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Endocrine

, Volume 55, Issue 1, pp 200–208 | Cite as

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

  • Fabian PitoiaEmail author
  • Erika Abelleira
  • Graciela Cross
Original Article

Abstract

The objective of our study was to evaluate the prognostic value of stimulated thyroglobulin levels at the moment of remnant ablation for predicting an initial excellent or a structural incomplete response to treatment according to the risk of recurrence in patients with differentiated thyroid cancer. Patients were divided into two groups according to the preparation mode for remnant ablation (thyroid hormone withdrawal or recombinant human TSH). We included 219 patients followed-up for at least for 24 months after remnant ablation. The primary endpoint was the best response to initial therapy assessed in the first 9–18 months of follow-up. An excellent response was observed in 45.1 % of patients prepared after recombinant human TSH compared to 44.6 % of patients prepared after thyroid hormone withdrawal (P = NS). The cutoff value of thyroglobulin level after recombinant human TSH for predicting an excellent response was 8 ng/ml (n = 51), with a sensitivity of 73.9 %, and a positive predictive value of 61 %. It was similar for patients with low vs. intermediate to high risk of recurrence. This cutoff value for thyroglobulin level after thyroid hormone withdrawal was 22 ng/ml (n = 168), with a sensitivity of 94.7 % and a positive predictive value of 61.7 %. In the thyroid hormone withdrawal group the thyroglobulin cutoff level was 12 ng/ml for low-risk patients compared to 16 ng/ml for those with intermediate to high risk of recurrence (P = 0.003). The cutoff value of the thyroglobulin level for predicting a structural incomplete response to initial treatment was 20 ng/ml after rhTSH, with a negative predictive value of 91.4 %. This level was higher in thyroid hormone withdrawal group, and it was established at 25 ng/ml, with a negative predictive value of 97.7 %. The stimulated Tg level seems to be different depending on the preparation mode (rhTSH or THW) for RA. It has a high NPV to predict the absence of a structural incomplete response and it is also a good predictor of the initial excellent response and the NED status at the end of follow-up.

Keywords

Thyroglobulin levels Remnant ablation Differentiated thyroid cancer Excellent response Preparation mode Risk of recurrence 

Notes

Compliance with ethical standards

Conflict of interest

Fabian Pitoia is consultant for Genzyme- Sanofi. The other authors declare no conflict of interests.

