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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

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Volume 55, Issue 12


Thyroglobulin autoantibodies before radioiodine ablation predict differentiated thyroid cancer outcome

Pierpaolo Trimboli
  • Corresponding author
  • Department of Nuclear Medicine and Thyroid Centre, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Valentina Zilioli / Mauro Imperiali / Luca Giovanella
  • Department of Nuclear Medicine and Thyroid Centre, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
  • Department of Laboratory Medicine, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2017-05-03 | DOI: https://doi.org/10.1515/cclm-2017-0033



Serum thyroglobulin (Tg) is essential to manage differentiated thyroid carcinoma (DTC). However, Tg determination is affected by circulating Tg antibodies (TgAb), and a role of TgAb as surrogate biomarker has been proposed. Here we evaluated the role of TgAb measured before and after radioiodine ablation (RRA) as potential predictors of prognosis.


Patients treated since 2006 were screened. Cancers with structural relapse were defined as recurrent. Both Tg and TgAb were measured by immunoassays on the fully automated Kryptor® platform (BRAHMS Gmbh, Henningsdorf, Germany).


A series of 215 DTC patients was enrolled, of whom 28.8% had positive preablation TgAb. Overall, 2.8% patients died by DTC and 11% recurred. High-risk class (p=0.004) and cancer relapse (p=0.007) occurred more frequently in positive TgAb, whereas better disease-free survival was observed in negative group (hazard ratio 2.59, p=0.01). Having positive preablation TgAb was significantly associated with risk to develop recurrence (odds ratio 3.57, p=0.004). Among positive TgAb subgroup, higher levels were recorded in recurrent cases (p=0.0001), and the most accurate preablation TgAb threshold was 107.5 IU/mL. When TgAb were measured at first follow-up, recurrence rate was significantly (p<0.0001) higher in persistently TgAb-positive patients (75%) than normalized ones (2.4%). At that time, the highest negative predictive value could be obtained when considering TgAb normalization (<33 IU/mL) or reduction by ≥36.4%.


Positive TgAb before RRA indicates higher risk of poor prognosis, but their significant drop 6–12 months later could be considered a favorable factor.

Keywords: differentiated thyroid carcinoma; high sensitive; outcome; TgAb; thyroglobulin


  • 1.

    Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, 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.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 2.

    Giovanella L, Treglia G, Sadeghi R, Trimboli P, Ceriani L, Verburg FA. Unstimulated highly sensitive thyroglobulin in follow-up of differentiated thyroid cancer patients: a meta-analysis. J Clin Endocrinol Metab 2014;99:440–7.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 3.

    Giovanella L, Clark PM, Chiovato L, Duntas L, Elisei R, Feldt-Rasmussen U, 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.Web of ScienceGoogle Scholar

  • 4.

    Webb RC, Howard RS, Stojadinovic A, Gaitonde DY, Wallace MK, Ahmed J, et al. The utility of serum thyroglobulin measurement at the time of remnant ablation for predicting disease-free status in patients with differentiated thyroid cancer: a meta-analysis involving 3947 patients. J Clin Endocrinol Metab 2012;97:2754–63.Web of ScienceCrossrefPubMedGoogle Scholar

  • 5.

    Spencer CA, Takeuchi M, Kazarosyan M, Wang CC, Guttler RB, Singer PA, 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;83:1121–7.PubMedGoogle Scholar

  • 6.

    Verburg FA, Luster M, Cupini C, Chiovato L, Duntas L, Elisei R, et al. Implications of thyroglobulin antibody positivity in patients with differentiated thyroid cancer: a clinical position statement. Thyroid 2013;23:1211–5.Web of ScienceCrossrefPubMedGoogle Scholar

  • 7.

    Spencer C. Commentary on: Implications of thyroglobulin antibody positivity in patients with differentiated thyroid cancer: a clinical position statement. Thyroid 2013;23:1190–2.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 8.

