Advertisement

Surveillance of patients with differentiated thyroid cancer and indeterminate response: a longitudinal study on basal thyroglobulin trend

  • P. MalandrinoEmail author
  • D. Tumino
  • M. Russo
  • S. Marescalco
  • R. A. Fulco
  • F. Frasca
Original Article
  • 17 Downloads

Abstract

Purpose

This is a longitudinal study of retrospective data aimed at verifying whether repeated measurements of serum non-stimulated thyroglobulin (Tg) allow the prediction of persistent disease in patients with differentiated thyroid cancer (DTC) and indeterminate response.

Methods

We examined 145 DTC patients with indeterminate response to therapy followed up for a median time of 68 months. Tg measurements and neck ultrasound (US) were performed every 6–12 months. The changes over time of repeated measurements of basal Tg were analyzed through the multilevel linear regression.

Results

Seventy (48.3%) out of 145 patients spontaneously achieved an excellent response, while persistent indeterminate response was observed in 62 (42.7%) patients. The remaining 13 (9.0%) patients had progression: 3/13 with biochemical disease and 10/13 with structural disease. Tg steadily increased in patients with progressive disease (mean percentage change + 27.1% at each follow-up visit), while Tg decreased in patients without any evidence of progression (mean percentage change − 8.8%). This different trend between the two groups was not related to either different values of median TSH at baseline (0.32 vs 0.28 mIU/l, respectively) or to different trend of TSH during follow-up (p = 0.76). Basal Tg values did not increase in three out of ten patients with structural disease that was identified by neck US.

Conclusions

The importance of the study is that, in DTC patients with indeterminate response, rising values of unstimulated Tg, independently from the basal levels, may be useful to identify patients with progressive disease. These results are also useful to avoid unnecessary TSH stimulation.

Keywords

Thyroid cancer Thyroglobulin Ultrasensitive assay Ongoing risk Indeterminate response 

Notes

Acknowledgements

This work was supported by the Italian Ministry of Education, Universities and Research to F.F.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was carried out in accordance with the recommendations for retrospective studies of the Institutional Review Board.

Informed consent

Written informed consent was obtained from all individual participants.

