External Validation of the GREAT Score in Turkish Patients with Gravesʼ Hyperthyroidism Treated with the Titration Regimen Method of Antithyroid Drugs: A Multicenter Study

Abstract

Recently, the Gravesʼ Recurrent Events After Therapy score (GREAT) was proposed as a useful tool to predict relapse before starting antithyroid drugs (ATD) in patients with Gravesʼ disease (GD). Therefore, we intended to assess the validity of the GREAT score in Turkish patients with GD, including patients who experienced a poorly controlled disease (multiple episodes of hyperthyroidism followed by euthyroidism or rarely hypothyroidism) during ATD dose titration. This is a retrospective multicenter study including 517 patients with the first episode of GD who were treated for at least 12 months. The patients were classified as relapse+poorly controlled disease (non-remission) and remission groups. During a median follow-up time of 35 months (12–144 months), 191 (37%) patients experienced a relapse, 136 (26.3%) a poorly controlled disease, and 190 (36.7%) remained in remission. Patients with non-remission disease tended to have significantly higher serum levels of TRAb, fT4, and fT3, and have larger goiter sizes on palpation at baseline, as compared with the remission group. Non-remission disease occurred in 12, 35, and, 53% of the patients falling into GREAT class I, II, and III, respectively (hazard ratio 2.56, 95% CI 2.02–3.51, p=0.012, and hazard ratio 3.54, 95% CI 2.12–5.91, p<0.001, for GREAT class II and III against class I, respectively). According to our study, the GREAT score is a useful tool to predict the risk of relapse as well as the occurrence of poorly controlled disease before starting treatment with ATDs.

Key words

Gravesʼ disease - relapse - antithyroid drugs - GREAT score

• References

• 1 Ross DS, Burch HB, Cooper D. et al. 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid 2016; 26: 1343-1421
• 2 Kahaly GJ, Bartalena L, Hegedüs L. et al. 2018 European Thyroid Association guideline for the management of Gravesʼ hyperthyroidism. Eur Thyroid J 2018; 7: 167-186
• 3 Struja T, Kaeslin M, Boesiger F. et al. External validation of the GREAT score to predict relapse risk in Gravesʼ disease: Results from a multicenter, retrospective study with 741 patients. Eur J Endocrinol 2017; 176: 413-419
• 4 Cooper DS. Antithyroid drugs. N Engl J Med 2005; 352: 905-917
• 5 Struja T, Fehlberg H, Kutz A. et al. Can we predict relapse in Gravesʼ disease? Results from a systematic review and meta-analysis. Eur J Endocrinol 2017; 176: 87-97
• 6 Vos XG, Endert E, Zwinderman AH. et al. Predicting the risk of recurrence before the start of antithyroid drug therapy in patients with Gravesʼ hyperthyroidism. J Clin Endocrinol Metab 2016; 101: 1381-1389
• 7 Kruljac I, Solter D, Vrkljan AM. et al. Remission of Gravesʼ disease is not related to early restoration of euthyroidism with high-dose methimazole therapy. Endocr Res 2015; 40: 25-28
• 8 Wenzel KW, Lente JR. Syndrome of persisting thyroid stimulating immunoglobulins and growth promotion of goiter combined with low thyroxine and high triiodothyronine serum levels in drug-treated Gravesʼ disease. J Endocrinol Invest 1983; 6: 389-394
• 9 Marino M, Latrofa F. Menconi et al. An update on the medical treatment of Gravesʼ hyperthyroidism. J Endocrinol Invest 2014; 37: 1041-1048
• 10 Laurberg P, Krejbjerg A, Anderson SL. Relapse following antithyroid drug therapy for Gravesʼ hyperthyroidism. Curr Opin Endocrinol Diabetes Obes 2014; 21: 415-421
• 11 Werner SC. Modification of the classification of the eye changes of Gravesʼ disease: Recommendations of the ad hoc committee of the American Thyroid Association. J Clin Endocrinol Metab 1977; 44: 203-204
• 12 Sundaresh V, Brito JP, Wang Z. et al. Comparative effectiveness of therapies for Gravesʼ hyperthyroidism: A systematic review and network meta-analysis. J Clin Endocrinol Metab 2013; 98: 3671-3677
• 13 Piantanida E, Lai A, Sassi L. et al. Outcome prediction of treatment of gravesʼ hyperthyroidism with antithyroid drugs. Horm Metab Res 2003; 47: 767-772
• 14 Kim TY, Park YJ, Park DJ. et al. Epitope heterogeneity of thyroid-stimulating antibodies predicts long-term outcome in Gravesʼ patients treated with antithyroid drugs. J Clin Endocrinol Metab 2003; 88: 117-124
• 15 Tanrikulu S, Erbil Y, Ademoglu E. et al. The predictive value of CTLA-4 and Tg polymorphisms in the recurrence of Gravesʼ disease after antithyroid withdrawal. Endocrine 2006; 30: 377-381
• 16 Vitti P, Rago T, Chiovato L. et al. Clinical features of patients with Gravesʼ disease undergoing remission after antithyroid drug treatment. Thyroid 1997; 7: 369-375
• 17 Allahabadia A, Daykin J, Holder RL. et al. Ag, and gender predict the outcome of treatment for Gravesʼ hyperthyroidism. J Clin Endocrinol Metab 2000; 85: 1038-1042
• 18 Eckstein AK, Lax H, Lösch C. et al. Patients with severe Gravesʼ ophthalmopathy have a higher risk of relapsing hyperthyroidism and are unlikely to remain in remission. Clin Endocrinol (Oxf) 2007; 67: 607-612
• 19 Abraham P, Avenell A, McGeoch SC. et al. Antithyroid drug regimen for treating Gravesʼ hyperthyroidism. Cochrane Database Syst Re 2010; 20: CD003420. doi:10.1002/14651858.CD003420.pub4