Home Thyroglobulin autoantibodies before radioiodine ablation predict differentiated thyroid cancer outcome
Article
Licensed
Unlicensed Requires Authentication

Thyroglobulin autoantibodies before radioiodine ablation predict differentiated thyroid cancer outcome

  • Pierpaolo Trimboli EMAIL logo , Valentina Zilioli , Mauro Imperiali and Luca Giovanella
Published/Copyright: May 3, 2017
Become an author with De Gruyter Brill
Submit Manuscript Author Information
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 55 Issue 12

Abstract

Background:

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.

Methods:

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).

Results:

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%.

Conclusions:

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

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

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. 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.

References

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;26:1–133.10.1089/thy.2015.0020Search in Google Scholar PubMed PubMed Central

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;99:440–7.10.1210/jc.2013-3156Search in Google Scholar PubMed

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–R46.10.1530/EJE-14-0148Search in Google Scholar PubMed PubMed Central

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;97:2754–63.10.1210/jc.2012-1533Search in Google Scholar PubMed

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;83:1121–7.10.1210/jc.83.4.1121Search in Google Scholar PubMed

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;23:1211–5.10.1089/thy.2012.0606Search in Google Scholar PubMed

7. Spencer C. Commentary on: Implications of thyroglobulin antibody positivity in patients with differentiated thyroid cancer: a clinical position statement. Thyroid 2013;23:1190–2.10.1089/thy.2013.0496Search in Google Scholar PubMed PubMed Central

8. Pickett AJ, Jones M, Evans C. Causes of discordance between thyroglobulin antibody assays. Ann Clin Biochem 2012;49:463–7.10.1258/acb.2012.012008Search in Google Scholar PubMed

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;153:49–55.10.1530/eje.1.01940Search in Google Scholar PubMed

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;21:3687–92.10.2174/0929867321666140826120844Search in Google Scholar PubMed

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;24:35–42.10.1089/thy.2013.0062Search in Google Scholar PubMed PubMed Central

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;21:1301–8.10.1089/thy.2011.0122Search in Google Scholar PubMed

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;23:54–9.10.4274/mirt.39200Search in Google Scholar PubMed PubMed Central

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;21:2725–32.10.1245/s10434-014-3593-xSearch in Google Scholar PubMed

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;24:1139–45.10.1089/thy.2013.0698Search in Google Scholar PubMed PubMed Central

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;27:701–12.10.1016/j.beem.2013.07.003Search in Google Scholar PubMed

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;35:1941–59.10.1007/s00259-008-0883-1Search in Google Scholar PubMed

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;40:874–80.10.1007/s00259-013-2370-6Search in Google Scholar PubMed

19. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457–81.10.1080/01621459.1958.10501452Search in Google Scholar

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

22. Sackett DL, HaynesRB, Tugwell P, Guyatt G. Clinical epidemiology: a basic science for clinical medicine. Boston: Little, Brown & Co, 1991.Search in 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;20:885–91.10.1089/thy.2009.0384Search in Google Scholar PubMed

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;37:260–4.10.1002/hed.23587Search in Google Scholar PubMed

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;212:946–52.10.1016/j.amjsurg.2015.12.030Search in Google Scholar PubMed

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;93:4683–9.10.1210/jc.2008-0962Search in Google Scholar PubMed

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: 558–63.10.1111/j.1365-2265.2009.03693.xSearch in Google Scholar PubMed

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;60:871–76.10.1507/endocrj.EJ12-0410Search in Google Scholar PubMed

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;24:488–93.10.1089/thy.2012.0611Search in Google Scholar PubMed

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;96:1283–91.10.1210/jc.2010-2762Search in Google Scholar PubMed

31. Spencer CA. Clinical review: clinical utility of thyroglobulin antibody (TgAb) measurements for patients with differentiated thyroid cancers (DTC). J Clin Endocrinol Metab 2011;96:3615–27.10.1210/jc.2011-1740Search in Google Scholar PubMed

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;53:1301–14.10.1515/cclm-2014-0813Search in Google Scholar PubMed

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;100:1074–83.10.1210/jc.2015-1967Search in Google Scholar PubMed PubMed Central