References

  1. 1.
    Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward DL, Tuttle RM, Wartofsky L (2016) 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):1–133.  https://doi.org/10.1089/thy.2015.0020 CrossRefGoogle Scholar
  2. 2.
    Tuttle RM, Tala H, Shah J, Leboeuf R, Ghossein R, Gonen M, Brokhin M, Omry G, Fagin JA, Shaha A (2010) 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(12):1341–1349.  https://doi.org/10.1089/thy.2010.0178 CrossRefGoogle Scholar
  3. 3.
    Vaisman F, Momesso D, Bulzico DA, Pessoa CH, Dias F, Corbo R, Vaisman M, Tuttle RM (2012) Spontaneous remission in thyroid cancer patients after biochemical incomplete response to initial therapy. Clin Endocrinol (Oxf) 77(1):132–138.  https://doi.org/10.1111/j.1365-2265.2012.04342.x CrossRefGoogle Scholar
  4. 4.
    Dominguez JM, Nilo F, Contreras T, Carmona R, Droppelmann N, Gonzalez H, Iturrieta V, Tuttle RM (2017) Neck sonography and suppressed thyroglobulin have high sensitivity for identifying recurrent/persistent disease in patients with low-risk thyroid cancer treated with total thyroidectomy and radioactive iodine ablation, making stimulated thyroglobulin unnecessary. J Ultrasound Med 36(11):2299–2307.  https://doi.org/10.1002/jum.14260 CrossRefGoogle Scholar
  5. 5.
    Malandrino P, Latina A, Marescalco S, Spadaro A, Regalbuto C, Fulco RA, Scollo C, Vigneri R, Pellegriti G (2011) Risk-adapted management of differentiated thyroid cancer assessed by a sensitive measurement of basal serum thyroglobulin. J Clin Endocrinol Metab 96(6):1703–1709.  https://doi.org/10.1210/jc.2010-2695 CrossRefGoogle Scholar
  6. 6.
    Chindris AM, Diehl NN, Crook JE, Fatourechi V, Smallridge RC (2012) Undetectable sensitive serum thyroglobulin (< 0.1 ng/ml) in 163 patients with follicular cell-derived thyroid cancer: results of rhTSH stimulation and neck ultrasonography and long-term biochemical and clinical follow-up. J Clin Endocrinol Metab 97(8):2714–2723.  https://doi.org/10.1210/jc.2011-3017 CrossRefGoogle Scholar
  7. 7.
    Giovanella L, Treglia G, Sadeghi R, Trimboli P, Ceriani L, Verburg FA (2014) Unstimulated highly sensitive thyroglobulin in follow-up of differentiated thyroid cancer patients: a meta-analysis. J Clin Endocrinol Metab 99(2):440–447.  https://doi.org/10.1210/jc.2013-3156 CrossRefGoogle Scholar
  8. 8.
    Taieb D, Sebag F, Cherenko M, Baumstarck-Barrau K, Fortanier C, Farman-Ara B, De Micco C, Vaillant J, Thomas S, Conte-Devolx B, Loundou A, Auquier P, Henry JF, Mundler O (2009) Quality of life changes and clinical outcomes in thyroid cancer patients undergoing radioiodine remnant ablation (RRA) with recombinant human TSH (rhTSH): a randomized controlled study. Clin Endocrinol (Oxf) 71(1):115–123.  https://doi.org/10.1111/j.1365-2265.2008.03424.x CrossRefGoogle Scholar
  9. 9.
    Tuttle RM (2008) Risk-adapted management of thyroid cancer. Endocr Pract 14(6):764–774.  https://doi.org/10.4158/EP.14.6.764 CrossRefGoogle Scholar
  10. 10.
    Tuttle RM, Leboeuf R (2008) Follow up approaches in thyroid cancer: a risk adapted paradigm. Endocrinol Metab Clin N Am 37(2):419–435.  https://doi.org/10.1016/j.ecl.2008.02.008 (ix–x) CrossRefGoogle Scholar
  11. 11.
    Haugen BR, Pacini F, Reiners C, Schlumberger M, Ladenson PW, Sherman SI, Cooper DS, Graham KE, Braverman LE, Skarulis MC, Davies TF, DeGroot LJ, Mazzaferri EL, Daniels GH, Ross DS, Luster M, Samuels MH, Becker DV, Maxon HR 3rd, Cavalieri RR, Spencer CA, McEllin K, Weintraub BD, Ridgway EC (1999) A comparison of recombinant human thyrotropin and thyroid hormone withdrawal for the detection of thyroid remnant or cancer. J Clin Endocrinol Metab 84(11):3877–3885.  https://doi.org/10.1210/jcem.84.11.6094 Google Scholar
  12. 12.
    Lamartina L, Montesano T, Trulli F, Attard M, Torlontano M, Bruno R, Meringolo D, Monzani F, Tumino S, Ronga G, Maranghi M, Biffoni M, Filetti S, Durante C (2016) Papillary thyroid carcinomas with biochemical incomplete or indeterminate responses to initial treatment: repeat stimulated thyroglobulin assay to identify disease-free patients. Endocrine 54(2):467–475.  https://doi.org/10.1007/s12020-015-0823-3 CrossRefGoogle Scholar
  13. 13.