    Pickett AJ, Jones M, Evans C. Causes of discordance between thyroglobulin antibody assays. Ann Clin Biochem 2012;49:463–7.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 9.

    Gorges R, Maniecki M, Jentzen W, Sheu SN, Mann K, Bockisch A, 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.CrossrefPubMedGoogle Scholar

  • 10.

    Feldt-Rasmussen U, Verburg FA, Luster M, Cupini C, Chiovato L, Duntas L, et al. Thyroglobulin autoantibodies as surrogate biomarkers in the management of patients with differentiated thyroid carcinoma. Curr Med Chem 2014;21:3687–92.Web of SciencePubMedCrossrefGoogle Scholar

  • 11.

    McLeod DS, Cooper DS, Ladenson PW, Ain KB, Brierley JD, Fein HG, et al. Prognosis of differentiated thyroid cancer in relation to serum thyrotropin and thyroglobulin antibody status at time of diagnosis. Thyroid 2014;24:35–42.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 12.

    Soyluk O, Boztepe H, Aral F, Alagol F, Özbey NC. Papillary thyroid carcinoma patients assessed to be at low or intermediary risk after primary treatment are at greater risk of long term recurrence if they are thyroglobulin antibody positive or do not have distinctly low thyroglobulin at initial assessment. Thyroid 2011;21:1301–8.PubMedWeb of ScienceGoogle Scholar

  • 13.

    Neshandar Asli I, Siahkali AS, Shafie B, Javadi H, Assadi M. Prognostic value of basal serum thyroglobulin levels, but not basal antithyroglobulin antibody (TgAb) levels, in patients with differentiated thyroid cancer. Mol Imaging Radionucl Ther 2014;23:54–9.PubMedGoogle Scholar

  • 14.

    Vasileiadis I, Boutzios G, Charitoudis G, Koukoulioti E, Karatzas T. Thyroglobulin antibodies could be a potential predictive marker for papillary thyroid carcinoma. Ann Surg Oncol 2014;21:2725–32.CrossrefWeb of SciencePubMedGoogle Scholar

  • 15.

    Durante C, Tognini S, Montesano T, Orlandi F, Torlontano M, Puxeddu E, et al. Clinical aggressiveness and long-term outcome in patients with papillary thyroid cancer and circulating anti-thyroglobulin autoantibodies. Thyroid 2014;24:1139–45.Web of ScienceCrossrefPubMedGoogle Scholar

  • 16.

    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;27:701–12.CrossrefWeb of SciencePubMedGoogle Scholar

  • 17.

    Luster M, Clarke SE, Dietlein M, Lassmann M, Lind P, Oyen WJ, et al. Guidelines for radioiodine therapy of differentiated thyroid cancer. Eur J Nucl Med Mol Imaging 2008;35:1941–59.CrossrefWeb of SciencePubMedGoogle Scholar

  • 18.

    Giovanella L, Trimboli P, Verburg FA, Treglia G, Piccardo A, Foppiani L, et al. Thyroglobulin levels and thyroglobulin doubling time independently predict a positive 18F-FDG PET/CT scan in patients with biochemical recurrence of differentiated thyroid carcinoma. Eur J Nucl Med Mol Imaging 2013;40:874–80.CrossrefPubMedGoogle Scholar

  • 19.

    Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457–81.CrossrefGoogle Scholar

  • 20.

    Kalbfleisch JD, Prentice RL. The statistical analysis of failure time data New York: John Wiley & Sons, 1980.Google Scholar

  • 21.

    Galen RS, Gambino SL. How to determine the predictive value and efficiency of a test when reading a scientific paper. Beyond normality: the predictive value and efficiency of medical diagnosis. New York: John Wiley, 1975:29–40.Google Scholar

  • 22.

    Sackett DL, HaynesRB, Tugwell P, Guyatt G. Clinical epidemiology: a basic science for clinical medicine. Boston: Little, Brown & Co, 1991.Google Scholar

  • 23.

