Endocrinol Metab.  2019 Sep;34(3):268-274. 10.3803/EnM.2019.34.3.268.

Changes in Thyroid Peroxidase and Thyroglobulin Antibodies Might Be Associated with Graves' Disease Relapse after Antithyroid Drug Therapy

• Choi YM
• Kwak MK
• Hong SM
• Hong EG

• KMID: 2458629
• DOI: http://doi.org/10.3803/EnM.2019.34.3.268

Abstract

BACKGROUND
Graves' disease (GD) is an autoimmune thyroid disorder caused by antibodies stimulating the thyrotropin (TSH) receptor. TSH receptor antibody (TRAb) measurement is useful for predicting GD relapse after antithyroid drug (ATD) treatment. However, the association of other thyroid autoantibodies with GD relapse remains obscure.
METHODS
This retrospective study enrolled patients with GD who were initially treated with ATD. TRAb, thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) were measured at the initial diagnosis and at the time of ATD discontinuation.
RESULTS
A total of 55 patients were enrolled. The mean age was 49.7 years, and 39 patients (70.9%) were female. Antibody positivity at diagnosis was 90.9%, 69.1%, and 61.9% for TRAb, TPOAb, TgAb, respectively. Median ATD treatment period was 15.1 months. At the time of ATD withdrawal, TRAb titers decreased uniformly overall. Conversely, TPOAb and TgAb showed various changes. After withdrawal of ATD, 19 patients (34.5%) experienced relapse. No clinical features or laboratory results were significantly related to relapse in the overall patient group. However, in the TPOAb positive group at diagnosis, increasing titer of TPOAb or TgAb after ATD treatment was significantly and independently related to relapse free survival (TPOAb: hazard ratio [HR], 17.99; 95% confidence interval [CI], 1.66 to 195.43; P=0.02) (TgAb: HR, 5.73; 95% CI, 1.21 to 27.26; P=0.03).
CONCLUSION
Changes in TPOAb or TgAb titers during treatment might be useful for predicting relapse after ATD treatment in patients with positive TPOAb at diagnosis.

Keyword

Graves disease; Autoantibodies; Thyroid peroxidase antibody; Recurrence

MeSH Terms

Antibodies*
Autoantibodies
Diagnosis
Drug Therapy*
Female
Graves Disease*
Humans
Iodide Peroxidase*
Receptors, Thyrotropin
Recurrence*
Retrospective Studies
Thyroglobulin*
Thyroid Gland*
Thyrotropin
Antibodies
Autoantibodies
Iodide Peroxidase
Receptors, Thyrotropin
Thyroglobulin
Thyrotropin

Figure

• 

  Fig. 1 Changes in (A) thyrotropin (TSH) receptor antibody (TRAb), (B) thyroid peroxidase antibody (TPOAb), and (C) thyroglobulin antibody (TgAb) during treatment with antithyroid drug in patients with Graves' disease.

• 

  Fig. 2 Overall relapse free survival of study population.

• 

  Fig. 3 Relapse free survival of Graves' disease patients with positive thyroid peroxidase antibody (TPOAb) at diagnosis, according to (A) TPOAb changes and (B) thyroglobulin antibody (TgAb) changes.

Reference

1. Burch HB, Cooper DS. Management of Graves disease: a review. JAMA. 2015; 314:2544–2554. PMID: 26670972.

2. Struja T, Fehlberg H, Kutz A, Guebelin L, Degen C, Mueller B, et al. Can we predict relapse in Graves' disease? Results from a systematic review and meta-analysis. Eur J Endocrinol. 2017; 176:87–97. PMID: 27780830.

3. Laurberg P. Remission of Graves' disease during anti-thyroid drug therapy. Time to reconsider the mechanism? Eur J Endocrinol. 2006; 155:783–786. PMID: 17132745.

4. Guilhem I, Massart C, Poirier JY, Maugendre D. Differential evolution of thyroid peroxidase and thyrotropin receptor antibodies in Graves' disease: thyroid peroxidase antibody activity reverts to pretreatment level after carbimazole withdrawal. Thyroid. 2006; 16:1041–1045. PMID: 17042691.

5. Moon JH, Yi KH. The diagnosis and management of hyperthyroidism in Korea: consensus report of the Korean Thyroid Association. Endocrinol Metab (Seoul). 2013; 28:275–279. PMID: 24396691.

6. Laurberg P, Krejbjerg A, Andersen SL. Relapse following antithyroid drug therapy for Graves' hyperthyroidism. Curr Opin Endocrinol Diabetes Obes. 2014; 21:415–421. PMID: 25111942.

