{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T21:31:39Z","timestamp":1740173499657,"version":"3.37.3"},"reference-count":25,"publisher":"Endocrinology Research Centre","issue":"5","license":[{"start":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T00:00:00Z","timestamp":1699574400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.probl-endojournals.ru\/jour\/about\/editorialPolicies#openAccessPolicy"}],"content-domain":{"domain":["www.probl-endojournals.ru"],"crossmark-restriction":true},"short-container-title":["Probl Endokrinol (Mosk)"],"abstract":"<jats:p><jats:bold>BACKGROUND:<\/jats:bold> Data on the effect of <jats:sup>131<\/jats:sup>I on the course of Graves\u2019 orbitopathy (GO) are contradictory. A number of studies indicate a deterioration in the course of GO against the background of RAIT, in other studies such a connection has not been established. Cytokines that regulate inflammation could potentially be biomarkers for assessing GO activity and predicting the course of GO after RAIT.<\/jats:p><jats:p><jats:bold>AIM:<\/jats:bold> The purpose of this study was to evaluate the dynamics of eye symptoms and analyze immunological parameters: cytokine TGF-\u03b21 and cytokine receptors: sTNF\u03b1-R1, sTNF\u03b1-R2, sIL-2R, sIL-6R over time after RAIT, as possible predictors of GO activation.<\/jats:p><jats:p><jats:bold>MATERIALS AND METHODS<\/jats:bold>: The study included 59 patients (118 orbits) with GD in the state of euthyroidism and subclinical hyperthyroidism and low active and inactive GO, aimed at conducting RAIT. Concentrations of cytokine TGF-\u03b21, sTNF\u03b1-RI and sTNF\u03b1-R2, sIL-2R, sIL-6R, TSH receptor antibodies (rTSH-Ab), free thyroxine (FT4) and free triiodothyronine (FT3), \u00adthyroid-stimulating hormone (TSH) in the blood serum were determined. Ultrasound examination of the thyroid gland, multispiral computed tomography (MSCT)\/magnetic resonance imaging (MRI) of the orbits was performed. The examination was carried out 3, 6, 12 months after the RAIT.<\/jats:p><jats:p><jats:bold>RESULTS<\/jats:bold>: The deterioration of the course of the GO (1\u20132 points according to CAS) was noted after 3 months. (32.5%) and to a lesser degree after 6 and 12 months (13.2% and 8.45%, respectively). Dynamics were not noted, approximately, in the same number of patients (40.5%, 41.5%, 45.8%, respectively). An improvement in the course of the GO was noted after 6 and 12 months (45.3, 45.8, respectively). After 3 and 6 months, the achievement of hypothyroidism and a significant increase in the level of rTSH-Ab were noted. In the analysis of cytokines and their receptors a significant decrease in the level of TGF-\u03b21 was noted after 3, 6 and 12 months. There was also a significant decrease in sTNF-R1 and sIL-2R at 3 and 6 months. The level of sTNF\u03b1-R2 significantly decreased 3 months after RAIT. The level of sIL-6R has not changed significantly. After 3 months in patients with positive dynamics of image intensification, the level of TGF-\u03b21 did not significantly change compared with the level before RAIT, in patients with worsening of the course of GO or without dynamics, the level of TGF-\u03b21 significantly decreased. After 6 months, there was the same trend, not reaching statistical significance. The IgG4 level and the IgG4\/IgG ratio increased to 6 and 12 months, which corresponded to an increase in diplopia index.<\/jats:p><jats:p><jats:bold>CONCLUSION<\/jats:bold>: The main limiting factor in the conduct of RAIT is the activity of the autoimmune process in the orbits. Since patients with inactive (CAS 0\u20132) or low activity (CAS 3\u20134) GO were referred for RAIT, there was no pronounced activation of GO after RAIT. There was a slight deterioration in the course of GO by only 1\u20132 points according to CAS after 3 months. (32.5%) and to a lesser degree after 6 months (13.2%). In the study, it was found that the main predictors of the deterioration of the course of GO after RAIT are uncompensated hypothyroidism, a high level of rTSH-Ab and a decrease in the level of cytokine TGF-\u03b21.