Vol 71, No 3 (2020)
Original paper
Published online: 2020-03-04

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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

Sayid Shafi Zuhur1, Ismail Yildiz1, Yuksel Altuntas2, Taner Bayraktaroglu3, Selvinaz Erol2, Serdar Sahin4, Faruk Kilinc5, Gulhan Akbaba6, Birol Topcu7, Gulsah Elbuken1, Pinar Kadioglu4
Pubmed: 32154572
Endokrynol Pol 2020;71(3):207-212.


Introduction: The outcome of medical treatment in patients with Graves’ disease (GD) is generally difficult to predict. In this study, we examined the hypothesis that gender may affect the outcome of treatment with antithyroid drugs (ATDs).

Material and methods: This is a retrospective multicentre study including 717 (514 female and 203 male) patients with the first episode of GD treated for at least 12 months. Patients were classified as relapse, poorly controlled (several episodes of hyperthyroidism followed by euthyroidism and rarely hypothyroidism, occurring after titration of ATDs), and remission.

Results: During the mean follow-up time of 26.75 ± 21.25 months (between 1 and 120 months), 269 (37.5%), 176 (24.5%), and 272 (37.9%) patients experienced a relapse, a poorly controlled disease, and remained in remission, respectively. During the follow-up time, 223 (43.4%) of the female and only 49 (24%) of the male patients remained in remission. Relapse and poorly controlled disease (non-remitting GD) were more common in male compared to female patients with GD (hazard ratio 1.26, 95% CI: 1.03–1.53, p = 0.025). Graves’ disease in male patients tended to relapse earlier, and male patients tended to have larger goiter sizes at diagnosis as well. The smoking habit was
also significantly more frequent in males compared to female patients with GD.

Conclusion: Male patients with GD have a markedly higher frequency of relapse and poorly controlled disease, as compared to female patients. Larger goiter sizes and higher frequency of smoking may contribute to the higher frequency of relapse and poorly controlled disease in male patients. 

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  1. Nyström HF, Jansson S, Berg G. Incidence rate and clinical features of hyperthyroidism in a long-term iodine sufficient area of Sweden (Gothenburg) 2003-2005. Clin Endocrinol (Oxf). 2013; 78(5): 768–776.
  2. Struja T, Fehlberg H, Kutz A, et al. Can we predict relapse in Graves' disease? Results from a systematic review and meta-analysis. Eur J Endocrinol. 2017; 176(1): 87–97.
  3. Zuhur SS, Elbuken G, Yildiz I, et al. External Validation of the GREAT Score in Turkish Patients with Graves' Hyperthyroidism Treated with the Titration Regimen Method of Antithyroid Drugs: A Multicenter Study. Horm Metab Res. 2019; 51(10): 627–633.
  4. Allahabdia A, Daykin J, Holder RL, et al. Age and Gender Predict the Outcome of Treatment for Graves’ Hyperthyroidism. J Clin Endocrinol Metab. 2000; 85(3): 1038–1042.
  5. Werner SC. Modification of the classification of the eye changes of Graves' disease: recommendations of the Ad Hoc Committee of the American Thyroid Association. J Clin Endocrinol Metab. 1977; 44(1): 203–204.
  6. Vos XG, Endert E, Zwinderman AH, et al. Predicting the Risk of Recurrence Before the Start of Antithyroid Drug Therapy in Patients With Graves' Hyperthyroidism. J Clin Endocrinol Metab. 2016; 101(4): 1381–1389.
  7. Alsanea O, Clark OH. Treatment of Graves' disease: the advantages of surgery. Endocrinol Metab Clin North Am. 2000; 29(2): 321–337.
  8. Struja T, Kaeslin M, Boesiger F, 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): 413–419.
  9. Kahaly GJ, Bartalena L, Hegedüs L, et al. 2018 European Thyroid Association Guideline for the Management of Graves' Hyperthyroidism. Eur Thyroid J. 2018; 7(4): 167–186.
  10. Cooper DS. Antithyroid drugs. N Engl J Med. 2005; 352(9): 905–917.
  11. Sundaresh V, Brito JP, Wang Z, et al. Comparative effectiveness of therapies for Graves' hyperthyroidism: a systematic review and network meta-analysis. J Clin Endocrinol Metab. 2013; 98(9): 3671–3677.
  12. Piantanida E, Lai A, Sassi L, et al. Outcome Prediction of Treatment of Graves' Hyperthyroidism with Antithyroid Drugs. Horm Metab Res. 2015; 47(10): 767–772.
  13. Desai MK, Brinton RD. Autoimmune Disease in Women: Endocrine Transition and Risk Across the Lifespan. Front Endocrinol (Lausanne). 2019; 10: 265.
  14. Fatourechi V. Is sex a predictor of outcome of antithyroid therapy of Graves hyperthyroidism. Endocr Pract. 2019; 25(1): 109–111.
  15. Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016; 26(10): 1343–1421.
  16. Diker-Cohen T, Duskin-Bitan H, Shimon I, et al. Disease presentation and remission rate in Graves disease treated with antithyroid drugs: Is gender really a factor? Endocr Pract. 2019; 25(1): 43–50.
  17. Ovadia YS, Arbelle JE, Gefel D, et al. First Israeli National Iodine Survey Demonstrates Iodine Deficiency Among School-Aged Children and Pregnant Women. Thyroid. 2017; 27(8): 1083–1091.
  18. Magri F, Zerbini F, Gaiti M, et al. Gender influences the clinical presentation and long-term outcome of Graves’ disease. Endocr Pract. 2016; 22(11): 1336–1342.
  19. Berghout A, Wiersinga WM, Smits NJ, et al. Determinants of thyroid volume as measured by ultrasonography in healthy adults in a non-iodine deficient area. Clin Endocrinol (Oxf). 1987; 26(3): 273–280.
  20. Erdoğan MF, Ağbaht K, Altunsu T, et al. Current iodine status in Turkey. J Endocrinol Invest. 2009; 32(7): 617–622.
  21. Kimball LE, Kulinskaya E, Brown B, et al. Does smoking increase relapse rates in Graves' disease? J Endocrinol Invest. 2002; 25(2): 152–157.
  22. Bartalena L, Baldeschi L, Boboridis K, et al. European Group on Graves' Orbitopathy (EUGOGO). The 2016 European Thyroid Association/European Group on Graves' Orbitopathy Guidelines for the Management of Graves' Orbitopathy. Eur Thyroid J. 2016; 5(1): 9–26.