Clinical Results of Combined Systemic Steroid and Retroorbital Radiotherapy Treatment in Active Thyroid Associated Ophthalmopathy

Öz

Objective: The aim of this study is to evaluate the efficacy of a different steroid dosage protocol which consists of intravenous pulse methylprednisolone combined with retroorbital radiotherapy in the treatment of active thyroid associated ophthalmopathy. Methods: The medical records of 29 patients who were treated with a standard protocol and who were followed-up for at least 6 months were retrospectively analyzed. The treatment protocol consisted of intravenous pulse methylprednisolone 1gram/day for 3 consecutive days, followed by retroorbital radiotherapy. Oral prednisolone which was tapered over a 3-month course was given as a maintenance dose. Results: 58 eyes of 29 patients were included in the study. Twelve patients were female (41%) and 17 were male (59%) with a mean age of 47.7 ± 12.6 years. The clinical activity score was 4.8 ± 1.3 and 2.8 ± 1.2, before and after treatment, respectively (P <0.05). 14 eyes (31%) had an improvement in best corrected visual acuity. In 28 eyes with had proptosis, proptosis regressed after treatment. Among 21 patients with diplopia, 13 (61%) patients reported an improvement in diplopia after treatment (P <0.05). None of our patients had any adverse event due to systemic steroid and retroorbital radiotherapy. Conclusions: Pulse intravenously applied methylprednisolone for 3 days as 1 gram/day, combined with retroorbital radiotherapy proved to be effective in control of moderate to severe and active thyroid associated ophthalmopathy. In the 6-month follow-up significant decrease in clinical activity score and improvement in diplopia was observed in addition to improvement in best corrected visual acuity.

Anahtar Kelimeler

• Orbital radiotherapy
• Thyroid ophthalmopathy
• Graves’ disease

Kaynakça

1. 1.Ginsberg J. Diagnosis and management of Graves'disease. CMAJ. 2003 Mar 4;168(5):575-85.
2. 2.Bahn RS. Graves' ophthalmopathy. N Engl J Med.2010 Feb 25;362(8):726-38. doi: 10.1056/NEJMra0905750.
3. 3.Bartalena L, Tanda ML, Bogazzi F, et al. An update onthe pharmacological management of hyperthyroidismdue to Graves' disease. Expert Opin Pharmacother.2005 Jun;6(6):851-61. doi:10.1517/14656566.6.6.851.
4. 4.Marcocci C, Bartalena L, Bogazzi F, Panicucci M,Pinchera A. Studies on the occurrence ofophthalmopathy in Graves' disease. Acta Endocrinol(Copenh). 1989 Apr;120(4):473-8. doi:10.1530/acta.0.1200473.
5. 5.Bartalena L, Pinchera A, Marcocci C. Management ofGraves' ophthalmopathy: reality and perspectives.Endocr Rev. 2000 Apr;21(2):168-99. doi:10.1210/edrv.21.2.0393.
6. 6.Gunji K, Kubota S, Stolarski C, et al. A 63 kDa skeletalmuscle protein associated with eye muscleinflammation in Graves' disease is identified as thecalcium binding protein calsequestrin. Autoimmunity.1999;29(1):1-9. doi: 10.3109/08916939908995967.
7. 7.Wall JR, Lahooti H. Pathogenesis of thyroid eyedisease - does autoimmunity against the TSH receptorexplain all cases? Endokrynol Pol. 2011;62 Suppl 1:1-7.
8. 8.Douglas RS, Gianoukakis AG, Kamat S, Smith TJ.Aberrant expression of the insulin-like growth factor-1 receptor by T cells from patients with Graves' disease may carry functional consequences for diseasepathogenesis. J Immunol. 2007 Mar 1;178(5):3281-7.doi: 10.4049/jimmunol.178.5.3281.

