The Relationship of Thyroid Stimulating Hormone Receptor Antibody (TRAb) Levels to Activity and Clinical Severity of Graves' Ophthalmopathy in RSUP Dr. Sardjito

Kharisma Wibawa Nurdin Putra Putra; M. Robikhul Ikhsan; Vina Yanti Susanti

doi:10.22146/actainterna.98252

The Relationship of Thyroid Stimulating Hormone Receptor Antibody (TRAb) Levels to Activity and Clinical Severity of Graves' Ophthalmopathy in RSUP Dr. Sardjito

https://doi.org/10.22146/actainterna.98252

Kharisma Wibawa Nurdin Putra Putra^(1*), M. Robikhul Ikhsan⁽²⁾, Vina Yanti Susanti⁽³⁾

(1) Internal Medicine Specialist Program, Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital
(2) Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital
(3) Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital
(*) Corresponding Author

Abstract

Background: Graves' disease (GD) is an autoimmune disease that is the most common cause of hyperthyroidism. Thyroid stimulating hormone receptor antibody (TRAb) is a specific biomarker for diagnosing GD. Graves' ophthalmopathy (GO) is the most common extrathyroid manifestation in Graves'. Each GO was assessed for activity and clinical severity for treatment.

Objectives: To determine the relationship between TRAb levels and GO clinical activity in Clinical Activity Score (CAS) classification and clinical severity of The European Group on Graves' Orbitopathy (EUGOGO).

Methods: This is a cross-sectional study, conducted from January to August 2021 at RSUP Dr. Sardjito Yogyakarta. 30 newly diagnosed Graves' patients or previously diagnosed with Graves' presented symptoms of hyperthyroidism were included. The patients had TRAb levels > 1.75 IU/L, and diagnosed with Graves' ophthalmopathy based on clinical criteria according to Bartley and Gorman and has not received steroid injections. Serum TRAb examination by electrochemiluminescence immunoassay (ECLIA) method. Clinical activity are assessed with CAS, while severity are assessed with EUGOGO criteria. The data are analyzed using Spearman correlation, multivariate analysis with linear regression and logistic regression.

Results: 30 study subjects mean age 35.43 years, female dominant (80%), median GD duration of 13 months. Median TRAb 8.15 IU/L, median CAS score 2 with 46.3% active. Mild severity 40% and moderate-severe 60%. Correlation of TRAb with CAS (r=0.576, p=0.001), EUGOGO (r=0.535, p=0.002). Multivariate analysis of TRAb with CAS (B= 0.076, p=0.01) while EUGOGO (OR=1.198, p=0.045)

Conclusion: TRAb is positively correlated with activity and clinical severity of OG.

Keywords

Thyroid stimulating hormone receptor antibody (TRAb), Graves' Ophthalmopathy, Clinical Activity Score (CAS), The European Group on Graves' Orbitopathy (EUGOGO).

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References

Tomer Y. Mechanisms of autoimmune thyroid diseases: from genetics to epigenetics. Annu Rev Pathol. 2014;9:147–56.

Zimmermann MB, Boelaert K. Iodine deficiency and thyroid disorders. Lancet Diabetes Endocrinol. 2015 Apr;3(4):286–95.

Bartalena L. Diagnosis and management of Graves disease: a global overview. Nat Rev Endocrinol. 2013 Dec;9(12):724–34.

Matthews DC, Syed AA. The role of TSH receptor antibodies in the management of Graves’ disease. Eur J Intern Med. 2011 Jun;22(3):213–6.

Tozzoli R, Bagnasco M, Giavarina D, Bizzaro N. TSH receptor autoantibody immunoassay in patients with Graves’ disease: improvement of diagnostic accuracy over different generations of methods. Systematic review and meta-analysis. Autoimmun Rev. 2012 Dec;12(2):107–13.

Bartalena L, Baldeschi L, Boboridis K, Eckstein A, Kahaly GJ, Marcocci C, et al. The 2016 European Thyroid Association/European Group on Graves’ Orbitopathy Guidelines for the Management of Graves’ Orbitopathy. Eur Thyroid J. 2016 Mar;5(1):9–26.

Maheshwari R, Weis E. Thyroid-associated orbitopathy. Indian J Ophthalmol. 2012 Apr;60(2):87–93.

Wang Y, Patel A, Douglas RS. Thyroid Eye Disease: How A Novel Therapy May Change The Treatment Paradigm. Ther Clin Risk Manag. 2019;15:1305–18.

Mourits MP, Koornneef L, Wiersinga WM, Prummel MF, Berghout A, van der Gaag R. Clinical criteria for the assessment of disease activity in Graves’ ophthalmopathy: a novel approach. Br J Ophthalmol. 1989 Aug;73(8):639–44.

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.

Pouso-Diz JM, Abalo-Lojo JM, Gonzalez F. Thyroid eye disease: current and potential medical management. Int Ophthalmol. 2020 Jan 9;

Campi I, Vannucchi G, Salvi M. THERAPY OF ENDOCRINE DISEASE: Endocrine dilemma: management of Graves’ orbitopathy. Eur J Endocrinol. 2016 Sep;175(3):R117-133.