    Yim JH, Kim EY, Bae Kim W, Kim WG, Kim TY, Ryu JS, Gong G, Hong SJ, Yoon JH, Shong YK (2013) Long-term consequence of elevated thyroglobulin in differentiated thyroid cancer. Thyroid 23(1):58–63.  https://doi.org/10.1089/thy.2011.0487 CrossRefGoogle Scholar
  14. 14.
    Pacini F, Agate L, Elisei R, Capezzone M, Ceccarelli C, Lippi F, Molinaro E, Pinchera A (2001) 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 86(9):4092–4097.  https://doi.org/10.1210/jcem.86.9.7831 CrossRefGoogle Scholar
  15. 15.
    Baudin E, Do Cao C, Cailleux AF, Leboulleux S, Travagli JP, Schlumberger M (2003) 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 88(3):1107–1111.  https://doi.org/10.1210/jc.2002-021365 CrossRefGoogle Scholar
  16. 16.
    Rosario PW, Furtado Mde S, Mourao GF, Calsolari MR (2015) Patients with papillary thyroid carcinoma at intermediate risk of recurrence according to american thyroid association criteria can be reclassified as low risk when the postoperative thyroglobulin is low. Thyroid 25(11):1243–1248.  https://doi.org/10.1089/thy.2015.0294 CrossRefGoogle Scholar
  17. 17.
    Miyauchi A, Kudo T, Miya A, Kobayashi K, Ito Y, Takamura Y, Higashiyama T, Fukushima M, Kihara M, Inoue H, Tomoda C, Yabuta T, Masuoka H (2011) Prognostic impact of serum thyroglobulin doubling-time under thyrotropin suppression in patients with papillary thyroid carcinoma who underwent total thyroidectomy. Thyroid 21(7):707–716.  https://doi.org/10.1089/thy.2010.0355 CrossRefGoogle Scholar
  18. 18.
    Brassard M, Borget I, Edet-Sanson A, Giraudet AL, Mundler O, Toubeau M, Bonichon F, Borson-Chazot F, Leenhardt L, Schvartz C, Dejax C, Brenot-Rossi I, Toubert ME, Torlontano M, Benhamou E, Schlumberger M, Group TW (2011) Long-term follow-up of patients with papillary and follicular thyroid cancer: a prospective study on 715 patients. J Clin Endocrinol Metab 96(5):1352–1359.  https://doi.org/10.1210/jc.2010-2708 CrossRefGoogle Scholar
  19. 19.
    Schlumberger M, Berg G, Cohen O, Duntas L, Jamar F, Jarzab B, Limbert E, Lind P, Pacini F, Reiners C, Sanchez Franco F, Toft A, Wiersinga WM (2004) Follow-up of low-risk patients with differentiated thyroid carcinoma: a European perspective. Eur J Endocrinol 150(2):105–112CrossRefGoogle Scholar
  20. 20.
    Bachelot A, Leboulleux S, Baudin E, Hartl DM, Caillou B, Travagli JP, Schlumberger M (2005) Neck recurrence from thyroid carcinoma: serum thyroglobulin and high-dose total body scan are not reliable criteria for cure after radioiodine treatment. Clin Endocrinol (Oxf) 62(3):376–379.  https://doi.org/10.1111/j.1365-2265.2005.02228.x CrossRefGoogle Scholar
  21. 21.
    Cherk MH, Francis P, Topliss DJ, Bailey M, Kalff V (2012) Incidence and implications of negative serum thyroglobulin but positive I-131 whole-body scans in patients with well-differentiated thyroid cancer prepared with rhTSH or thyroid hormone withdrawal. Clin Endocrinol (Oxf) 76(5):734–740.  https://doi.org/10.1111/j.1365-2265.2011.04278.x CrossRefGoogle Scholar
  22. 22.
    Giovanella L, Suriano S, Ceriani L, Verburg FA (2011) Undetectable thyroglobulin in patients with differentiated thyroid carcinoma and residual radioiodine uptake on a postablation whole-body scan. Clin Nucl Med 36(2):109–112.  https://doi.org/10.1097/RLU.0b013e318203bb84 CrossRefGoogle Scholar
  23. 23.
    Pacini F, Schlumberger M, Dralle H, Elisei R, Smit JW, Wiersinga W, European Thyroid Cancer T (2006) European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur J Endocrinol 154(6):787–803.  https://doi.org/10.1530/eje.1.02158 CrossRefGoogle Scholar
  24. 24.
    Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Pacini F, Schlumberger M, Sherman SI, Steward DL, Tuttle RM (2009) Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 19(11):1167–1214.  https://doi.org/10.1089/thy.2009.0110 CrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2019

Authors and Affiliations

  • P. Malandrino
    • 1
    Email author
  • D. Tumino
    • 1
  • M. Russo
    • 1
  • S. Marescalco
    • 2
  • R. A. Fulco
    • 2
  • F. Frasca
    • 1
  1. 1.Endocrinology, Department of Clinical and Experimental Medicine, University of CataniaGaribaldi-Nesima Medical CenterCataniaItaly
  2. 2.Clinical PathologyGaribaldi-Nesima Medical CenterCataniaItaly

Personalised recommendations