Received: 04 October 2021; Published on-line: 15 March 2022
Assessing the efficacy of various treatment regimens for patients with endocrine ophthalmopathy associated with Graves’ disease
Yu. V. Buldygina 1, G. M. Terekhova 1, L. S. Strafun1, I. I. Savosko 1, Z. G. Lysova 1, S. L. Shlyakhtych 2
1 SI "V.P. Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine"; Kyiv (Ukraine)
2 Kyiv City Center of Endocrinology, Clinical Hospital No.3 of the City of Kyiv; Kyiv, (Ukraine)
TO CITE THIS ARTICLE: Buldygina Yu. V., Terekhova G. M., Strafun L. S., Savosko I. I., Lysova Z. G., Shlyakhtych S. L. Assessing the efficacy of various treatment regimens for patients with endocrine ophthalmopathy associated with Graves’ disease. J.ophthalmol.(Ukraine).2022;1:51-7. http://doi.org/10.31288/oftalmolzh202215157
Purpose: To assess the efficacy of various treatment regimens for patients with EO associated with Graves’ disease based on the retrospective analysis of clinical data, thyroid-stimulating hormone (TSH) receptor autoantibodies (TSHR-Ab) titers and orbital ultrasound imaging findings.
Material and Methods: We retrospectively reviewed the medical records (including clinical and laboratory data and findings of ultrasound imaging of retrobulbar adipose tissue) of 155 patients with EO associated with Graves’ disease and either euthyroidism (in the presence of antithyroid therapy) or postoperative compensated hypothyroidism that underwent treatment at Komisarenko Institute for Endocrinology and Metabolism between 2009 and 2019. The duration of EO ranged from 8 months to 36 months. Patients with EO associated with Graves’ disease were medically treated in the presence of stable euthyroidism. Patients were divided into 4 groups based on the glucocorticoid treatment scheme. Group 1 of 15 patients received prednisolone tablets per os; group 2 of 68 patients, intravenous methylprednisolone (MP) pulse therapy only; group 3 of 32 patients, intravenous MP pulse therapy plus vitamin D3; and group 4 of 40 patients, intravenous MP pulse therapy 8 to 12 months after thyroidectomy.
Results: As soon as 3 months after treatment initiation, there was an improvement in condition of patients in all groups as assessed by clinical examination, followed by further improvement by 6 months and 12 months. The best results were obtained in patients of group 4, with a statistically significant improvement in clinical condition (p < 0.05). Retrobulbar adipose tissue thickness as assessed by orbital ultrasound at baseline and at 6 months and 12 months was statistically significantly greater in patients of all the four groups than controls (p < 0.05). At 6 months, serum TSHR-Ab levels in groups 1, 2 and 3 significantly decreased compared to baseline, with no significant difference between these groups, whereas serum TSHR-Ab level in group 4 was significantly higher than in other groups both at baseline and at 6 months. At 12 months, serum TSHR-Ab level in group 4 was significantly lower (р < 0.05) than in other groups (2.41 ± 0.81 mU/L versus 5.97 ± 1.71 mU/L for group 1, 5.49 ± 1.27 mU/L for group 2, and 6.17 ± 1.18 mU/L for group 3).
Conclusion: Patients with EO associated with Graves’ disease in group 4 (intravenous MP pulse therapy after thyroidectomy) showed a significantly better (р < 0.05) treatment outcome than patients in other groups. Ultrasound imaging of retrobulbar adipose tissue thickness is inadequately informative for assessing treatment efficacy.
Keywords: Graves’ disease, endocrine ophthalmopathy, TSHR-Ab, glucocorticoid pulse therapy, thyroidectomy, ultrasound imaging
1.Taskina ES, Charinzeva SV, Charinzev VV, Serkin DM. [New opportunities in endocrine ophthalmopathy diagnostics (review)]. Klinicheskaya i eksperimental'naya tireoidologiya. 2017;13(3):20-28. Russian.
2.Taylor PN, Zhang L, Lee RWJ, Muller I, Ezra DG, Dayan CM, et al. New insights into the pathogenesis and nonsurgical management of Graves’ orbitopathy. Nat Rev Endocrinol. 2020 Feb;16(2):104-16.
3.Weiler DL. Thyroid eye disease: a review. Clin Exp Optom. 2017 Jan;100(1):20-25.
4.Khong JJ, McNab AA, Ebeling PR, Craig JE, Selva D. Pathogenesis of thyroid eye disease: review and update on molecular mechanisms. Br J Ophthalmol. 2016 Jan;100(1):142-50.
5.Dedov II, Melnichenko GA, Sviridenko NYu, Troshina EA, Fadeev VV, Belovalova IM, et al. [Federal clinical recommendations on diagnostics and treatment of endocrine ophthalmopathy associated with autoimmune thyroid pathology]. Problemy Endokrinologii. 2015;61(1):61-74. Russian. Crossref
6.Bartalena L, Piantanida E, Gallo D, Lai A, Tanda ML. Epidemiology, natural history, risk factors, and prevention of Graves' orbitopathy. Front Endocrinol (Lausanne). 2020 Nov 30;11:615993.
7.Kahaly GJ. Immunotherapies for thyroid eye disease. Curr Opin Endocrinol Diabetes Obes. 2019 Oct;26(5):250-5.
8.Olyinyk VA, Terekhovа GM, Buldygina YuV, Fed’ko TV, Klochkova VM, Rakov OV, Lysova ZG. Treatment of autoimmune ophthalmopathy in patients with diffuse toxic goiter by glucocorticoids. Endokrynolohiya. 2017; 22(2):108–14.
9.Novaes P, Diniz Grisolia AB, Smith TJ. Update on thyroid-associated Ophthalmopathy with a special emphasis on the ocular surface. Clin Diabetes Endocrinol. 2016 Nov 16;2:19.
