and antithyroid drugs. Clin Endocrinol (Oxford). 1979;11:585-594.Google Scholar
  135. 135.
    Glinoer D, De Nayer P, Bourdoux P, et al. Regulation of maternal thyroid during pregnancy. J Clin Endocrinol Metab. 1990;71:276-287.PubMedGoogle Scholar
  136. 136.
    Berghout A, Endert E, Ross A, Hogerzeil HV, Smits NJ, Wiersinga WM. Thyroid function and thyroid size in normal pregnant women living in an iodine replete area. Clin Endocrinol (Oxford). 1994;41:375-379.Google Scholar
  137. 137.
    Leboeuf R, Emerick LE, Martorella AJ, Tuttle RM. Impact of pregnancy on serum thyroglobulin and detection of recurrent disease shortly after delivery in thyroid cancer survivors. Thyroid. 2007;17:543-547.PubMedGoogle Scholar
  138. 138.
    Derumeaux H, Valeix P, Castetbon K, et al. Association of selenium with thyroid volume and echostructure in 35- to 60-year-old French adults. Eur J Endocrinol. 2003;148:309-315.PubMedGoogle Scholar
  139. 139.
    Shih ML, Lee JA, Hsieh CB, et al. Thyroidectomy for Hashimoto's thyroiditis: complications and associated cancers. Thyroid. 2008;18:729-734.PubMedGoogle Scholar
  140. 140.
    Fraser CG. Generation and application of data on biological variation in clinical chemistry. Crit Rev Clin Lab Sci. 1989;27:409-437.PubMedGoogle Scholar
  141. 141.
    Buchinger W, Lorenz-Wawschinek O, Semlitsch G, et al. Thyrotropin and thyroglobulin as an index of optimal iodine intake: correlation with iodine excretion of 39,913 euthyroid patients. Thyroid. 1997;7:593-597.PubMedGoogle Scholar
  142. 142.
    WHO/ICCIDD/UNICEF. Indicators for assessing iodine deficiency disorders and their control through salt iodization. Document WHO/NUT. 1994;6:36.Google Scholar
  143. 143.
    Rasmussen LB, Ovesen L, Bülow I, et al. Relations between various measures of iodine intake and thyroid volume, thyroid nodularity, and serum thyroglobulin. Am J Clin Nutr. 2002;76:1069-1076.PubMedGoogle Scholar
  144. 144.
    van den Briel T, West CE, Hautvast JG, Vulsma T, de Vijlder JJ, Ategbo EA. Serum thyroglobulin and urinary iodine concentration are the most appropriate indicators of iodine status and thyroid function under conditions of increasing iodine supply in schoolchildren in Benin. J Nutr. 2001;131:2701-2706.PubMedGoogle Scholar
  145. 145.
    Knudsen N, Bülow I, Jørgensen T, Perrild H, Ovesen L, Laurberg P. Serum Tg—a sensitive marker of thyroid abnormalities and iodine deficiency in epidemiological studies. J Clin Endocrinol Metab. 2001;86:2599-2603.Google Scholar
  146. 146.
    Rasmussen LB, Ovesen L, Christiansen E. Day-to-day and within-day variation in urinary iodine excretion. Eur J Clin Nutr. 1999;53:401-407.PubMedGoogle Scholar
  147. 147.
    Zimmermann MB, de Benoist B, Corigliano S, et al. Assessment of iodine status using dried blood spot thyroglobulin: development of reference material and establishment of an international reference range in iodine-sufficient children. J Clin Endocrinol Metab. 2006;91:4881-4887.PubMedGoogle Scholar
  148. 148.
    Brown RS, Demmer LA. The etiology of thyroid dysgenesis-still an enigma after all these years. J Clin Endocrinol Metab. 2002;87:4069-4071.PubMedGoogle Scholar
  149. 149.
    Brown AL, Fernhoff PM, Milner J, McEwen C, Elsas LS. Racial differences in the incidence of congenital hypothyroidism. J Pediatr. 1981;99:934-936.PubMedGoogle Scholar
  150. 150.
    Djemli A, Fillion M, Belgoudi J, et al. Twenty years later: a reevaluation of the contribution of plasma thyroglobulin to the diagnosis of thyroid dysgenesis in infants with congenital hypothyroidism. Clin Biochem. 2004;37:818-822.PubMedGoogle Scholar
  151. 151.
    Simsek E, Karabay M, Kocabay K. Neonatal screening for congenital hypothyroidism in West Black Sea area, Turkey. Int J Clin Pract. 2005;59:336-341.PubMedGoogle Scholar
  152. 152.
