Research Article
No access
Published Online: 1 April 2017

The Second Antithyroid Drug Treatment Is Effective in Relapsed Graves' Disease Patients: A Median 11-Year Follow-Up Study

Publication: Thyroid
Volume 27, Issue Number 4

Abstract

Background: Antithyroid drug (ATD) is a widely used treatment for Graves' disease (GD). However, its long-term efficiency remains unclear. This study investigated the long-term disease prognosis and predictive factors for relapse in ATD-treated GD patients.
Methods: Newly diagnosed, ATD-treated GD patients with at least four years of follow-up were recruited (n = 187). Remission was defined as maintaining a euthyroid status for more than one year after ATD withdrawal.
Results: During 11.1 years (range 4.0–23.7 years) of median follow-up, overall, 51.9% of the newly diagnosed ATD-treated GD patients achieved remission, 32.1% continued ATD treatment, and 13.4% underwent other ablation treatments. The 10-year remission rates were higher in the first (34.2%) and second (25.5%) ATD courses than in any of the other subsequent ATD courses, and decreased as ATD treatments were repeated. The 10-year relapse rate was the highest after the third ATD treatment (71.4%) compared with that after the first (60.5%) and second (58.3%) courses. Longer duration of ATD treatment (odds ratio [OR] = 1.4 [confidence interval (CI) 1.2–1.7], p < 0.001), higher number of relapses (OR = 4.7 [CI 2.3–9.8], p < 0.001), and moderate to severe Graves' ophthalmopathy (OR = 4.1 [CI 1.1–15.2], p = 0.032) were associated with persistent disease status.
Conclusions: A second course of ATD can be considered for GD patients after the first relapse because the chance of remission and the relapse rate are similar to the one after the first ATD treatment course. For GD patients with more than two relapses, or with an ATD treatment duration of more than four to five years, low-dose maintenance of ATD or ablative treatment needs to be considered.

Get full access to this article

View all available purchase options and get full access to this article.

