{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T12:21:34Z","timestamp":1782476494875,"version":"3.54.5"},"reference-count":23,"publisher":"Endocrinology Research Centre","issue":"2","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"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>Graves\u2019 orbitopathy (GO) is a progressive autoimmune disorder of visual organ, mostly associated with Graves\u2019 disease (GD). Although rituximab has been used as an off-label therapy for steroid-resistant GO, paradoxical immune reactivation has also been reported. We present a rare case of GO that developed after bendamustine-rituximab (BR) therapy for chronic lymphocytic leukemia (CLL). A 73-year-old male with a 3-year history of GD, presented with new onset of bilateral proptosis, diplopia, and decreased visual acuity, that happened two weeks after his second BR cycle for CLL. The anamnesis was negative for both smoking, and radioiodine therapy. Laboratory studies showed persistently elevated thyrotropin receptor antibodies levels in plasma, and extraocular muscle enlargement on orbital MRI. The active phase (CAS 6\/6) of moderate-to-severe (EUGOGO) GO was diagnosed. Despite two courses of intravenous methylprednisolone (cumulative dose \u2014 12.2 g) and 10\u00a0retrobulbar dexamethasone injections, the patient progressed to dysthyroid optic neuropathy. Although the patient had a predisposing autoimmune background, the close temporal association with BR therapy, progressive disease course, and glucocorticoid resistance suggest that chemotherapy-induced immune dysregulation played a critical role in triggering GO. Rituximab-related B-cell depletion and cytokine release syndrome may have facilitated T-cell\u2013mediated orbital inflammation, while bendamustine-induced lymphopenia further disrupted immune tolerance. This case illustrates the potential for paradoxical autoimmune activation following BR therapy in a predisposed patient. Clinicians should monitor for GO signs, and symptoms before, during, and after BR therapy in patients with underlying thyroid autoimmunity. Further clinical trials are needed to verify this phenomenon.<\/jats:p>","DOI":"10.14341\/probl13616","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T19:22:08Z","timestamp":1779304928000},"page":"13-22","update-policy":"https:\/\/doi.org\/10.14341\/crossmarkpolicy2018","source":"Crossref","is-referenced-by-count":1,"title":["New Onset of Graves\u2019 Orbitopathy Following Bendamustine-Rituximab (BR) therapy in a Patient with Chronic Lymphocytic Leukemia: A Case Report and Literature Review"],"prefix":"10.14341","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8373-6109","authenticated-orcid":true,"given":"E. D.","family":"Kozlov","sequence":"first","affiliation":[{"name":"Ogarev Mordovia State University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5910-6502","authenticated-orcid":true,"given":"E. G.","family":"Bessmertnaya","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2883-9966","authenticated-orcid":true,"given":"S. Sh.","family":"Chandola","sequence":"additional","affiliation":[{"name":"Ogarev Mordovia State University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5092-7872","authenticated-orcid":true,"given":"E. I.","family":"Yamashkina","sequence":"additional","affiliation":[{"name":"Ogarev Mordovia State University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"5458","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Gazdanova AA, Knyazeva SA, Marakhovskaya AA, et al. Ophthalmic manifestations of endocrine diseases. Russian Medical Inquiry. 2023;7(9):586-591. (in Russ). doi: https:\/\/doi.org\/10.32364\/2587-6821-2023-7-9-4","DOI":"10.32364\/2587-6821-2023-7-9-4"},{"key":"ref2","unstructured":"Brovkina AF. Endocrine ophthalmopathy. \u2013 Moscow: GEOTAR-MEDIA; 2008. (in Russ.)"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Hiromatsu Y, Eguchi H, Tani J, Kasaoka M, Teshima Y. Graves\u2019 ophthalmopathy: epidemiology and natural history. Intern Med. 2014;53(5):353-360. doi: https:\/\/doi.org\/10.2169\/internalmedicine.53.1518","DOI":"10.2169\/internalmedicine.53.1518"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Bartalena L, Piantanida E, Gallo D, Lai A, Tanda ML. Epidemiology, Natural History, Risk Factors, and Prevention of Graves\u2019 Orbitopathy. Front Endocrinol (Lausanne). 2020;11:615993. doi: https:\/\/doi.org\/10.3389\/fendo.2020.615993","DOI":"10.3389\/fendo.2020.615993"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Hu Y, Chen J, Lin K, Yu X. 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