    Caputo M, Rivolta CM, Esperante SA, et al. Congenital hypothyroidism with goitre caused by new mutations in the thyroglobulin gene. Clin Endocrinol (Oxford). 2007;67:351-357.Google Scholar
  153. 153.
    Vono-Toniolo J, Rivolta CM, Targovnik HM, Medeiros-Neto G, Kopp P. Naturally occurring mutations in the thyroglobulin gene. Thyroid. 2005;15:1021-1033.PubMedGoogle Scholar
  154. 154.
    Rivolta CM, Targovnik HM. Molecular advances in thyroglobulin disorders. Clin Chim Acta. 2006;374:8-24.PubMedGoogle Scholar
  155. 155.
    Cohen JH, Ingbar SH, Braverman LE. Thyrotoxicosis due to ingestion of excess thyroid hormone. Endocr Rev. 1989;10:113-124.PubMedGoogle Scholar
  156. 156.
    Matsubara S, Inoh M, Tarumi Y, Sato M, Takahara J. An outbreak (159 cases) of transient thyrotoxicosis without hyperthyroidism in Japan. Intern Med. 1995;34:514-519.PubMedGoogle Scholar
  157. 157.
    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.PubMedGoogle Scholar
  158. 158.
    Chow E, Siddique F, Gama R. Thyrotoxicosis factitia: role of thyroglobulin. Ann Clin Biochem. 2008;45:447-448.PubMedGoogle Scholar
  159. 159.
    Parmar MS, Sturge C. Recurrent hamburger thyrotoxicosis. CMAJ. 2003;169:45-47.Google Scholar
  160. 160.
    Fatourechi V, Aniszewski JP, Fatourechi GZ, et al. Clinical features and outcome of subacute thyroiditis in an incidence cohort: Olmsted County, Minnesota, study. J Clin Endocrinol Metab. 2003;88:2100-2105.PubMedGoogle Scholar
  161. 161.
    Parkes AB, Black EG, Adams H, et al. Serum thyroglobulin: an early indicator of autoimmune post-partum thyroiditis. Clin Endocrinol. 1994;41:9-14.Google Scholar
  162. 162.
    Fragu P, Rougier P, Schlumberger M, Tubiana M. Evolution of thyroid 127-I stores measured by X-ray fluorescence in subacute thyroiditis. J Clin Endocrinol Metab. 1982;54:162-166.PubMedGoogle Scholar
  163. 163.
    Madeddu G, Casu AR, Costanza C, et al. Serum thyroglobulin levels in the diagnosis and follow-up of subacute ‘painful’ thyroiditis. Arch Intern Med. 1985;145:243-247.PubMedGoogle Scholar
  164. 164.
    Feldt-Rasmussen U. Relationship between serum thyroglobulin, thyroid volume and serum TSH in healthy non-goitrous subjects and the relationship to seasonal variations in iodine intake. Thyroidol Clin Exp. 1989;1:115-118.PubMedGoogle Scholar
  165. 165.
    Hershman JM, Due DT, Sharp B, et al. Endemic goiter in Vietnam. J Clin Endocrinol Metab. 1983;57:243-249.PubMedGoogle Scholar
  166. 166.
    Feldt-Rasmussen U, Hegedus L, Hansen JM, Perrild H. Relationship between thyroid volume and serum thyroglobulin during long-term suppression with triiodothyronine in patients with diffuse non-toxic goitre. Acta Endocrinol. 1984;105:184-189.PubMedGoogle Scholar
  167. 167.
    Unger J, De Maertelaer V, Golstein J, Decoster C, Jonckheer MH. Relationship between serum thyroglobulin and intrathyroidal stable iodine in human simple goiter. Clin Endocrinol. 1985;23:1-6.Google Scholar
  168. 168.
    Glinoer D, De Nayer P, Delange F, et al. A randomized trial for the treatment of mild iodine deficiency during pregnancy: maternal and neonatal effects. J Clin Endocrinol Metab. 1995;80:258-269.PubMedGoogle Scholar
  169. 169.
    Date J, Feldt-Rasmussen U, Blichert-Toft M, Hegedus L, Graversen HP. Long-term observation of serum thyroglobulin after resection of nontoxic goiter and relation to ultrasonographically demonstrated relapse. World J Surg. 1996;20:351-356.PubMedGoogle Scholar
  170. 170.
    Lazar V, Bidart JM, Caillou B, et al. Expression of the Na+/I- symporter gene in human thyroid tumors: a comparison study with other thyroid-specific genes. J Clin Endocrinol Metab. 1999;84:3228-3234.PubMedGoogle Scholar
  171. 171.