References

  1. 1.
    S.A. Hundahl, I.D. Fleming, A.M. Fremgen, H.R. Menck, A National Cancer Data Base report on 53 856 cases of thyroid carcinoma treated in the US, 1985–1995. Cancer 83, 2638–2648 (1998)CrossRefPubMedGoogle Scholar
  2. 2.
    B.R. Haugen, E.K. Alexander, K.C. Bible, G.M. Doherty, S.J. Mandel, Y.E. Nikiforov, F. Pacini, G.W. Randolph, A.M. Sawka, M. Schlumberger, K.G. Schuff, S.I. Sherman, J.A. Sosa, D.L. Steward, R.M. Tuttle, L. Wartofsky, 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 26, 1–133 (2016)CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    B.R. Haugen, F. Pacini, C. Reiners, M. Schlumberger, P.W. Ladenson, S.I. Sherman, D.S. Cooper, K.E. Graham, L.E. Braverman, M.C. Skarulis, T.F. Davies, L.J. DeGroot, E.L. Mazzaferri, G.H. Daniels, D.S. Ross, M. Luster, M.H. Samuels, D.V. Becker, H.R. Maxon 3rd, R.R. Cavalieri, C.A. Spencer, K. McEllin, B.D. Weintraub, E.C. Ridgway, A comparison of recombinant human thyrotropin and thyroid hormone withdrawal for the detection of thyroid remnant or cancer. J. Clin. Endocrinol. Metab. 84, 3877–3885 (1999)PubMedGoogle Scholar
  4. 4.
    M. Toubeau, C. Touzery, P. Arveux, G. Chaplain, G. Vaillant, A. Berriolo, J.M. Riedinger, C. Boichot, A. Cochet, F. Brunotte, 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. 45, 988–994 (2004)PubMedGoogle Scholar
  5. 5.
    K.A. Heemstra, Y.Y. Liu, M. Stokkel, J. Kievit, E. Corssmit, A.M. Pereira, J.A. Romijn, J.W. Smit, Serum thyroglobulin concentrations predict disease-free remission and death in differentiated thyroid carcinoma. Clin. Endocrinol. (Oxf) 66, 58–64 (2007)Google Scholar
  6. 6.
    T.Y. Kim, W.B. Kim, E.S. Kim, J.S. Ryu, J.S. Yeo, S.C. Kim, S.J. Hong, Y.K. Shong, 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. 90, 1440–1445 (2005)CrossRefPubMedGoogle Scholar
  7. 7.
    D.B. Kendler, F. Vaisman, R. Corbo, R. Martins, M. Vaisman, Preablation stimulated thyroglobulin is a good predictor of successful ablation in patients with differentiated thyroid cancer. Clin. Nucl. Med. 37, 545–549 (2012)CrossRefPubMedGoogle Scholar
  8. 8.
    R.C. Webb, R.S. Howard, A. Stojadinovic, D.Y. Gaitonde, M.K. Wallace, J. Ahmed, H.B. Burch, 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. 97, 2754–2763 (2012)CrossRefPubMedGoogle Scholar
  9. 9.
    F. Pacini, E. Molinaro, F. Lippi, M.G. Castagna, L. Agate, C. Ceccarelli, D. Taddei, R. Elisei, M. Capezzone, A. Pinchera, Prediction of disease status by recombinant human TSH-stimulated serum Tg in the postsurgical follow-up of differentiated thyroid carcinoma. J. Clin. Endocrinol. Metab. 86, 5686–5690 (2001)CrossRefPubMedGoogle Scholar
  10. 10.
    M. Melo, G. Costa, C. Ribeiro, F. Carrilho, M.J. Martins, A.G. da Rocha, M. Sobrinho-Simoes, M. Carvalheiro, P. Soares, Stimulated thyroglobulin at recombinant human TSH-aided ablation predicts disease-free status one year later. J. Clin. Endocrinol. Metab. 98, 4364–4372 (2013)CrossRefPubMedGoogle Scholar
  11. 11.
    R. Ciappuccini, J. Hardouin, N. Heutte, D. Vaur, E. Quak, J.P. Rame, D. Blanchard, D. De Raucourt, S. Bardet, Stimulated thyroglobulin level at ablation in differentiated thyroid cancer: the impact of treatment preparation modalities and tumor burden. Eur. J. Endocrinol 171, 247–252 (2014)CrossRefPubMedGoogle Scholar
  12. 12.
    P.W. Rosario, L.T. Siman, M.R. Calsolari, Day 3 thyroglobulin ≤ 1 ng/ml after recombinant human TSH just prior to radioactive iodine is predictive of low risk for persistent/ recurrent disease in patients with papillary thyroid carcinoma. Endocrine 49, 170–174 (2015)CrossRefPubMedGoogle Scholar
  13. 13.
    M.S. Torres, L. Ramirez, P.H. Simkin, L.E. Braverman, C.H. Emerson, Effect of various doses of recombinant human thyrotropin on the thyroid radioactive iodine uptake and serum levels of thyroid hormones and thyroglobulin in normal subjects. J Clin. Endocrinol. Metab. 86, 1660–1664 (2001)CrossRefPubMedGoogle Scholar