    Kim ES, Lim DJ, Baek KH, Lee JM, Kim MK, Kwon HS, et al. Thyroglobulin antibody is associated with increased cancer risk in thyroid nodules. Thyroid 2010;20:885–91.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 24.

    Grani G, Calvanese A, Carbotta G, D’Alessandri M, Nesca A, Bianchini M, et al. Thyroid autoimmunity and risk of malignancy in thyroid nodules submitted to fine-needle aspiration cytology. Head Neck 2015;37:260–4.Web of ScienceCrossrefPubMedGoogle Scholar

  • 25.

    Karatzas T, Vasileiadis I, Zapanti E, Charitoudis G, Karakostas E, Boutzios G. Thyroglobulin antibodies as a potential predictive marker of papillary thyroid carcinoma in patients with indeterminate cytology. Am J Surg 2016;212:946–52.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 26.

    Kim WG, Yoon JH, Kim WB, Kim TY, Kim EY, Kim JM, et al. Change of serum antithyroglobulin antibody levels is useful for prediction of clinical recurrence in thyroglobulin-negative patients with differentiated thyroid carcinoma. J Clin Endocrinol Metab 2008;93:4683–9.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 27.

    Seo JH, Lee SW, Ahn BC, Lee J. Recurrence detection in differentiated thyroid cancer patients with elevated serum level of antithyroglobulin antibody: special emphasis on using (18)F-FDG PET/CT. Clin Endocrinol (Oxf) 2010;72: 558–63.PubMedCrossrefGoogle Scholar

  • 28.

    Tsushima Y, Miyauchi A, Ito Y, Kudo T, Masuoka H, Yabuta T, et al. Prognostic significance of changes in serum thyroglobulin antibody levels of pre- and post-total thyroidectomy in thyroglobulin antibody-positive papillary thyroid carcinoma patients. Endocr J 2013;60:871–76.CrossrefWeb of SciencePubMedGoogle Scholar

  • 29.

    Hsieh C-J, Wang P-W. Sequential changes of serum antithyroglobulin antibody levels are a good predictor of disease activity in thyroglobulin-negative patients with papillary thyroid carcinoma. Thyroid 2014;24:488–93.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 30.

    Spencer C, Petrovic I, Fatemi S. Current thyroglobulin autoantibody (TgAb) assays often fail to detect interfering TgAb that can result in the reporting of falsely low/undetectable serum Tg IMA values for patients with differentiated thyroid cancer. J Clin Endocrinol Metab 2011;96:1283–91.CrossrefWeb of SciencePubMedGoogle Scholar

  • 31.

    Spencer CA. Clinical review: clinical utility of thyroglobulin antibody (TgAb) measurements for patients with differentiated thyroid cancers (DTC). J Clin Endocrinol Metab 2011;96:3615–27.CrossrefPubMedGoogle Scholar

  • 32.

    Giovanella L, Feldt-Rasmussen U, Verburg FA, Grebe SK, Plebani M, Clark PM. Thyroglobulin measurement by highly sensitive assays: focus on laboratory challenges. Clin Chem Lab Med 2015;53:1301–14.Web of SciencePubMedGoogle Scholar

  • 33.

    Netzel BC, Grebe SK, Carranza Leon BG, Castro MR, Clark PM, Hoofnagle AN, et al. Thyroglobulin (Tg) testing revisited: Tg assays, TgAb assays and correlation of results with clinical outcomes. J Clin Endocrinol Metab 2015;100:1074–83.Web of ScienceCrossrefGoogle Scholar

About the article

Corresponding author: Pierpaolo Trimboli, MD, Department of Nuclear Medicine and Thyroid Centre, Oncology Institute of Southern Switzerland, Via Ospedale 12, 6500 Bellinzona, Switzerland

Received: 2017-01-13

Accepted: 2017-04-03

Published Online: 2017-05-03

Published in Print: 2017-10-26

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 55, Issue 12, Pages 1995–2001, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2017-0033.

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