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Abstract
Graves' Orbitopathy (GO), also known as thyroid eye disease or thyroid-associated orbitopathy is characterized by inflammation, ocular muscle hypertrophy, adipogenesis, and oedema (due to glycosaminoglycan accumulation). This condition leads to remodeling, tissue expansion, and/or fibrosis within the fibroadipose tissue or extraocular muscles of the orbit. GO manifests as an extrathyroidal aspect of autoimmune thyroid diseases in both Grave's disease (GD) and Hashimoto's thyroiditis.
The pathophysiological foundation of GO entails the infiltration of B cells, T cells, and CD34+ fibroblasts in the orbit. B cells generate IGF (insulin-like growth factor), wherein IGF and TRab (Thyroid-Receptor antibodies) stimulate the IGF receptor complex and thyrotropin receptor (respectively) on the surface of CD34+ cells which triggers orbital tissue expansion, orbital protrusion, optic nerve compression, and eyeball displacement, resulting in exophthalmos.
GO progress through an active phase (characterized by inflammation with visible manifestations), followed by a plateau phase (stabilization of GO manifestations), and a gradual resolution of distinctive residual signs and symptoms (inactive phase). This entire process spans between 18-24 months in untreated patients, where disease manifestations significantly depend on the phase during which the disease is identified.
GO therapy is intended to shorten the active phase and supress its residual eye manifestations during the inactive phase. In general, GO therapy is categorized into general and disease severity-specific approaches.
GO therapy often falls short of providing satisfactory results, prompting need of surgery to address lingering clinical manifestations. This review presents the latest insights into the pathogenesis and treatment of GO for better management and outcomes.
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
How to Cite
Ujianto, M., Sari, F., & Rakhman, M. F. (2024). Unveiling Modern Strategies for Diagnosing and Treating Grave Orbitopathy. Jurnal Klinik Dan Riset Kesehatan, 3(2), 89-106. https://doi.org/10.11594/jk-risk.03.2.4
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6. Ren Z, Zhang H, Yu H, Zhu X, Lin J. Roles of four targets in the pathogenesis of graves’ orbitopathy. Heliyon. 2023;9(9):e19250.
7. Savitri AD, Sutjahjo A, Soelistijo SA, Baskoro A. Comparison of thyroid stimulating hormone receptor antibody (Trab) in graves’ disease patients with and without ophtalmopathy. New Armen Med J. 2019;13(4):39–46.
8. Subekti I, Boedisantoso A, Moeloek ND, Waspadji S, Mansyur M. Association of TSH receptor antibody, thyroid stimulating antibody, and thyroid blocking antibody with clinical activity score and degree of severity of Graves ophthalmopathy. Acta Med Indones. 2012;44(2):114–21.
9. Bartalena L, Piantanida E, Gallo D, Lai A, Tanda ML. Epidemiology, Natural History, Risk Factors, and Prevention of Graves’ Orbitopathy. Front Endocrinol (Lausanne). 2020;11(November):1–10.
10. Bartalena L, Tanda ML. Current concepts regarding Graves’ orbitopathy. J Intern Med. 2022;292(5):692–716.
11. Smith TJ. New advances in understanding thyroid-associated ophthalmopathy and the potential role for insulin-like growth factor-I receptor. F1000Research. 2018;7(0):1–9.
12. Muñoz-Ortiz J, Sierra-Cote MC, Zapata-Bravo E, Valenzuela-Vallejo L, Marin-Noriega MA, Uribe-Reina P, et al. Prevalence of hyperthyroidism, hypothyroidism, and euthyroidism in thyroid eye disease: A systematic review of the literature. Syst Rev. 2020;9(1).
13. Turck N, Eperon S, De Los Angeles Gracia M, Obéric A, Hamédani M. Thyroid-associated orbitopathy and biomarkers: Where we are and what we can hope for the future. Dis Markers. 2018;2018.
