Is Stimulated Thyroglobulin Before Radioiodine Therapy a Useful Tool in Predicting Response to Initial Therapy in Patients with Differentiated Thyroid Carcinoma?

 

 Buy Article Permissions and Reprints

Abstract

Thyroglobulin (Tg) is an important tool to evaluate the persistence and recurrence risk in differentiated thyroid cancer (DTC). We aimed to evaluate the correlation between pre-radioiodine therapy stimulated Tg (pre-RAI Tg) levels and the first response to treatment evaluation, and to establish a cut-off pre-RAI Tg threshold for predicting an initial excellent response. Retrospective cohort study of DTC patients who underwent total thyroidectomy and radioiodine therapy. Response to therapy was evaluated 6 to 24 months after initial therapy, and patients were classified as: excellent response (ER); indeterminate response (IndR) and incomplete response (IncR). Total patients: 166 among which 85.5% female with mean age of 47.6 ± 13 years. The ER had a significantly lower pre-RAI Tg in comparison to IndR (p<0.001) and IncR (p<0.001), and pre-RAI Tg were different between the IndR and IncR (p=0.02). A cut-off pre-RAI Tg value at 7.55ng/ml was obtained by receiver operating characteristics curve for differentiating ER from IndR and IncR. The area under curve was 0.832 (95% CI 0.76–0.91). In multivariate analysis, ATA low-risk (RR 1.61, 95% CI 1.06–2.43, p=0.025) and Tg below 7.55ng/ml (RR 2.17, 95% CI 1.52–3.10, p<0.001) were associated with ER. After a median of 7.4-year follow-up, 124 (74.7%) patients were allocated into ER, 22 (13.2%) into IndR, and 20 (12%) into IncR. In conclusion, pre-RAI Tg predicts first evaluation of treatment response. Pre-RAI Tg cut-off was a key predictor of initial excellent response to therapy and may be an important tool in the follow-up of DTC patients.

Publication History

Received: 29 November 2023

Accepted after revision: 01 May 2024

Article published online:
21 May 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

