Relapse rate and factors associated with recurrence of Graves’ disease after antithyroid drug withdrawal
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Abstract
BACKGROUND: Graves' disease is the most common cause of hyperthyroidism. Current treatment guidelines recommend the use of antithyroid drugs for at least 12-18 months and measurement of TSH receptor antibody (TRAb) level before withdrawal of antithyroid drugs. Relapse of Graves' disease after discontinuation of antithyroid drugs occurs with a frequency of 20-50%.
OBJECTIVE: To study the recurrence rate and factors associated with recurrence of Graves' disease after withdrawal of antithyroid drugs.
METHODS: A retrospective cohort study was conducted using an electronic database search for ICD-10 code E05.0. Data were collected from medical records of patients with Graves' disease aged 18 years and older who were treated at Chiangrai Prachanukroh Hospital between January 2015 and December 2024.
RESULTS: A total of 284 patients with Graves' disease were included; 80% were female, with a mean age of 40 years. Recurrence after withdrawal of antithyroid drugs occurred in 121 patients (42.6%). Factors significantly associated with recurrence included thyroid-associated ophthalmopathy (adjusted odds ratio [aOR] 2.55; 95% CI: 1.34-4.88; p=0.005), enlarged thyroid gland (aOR 2.74; 95% CI: 1.39-5.39; p=0.003), FT4 level at diagnosis ≥2 times the upper limit of normal (aOR 2.07; 95% CI: 1.08-3.97; p=0.028), receiving methimazole (MMI) >2.5 mg/day before drug withdrawal (aOR 1.79; 95% CI: 1.04-3.13; p=0.037), and a titration interval longer than 6 months (aOR 2.26; 95%CI 1.21-4.23; p=0.011).
CONCLUSIONS AND RECOMMENDATIONS: Patients with Graves' disease who have thyroid-associated ophthalmopathy, an enlarged thyroid gland, a high FT4 level at diagnosis, require an MMI dose before >2.5 mg/day before drug withdrawal, and have a longer titration interval are at increased risk of disease recurrence. In these patients, measurement of TRAb levels before antithyroid drug withdrawal should be considered. Schedule follow-up for symptoms and thyroid function tests is recommended, especially during the first 2 years after drug withdrawal. Alternatively, long-term low-dose antithyroid drug therapy may be considered to increase the chance of disease remission.
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References
Antonelli A, Ferrari SM, Ragusa F, Elia G, Paparo SR, Ruffilli I, et al. Graves' disease: Epidemiology, genetic and environmental risk factors and viruses. Best Pract Res Clin Endocrinol Metab. 2020;34(1):101387.
Terry F, Davies PL, Bahn RS. Hyperthyroid disorders. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, editors. William textbook of endocrinology. Philadelphia, PA: Elsevier; p. 369–415.
Endocrine Society of Thailand. Clinical practice guideline for thyroid disorders 2025. Bangkok: Endocrine Society of Thailand; 2025.
Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, et al. 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid. 2016;26(10):1343-421.
Kahaly GJ, Bartalena L, Hegedüs L, Leenhardt L, Poppe K, Pearce SH. 2018 European Thyroid Association guideline for the management of Graves' hyperthyroidism. Eur Thyroid J. 2018;7(4):167-86.
Struja T, Kaeslin M, Boesiger F, Jutzi R, Imahorn N, Kutz A, et al. External validation of the GREAT score to predict relapse risk in Graves' disease: results from a multicenter, retrospective study with 741 patients. Eur J Endocrinol. 2017;176(4):413-19.
Shi H, Sheng R, Hu Y, Liu X, Jiang L, Wang Z, et al. Risk factors for the relapse of Graves' disease treated with antithyroid drugs: a systematic review and Meta-analysis. Clin Ther. 2020;42(4):662-75.e4.
Thinwong S. Risk factor of recurrence Graves’ disease after treated with anti-thyroid drug in Damnoen Saduak hospital. Journal of Research for Health Improvement and Quality of Life. 2024;4(3):88–98.
Kiatpanabhikul P. Relapse rate and clinical risk factors affecting the treatment of Graves’ disease. Siriraj Medical Journal. 2021;73(7):451–61.
Thewjitcharoen Y, Karndumri K, Chatchomchuan W, Porramatikul S, Krittiyawong S, Wanothayaroj E, et al. Serum T3 level and duration of minimum maintenance dose therapy predict relapse in Methimazole-treated Graves disease. J Endocr Soc. 2021;5(4):bvab015.
Allahabadia A, Daykin J, Holder RL, Sheppard MC, Gough SC, Franklyn JA. Age and gender predict the outcome of treatment for Graves' hyperthyroidism. J Clin Endocrinol Metab. 2000;85(3):1038-42.
Vos XG, Endert E, Zwinderman AH, Tijssen JG, Wiersinga WM. Predicting the risk of recurrence before the start of antithyroid drug therapy in patients With Graves' hyperthyroidism. J Clin Endocrinol Metab. 2016;101(4):1381-9.
Piantanida E, Lai A, Sassi L, Gallo D, Spreafico E, Tanda ML, et al. Outcome prediction of treatment of Graves' hyperthyroidism with antithyroid drugs. Horm Metab Res. 2015;47(10):767-72.
Park SY, Kim BH, Kim M, Hong AR, Park J, Park H, et al. The longer the antithyroid drug is used, the lower the relapse rate in Graves' disease: a retrospective multicenter cohort study in Korea. Endocrine. 2021;74(1):120-27.
Azizi F, Amouzegar A, Khalili D, Abdi H, Tohidi M, Hedayati M, et al. Risk of recurrence at the time of withdrawal of short- or long-term methimazole therapy in patients with Graves' hyperthyroidism: a randomized trial and a risk-scoring model. Endocrine. 2024;84(2):577-88.
Rosner B. Fundamentals of biostatistics. 7th ed. Boston (MA): Brooks/Cole, Cengage
Learning; 2011.
Abbott Laboratories. Alinity i TSH [Package Insert]. Abbott Park, IL: Abbott Laboratories; 2019.
Abbott Laboratories. Alinity i TSH reagent instructions for use (Ref 7K62). Abbott Park, IL: Abbott Laboratories; 2021.
Manji N, Carr-Smith JD, Boelaert K, Allahabadia A, Armitage M, Chatterjee VK, et al. Influences of age, gender, smoking, and family history on autoimmune thyroid disease phenotype. J Clin Endocrinol Metab. 2006;91(12):4873-80.
Zuhur SS, Yildiz I, Altuntas Y, Bayraktaroglu T, Erol S, Sahin S, et al. The effect of gender on response to antithyroid drugs and risk of relapse after discontinuation of the antithyroid drugs in patients with Graves' hyperthyroidism: a multicentre study. Endokrynol Pol. 2020;71(3):207-12.
Bano A, Gan E, Addison C, Narayanan K, Weaver JU, Tsatlidis V et al. Age may influence the impact of TRAbs on thyroid function and relapse-risk in patients with Graves disease. J Clin Endocrinol Metab. 2019;104(5):1378-85.
Park S, Song E, Oh HS, Kim M, Jeon MJ, Kim WG, et al. When should antithyroid drug therapy to reduce the relapse rate of hyperthyroidism in Graves' disease be discontinued? Endocrine. 2019;65(2):348-56.