7. Wiersinga WM. Graves' disease: can it be cured? Endocrinol Metab (Seoul). 2019; 34:29–38. PMID: 30912336.

8. Smith TJ, Hegedus L. Graves' disease. N Engl J Med. 2016; 375:1552–1565. PMID: 27797318.

9. Liu J, Fu J, Xu Y, Wang G. Antithyroid drug therapy for Graves' disease and implications for recurrence. Int J Endocrinol. 2017; 2017:3813540. PMID: 28529524.

10. Kwon H, Kim WG, Jang EK, Kim M, Park S, Jeon MJ, et al. Usefulness of measuring thyroid stimulating antibody at the time of antithyroid drug withdrawal for predicting relapse of Graves disease. Endocrinol Metab (Seoul). 2016; 31:300–310. PMID: 27118279.

11. Carella C, Mazziotti G, Sorvillo F, Piscopo M, Cioffi M, Pilla P, et al. Serum thyrotropin receptor antibodies concentrations in patients with Graves' disease before, at the end of methimazole treatment, and after drug withdrawal: evidence that the activity of thyrotropin receptor antibody and/or thyroid response modify during the observation period. Thyroid. 2006; 16:295–302. PMID: 16571093.

12. Choi HS, Yoo WS. Free thyroxine, anti-thyroid stimulating hormone receptor antibody titers, and absence of goiter were associated with responsiveness to methimazole in patients with new onset Graves' disease. Endocrinol Metab (Seoul). 2017; 32:281–287. PMID: 28685517.

13. Huh JE, Suk JH, Kim MK, Choi IJ, Son SM, Kim IJ, et al. Clinical usefulness of the second generation TSH-binding inhibitory immunoglobulin assay using recombinant human TSH receptor in patients with Graves' disease. J Korean Endocr Soc. 2008; 23:179–185.

14. Takaichi Y, Tamai H, Honda K, Nagai K, Kuma K, Nakagawa T. The significance of antithyroglobulin and antithyroidal microsomal antibodies in patients with hyperthyroidism due to Graves' disease treated with antithyroidal drugs. J Clin Endocrinol Metab. 1989; 68:1097–1100. PMID: 2470772.

15. Smycznyska J, Cyniak-Magierska A, Stasiak M, Karbownik-Lewinska M, Lewinski A. Persistent remission of Graves' disease or evolution from Graves' disease to Hashimoto's thyroiditis in childhood: a report of 6 cases and clinical implications. Neuro Endocrinol Lett. 2014; 35:335–341. PMID: 25275265.

16. Schott M, Eckstein A, Willenberg HS, Nguyen TB, Morgenthaler NG, Scherbaum WA. Improved prediction of relapse of Graves' thyrotoxicosis by combined determination of TSH receptor and thyroperoxidase antibodies. Horm Metab Res. 2007; 39:56–61. PMID: 17226115.

17. Hamada N, Ito K, Mimura T, Ishikawa N, Momotani N, Noh J, et al. Retrospective reevaluation of the significance of thyroid microsomal antibody in the treatment of Graves' disease. Acta Endocrinol (Copenh). 1987; 114:328–335. PMID: 2436426.

18. Romaldini JH, Bromberg N, Werner RS, Tanaka LM, Rodrigues HF, Werner MC, et al. Comparison of effects of high and low dosage regimens of antithyroid drugs in the management of Graves' hyperthyroidism. J Clin Endocrinol Metab. 1983; 57:563–570. PMID: 6192139.

19. Weetman AP. The immunomodulatory effects of antithyroid drugs. Thyroid. 1994; 4:145–146. PMID: 7522682.

20. Marcocci C, Chiovato L, Mariotti S, Pinchera A. Changes of circulating thyroid autoantibody levels during and after the therapy with methimazole in patients with Graves' disease. J Endocrinol Invest. 1982; 5:13–19. PMID: 6896520.

21. Chiovato L, Vitti P, Lombardi A, Kohn LD, Pinchera A. Expression of the microsomal antigen on the surface of continuously cultured rat thyroid cells is modulated by thyrotropin. J Clin Endocrinol Metab. 1985; 61:12–16. PMID: 3889033.

22. Stefanic M, Karner I. Thyroid peroxidase autoantibodies are associated with a lesser likelihood of late reversion to hyperthyroidism after successful non-ablative treatment of Graves' disease in Croatian patients. J Endocrinol Invest. 2014; 37:71–77. PMID: 24464453.

23. Katahira M, Ogata H. Thyroglobulin autoantibodies are associated with refractoriness to antithyroid drug treatment for Graves' disease. Intern Med. 2016; 55:1519–1524. PMID: 27301499.

24. Hwang SM, Kim MS, Lee DY. Predictive factors for early response to methimazole in children and adolescents with Graves disease: a single-institute study between 1993 and 2013. Ann Pediatr Endocrinol Metab. 2016; 21:70–74. PMID: 27462582.