References

1.
Laurberg P 2006 Remission of Graves' disease during anti-thyroid drug therapy. Time to reconsider the mechanism? Eur J Endocrinol 155:783–786.
2.
Yi KH, Moon JH, Kim I-J, Bom H-S, Lee J, Chung WY, Chung JH, Shong YK 2013 The diagnosis and management of hyperthyroidism consensus—report of the Korean Thyroid Association. J Korean Thyroid Assoc 6:1–11.
3.
Moon JH, Yi KH 2013 The diagnosis and management of hyperthyroidism in Korea: consensus report of the Korean Thyroid Association. Endocrinol Metab (Seoul) 28:275–279.
4.
Burch HB, Burman KD, Cooper DS 2012 A 2011 survey of clinical practice patterns in the management of Graves' disease. J Clin Endocrinol Metab 97:4549–4558.
5.
Abraham P, Avenell A, McGeoch SC, Clark LF, Bevan JS 2010 Antithyroid drug regimen for treating Graves' hyperthyroidism. Cochrane Database Syst Rev CD003420.
6.
Bahn RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa JA, Stan MN 2011 Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Endocr Pract 17:456–520.
7.
Maugendre D, Gatel A, Campion L, Massart C, Guilhem I, Lorcy Y, Lescouarch J, Herry JY, Allannic H 1999 Antithyroid drugs and Graves' disease—prospective randomized assessment of long-term treatment. Clin Endocrinol (Oxf) 50:127–132.
8.
Garcia-Mayor RV, Paramo C, Luna Cano R, Perez Mendez LF, Galofre JC, Andrade A 1992 Antithyroid drug and Graves' hyperthyroidism. Significance of treatment duration and TRAb determination on lasting remission. J Endocrinol Invest 15:815–820.
9.
Laurberg P, Krejbjerg A, Andersen SL 2014 Relapse following antithyroid drug therapy for Graves' hyperthyroidism. Curr Opin Endocrinol Diabetes Obes 21:415–421.
10.
Carle A, Knudsen N, Pedersen IB, Perrild H, Ovesen L, Rasmussen LB, Laurberg P 2013 Determinants of serum T4 and T3 at the time of diagnosis in nosological types of thyrotoxicosis: a population-based study. Eur J Endocrinol 169:537–545.
11.
Nedrebo BG, Holm PI, Uhlving S, Sorheim JI, Skeie S, Eide GE, Husebye ES, Lien EA, Aanderud S 2002 Predictors of outcome and comparison of different drug regimens for the prevention of relapse in patients with Graves' disease. Eur J Endocrinol 147:583–589.
12.
Allahabadia A, Daykin J, Holder RL, Sheppard MC, Gough SC, Franklyn JA 2000 Age and gender predict the outcome of treatment for Graves' hyperthyroidism. J Clin Endocrinol Metab 85:1038–1042.
13.
Eckstein AK, Lax H, Losch C, Glowacka D, Plicht M, Mann K, Esser J, Morgenthaler NG 2007 Patients with severe Graves' ophthalmopathy have a higher risk of relapsing hyperthyroidism and are unlikely to remain in remission. Clin Endocrinol (Oxf) 67:607–612.
14.
Dauksiene D, Dauksa A, Mickuviene N 2013 Independent pretreatment predictors of Graves' disease outcome. Medicina (Kaunas) 49:427–434.
15.
Mohlin E, Filipsson Nystrom H, Eliasson M 2014 Long-term prognosis after medical treatment of Graves' disease in a northern Swedish population 2000–2010. Eur J Endocrinol 170:419–427.
16.
Cappelli C, Gandossi E, Castellano M, Pizzocaro C, Agosti B, Delbarba A, Pirola I, De Martino E, Rosei EA 2007 Prognostic value of thyrotropin receptor antibodies (TRAb) in Graves' disease: a 120 months prospective study. Endocr J 54:713–720.
17.
Anagnostis P, Adamidou F, Polyzos SA, Katergari S, Karathanasi E, Zouli C, Panagiotou A, Kita M 2013 Predictors of long-term remission in patients with Graves' disease: a single center experience. Endocrine 44:448–453.
18.
Ohye H, Minagawa A, Noh JY, Mukasa K, Kunii Y, Watanabe N, Matsumoto M, Suzuki M, Yoshihara A, Ito K, Ito K 2014 Antithyroid drug treatment for Graves' disease in children: a long-term retrospective study at a single institution. Thyroid 24:200–207.
19.
Kwon H, Kim WG, Jang EK, Kim M, Park S, Jeon MJ, Kim TY, Ryu J-S, Shong YK, Kim WB 2016 Usefulness of measuring thyroid stimulating antibody at the time of antithyroid drug withdrawal for predicting relapse of Graves disease. Endocrinol Metab (Seoul) 31:300–310.
20.
Kim WB, Chung HK, Park YJ, Park DJ, Tahara K, Kohn LD, Cho BY 2000 The prevalence and clinical significance of blocking thyrotropin receptor antibodies in untreated hyperthyroid Graves' disease. Thyroid 10:579–586.
21.
Kim WB, Chung HK, Lee HK, Kohn LD, Tahara K, Cho BY 1997 Changes in epitopes for thyroid-stimulating antibodies in Graves' disease sera during treatment of hyperthyroidism: therapeutic implications. J Clin Endocrinol Metab 82:1953–1959.
22.
Cho BY, Shong MH, Yi KH, Lee HK, Koh CS, Min HK 1992 Evaluation of serum basal thyrotrophin levels and thyrotrophin receptor antibody activities as prognostic markers for discontinuation of antithyroid drug treatment in patients with Graves' disease. Clin Endocrinol (Oxf) 36:585–590.
23.
Werner SC 1969 Classification of the eye changes of Graves' disease. Am J Ophthalmol 68:646–648.
24.
Liu X, Qiang W, Liu X, Liu L, Liu S, Gao A, Gao S, Shi B 2015 A second course of antithyroid drug therapy for recurrent Graves' disease: an experience in endocrine practice. Eur J Endocrinol 172:321–326.
25.
Howard JE 1967 Treatment of thyrotoxicosis. JAMA 202:706–709.
26.
Azizi F, Ataie L, Hedayati M, Mehrabi Y, Sheikholeslami F 2005 Effect of long-term continuous methimazole treatment of hyperthyroidism: comparison with radioiodine. Eur J Endocrinol 152:695–701.
27.
Villagelin D, Romaldini JH, Santos RB, Milkos AB, Ward LS 2015 Outcomes in relapsed Graves' disease patients following radioiodine or prolonged low dose of methimazole treatment. Thyroid 25:1282–1290.
28.
Carella C, Mazziotti G, Sorvillo F, Piscopo M, Cioffi M, Pilla P, Nersita R, Iorio S, Amato G, Braverman LE, Roti E 2006 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 16:295–302.
29.
Hwang S, Shin DY, Song MK, Lee EJ 2015 High cut-off value of a chimeric TSH receptor (Mc4)-based bioassay may improve prediction of relapse in Graves' disease for 12 months. Endocrine 48:89–95.
30.
Tozzoli R, Bagnasco M, Giavarina D, Bizzaro N 2012 TSH receptor autoantibody immunoassay in patients with Graves' disease: improvement of diagnostic accuracy over different generations of methods. Systematic review and meta-analysis. Autoimmun Rev 12:107–113.

Information & Authors

Information

Published In

cover image Thyroid®
Thyroid
Volume 27Issue Number 4April 2017
Pages: 491 - 496
PubMed: 28001121

History

Published in print: April 2017
Published online: 1 April 2017
Published ahead of print: 24 January 2017
Published ahead of production: 21 December 2016

Permissions

Request permissions for this article.

Topics

Authors

Affiliations

Ye An Kim*
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Department of Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea.
Sun Wook Cho*
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Hoon Sung Choi
Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea.
Shinje Moon
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Jae Hoon Moon
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Kyung Won Kim
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Department of Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea.
Do Joon Park
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Ka Hee Yi
Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.
Young Joo Park
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Bo Youn Cho
Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.

Notes

*
These authors contributed equally to this work.
Address correspondence to:Young Joo Park, MD, PhDDepartment of Internal MedicineSeoul National University College of Medicine101 Daehak-roJongno-guSeoul 03080KoreaE-mail: [email protected]
Ka Hee Yi, MD, PhDDepartment of Internal MedicineSeoul National University Boramae Medical Center20 Boramae-ro 5-gilDongjak-guSeoul 07061KoreaE-mail: [email protected]

Author Disclosure Statement

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Metrics & Citations

Metrics

Citations

Export citation

Select the format you want to export the citations of this publication.

View Options

Get Access

Access content

To read the fulltext, please use one of the options below to sign in or purchase access.

Society Access

If you are a member of a society that has access to this content please log in via your society website and then return to this publication.

Restore your content access

Enter your email address to restore your content access:

Note: This functionality works only for purchases done as a guest. If you already have an account, log in to access the content to which you are entitled.

View options

PDF/EPUB

View PDF/ePub

Full Text

View Full Text

Media

Figures

Other

Tables

Share

Share

Copy the content Link

Share on social media

Back to Top