• References

• 1 Haugen BR, Alexander EK, Bible KC. 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
  CrossrefPubMedGoogle Scholar
• 2 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
  CrossrefPubMedGoogle Scholar
• 3 Tuttle RM, Tala H, Shah J. et al. Estimating risk of recurrence in differentiated thyroid cancer after total thyroidectomy and radioactive iodine remnant ablation: using response to therapy variables to modify the initial risk estimates predicted by the new American thyroid association staging system. Thyroid 2010; 20: 1341-1349
  CrossrefPubMedGoogle Scholar
• 4 Momesso DP, Vaisman F, Yang SP. et al. Dynamic risk stratification in patients with differentiated thyroid cancer treated without radioactive iodine. J Clin Endocrinol Metab 2016; 101: 2692-2700
  CrossrefPubMedGoogle Scholar
• 5 Evans C, Tennant S, Perros P. Thyroglobulin in differentiated thyroid cancer. Clin Chim Acta 2015; 444: 310-317
  CrossrefPubMedGoogle Scholar
• 6 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
  CrossrefPubMedGoogle Scholar
• 7 Giovanella L, Ceriani L, Ghelfo A. et al. Thyroglobulin assay 4 weeks after thyroidectomy predicts outcome in low-risk papillary thyroid carcinoma. Clin Chem Lab Med 2005; 43: 843-847
  CrossrefPubMedGoogle Scholar
• 8 Webb RC, Howard RS, Stojadinovic A. 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: 2754-2763
  CrossrefPubMedGoogle Scholar
• 9 Chou R, Dana T, Brent GA. et al. Serum thyroglobulin measurement following surgery without radioactive iodine for differentiated thyroid cancer: a systematic review. Thyroid 2022; 32: 613-639
  CrossrefPubMedGoogle Scholar
• 10 Melo M, Costa G, Ribeiro C, Carrilho F. et al. Stimulated thyroglobulin at recombinant human TSH-aided ablation predicts disease-free status one year later. J Clin Endocrinol Metab 2013; 98: 4364-4372
  CrossrefPubMedGoogle Scholar
• 11 Barres B, Kelly A, Kwiatkowski F. et al. Stimulated thyroglobulin and thyroglobulin reduction index predict excellent response in differentiated thyroid cancers. J Clin Endocrinol Metab 2019; 104: 3462-3472
  CrossrefPubMedGoogle Scholar
• 12 Pitoia F, Abelleira E, Cross G. Thyroglobulin levels measured at the time of remnant ablation to predict response to treatment in differentiated thyroid cancer after thyroid hormone withdrawal or recombinant human TSH. Endocrine 2017; 55: 200-208
  CrossrefPubMedGoogle Scholar
• 13 Tian T, Xu Y, Zhang X. et al. Prognostic implications of preablation stimulated Tg: a retrospective analysis of 2500 thyroid cancer patients. J Clin Endocrinol Metab 2021; 106: e4688-e4697
  CrossrefPubMedGoogle Scholar
• 14 Lamartina L, Grani G, Durante C. et al. Follow-up of differentiated thyroid cancer - what should (and what should not) be done. Nat Rev Endocrinol 2018; 14: 538-551
  CrossrefPubMedGoogle Scholar
• 15 Aschebrook-Kilfoy B, Schechter RB, Shih YC. et al. The clinical and economic burden of a sustained increase in thyroid cancer incidence. Cancer Epidemiol Biomarkers Prev 2013; 22: 1252-1259
  CrossrefPubMedGoogle Scholar
• 16 Pacini F, Fuhrer D, Elisei R. et al. 2022 ETA consensus statement: what are the indications for post-surgical radioiodine therapy in differentiated thyroid cancer?. Eur Thyroid J 2022; 11: e210046
  CrossrefPubMedGoogle Scholar
• 17 Mukhtar N, Aljamei H, Aljomaiah A. et al. Natural course of the American thyroid association response to therapy statuses (dynamic risk stratification) in differentiated thyroid cancer. Eur Thyroid J 2021; 10: 198-207
  CrossrefPubMedGoogle Scholar
• 18 Brierley J, G. M. W. C. TNM Classification of malignant tumours, 8th Edition. Hoboken: Wiley, 2017
  PubMed
• 19 Malandrino P, Tumino D, Russo M. et al. Surveillance of patients with differentiated thyroid cancer and indeterminate response: a longitudinal study on basal thyroglobulin trend. J Endocrinol Invest 2019; 42: 1223-1230
  CrossrefPubMedGoogle Scholar
• 20 Polachek A, Hirsch D, Tzvetov G. et al. Prognostic value of post-thyroidectomy thyroglobulin levels in patients with differentiated thyroid cancer. J Endocrinol Invest 2011; 34: 855-860
  PubMedGoogle Scholar
• 21 Kim H, Kim SJ, Kim IJ. et al. Limited clinical value of periablative changes of serum markers in the prediction of biochemical remission in patients with papillary thyroid cancer. Nucl Med Mol Imaging 2013; 47: 268-272
  CrossrefPubMedGoogle Scholar
• 22 Bandeira L, Padovani RDP, Ticly AL. et al. Thyroglobulin levels before radioactive iodine therapy and dynamic risk stratification after 1 year in patients with differentiated thyroid cancer. Arch Endocrinol Metab 2017; 61: 590-599
  CrossrefPubMedGoogle Scholar
• 23 González C, Aulinas A, Colom C. et al. Thyroglobulin as early prognostic marker to predict remission at 18-24 months in differentiated thyroid carcinoma. Clin Endocrinol (Oxf) 2014; 80: 301-306
  CrossrefPubMedGoogle Scholar
• 24 Campennì A, Ruggeri RM, Siracusa M. et al. Early preablation rhTSH-stimulated thyroglobulin predicts outcome of differentiated thyroid cancer (DTC) patients. Eur J Nucl Med Mol Imaging 2021; 48: 2466-2475
  CrossrefPubMedGoogle Scholar
• 25 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
  CrossrefPubMedGoogle Scholar
• 26 Moreno I, Hirsch D, Duskin-Bitan H. et al. Response to therapy assessment in intermediate-risk thyroid cancer patients: is thyroglobulin stimulation required?. Thyroid 2020; 30: 863-870
  CrossrefPubMedGoogle Scholar
• 27 Rosario PW, Mourão GF, Calsolari MR. Definition of the response to initial therapy with radioiodine in patients with differentiated thyroid carcinoma: basal or stimulated thyroglobulin?. Horm Metab Res 2019; 51: 634-638
  Article in Thieme ConnectPubMedGoogle Scholar
• 28 Scheffel RS, Zanella AB, Antunes D. et al. Low recurrence rates in a cohort of differentiated thyroid carcinoma patients: a referral center experience. Thyroid 2015; 25: 883-889
  CrossrefPubMedGoogle Scholar
• 29 Mehanna H, Al-Maqbili T, Carter B. et al. Differences in the recurrence and mortality outcomes rates of incidental and nonincidental papillary thyroid microcarcinoma: a systematic review and meta-analysis of 21 329 person-years of follow-up. J Clin Endocrinol Metab 2014; 99: 2834-2843
  CrossrefPubMedGoogle Scholar

• Supplementary Material