    Boelaert K, Horacek J, Holder RL, Watkinson JC, Sheppard MC, Franklyn JA. Serum thyrotropin concentration as a novel predictor of malignancy in thyroid nodules investigated by fine-needle aspiration. J Clin Endocrinol Metab. 2006;91:4295-4301.PubMedGoogle Scholar
  172. 172.
    Haymart MR, Repplinger DJ, Leverson GE, et al. Higher serum thyroid stimulating hormone level in thyroid nodule patients is associated with greater risks of differentiated thyroid cancer and advanced tumor stage. J Clin Endocrinol Metab. 2008;93:809-814.PubMedGoogle Scholar
  173. 173.
    Jonklaas J, Nsouli-Maktabi H, Soldin S. Endogenous thyrotropin and triiodothyronine concentrations in individuals with thyroid cancer. Thyroid. 2008;18:943-952.PubMedGoogle Scholar
  174. 174.
    Ronga G, Filesi M, Ventroni G, Signore A. Value of the first serum thyroglobulin level after total thyroidectomy for the diagnosis of metastases from differentiated thyroid carcinoma. Eur J Nucl Med. 1999;26:1448-1452.PubMedGoogle Scholar
  175. 175.
    Lima N, Cavaliere H, Tomimori E, Knobel M, Medeiros-Neto G. Prognostic value of serial serum thyroglobulin determinations after total thyroidectomy for differentiated thyroid cancer. J Endocrinol Invest. 2002;25:110-115.PubMedGoogle Scholar
  176. 176.
    Lin JD, Huang MJ, Hsu BR, et al. Significance of postoperative serum thyroglobulin levels in patients with papillary and follicular thyroid carcinomas. J Surg Oncol. 2002;80:45-51.PubMedGoogle Scholar
  177. 177.
    Toubeau M, Touzery C, Arveux P, et al. Predictive value for disease progression of serum thyroglobulin levels measured in the postoperative period and after 131-I ablation therapy in patients with differentiated thyroid cancer. J Nucl Med. 2004;45:988-994.PubMedGoogle Scholar
  178. 178.
    Kloos RT, Mazzaferri EL. A single recombinant human thyrotropin-stimulated serum thyroglobulin measurement predicts differentiated thyroid carcinoma metastases three to five years later. J Clin Endocrinol Metab. 2005;90:5047-5057.PubMedGoogle Scholar
  179. 179.
    Makarewicz J, Adamczewski Z, Knapska-Kucharska M, Lewinski A. Evaluation of the diagnostic value of the first thyroglobulin determination in detecting metastases after differentiated thyroid carcinoma surgery. Exp Clin Endocrinol Diabetes. 2006;114:485-489.PubMedGoogle Scholar
  180. 180.
    Kim TY, Kim WB, Kim ES, et al. Serum thyroglobulin levels at the time of 131I remnant ablation just after thyroidectomy are useful for early prediction of clinical recurrence in low-risk patients with differentiated thyroid carcinoma. J Clin Endocrinol Metab. 2005;90:1440-1445.PubMedGoogle Scholar
  181. 181.
    Heemstra KA, Liu YY, Stokkel M, et al. Serum thyroglobulin concentrations predict disease-free remission and death in differentiated thyroid carcinoma. Clin Endocrinol (Oxford). 2007;66:58-64.Google Scholar
  182. 182.
    Hall FT, Beasley NJ, Eski SJ, Witterick IJ, Walfish PG, Freeman JL. Predictive value of serum thyroglobulin after surgery for thyroid carcinoma. Laryngoscope. 2003;113:77-81.PubMedGoogle Scholar
  183. 183.
    Pacini F, Schlumberger M, Harmer C, et al. Post-surgical use of radioiodine (131I) in patients with papillary and follicular thyroid cancer and the issue of remnant ablation: a consensus report. Eur J Endocrinol. 2005;153:651-659.PubMedGoogle Scholar
  184. 184.
    Verkooijen RB, Verburg FA, van Isselt JW, Lips CJ, Smit JW, Stokkel MP. The success rate of I-131 ablation in differentiated thyroid cancer: comparison of uptake-related and fixed-dose strategies. Eur J Endocrinol. 2008;159:301-307.PubMedGoogle Scholar
  185. 185.
    Torlontano M, Attard M, Crocetti U, et al. Follow-up of low risk patients with papillary thyroid cancer: role of neck ultrasonography in detecting lymph node metastases. J Clin Endocrinol Metab. 2004;89:3402-3407.PubMedGoogle Scholar
  186. 186.