  14. 14.
    D. Taieb, D. Lussato, E. Guedj, F. Roux, O. Mundler, Early sequential changes in serum thyroglobulin after radioiodine ablation for thyroid cancer: possible clinical implications for recombinant human thyrotropin-aided therapy. Thyroid 16, 177–179 (2006)CrossRefPubMedGoogle Scholar
  15. 15.
    American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, D.S. Cooper, G.M. Doherty, B.R. Haugen, R.T. Kloos, S.L. Lee, S.J. Mandel, E.L. Mazzaferri, B. McIver, F. Pacini, M. Schlumberger, S.I. Sherman, D.L. Steward, R.M. Tuttle, Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 19, 1167–1214 (2009)CrossRefGoogle Scholar
  16. 16.
    F. Pitoia, L. Ward, N. Wohllk, C. Friguglietti, E. Tomimori, A. Gauna, R. Camargo, M. Vaisman, R. Harach, F. Munizaga, S. Corigliano, E. Pretell, H. Niepomnizcze, Recommendations of the Latin American Thyroid Society on diagnosis and management of differentiated thyroid cancer. Arq. Bras. Endocrinol. Metabol. 53, 884–887 (2009)CrossRefPubMedGoogle Scholar
  17. 17.
    R.M. Tuttle, H. Tala, J. Shah, R. Leboeuf, R. Ghossein, M. Gonen, M. Brokhin, G. Omry, J.A. Fagin, A. Shaha, 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 20, 1341–1349 (2010)CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    F. Pitoia, F. Bueno, C. Urciuoli, E. Abelleira, G. Cross, R.M. Tuttle, Outcomes of Patients with Differentiated Thyroid Cancer Risk Stratified According to the American Thyroid Association and Latin American Thyroid Society Risk of Recurrence Classification Systems. Thyroid 23, 1401–1407 (2013)CrossRefPubMedGoogle Scholar
  19. 19.
    F. Vaisman, D. Momesso, D.A. Bulzico, C.H. Pessoa, F. Dias, R. Corbo, M. Vaisman, R.M. Tuttle, Spontaneous remission in thyroid cancer patients after biochemical incomplete response to initial therapy. Clin. Endocrinol. (Oxf) 77, 132–138 (2011)CrossRefGoogle Scholar
  20. 20.
    F. Pitoia, F. Jerkovich, C. Urciuoli, A. Schmidt, E. Abelleira, F. Bueno, G. Cross, R.M. Tuttle, Implementing the Modified 2009 American Thyroid Association Risk Stratification System in Thyroid Cancer Patients with Low and Intermediate Risk of Recurrence. Thyroid 25, 1235–1242 (2015)CrossRefPubMedGoogle Scholar
  21. 21.
    M.G. Castagna, F. Maino, C. Cipri, V. Belardini, A. Theodoropoulou, G. Cevenini, F. Pacini, Delayed risk stratification, to include the response to initial treatment (surgery and radioiodine ablation), has better outcome predictivity in differentiated thyroid cancer patients. Eur. J. Endocrinol. 165, 441–446 (2011)CrossRefPubMedGoogle Scholar
  22. 22.
    F.T. Hall, N.J. Beasley, S.J. Eski, I.J. Witterick, P.G. Walfish, J.L. Freeman, Predictive value of serum thyroglobulin after surgery for thyroid carcinoma. Laryngoscope 113, 77–81 (2003)CrossRefPubMedGoogle Scholar
  23. 23.
    T. Ibrahimpasic, I.J. Nixon, F.L. Palmer, M.M. Whitcher, R.M. Tuttle, A. Shaha, S.G. Patel, J.P. Shah, I. Ganly, Undetectable thyroglobulin after total thyroidectomy in patients with low- and intermediate-risk papillary thyroid cancer--is there a need for radioactive iodine therapy?. Surgery 152, 1096–1105 (2012)CrossRefPubMedGoogle Scholar
  24. 24.
    P.W. Rosario, A.C. Xavier, M.R. Calsolari, Value of postoperative thyroglobulin and ultrasonography for the indication of ablation and 131I activity in patients with thyroid cancer and low risk of recurrence. Thyroid 21, 49–53 (2011)CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Fabian Pitoia
    • 1
    Email author
  • Erika Abelleira
    • 1
  • Graciela Cross
    • 1
  1. 1.Division of Endocrinology–Hospital de ClínicasUniversity of Buenos AiresBuenos AiresArgentina

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