Thyroid Receptor Antibody and the Development of Graves’ Orbitopathy: Clinical Experience of using Radioiodine Ablation in the Management of Graves’ Orbitopathy in post-iodine ablation hypothyroid patient

Document Type : Case report

Authors

1 Department of Nuclear Medicine, Padjadjaran University, Bandung, Indonesia

2 Department of Nuclear Medicine, Mochtar Riady Comprehensive Cancer Center Siloam Hospital, Jakarta, Indonesia

3 Department of Nuclear Medicine, Hasan Sadikin Central Hospital, Bandung, Indonesia

Abstract

Graves’ disease (GD) is the commonest cause of hyperthyroidism, accounted for 70-80% in iodine sufficient countries and up to 50% in iodine deficient countries. Combination of genetic predisposition and environmental factors influences the development of GD. Graves’ orbitopathy (GO) represents the most common extra-thyroidal manifestation of GD with substantial impact on morbidity and quality of life. Expression of thyroid stimulating hormone receptor (TSHR) mRNA and protein in orbital tissues infiltrated by the activated lymphocytes produced by thyroid cells (Thyroid Receptor Antibody) results in the secretion of inflammatory cytokines that leads to the development of histological and clinical characteristics of GO. A subdivision of TRAb, thyroid stimulating antibody (TSAb), was found to have a close relationship with the activity and severity of GO, and suggested to be considered as a direct parameter of GO. Here, we present a 75-year-old female with a history of GD that has successfully been treated with radioiodine treatment, who developed GO 13 months after therapy while being hypothyroid with high TRAb level. The patient was given a second dose of radioiodine ablation to maintain GO with successful result.

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  1. Taylor PN, Albrecht D, Scholz A, Gutierrez-Buey G, Lazarus JH, Dayan CM, et al. Global epidemiology of hyperthyroidism and hypothyroidism. Nat Rev Endocrinol. 2018; 14(5):301–16.
  2. Tomer Y, Huber A. The etiology of autoimmune thyroid disease: A story of genes and environment. J Autoimmun. 2009; 32(3–4):231–9.
  3. Brix TH, Kyvik KO, Christensen K, Hegedüs L. Evidence for a major role of heredity in Graves’ disease: A population-based study of two danish twin cohorts. J Clin Endocrinol Metab. 2001; 86(2):930–4.
  4. Prabhakar BS, Bahn RS, Smith TJ. Current perspective on the pathogenesis of Graves’ disease and ophthalmopathy. Endocr Rev. 2003; 24(6):802–35.
  5. 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):1–17.
  6. Wiersinga WM. Quality of life in Graves’ ophthalmopathy. Best practice & research Clinical endocrinology & metabolism. 2012; 26(3):359-70.
  7. Bahn R. TSH receptor expression in orbital tissue and its role in the pathogenesis of Graves’ ophtalmopathy. J Endocrinol Investig. 2004; 27:216–20.
  8. Bartley GB. The epidemiologic characteristics and clinical course of ophthalmopathy associated with autoimmune thyroid disease in Olmstead County, Minnesota. Trans Am Ophthalmol Soc. 1994; 92:477–588.
  9. Wu SL, Yang CSJ, Wang HJ, Liao CL, Chang TJ, Chang TC. Demonstration of thyrotropin receptor mRNA in orbital fat and eye muscle tissues from patients with Graves’ ophthalmopathy by in situ hybridization. J Endocrinol Invest. 1999; 22(4):289–95.
  10. Wakelkamp IMMJ, Bakker O, Baldeschi L, Wiersinga WM, Prummel MF. TSH-R expression and cytokine profile in orbital tissue of active vs. inactive Graves’ ophthalmopathy patients. Clin Endocrinol (Oxf). 2003; 58(3):280–7.
  11. Gerding MN, Van Der Meer JWC, Broenink M, Bakker O, Wiersinga WM, Prummel MF. Association of thyrotrophin receptor antibodies with the clinical features of Graves’ ophthalmopathy. Clin Endocrinol (Oxf). 2000; 52(3):267–71.
  12. Bahn RS. Pathophysiology of Graves’ ophthalmopathy: The cycle of disease. J Clin Endocrinol Metab. 2003; 88(5):1939–46.
  13. Noh JY, Hamada N, Inoue Y, Abe Y, Ito K, Ito K. Thyroid-stimulating antibody is related to graves’ ophthalmopathy, but thyrotropin-binding inhibitor immunoglobulin is related to hyperthyroidism in patients with Graves’ disease. Thyroid. 2000; 10(9):809–13.
  14. Seo S, Sánchez Robledo M. Usefulness of TSH receptor antibodies as biomarkers for Graves’ ophthalmopathy: a systematic review. J Endocrinol Invest. 2018; 41(12): 1457–68.
  15. Ponto KA, Zang S, Kahaly GJ. The tale of radioiodine and Graves’ orbitopathy. Thyroid. 2010; 20(7):785–93.
  16. Ariamanesh S, Ayati N, Mazloum Khorasani Z, Mousavi Z, Kiavash V, Kiamanesh Z, et al. Effect of different 131I dose strategies for treatment of hyperthyroidism on Graves’ ophthalmopathy. Clin Nucl Med. 2020; 45(7):514–8.
  17. Tallstedt L, Lundell G, Blomgren H, Bring J. Does early administration of thyroxine reduce the development of Graves’ ophthalmopathy after radioiodine treatment? Eur J Endocrinol. 1994; 130(5):494–7.
  18. 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.
  19. Sisson JC, Schipper MJ, Nelson CC, Freitas JE, Frueh BR. Radioiodine therapy and Graves’ ophthalmopathy. J Nucl Med. 2008; 49(6): 923–30.
  20. Marcocci C, Bartalena L, Bogazzi F, Bruno-Bossio G, Pinchera A. Relationship between Graves’ ophthalmopathy and type of treatment of Graves’ hyperthyroidism. Thyroid. 1992; 2(2):171–8.
  21. Konturek A, Barczyński M, Cichoń S, Anielski R, Cichoń W, Jonkisz J, et al. Total Thyroidectomy in Treatment of Graves’ Ophtalmopathy. Pol Przegl Chir. 2008; 80(9):455–64.
  22. Degroot LJ, Benjasuratwong Y. Evaluation of thyroid ablative therapy for ophthalmo-pathy of Graves' disease. Orbit. 1996; 15(3):187-96.
  23. Moleti M, Mattina F, Salamone I, Violi MA, Nucera C, Baldari S, et al. Effects of thyroidectomy alone or followed by radioiodine ablation of thyroid remnants on the outcome of Graves' ophthalmopathy. Thyroid. 2003; 13(7):653-8.
  24. Barrio-Barrio J, Sabater AL, Bonet-Farriol E, Velázquez-Villoria Á, Galofré JC. Graves’ ophthalmopathy: VISA versus EUGOGO classification, assessment, and management. J Ophthalmol. 2015; 2015: 249125.