9. 9.Sorisky A, Pardasani D, Gagnon A, Smith TJ. Evidence of adipocyte differentiation in human orbitalfibroblasts in primary culture. J Clin Endocrinol Metab.1996 Sep;81(9):3428-31. doi:10.1210/jcem.81.9.8784110.
10. 10.Bahn RS. Clinical review 157: Pathophysiology ofGraves' ophthalmopathy: the cycle of disease. J ClinEndocrinol Metab. 2003 May;88(5):1939-46. doi:10.1210/jc.2002-030010.
11. 11.Bartalena L, Marcocci C, Manetti L, et al. Orbitalradiotherapy for Graves' ophthalmopathy. Thyroid.1998 May;8(5):439-41. doi: 10.1089/thy.1998.8.439
12. 12.Wang Y, Zhou H, Fan X. The effect of orbitalradiation therapy on thyroid-associated orbitopathycomplicated with dysthyroid optic neuropathy. FrontMed. 2017 Sep;11(3):359-364. doi: 10.1007/s11684-017-0528-5.
13. 13.Gillis CC, Chang EH, Al-Kharazi K, Pickles T.Secondary malignancy following radiotherapy forthyroid eye disease. Rep Pract Oncol Radiother. 2016May-Jun;21(3):156-61. doi: 10.1016/j.rpor.2016.01.001.;
14. 14.Haenssle HA, Richter A, Buhl T, et al. Pigmentedbasal cell carcinomas 15 years after orbital radiationtherapy for Graves ophthalmopathy. Arch Dermatol.2011 Apr;147(4):511-2. doi: 10.1001/archdermatol.2011.74.
15. 15. Kinyoun JL, Kalina RE, Brower SA, Mills RP, Johnson RH. Radiation retinopathy after orbital irradiation forGraves' ophthalmopathy. Arch Ophthalmol. 1984Oct;102(10):1473-6. doi: 10.1001/archopht.1984.01040031193016.
16. 16.Bartalena L, Kahaly GJ, Baldeschi L, et al. EUGOGO†. The 2021 European Group on Graves' orbitopathy(EUGOGO) clinical practice guidelines for the medicalmanagement of Graves' orbitopathy. Eur J Endocrinol.2021 Aug 27;185(4):G43-G67. doi: 10.1530/EJE-21-0479.
17. 17.Kahaly GJ. Management of Graves Thyroidal andExtrathyroidal Disease: An Update. J Clin EndocrinolMetab. 2020 Dec 1;105(12):3704–20. doi:10.1210/clinem/dgaa646.
18. 18.Schovanek J, Cibickova L, Karhanova M, et al.Retrospectıve analysis of patients wıth Gravesorbitopathy treated by pulses of methylprednisolone,with a focus on adverse events. Endocr Pract. 2018Jul;24(7):652-657. doi: 10.4158/EP-2018-0047.
19. 19.Sobel RK, Aakalu VK, Vagefi MR, et al. OrbitalRadiation for Thyroid Eye Disease: A Report by theAmerican Academy of Ophthalmology. Ophthalmology. 2022 Apr;129(4):450-455. doi: 10.1016/j.ophtha.2021.10.025. Epub 2021 Dec 9.
20. 20.Oeverhaus M, Witteler T, Lax H, et al. CombinationTherapy of Intravenous Steroids and OrbitalIrradiation is More Effective Than IntravenousSteroids Alone in Patients with Graves' Orbitopathy.Horm Metab Res. 2017 Oct;49(10):739-747. doi:10.1055/s-0043-116945. Epub 2017 Sep 18.
21. 21.Kim JW, Han SH, Son BJ, et al. Efficacy of combinedorbital radiation and systemic steroids in themanagement of Graves' orbitopathy. Graefes Arch ClinExp Ophthalmol. 2016 May;254(5):991-8. doi:10.1007/s00417-016-3280-7. Epub 2016 Feb 15.
22. 22.Mourits MP, Prummel MF, Wiersinga WM,Koornneef L. Clinical activity score as a guide in themanagement of patients with Graves' ophthalmopathy. Clin Endocrinol (Oxf). 1997 Jul;47(1):9-14. doi:10.1046/j.1365-2265.1997.2331047.x
23. 23.Ng CM, Yuen HK, Choi KL, et al. Combined orbitalirradiation and systemic steroids compared withsystemic steroids alone in the management ofmoderate-to-severe Graves' ophthalmopathy: apreliminary study. Hong Kong Med J. 2005Oct;11(5):322-30.
24. 24.Limone PP, Bianco L, Mellano M, et al. Isconcomitant treatment with steroids and radiotherapy more favorable than sequential treatment inmoderate-to-severe graves orbitopathy? Radiol Med.2021 Feb;126(2):334-342. doi: 10.1007/s11547-020-01244-5
25. 25.Sisti E, Menconi F, Leo M, et al. Long-term outcomeof Graves' orbitopathy following high-doseintravenous glucocorticoids and orbital radiotherapy. J Endocrinol Invest. 2015 Jun;38(6):661-8. doi:10.1007/s40618-015-0241-7.
26. 26.Ohtsuka K, Sato A, Kawaguchi S, Hashimoto M,Suzuki Y. Effect of steroid pulse therapy with andwithout orbital radiotherapy on Graves'ophthalmopathy. Am J Ophthalmol. 2003Mar;135(3):285-90. doi: 10.1016/s0002-9394(02)01970-0.
27. 27.Ueki S, Hasegawa Y, Hatase T, Kiyokawa M, FukuchiT.One-year recurrence rate of Graves ophthalmopathy presenting as diplopia in the primary position aftervaried doses of intravenous methylprednisolonefollowed by oral prednisolone with dosing based onthe magnetic resonance imaging findings. Jpn JOphthalmol. 2023 Jan;67(1):91-96. doi:10.1007/s10384-022-00954-9.
28. 28.Tsirouki T, Bargiota A, Tigas S, et al. Clinical andimaging evaluation of the response to intravenoussteroids in patients with Graves' orbitopathy andanalysis on who requires additional therapy. ClinOphthalmol. 2016 Nov 17;10:2277-2289. doi:10.2147/OPTH.S118555.
29. 29.Shams PN, Ma R, Pickles T, Rootman J, Dolman PJ.Reduced risk of compressive optic neuropathy usingorbital radiotherapy in patients with active thyroid eye disease. Am J Ophthalmol. 2014 Jun;157(6):1299-305.doi: 10.1016/j.ajo.2014.02.044.