Received: 2017-1-13
Accepted: 2017-4-3
Published Online: 2017-5-3
Published in Print: 2017-10-26

©2017 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Tumor microenvironment and systemic disease: a dual target in medical oncology (also in the case of biomarkers)
  4. Reviews
  5. Sample types applied for molecular diagnosis of therapeutic management of advanced non-small cell lung cancer in the precision medicine
  6. The impact of pneumatic tube system on routine laboratory parameters: a systematic review and meta-analysis
  7. Opinion Paper
  8. How to reduce scientific irreproducibility: the 5-year reflection
  9. EFLM Paper
  10. Strategies to define performance specifications in laboratory medicine: 3 years on from the Milan Strategic Conference
  11. General Clinical Chemistry and Laboratory Medicine
  12. Intensive educational efforts combined with external quality assessment improve the preanalytical phase in general practitioner offices and nursing homes
  13. Separate patient serum sodium medians from males and females provide independent information on analytical bias
  14. Are admission procalcitonin levels universal mortality predictors across different medical emergency patient populations? Results from the multi-national, prospective, observational TRIAGE study
  15. Biochemical testing in a laboratory tent and semi-intensive care of Ebola patients on-site in a remote part of Guinea: a paradigm shift based on a bleach-sensitive point-of-care device
  16. Efficient reporting of the estimated glomerular filtration rate without height in pediatric patients with cancer
  17. Evaluation of thyroid test utilization through analysis of population-level data
  18. Relation of serum γ-glutamyl transferase activity with copper in an adult population
  19. Impact of a single oral dose of 100,000 IU vitamin D3 on profiles of serum 25(OH)D3 and its metabolites 24,25(OH)2D3, 3-epi-25(OH)D3, and 1,25(OH)2D3 in adults with vitamin D insufficiency
  20. Automated antinuclear immunofluorescence antibody analysis is a reliable approach in routine clinical laboratories
  21. Infrared analyzers for breast milk analysis: fat levels can influence the accuracy of protein measurements
  22. Hematology and Coagulation
  23. A new approach to define acceptance limits for hematology in external quality assessment schemes
  24. The effects of transport by car on coagulation tests
  25. Combined measurement of factor XIII and D-dimer is helpful for differential diagnosis in patients with suspected pulmonary embolism
  26. Reference Values and Biological Variations
  27. Influence of age, gender and body mass index on late-night salivary cortisol in healthy adults
  28. Cancer Diagnostics
  29. Assessment of real-time PCR method for detection of EGFR mutation using both supernatant and cell pellet of malignant pleural effusion samples from non-small-cell lung cancer patients
  30. Detection of EGFR mutations in patients with non-small cell lung cancer by high resolution melting. Comparison with other methods
  31. Predicting outcomes of EGFR-targeted therapy in non-small cell lung cancer patients using pleural effusions samples and peptide nucleic acid probe assay
  32. Analytical and clinical performance of thyroglobulin autoantibody assays in thyroid cancer follow-up
  33. Thyroglobulin autoantibodies before radioiodine ablation predict differentiated thyroid cancer outcome
  34. Cardiovascular Diseases
  35. Real life dabigatran and metabolite concentrations, focused on inter-patient variability and assay differences in patients with atrial fibrillation
  36. Infectious Diseases
  37. HIV avidity index performance using a modified fourth-generation immunoassay to detect recent HIV infections
  38. Letters to the Editor
  39. Effect of age on serum prostate-specific antigen in women
  40. Falsely elevated thyroid-stimulating hormone value due to anti-ruthenium antibodies in a patient with primary hypothyroidism: a case report
  41. High titers of anti-infliximab antibody do not interfere with Abbott immunoassays
  42. Extraordinarily elevated serum CA19-9 in a patient with posterior mediastinum cyst: a case report
  43. Low levels of 25-OH vitamin D in women with endometriosis and associated pelvic pain
  44. Evaluation of serum cortisol biological variation in the evening withdrawal
  45. Distinction between urine crystals by automated urine analyzer SediMAX conTRUST is specific but lacks sensitivity
  46. Impact of heat-inactivation on anti-Toxoplasma IgM antibody levels
https://doi.org/10.1515/cclm-2017-0033
Keywords for this article
differentiated thyroid carcinoma; high sensitive; outcome; TgAb; thyroglobulin