10.Edmunds MR, Boelaert K. Knowledge of thyroid eye disease in Graves' disease patients with and without orbitopathy. Thyroid. 2019 Apr;29(4):557-62.
11.Perros P, Hegedüs L, Bartalena L, Marcocci C, Kahaly GJ, Baldeschi L, et al. Graves' orbitopathy as a rare disease in Europe: a European Group on Graves' Orbitopathy (EUGOGO) position statement. Orphanet J Rare Dis. 2017 Apr 20;12(1):72.
12.Bartalena L, Baldeschi L, Boboridis K, Eckstein A, Kahaly GJ, Marcocci C, et al; European Groupon Graves' Orbitopathy (EUGOGO). 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. Crossref PubMed
13.Pashkovska NV. [Endocrine ophthalmopathy in autoimmune diseases of the thyroid gland]. Mizhnarodnyi endokrynolohichnyi zhurnal. 2014;6 (62): 169–73.
14.Lanzolla G, Vannucchi G, Ionni I, Campi I, Sileo F, Lazzaroni E, Marinò M. Cholesterol serum levels and use of statins in Graves' orbitopathy: a new starting point for the therapy. Front Endocrinol (Lausanne). 2020 Jan 22;10:933.
15.Perros P, Dayan CM, Dickinson AJ, Ezra D, Estcourt S, Foley P, et al. Management of patients with Graves' orbitopathy: initial assessment, management outside specialised centers and referral pathways. Clin Med (Lond). 2015 Apr;15(2):173-8.
16.Strianese D. Efficacy and safety of immunosuppressive agents for thyroid eye disease. Ophthalmic Plast Reconstr Surg. 2018 Jul/Aug;34(4S Suppl 1):S56-S59.
17.Hales IB, Thoma ID. Treatment of thyroid ophthalmopathy with corticoid analogues. Australas Ann Med. 1962 May;11:113-7.
18.Hodgson NM, Rajaii F. Current understanding of the progression and management of thyroid associated orbitopathy: a systematic review. Ophthalmol Ther. 2020 Mar;9(1):21-33.
19.Stan MN, Salvi M. Management of endocrine disease: Rituximab therapy for Graves' orbitopathy–lessons from randomized control trials. Eur J Endocrinol. 2017 Feb;176(2):R101-R109.
20.Salvi M, Vannucchi G, Currò N, Campi I, Covelli D, Dazzi D, et al. Efficacy of B-cell targeted therapy with rituximab in patients with active moderate to severe Graves' orbitopathy: a randomized controlled study. J Clin Endocrinol Metab. 2015 Feb;100(2):422-31.
21.Moleti M, Giuffrida G, Sturniolo G, Squadrito G, Campennì A, Morelli S, et al. Acute liver damage following intravenous glucocorticoid treatment for Graves' ophthalmopathy. Endocrine. 2016 Oct;54(1):259-68.
22.Nikonova LV, Tishkovskiy SV, Hadomskaya VI, Davydchyk EV, Doroshkevich IP. [Modern approaches to the therapy of endocrine ophthalmopathy]. Zhurnal Grodnenskogo meditsinskogo universiteta. 17(1):83-1. Russian. http://journal-grsmu.by/index.php/ojs/article/view/2371.
23.Riedl M, Kolbe E, Kampmann E, Krämer I, Kahaly GJ. Prospectively recorded and MedDRA-coded safety data of intravenous methylprednisolone therapy in Graves' orbitopathy. J Endocrinol Invest. 2015 Feb;38(2):177-82.
24.Covelli D, Vannucchi G, Campi I, Currò N, D'Ambrosio R, Maggioni M, Gianelli U, Beck-Peccoz P, Salvi M. Statins may increase the risk of liver dysfunction in patients treated with steroids for active graves' orbitopathy. J Clin Endocrinol Metab. 2015 May;100(5):1731-7.
25.Zoubek ME, Pinazo-Bandera J, Ortega-Alonso A, Hernández N, Crespo J, Contreras F, et al. Liver injury after methylprednisolone pulses: A disputable cause of hepatotoxicity. A case series and literature review. United European Gastroenterol J. 2019 Jul;7(6):825-837.
26.Kahaly GJ. Imaging in thyroid-associated orbitopathy. Eur J Endocrinol. 2001 Aug;145(2):107-18.
27.Yanik B, Conkbayir I, Acaroglu G, Hekimoglu B. Graves' ophthalmopathy: comparison of the Doppler sonography parameters with the clinical activity score. J Clin Ultrasound. 2005 Oct;33(8):375-80.
28.Nagy EV, Toth J, Kaldi I, Damjanovich J, Mezosi E, Lenkey A, et al. Graves' ophthalmopathy: eye muscle involvement in patients with diplopia. Eur J Endocrinol. 2000 Jun;142(6):591-7.
29.Marcocci C, Bartalena L, Tanda ML, Manetti L, Dell'Unto E, Rocchi R, et al. Comparison of the effectiveness and tolerability of intravenous or oral glucocorticoids associated with orbital radiotherapy in the management of severe Graves' ophthalmopathy: results of a prospective, single-blind, randomized study. J Clin Endocrinol Metab. 2001 Aug;86(8):3562-7.
30.Buldygina YuV, Terekhova GM, Shlachtych SL, Fed’koTV, Klochkova VM, Strafun OS. [The results of surgical treatment of patients with diffuse toxic goiter and autoimmune ophthalmopathy]. Endokrynolohiya. 25(1): 5-10. Ukrainian.
Conflict of Interest Statement: The author states that there is no conflict of interest that could affect her opinion on the subject or materials of this manuscript.
Sources of Support: none.