<\/jats:p>","DOI":"10.14341\/probl13293","type":"journal-article","created":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T09:56:36Z","timestamp":1699955796000},"page":"16-24","update-policy":"https:\/\/doi.org\/10.14341\/crossmarkpolicy2018","source":"Crossref","is-referenced-by-count":0,"title":["Clinical and immunological predictors of Graves\u2019 orbitopathy after radioiodine therapy of Graves\u2019 disease"],"prefix":"10.14341","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3785-0335","authenticated-orcid":true,"given":"M. S.","family":"Sheremeta","sequence":"first","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5910-6502","authenticated-orcid":true,"given":"E. G.","family":"Bessmertnaya","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6935-3187","authenticated-orcid":true,"given":"A. R.","family":"Elfimova","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2812-7017","authenticated-orcid":true,"given":"D. M.","family":"Babaeva","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9954-7641","authenticated-orcid":true,"given":"I. M.","family":"Belovalova","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8538-5354","authenticated-orcid":true,"given":"N. Yu.","family":"Sviridenko","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"5458","published-online":{"date-parts":[[2023,11,10]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Ross DS. Radioiodine treatment in patients with Graves\u2019 disease. In: Bahn R. editor. Graves\u2019 Disease. New York: Springer NY; 2015. doi: https:\/\/doi.org\/10.1007\/978-1-4939-2534-6_7","DOI":"10.1007\/978-1-4939-2534-6_7"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Stan MN, Durski JM, Brito JP, et al. Cohort study on radioactive iodine-induced hypothyroidism: implications for Graves\u2019 ophthalmopathy and optimal timing for thyroid hormone assessment. Thyroid. 2013; 23(5):620-625. doi: https:\/\/doi.org\/10.1089\/thy.2012.0258","DOI":"10.1089\/thy.2012.0258"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Tra\u0308isk F, Tallstedt L, Abraham-Nordling M, et al. Thyroid-Associated Ophthalmopathy after Treatment for Graves\u2019 Hyperthyroidism with Antithyroid Drugs or Iodine-131. J Clin Endocrinol Metab. 2009; 94(10):3700-3707. doi: https:\/\/doi.org\/10.1210\/jc.2009-0747","DOI":"10.1210\/jc.2009-0747"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Watanabe N, Noh JY, Kozaki A, et al. Radioiodine-associated exacerbation of Graves\u2019 orbitopathy in the Japanese population: Randomized prospective study. J Clin Endocrinol Metab. 2015; 100(7):2700-2708. doi: https:\/\/doi.org\/10.1210\/jc.2014-4542","DOI":"10.1210\/jc.2014-4542"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Tallstedt L, Lundell G, T\u00f8rring O, et al. Occurrence of ophthalmopathy after treatment for Graves\u2019 hyperthyroidism. N Engl J Med. 1992; 326(26):1733-1738. doi: https:\/\/doi.org\/10.1056\/NEJM199206253262603","DOI":"10.1056\/NEJM199206253262603"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Khong JJ, Finch S, De Silva C, et al. Risk factors for Graves\u2019 orbitopathy; the Australian Thyroid-Associated Orbitopathy Research (ATOR) study. J Clin Endocrinol Metab. 2016; 101(7):2711-2720. doi: https:\/\/doi.org\/10.1210\/jc.2015-4294","DOI":"10.1210\/jc.2015-4294"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Stan MN, Bahn RS. Risk factors for development or deterioration of Graves\u2019 ophthalmopathy. Thyroid. 2010; 20(7):777-783. doi: https:\/\/doi.org\/10.1089\/thy.2010.1634","DOI":"10.1089\/thy.2010.1634"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Dreval AV, Tsyb AF, Nechaeva OA, Effects of radioiodine therapy on the natural history of Graves\u2019 ophtalmopathy. Clinical and experimental thyroidology. 2007; 3(3):33-40. (In Russ.) doi: https:\/\/doi.org\/10.14341\/ket20073333-40","DOI":"10.14341\/ket20073333-40"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Acharya SH, Avenell A, Philip S, et al. Radioiodine therapy (RAI) for Graves\u2019 disease (GD) and the effect on ophthalmopathy: a systematic review*. Clin Endocrinol (Oxf). 2008; 69(6):943-950. doi: https:\/\/doi.org\/10.1111\/j.1365-2265.2008.03279.x","DOI":"10.1111\/j.1365-2265.2008.03279.x"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Perros P, Kendall-Taylor P, Neoh C, et al. A prospective study of the effects of radioiodine therapy for hyperthyroidism in patients with minimally active Graves\u2019 ophthalmopathy. J Clin Endocrinol Metab. 2005; 90(9):5321-5323. doi: https:\/\/doi.org\/10.1210\/jc.2005-0507","DOI":"10.1210\/jc.2005-0507"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Ponto KA, Zang S, Kahaly GJ. The tale of radioiodine and Graves\u2019 orbitopathy. Thyroid. 2010; 20(7):785-793. doi: https:\/\/doi.org\/10.1089\/thy.2010.1640","DOI":"10.1089\/thy.2010.1640"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Plazinska MT, Sawicka-Gutaj N, Czarnywojtek A, et al. Radioiodine therapy and Graves\u2019 disease \u2013 Myths and reality. PLoS One. 2020; 15(1):e0226495. doi: https:\/\/doi.org\/10.1371\/journal.pone.0226495","DOI":"10.1371\/journal.pone.0226495"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Lantz M, Planck T, \u00c5sman P, Hallengren B. Increased TRAb and\/or low Anti-TPO titers at diagnosis of Graves\u2019 disease are associated with an increased risk of developing ophthalmopathy after onset. Exp Clin Endocrinol Diabetes. 