Published Jun 29, 2024

Camila Burch

Lanell Blakley  


Autoimmune thyroid disorders, including Hashimoto’s thyroiditis and Grave’s disease, represent complex conditions characterized by dysregulation of the immune system targeting the thyroid gland. Understanding the molecular and immunological mechanisms underlying the transition from Hashimoto’s thyroiditis to Grave’s disease is essential for unraveling the pathophysiology of these interconnected autoimmune conditions. We propose insights into the intricate interplay of genetic factors, immune responses, and hormonal pathways that drive the progression from hypothyroidism to hyperthyroidism, shedding light on new perspectives for diagnosis, management, and future research directions in autoimmune thyroid disorders.



Hashimoto’s Disease, Grave’s Disease, Antibody Shift, Immune Bystander, Genetic Predisposition, Environment Risks

1. Wong M, Inder WJ. Alternating hyperthyroidism and hypothyroidism in Graves’ disease. Clin Case Rep 2018; 6(9):1684-1688. DOI: https://doi.org/10.1002/ccr3.1700

2. Mincer DL, Jialal I. Hashimoto Thyroiditis. [Updated 2023 Jul 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan. Available at: https://www.ncbi.nlm.nih.gov/books/NBK459262/

3. Arata N, Ando T, Unger P, Davies TF. By-stander activation in autoimmune thyroiditis: Studies on experimental autoimmune thyroiditis in the GFP+ fluorescent mouse. Clin Immunol 2006; 121(1):108-117. DOI: https://doi.org/10.1016/j.clim.2006.03.011

4. Vassallo A, Ferrari F, di Filippo L, Giustina A, Loli P. Transition from Hashimoto thyroiditis to Graves’s Disease: An unpredictable change? Endocrine 2024; 84(2):541-548. DOI: https://doi.org/10.1007/s12020-023-03634-x

5. Daramjav N, Takagi J, Iwayama H, Uchino K, Inukai D, Otake K, Ogawa T, Takami A. Autoimmune thyroiditis shifting from Hashimoto’s Thyroiditis to Graves’ Disease. Medicina (Kaunas) 2023; 59(4):757. DOI: https://doi.org/10.3390/medicina59040757

6. Nishihara E, Amino N, Kudo T, Ito M, Fukata S, Nishikawa M, Nakamura H, Miyauchi A. Comparison of thyroglobulin and thyroid peroxidase antibodies measured by five different kits in autoimmune thyroid diseases. Endocr J 2017; 64(10):955-961. DOI: https://doi.org/10.1507/endocrj.EJ17-0164

7. McLachlan SM, Rapoport B. Thyrotropin-blocking autoantibodies and thyroid-stimulating autoantibodies: Potential mechanisms involved in the pendulum swinging from hypothyroidism to hyperthyroidism or vice versa. Thyroid 2013; 23(1):14-24. DOI: https://doi.org/10.1089/thy.2012.0374

8. Gonzalez-Aguilera B, Betea D, Lutteri L, Cavalier E, Geenen V, Beckers A, Valdes-Socin H. Conversion to Graves disease from Hashimoto thyroiditis: A study of 24 patients. Arch Endocrinol Metab 2018; 62(6):609-614. DOI: https://doi.org/10.20945/2359-3997000000086

9. Shahbaz A, Aziz K, Umair M, Sachmechi I. Prolonged duration of hashitoxicosis in a patient with Hashimoto’s Thyroiditis: A case report and review of literature. Cureus 2018; 10(6):e2804. DOI: https://doi.org/10.7759/cureus.2804

10. Vargas-Uricoechea H, Nogueira JP, Pinzón-Fernández MV, Schwarzstein D. The usefulness of thyroid antibodies in the diagnostic approach to autoimmune thyroid disease. Antibodies (Basel) 2023; 12(3):48. DOI: https://doi.org/10.3390/antib12030048

11. Shim CH, Cho S, Shin YM, Choi JM. Emerging role of bystander T cell activation in autoimmune diseases. BMB Rep 2022; 55(2):57-64. DOI: https://doi.org/10.5483/BMBRep.2022.55.2.183

12. Vargas-Uricoechea H. Molecular mechanisms in autoimmune thyroid disease. Cells 2023; 12(6):918. DOI: https://doi.org/10.3390/cells12060918

13. Tomer Y. Genetic susceptibility to autoimmune thyroid disease: Past, present, and future. Thyroid 2010; 20(7):715-725. DOI: https://doi.org/10.1089/thy.2010.1644

14. Eschler DC, Hasham A, Tomer Y. Cutting edge: The etiology of autoimmune thyroid diseases. Clin Rev Allergy Immunol 2011; 41(2):190-197. DOI: https://doi.org/10.1007/s12016-010-8245-8

15. Brent GA. Environmental exposures and autoimmune thyroid disease. Thyroid 2010; 20(7):755-761. DOI: https://doi.org/10.1089/thy.2010.1636

16. Pacheco Y, Acosta-Ampudia Y, Monsalve DM, Chang C, Gershwin ME, Anaya JM. Bystander activation and autoimmunity. J Autoimmun 2019; 103:102301. DOI: https://doi.org/10.1016/j.jaut.2019.06.012