14. Whitacre CC. Sex differences in autoimmune disease. Nat Immunol. 2001;2(9):777–80.
15. Vermeulen A, Kaufman JM, Goemaere S, Van Pottelberg I. Estradiol in elderly men. Aging Male. 2002;5(2):98–102.
16. Orwoll E, Lambert LC, Marshall LM, Phipps K, Blank J, Barrett-Connor E, et al. Testosterone and estradiol among older men. J Clin Endocrinol Metab. 2006;91(4):1336–44.
17. Chailurkit LO, Aekplakorn W, Ongphiphadhanakul B. The relationship between circulating estradiol and thyroid autoimmunity in males. Eur J Endocrinol. 2014;170(1):63–7.
18. Khong JJ, Finch S, De Silva C, Rylander S, Craig JE, Selva D, et al. Risk factors for graves’ orbitopathy; The australian thyroid-associated orbitopathy research (ATOR) study. J Clin Endocrinol Metab. 2016;101(7):2711–20.
19. Mathur C, Singh S, Sharma S. Prevalence and risk factors of thyroid-associated ophthalmopathy among Indians. Int J Adv Med. 2016;3(3):662–5.
20. Lat AMM, Jauculan MC, Sanchez CA, Jimeno C, Sison-Peña CM, Pe-Yan MR, et al. Risk factors associated with the activity and severity of graves’ ophthalmopathy among patients at the university of the Philippines Manila-Philippine general hospital. J ASEAN Fed Endocr Soc. 2017;32(2):151–7.
21. Xia N, Zhou S, Liang Y, Xiao C, Shen H, Pan H, et al. CD4+ T cells and the Th1/Th2 imbalance are implicated in the pathogenesis of Graves’ ophthalmopathy. Int J Mol Med. 2006;17(5):911–6.
22. Fang S, Lu Y, Huang Y, Zhou H, Fan X. Mechanisms That Underly T Cell Immunity in Graves’ Orbitopathy. Front Endocrinol (Lausanne). 2021;12(April):1–17.
23. Huang Y, Fang S, Li D, Zhou H, Li B, Fan X. The involvement of T cell pathogenesis in thyroid-associated ophthalmopathy. Eye. 2019;33(2):176–82.
24. Salvi M, Covelli D. B cells in Graves’ Orbitopathy: more than just a source of antibodies? Eye. 2019;33(2):230–4.
25. Tang F, Chen X, Mao Y, Wan S, Ai S, Yang H, et al. Orbital fibroblasts of Graves’ orbitopathy stimulated with proinflammatory cytokines promote B cell survival by secreting BAFF. Mol Cell Endocrinol. 2017;446:1–11.
26. Chen G, Ding Y, Li Q, Li Y, Wen X, Ji X, et al. Defective Regulatory B Cells Are Associated with Thyroid-Associated Ophthalmopathy. J Clin Endocrinol Metab. 2019;104(9):4067–77.
27. Fang S, Huang Y, Liu X, Zhong S, Wang N, Zhao B, et al. Interaction between CCR6 + TH17 cells and CD34 + fibrocytes promotes inflammation: Implications in graves’ orbitopathy in Chinese population. Investig Ophthalmol Vis Sci. 2018;59(6):2604–14.
28. Wang Y, Chen Z, Wang T, Guo H, Liu Y, Dang N, et al. A novel CD4+ CTL subtype characterized by chemotaxis and inflammation is involved in the pathogenesis of Graves’ orbitopathy. Cell Mol Immunol. 2021;18(3):735–45.
29. Smith TJ. Potential Roles of CD34 + Fibrocytes Masquerading as Orbital Fibroblasts in Thyroid-Associated Ophthalmopathy. J Clin Endocrinol Metab. 2018;104(2):581–94.
30. Douglas RS, Gianoukakis AG, Kamat S, Smith TJ. Aberrant Expression of the Insulin-Like Growth Factor-1 Receptor by T Cells from Patients with Graves’ Disease May Carry Functional Consequences for Disease Pathogenesis. J Immunol. 2007;178(5):3281–7.
31. Douglas RS, Naik V, Hwang CJ, Afifiyan NF, Gianoukakis AG, Sand D, et al. B Cells from Patients with Graves’ Disease Aberrantly Express the IGF-1 Receptor: Implications for Disease Pathogenesis. J Immunol. 2008;181(8):5768–74.
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