Eckstein AK, Plicht M, Lax H, Neuhäuser M, Mann K, Lederbogen S, et al. Thyrotropin receptor autoantibodies are independent risk factors for Graves’ ophthalmopathy and help to predict severity and outcome of the disease. J Clin Endocrinol Metab. 2006 Sep;91(9):3464–70.

Gerding MN, van der Meer JW, Broenink M, Bakker O, Wiersinga WM, Prummel MF. Association of thyrotrophin receptor antibodies with the clinical features of Graves’ ophthalmopathy. Clin Endocrinol (Oxf). 2000 Mar;52(3):267–71.

Jarusaitiene D, Verkauskiene R, Jasinskas V, Jankauskiene J. Predictive Factors of Development of Graves’ Ophthalmopathy for Patients with Juvenile Graves’ Disease. Vol. 2016, International Journal of Endocrinology. Hindawi; 2016.

Savitri, Ardyarini D. Perbandingan Kadar Thyroid Stimulating Hormone Receptor Antibody (TRAb) Pasien Penyakit Graves’ dengan dan tanpa Oftalmopati. repository UNAIR. 2016.

Hussain YS, Hookham JC, Allahabadia A, Balasubramanian SP. Epidemiology, management, and outcomes of Graves' disease-real life data. Endocrine. 2017 Jun;56(3):568–78.

Jabbar A, Pingitore A, Pearce SHS, Zaman A, Iervasi G, Razvi S. Thyroid hormones and cardiovascular disease. Nat Rev Cardiol. 2017 Jan;14(1):39–55.

Szkudlarek AC, Aldenucci B, Miyagui NI, Silva IK, Moraes RN, Ramos HE, et al. Short-term thyroid hormone excess affects the heart but does not affect adrenal activity in rats. Arq Bras Cardiol. 2014 Mar;102(3):270–8.

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 Off J Am Thyroid Assoc. 2016 Oct;26(10):1343–421.

Wiersinga WM. Graves’ Disease: Can It Be Cured? Endocrinol Metab Seoul Korea. 2019 Mar;34(1):29–38.

Bahn RS. Graves’ ophthalmopathy. N Engl J Med. 2010 Feb 25;362(8):726–38.

Weetman AP. Graves’ disease. N Engl J Med. 2000 Oct 26;343(17):1236–48.

Lat AM, 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.

Gonçalves ACP, Gebrim EMMS, Monteiro MLR. Imaging studies for diagnosing Graves’ orbitopathy and dysthyroid optic neuropathy. Clin Sao Paulo Braz. 2012 Nov;67(11):1327–34.

Lytton SD, Schluter A, Banga PJ. Functional diagnostics for thyrotropin hormone receptor autoantibodies: bioassays prevail over binding assays. Front Biosci Landmark Ed. 2018 Jun 1;23:2028–43.

Tozzoli R, D’Aurizio F, Villalta D, Giovanella L. Evaluation of the first fully automated immunoassay method for the measurement of stimulating TSH receptor autoantibodies in Graves’ disease. Clin Chem Lab Med. 2017 Jan 1;55(1):58–64.

Nicolì F, Lanzolla G, Mantuano M, Ionni I, Mazzi B, Leo M, et al. Correlation between serum anti-TSH receptor autoantibodies (TRAbs) and the clinical feature of Graves’ orbitopathy. J Endocrinol Invest. 2021 Mar;44(3):581–5.

Bahn RS, Dutton CM, Natt N, Joba W, Spitzweg C, Heufelder AE. Thyrotropin receptor expression in Graves’ orbital adipose/connective tissues: potential autoantigen in Graves’ ophthalmopathy. J Clin Endocrinol Metab. 1998 Mar;83(3):998–1002.

Ludgate M, Crisp M, Lane C, Costagliola S, Vassart G, Weetman A, et al. The thyrotropin receptor in thyroid eye disease. Thyroid Off J Am Thyroid Assoc. 1998 May;8(5):411–3.

Bahn RS. Current Insights into the Pathogenesis of Graves’ Ophthalmopathy. Horm Metab Res Horm Stoffwechselforschung Horm Metab. 2015 Sep;47(10):773–8.

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 Mar;58(3):280–7.

Kumar S, Nadeem S, Stan MN, Coenen M, Bahn RS. A stimulatory TSH receptor antibody enhances adipogenesis via phosphoinositide 3-kinase activation in orbital preadipocytes from patients with Graves’ ophthalmopathy. J Mol Endocrinol. 2011 Jun;46(3):155–63.

Hai YP, Lee ACH, Frommer L, Diana T, Kahaly GJ. Immunohistochemical analysis of human orbital tissue in Graves’ orbitopathy. J Endocrinol Invest. 2020 Feb;43(2):123–37.

Lacka K, Manuszewska E, Korczowska I, Lacki JK. The effect of methylprednisolone pulse treatment on cytokine network in Graves ophthalmopathy. Curr Eye Res. 2007 Mar;32(3):291–7.

Menconi F, Profilo MA, Leo M, Sisti E, Altea MA, Rocchi R, et al. Spontaneous improvement of untreated mild Graves’ ophthalmopathy: Rundle’s curve revisited. Thyroid Off J Am Thyroid Assoc. 2014 Jan;24(1):60–6.

DOI: https://doi.org/10.22146/actainterna.98252