2014; 122(02):113-117. doi: https:\/\/doi.org\/10.1055\/s-0033-1363193","DOI":"10.1055\/s-0033-1363193"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"Eckstein AK, Plicht M, Lax H, et al. Clinical results of anti-inflammatory therapy in Graves\u2019 ophthalmopathy and association with thyroidal autoantibodies*. Clin Endocrinol (Oxf). 2004; 61(5):612-618. doi: https:\/\/doi.org\/10.1111\/j.1365-2265.2004.02143.x","DOI":"10.1111\/j.1365-2265.2004.02143.x"},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"Eckstein AK, Plicht M, Lax H, et al. Thyrotropin receptor autoantibodies are independent risk factors for Graves\u2019 ophthalmopathy and help to predict severity and outcome of the disease. J Clin Endocrinol Metab. 2006; 91(9):3464-3470. doi: https:\/\/doi.org\/10.1210\/jc.2005-2813","DOI":"10.1210\/jc.2005-2813"},{"key":"ref16","unstructured":"Sviridenko NIu, Belovalova IM, Sheremeta MS, et al. Bolezn\u2019 Greivsa i endokrinnaia oftal\u2019mopatiia. Ed. by Dedov II, Mel\u2019nichenko GA. Moscow: MAI-Print; 2012. (In Russ.)."},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"Sviridenko NY, Bessmertnaya EG, Belovalova IM, et al. Autoantibodies, immunoglobulins and cytokine profile in patients with graves\u2019 disease and graves\u2019 orbitopathy. Problems of Endocrinology. 2020; 66(5):15-23. (In Russ.). doi: https:\/\/doi.org\/10.14341\/probl12544","DOI":"10.14341\/probl12544"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Sviridenko NY, Bessmertnaya EG, Belovalova IM, et al. Transforming growth factor \u03b21 (TGF-\u03b21) in patients with endocrine ophthalmopathy and Graves\u2019 disease: A predictor of treatment efficiency. Med Immunol. 2022; 24(5):993-1006. (In Russ.). doi: https:\/\/doi.org\/10.15789\/1563-0625-TGF-2514","DOI":"10.15789\/1563-0625-TGF-2514"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Kahaly GJ, Bartalena L, Heged\u00fcs L, et al. 2018 European Thyroid Association Guideline for the Management of Graves\u2019 Hyperthyroidism. Eur Thyroid J. 2018; 7(4):167-186. doi: https:\/\/doi.org\/10.1159\/000490384","DOI":"10.1159\/000490384"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Bartalena L, Kahaly GJ, Baldeschi L, et al. The 2021 European Group on Graves\u2019 orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves\u2019 orbitopathy. Eur J Endocrinol. 2021; 185(4):G43-G67. doi: https:\/\/doi.org\/10.1530\/EJE-21-0479","DOI":"10.1530\/EJE-21-0479"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Dedov II, Melnichenko GA, Sviridenko NY, et al. Federal clinical recommendations on diagnostics and treatment of endocrine ophthalmopathy associated with autoimmune thyroid pathology. Problems of Endocrinology. 2015; 61(1):61-74. (In Russ.). doi: https:\/\/doi.org\/10.14341\/probl201561161-74","DOI":"10.14341\/probl201561161-74"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"Yang DD, Gonzalez MO, Durairaj VD. Medical management of thyroid eye disease. Saudi J Ophthalmol. 2011; 25(1):3-13. doi: https:\/\/doi.org\/10.1016\/j.sjopt.2010.10.001","DOI":"10.1016\/j.sjopt.2010.10.001"},{"key":"ref23","unstructured":"Simbirtsev AS. Cytokines in the pathogenesis and treatment of human diseases. Saint Petersburg: Foliant; 2018: P. 10-55 (In Russ.)."},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"Taskina ES, Kharintseva SV. Morphofunctional characteristics and immunological regulation of the orbital fibroblasts function in endocrine ophthalmopathy. Clinical and experimental thyroidology. 2018; 14(4):183-191(In Russ.). doi: https:\/\/doi.org\/10.14341\/ket10147","DOI":"10.14341\/ket10147"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"Kajdaniuk D, Marek B, Niedzio\u0142ka-Zielonka D, et al. Transformuj\u0105cy czynnik wzrostu \u03b21 (TGF\u03b21) i naczyniowo-\u015br\u00f3db\u0142onkowy czynnik wzrostu (VEGF) we krwi ludzi zdrowych i chorych z orbitopati\u0105 Gravesa \u2014 nowy mechanizm dzia\u0142ania glikokortykosteroid\u00f3w? Endokrynol Pol. 2014; 65(5):348-356. doi: https:\/\/doi.org\/10.5603\/EP.2014.0048","DOI":"10.5603\/EP.2014.0048"}],"container-title":["Problems of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.probl-endojournals.ru\/jour\/article\/viewFile\/13293\/10532","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T09:57:29Z","timestamp":1699955849000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.probl-endojournals.ru\/jour\/article\/view\/13293"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,10]]},"references-count":25,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,11,12]]}},"URL":"https:\/\/doi.org\/10.14341\/probl13293","relation":{},"ISSN":["2308-1430","0375-9660"],"issn-type":[{"type":"electronic","value":"2308-1430"},{"type":"print","value":"0375-9660"}],"subject":[],"published":{"date-parts":[[2023,11,10]]}}}