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Tumor microenvironment and systemic disease: a dual target in medical oncology (also in the case of biomarkers)
  4. Reviews
  5. Sample types applied for molecular diagnosis of therapeutic management of advanced non-small cell lung cancer in the precision medicine
  6. The impact of pneumatic tube system on routine laboratory parameters: a systematic review and meta-analysis
  7. Opinion Paper
  8. How to reduce scientific irreproducibility: the 5-year reflection
  9. EFLM Paper
  10. Strategies to define performance specifications in laboratory medicine: 3 years on from the Milan Strategic Conference
  11. General Clinical Chemistry and Laboratory Medicine
  12. Intensive educational efforts combined with external quality assessment improve the preanalytical phase in general practitioner offices and nursing homes
  13. Separate patient serum sodium medians from males and females provide independent information on analytical bias
  14. Are admission procalcitonin levels universal mortality predictors across different medical emergency patient populations? Results from the multi-national, prospective, observational TRIAGE study
  15. Biochemical testing in a laboratory tent and semi-intensive care of Ebola patients on-site in a remote part of Guinea: a paradigm shift based on a bleach-sensitive point-of-care device
  16. Efficient reporting of the estimated glomerular filtration rate without height in pediatric patients with cancer
  17. Evaluation of thyroid test utilization through analysis of population-level data
  18. Relation of serum γ-glutamyl transferase activity with copper in an adult population
  19. Impact of a single oral dose of 100,000 IU vitamin D3 on profiles of serum 25(OH)D3 and its metabolites 24,25(OH)2D3, 3-epi-25(OH)D3, and 1,25(OH)2D3 in adults with vitamin D insufficiency
  20. Automated antinuclear immunofluorescence antibody analysis is a reliable approach in routine clinical laboratories
  21. Infrared analyzers for breast milk analysis: fat levels can influence the accuracy of protein measurements
  22. Hematology and Coagulation
  23. A new approach to define acceptance limits for hematology in external quality assessment schemes
  24. The effects of transport by car on coagulation tests
  25. Combined measurement of factor XIII and D-dimer is helpful for differential diagnosis in patients with suspected pulmonary embolism
  26. Reference Values and Biological Variations
  27. Influence of age, gender and body mass index on late-night salivary cortisol in healthy adults
  28. Cancer Diagnostics
  29. Assessment of real-time PCR method for detection of EGFR mutation using both supernatant and cell pellet of malignant pleural effusion samples from non-small-cell lung cancer patients
  30. Detection of EGFR mutations in patients with non-small cell lung cancer by high resolution melting. Comparison with other methods
  31. Predicting outcomes of EGFR-targeted therapy in non-small cell lung cancer patients using pleural effusions samples and peptide nucleic acid probe assay
  32. Analytical and clinical performance of thyroglobulin autoantibody assays in thyroid cancer follow-up
  33. Thyroglobulin autoantibodies before radioiodine ablation predict differentiated thyroid cancer outcome
  34. Cardiovascular Diseases
  35. Real life dabigatran and metabolite concentrations, focused on inter-patient variability and assay differences in patients with atrial fibrillation
  36. Infectious Diseases
  37. HIV avidity index performance using a modified fourth-generation immunoassay to detect recent HIV infections
  38. Letters to the Editor
  39. Effect of age on serum prostate-specific antigen in women
  40. Falsely elevated thyroid-stimulating hormone value due to anti-ruthenium antibodies in a patient with primary hypothyroidism: a case report
  41. High titers of anti-infliximab antibody do not interfere with Abbott immunoassays
  42. Extraordinarily elevated serum CA19-9 in a patient with posterior mediastinum cyst: a case report
  43. Low levels of 25-OH vitamin D in women with endometriosis and associated pelvic pain
  44. Evaluation of serum cortisol biological variation in the evening withdrawal
  45. Distinction between urine crystals by automated urine analyzer SediMAX conTRUST is specific but lacks sensitivity
  46. Impact of heat-inactivation on anti-Toxoplasma IgM antibody levels
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 9.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/cclm-2017-0033/html
Scroll to top button