17. Yao Z, Guo F, Tan Y, Zhang Y, Geng Y, Yang G, Wang S. Causal relationship between inflammatory cytokines and autoimmune thyroid disease: A bidirectional two-sample Mendelian randomization analysis. Front Immunol 2024; 15:1334772. DOI: https://doi.org/10.3389/fimmu.2024.1334772

18. Gianoukakis AG, Khadavi N, Smith TJ. Cytokines, Graves’ disease, and thyroid-associated ophthalmopathy. Thyroid 2008; 18(9):953-958. DOI: https://doi.org/10.1089/thy.2007.0405

19. Ganesh BB, Bhattacharya P, Gopisetty A, Prabhakar BS. Role of cytokines in the pathogenesis and suppression of thyroid autoimmunity. J Interferon Cytokine Res 2011; 31(10):721-731. DOI: https://doi.org/10.1089/jir.2011.0049

20. Hansen M, Cheever A, Weber KS, O’Neill KL. Characterizing the interplay of lymphocytes in Graves’ disease. Int J Mol Sci 2023; 24(7):6835. DOI: https://doi.org/10.3390/ijms24076835

21. Rapoport B, McLachlan SM. Graves’ hyperthyroidism is antibody-mediated but is predominantly a Th1-type cytokine disease. J Clin Endocrinol Metab 2014; 99(11):4060-4061. DOI: https://doi.org/10.1210/jc.2014-3011

22. Lai R, Yin B, Feng Z, Deng X, Lv X, Zhong Y, Peng D. The causal relationship between 41 inflammatory cytokines and hypothyroidism: Bidirectional two-sample Mendelian randomization study. Front Endocrinol (Lausanne) 2024; 14:1332383. DOI: https://doi.org/10.3389/fendo.2023.1332383

23. Zawadzka-Starczewska K, Tymoniuk B, Stasiak B, Lewiński A, Stasiak M. Actual Associations between HLA haplotype and Graves’ disease development. J Clin Med 2022; 11(9):2492. DOI: https://doi.org/10.3390/jcm11092492

24. Panicker V. Genetics of thyroid function and disease. Clin Biochem Rev 2011; 32(4):165-175.

25. Kyritsi EM, Kanaka-Gantenbein C. Autoimmune Thyroid Disease in Specific Genetic Syndromes in Childhood and Adolescence. Front Endocrinol (Lausanne) 2020; 11:543. DOI: https://doi.org/10.3389/fendo.2020.00543

26. Zaletel K, Gaberšček S. Hashimoto’s Thyroiditis: From genes to the disease. Curr Genomics 2011; 12(8):576-588. DOI: https://doi.org/10.2174/138920211798120763

27. Coppedè F. Epigenetics and autoimmune thyroid diseases. Front Endocrinol (Lausanne) 2017; 8:149. DOI: https://doi.org/10.3389/fendo.2017.00149

28. Wang B, Shao X, Song R, Xu D, Zhang JA. The emerging role of epigenetics in autoimmune thyroid diseases. Front Immunol 2017; 8:396. DOI: https://doi.org/10.3389/fimmu.2017.00396

29. Hong H, Lee J. Thyroid-stimulating hormone as a biomarker for stress after thyroid surgery: A prospective cohort study. Med Sci Monit 2022; 28:e937957. DOI: https://doi.org/10.12659/MSM.937957

30. Mizokami T, Wu Li A, El-Kaissi S, Wall JR. Stress and thyroid autoimmunity. Thyroid 2004; 14(12):1047-1055. DOI: https://doi.org/10.1089/thy.2004.14.1047

31. Narayana SK, Woods DR, Boos CJ. Management of amiodarone-related thyroid problems. Ther Adv Endocrinol Metab 2011; 2(3):115-126. DOI: https://doi.org/10.1177/2042018811398516

32. Ruggeri RM, Barbalace MC, Croce L, Malaguti M, Campennì A, Rotondi M, Cannavò S, Hrelia S. Autoimmune thyroid disorders: The mediterranean diet as a protective choice. Nutrients 2023; 15(18):3953. DOI: https://doi.org/10.3390/nu15183953

33. Kalarani IB, Veerabathiran R. Impact of iodine intake on the pathogenesis of autoimmune thyroid disease in children and adults. Ann Pediatr Endocrinol Metab 2022; 27(4):256-264. DOI: https://doi.org/10.6065/apem.2244186.093

34. Brown EDL, Obeng-Gyasi B, Hall JE, Shekhar S. The thyroid hormone axis and female reproduction. Int J Mol Sci 2023; 24(12):9815. DOI: https://doi.org/10.3390/ijms24129815

35. Dittfeld A, Gwizdek K, Michalski M, Wojnicz R. A possible link between the Epstein-Barr virus infection and autoimmune thyroid disorders. Cent Eur J Immunol 2016; 41(3):297-301. DOI: https://doi.org/10.5114/ceji.2016.63130

36. Thomsen H, Li X, Sundquist K, Sundquist J, Försti A, Hemminki K. Familial risks between Graves’ disease and Hashimoto thyroiditis and other autoimmune diseases in the population of Sweden. J Transl Autoimmun 2020; 3:100058. DOI: https://doi.org/10.1016/j.jtauto.2020.100058
How to Cite
Burch, C., & Blakley, L. (2024). On the Molecular and Immunological Mechanisms of the Transition from Hashimoto’s Thyroiditis to Grave’s Disease. Science Insights, 44(6), 1409–1414. https://doi.org/10.15354/si.24.re1016