    David A, Blotta A, Rossi R, et al. Clinical value of different responses of serum thyroglobulin to recombinant human thyrotropin in the follow-up of patients with differentiated thyroid carcinoma. Thyroid. 2005;15:267-273.PubMedGoogle Scholar
  187. 187.
    Giovanella L. Highly sensitive thyroglobulin measurements in differentiated thyroid carcinoma managemen. Clin Chem Lab Med. 2008;46:1067-1073.PubMedGoogle Scholar
  188. 188.
    Frasoldati A, Pesenti M, Gallo M, Caroggio A, Salvo D, Valcavi R. Diagnosis of neck recurrences in patients with differentiated thyroid carcinoma. Cancer. 2003;97:90-96.PubMedGoogle Scholar
  189. 189.
    Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973-2002. JAMA. 2006;295:2164-2167.Google Scholar
  190. 190.
    Hay ID, McConahey WM, Goellner JR. Managing patients with papillary thyroid carcinoma: insights gained from the Mayo Clinic's experience of treating 2,512 consecutive patients during 1940 through 2000. Trans Am Clin Climatol Assoc. 2002;113:241-260.Google Scholar
  191. 191.
    Mazzaferri EL. Managing small thyroid cancers. JAMA. 2006;295:2179-2182.PubMedGoogle Scholar
  192. 192.
    Pujol P, Daures JP, Nsakala N, Baldet L, Bringer J, Jaffiol C. Degree of thyrotropin suppression as a prognostic determinant in differentiated thyroid cancer. J Clin Endocrinol Metab. 1996;81:4318-4323.PubMedGoogle Scholar
  193. 193.
    Jonklaas J, Sarlis NJ, Litofsky D, et al. Outcomes of patients with differentiated thyroid carcinoma following initial therapy. Thyroid. 2006;16:1229-1242.PubMedGoogle Scholar
  194. 194.
    McGriff NJ, Csako G, Gourgiotis L, Lori CG, Pucino F, Sarlis NJ. Effects of thyroid hormone suppression therapy on adverse clinical outcomes in thyroid cancer. Ann Med. 2002;34:554-5564.PubMedGoogle Scholar
  195. 195.
    Hovens GC, Stokkel MP, Kievit J, et al. Associations of serum thyrotropin concentrations with recurrence and death in differentiated thyroid cancer. J Clin Endocrinol Metab. 2007;92:2610-2615.PubMedGoogle Scholar
  196. 196.
    Hay ID, McDougall IR, Sisson JC. Perspective: the case against radioiodine remnant ablation in patients with well-differentiated thyroid carcinoma. J Nucl Med. 2008;49:1395-1397.Google Scholar
  197. 197.
    Sawka AM, Brierley JD, Tsang RW, et al. An updated systematic review and commentary examining the effectiveness of radioactive iodine remnant ablation in well-differentiated thyroid cancer. Endocrinol Metabl Clin North Am. 2008;37:457-480.Google Scholar
  198. 198.
    Hay ID. Selective use of radioactive iodine in the postoperative management of patients with papillary and follicular thyroid carcinoma. J Surg Oncol. 2006;94:692-700.PubMedGoogle Scholar
  199. 199.
    Sawka AM, Goldstein DP, Thabane L, et al. Basis for physician recommendations for adjuvant radioiodine therapy in early-stage thyroid carcinoma: principal findings of the Canadian-American thyroid cancer survey. Endocr Pract. 2008;14:175-184.PubMedGoogle Scholar
  200. 200.
    Brown AP, Chen J, Hitchcock YJ, Szabo A, Shrieve DC, Tward JD. The risk of second primary malignancies up to three decades after the treatment of differentiated thyroid cancer. J Clin Endocrinol Metab. 2008;93:504-515.PubMedGoogle Scholar
  201. 201.
    Rubino C, de Vathaire F, Dottorini ME, et al. Second primary malignancies in thyroid cancer patients. Br J Cancer. 2003;89:1638-1644.PubMedGoogle Scholar
  202. 202.
    Sawka AM, Thephamongkhol K, Brouwers M, Thabane L, Browman G, Gerstein HC. Clinical review 170: a systematic review and metaanalysis of the effectiveness of radioactive iodine remnant ablation for well-differentiated thyroid cancer. J Clin Endocrinol Metab. 2004;89:3668-3676.PubMedGoogle Scholar
  203. 203.
    Robbins RJ, Srivastava S, Shaha A, et al. Factors influencing the basal and recombinant human thyrotropin-stimulated serum thyroglobulin in patients with metastatic thyroid carcinoma. J Clin Endocrinol Metab. 2004;89:6010-6016.PubMedGoogle Scholar
  204. 204.
    Serhal DI, Nasrallah MP, Arafah BM. Rapid rise in serum thyrotropin concentrations after thyroidectomy or withdrawal of suppressive thyroxine therapy in preparation for radioactive iodine administration to patients with differentiated thyroid cancer. J Clin Endocrinol Metab. 2004;89:3285-3289.PubMedGoogle Scholar
  205. 205.
    Mazzaferri EL, Kloos RT. Is diagnostic iodine-131 scanning with recombinant human TSH useful in the follow-up of differentiated thyroid cancer after thyroid ablation? J Clin Endocrinol Metab. 2002;87:1490-1498.PubMedGoogle Scholar
  206. 206.
    Eustatia-Rutten CF, Smit JW, Romijn JA, et al. Diagnostic value of serum thyroglobulin measurements in the follow-up of differentiated thyroid carcinoma, a structured meta-analysis. Clin Endocrinol (Oxford). 2004;61:61-74.Google Scholar
  207. 207.
    Schlumberger M, Pacini F, Wiersinga WM, et al. Follow-up and management of differentiated thyroid carcinoma: a European perspective in clinical practice. Eur J Endocrinol. 2004;151:539-548.PubMedGoogle Scholar
  208. 208.
    Unger J, Van Heuverswyn B, Decoster C, Cantraine F, Mockel J, Van Herle A. Thyroglobulin and thyroid hormone release after intravenous administration of bovine thyrotropin in man. J Clin Endocrinol Metab. 1980;51:590-594.PubMedGoogle Scholar
  209. 209.
    Schlumberger M, Ricard M, De Pouvourville G, Pacini F. How the availability of recombinant human TSH has changed the management of patients who have thyroid cancer. Nat Clin Pract Endocrinol Metab. 2007;3:641-650.PubMedGoogle Scholar
  210. 210.
    Phan HT, Jager PL, van der Wal JE, et al. The follow-up of patients with differentiated thyroid cancer and undetectable thyroglobulin (Tg) and Tg antibodies during ablation. Eur J Endocrinol. 2008;158:77-83.PubMedGoogle Scholar
  211. 211.
    Pacini F, Pinchera A. Serum and tissue thyroglobulin measurement: clinical applications in thyroid disease. Biochimie. 1999;81:463-467.PubMedGoogle Scholar
  212. 212.
    Rotman-Pikielny P, Reynolds JC, Barker WC, Yen PM, Skarulis MC, Sarlis NJ. Recombinant human thyrotropin for the diagnosis and treatment of a highly functional metastatic struma ovarii. J Clin Endocrinol Metab. 2000;85:237-244.PubMedGoogle Scholar
  213. 213.
    Machens A, Holzhausen HJ, Dralle H. The prognostic value of primary tumor size in papillary and follicular thyroid carcinoma. Cancer. 2005;103:2269-2273.PubMedGoogle Scholar
  214. 214.
    Passler C, Scheuba C, Prager G, et al. Prognostic factors of papillary and follicular thyroid cancer: differences in an iodine-replete endemic goiter region. Endocr Relat Cancer. 2004;11:131-139.PubMedGoogle Scholar
  215. 215.
    Rosário PW, de Faria S, Bicalho L, et al. Ultrasonographic differentiation between metastatic and benign lymph nodes in patients with papillary thyroid carcinoma. J Ultrasound Med. 2005;24:1385-1389.PubMedGoogle Scholar
  216. 216.
    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.PubMedGoogle Scholar
  217. 217.
    Uruno T, Miyauchi A, Shimizu K, et al. Usefulness of thyroglobulin measurement in fine-needle aspiration biopsy specimens for diagnosing cervical lymph node metastasis in patients with papillary thyroid cancer. World J Surg. 2005;29:483-485.PubMedGoogle Scholar
  218. 218.
    Boi F, Baghino G, Atzeni F, Lai ML, Faa G, Mariotti S. The diagnostic value for differentiated thyroid carcinoma metastases of thyroglobulin (Tg) measurement in washout fluid from fine-needle aspiration biopsy of neck lymph nodes is maintained in the presence of circulating anti-Tg antibodies. J Clin Endocrinol Metab. 2006;91:1364-1369.PubMedGoogle Scholar
  219. 219.
    Snozek CL, Chambers EP, Reading CC, et al. Serum thyroglobulin, high-resolution ultrasound, and lymph node thyroglobulin in diagnosis of differentiated thyroid carcinoma nodal metastases. J Clin Endocrinol Metab. 2007;92:4278-4281.PubMedGoogle Scholar

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Medicine, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA

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