Comparison of Different Intravenous Glucocorticoid Protocols in the Treatment of Graves' Orbitopathy: Single-Center Experience

Abstract

ABSTRACT Objective: To evaluate clinical data of patients receiving intravenous (IV) glucocorticoid treatment with the diagnosis of Graves' orbitopathy (GO) and to compare the treatment protocols. Material and Methods: We retrospectively examined the clinical and laboratory data of patients who received systemic glucocorticoid treatment for GO in our clinic. Group 1 (4 cycles of 15 mg/kg methylprednisolone in 2 doses every other day for 2 weeks apart, followed by 4 cycles of 7.5 mg/kg methylprednisolone at the same frequency (regimen A)) and Group 2 (500 mg methylprednisolone once a week for 6 weeks followed by 250 mg methylprednisolone once a week for 6 weeks (regimen B)) were formed. Group 1 and Group 2 data were compared. Results: A total of 36 patients were included in the study, 11 in group 1 and 25 in group 2. The average age of the patients was higher in group 1 than in group 2 (56±12.9 and 46.8±10.2, respectively, p=0.02). There was no difference between the groups in terms of gender distribution and the frequency of smokers. There was a history of another autoimmune disease in 20% of all patients. GO developed in the natural course of the disease in 88.9% of all patients, after radioactive iodine treatment in 8.3%, and after thyroid surgery in 2.8%. The clinical activity score (CAS) was found to decrease at a similar rate with treatment in both groups. In terms of, the European Group on Graves' Orbitopathy (EUGOGO) severity class, diplopia, soft tissue involvement, lid retraction, proptosis, and corneal damage, no statistically significant benefit was achieved with the treatment. Conclusion: Systemic intravenous glucocorticoid therapy is an effective treatment option to suppress inflammatory activity in GO patients who need systemic immunosuppressive therapy. The decrease in both groups of CAS was similar. The achievement of similar effects with a lower cumulative steroid dose supports the use of regimen B.

Keywords

• Graves orbitopathy
• Exophthalmos
• Thyroid ophthalmopathy

Graves Orbitopatisi Tedavisinde Farklı İntravenöz Glukokortikoid Protokollerinin Karşılaştırılması: Tek Merkez Deneyimi

Öz

ÖZ Amaç: Graves orbitopatisi (GO) sebebi ile intravenöz (IV) glukokortikoid tedavisi alan hastaların klinik verilerini değerlendirmek ve kullanılan tedavi protokollerini karşılaştırmak. Gereç ve Yöntemler: Merkezimizde GO sebebi ile sistemik glukokortikoid tedavisi alan hastaların klinik ve laboratuvar verileri retrospektif olarak incelendi. Rejim A (15 mg/kg metilprednizolon 2 hafta ara ile gün aşırı 2 doz şeklinde 4 siklus, sonrasında aynı sıklıkta 7,5 mg/kg metilprednizolon 4 siklus) alanlarla grup 1, rejim B (6 hafta boyunca haftada 1 gün 500 mg metilprenizolonu takiben 6 hafta boyunca haftada 1 gün 250 mg metilprednizolon) alanlarla ise grup 2 oluşturuldu. Grup 1 ve grup 2 verileri birbiri ile karşılaştırıldı. Bulgular: Çalışmaya; 11’i grup 1’de, 25’i ise grup 2’de olmak üzere toplam 36 hasta alındı. Hastaların yaş ortalaması grup 1’de grup 2’ye oranla daha yüksekti (Sırası ile 56±12,9 ve 46,8±10,2, p=0,02). Cinsiyet dağılımı ve sigara içen hasta sıklığı yönünden ise gruplar arasında fark saptanmadı. Ek otoimmun hastalık öyküsü tüm hastaların %20’sinde vardı. GO’nun tüm hastaların %88,9’unda hastalığın doğal seyrinde, %8,3’ünde radyoaktif iyot tedavisi sonrası, %2,8’inde ise tiroid cerrahisi sonrası geliştiği saptandı. Klinik aktivite skorunun her iki grupta tedavi ile benzer oranda azaldığı saptandı. The European Group on Graves’ Orbitopathy (EUGOGO) ciddiyet sınıfı, diplopi, yumuşak doku tutulumu, kapak retraksiyonu, propitozis ve kornea hasarı yönünden yapılan değerlendirmede tedavi ile istatistiksel anlamlılığa ulaşan yarar sağlanmadığı saptandı. Sonuç : Sistemik intravenöz glukokortikoid tedavisi, immünsüpressif tedavi endikasyonu konulan GO hastalarında hastalık aktivitesini baskılama yönünden etkili bir tedavi seçeneğidir. Her iki grupta KAS düşüşü benzer saptanmıştır. Daha düşük kümülatif steroid dozu kullanılarak benzer etki elde edilmesi rejim B kullanımını destekler niteliktedir.

Anahtar Kelimeler

• Graves orbitopatisi
• Ekzoftalmus
• Tiroid oftalmopatisi

References

1. 1. Bartalena L, Fatourechi V. Extrathyroidal manifestations of Graves’ disease: a 2014 update. Journal of endocrinological investigation 2014; 37:691-700.
2. 2. Chin YH, Ng CH, Lee MH, Koh JWH, Kiew J, Yang SP, Sundar G, Khoo CM. Prevalence of thyroid eye disease in Graves’ disease: A meta‐analysis and systematic review. Clinical endocrinology 2020; 93(4):363-74.
3. 3. Ippolito S , Cusini C, Lasalvia P, Gianfagna F, Veronesi G, Gallo D, Masiello E, Premoli P, Sabatino J, Mercuriali A, Lai A, Piantanida E, Tanda ML, Bartalena L. Change in newly diagnosed Graves’ disease phenotype between the twentieth and the twenty-first centuries: meta-analysis and meta-regression. Journal of Endocrinological Investigation 2021; 44:1707-18.
4. 4. Tanda ML, Piantanida E, Liparulo L, Veronesi G, Lai A, Sassi L, Pariani N, Gallo D, Azzolini C, Ferrario M, Bartalena L. Prevalence and natural history of Graves' orbitopathy in a large series of patients with newly diagnosed graves' hyperthyroidism seen at a single center. The Journal of Clinical Endocrinology & Metabolism 2013; 98(4):1443-9.
5. 5. Piantanida E, Tanda M, Lai A, Sassi L, Bartalena L. Prevalence and natural history of Graves’ orbitopathy in the XXI century. Journal of endocrinological investigation 2013; 36:444-9.
6. 6. Bartalena L, Tanda ML. Current concepts regarding Graves’ orbitopathy. Journal of Internal Medicine 2022; 292(5):692-716.
7. 7. Bartley GB, Gorman CA. Diagnostic criteria for Graves' ophthalmopathy. American journal of ophthalmology 1995; 119(6):792-5.
8. 8. Şahlı E, Gündüz K. Thyroid-associated ophthalmopathy. Turkish journal of ophthalmology 2017; 47(2):94-105.

9. 9. Bartalena L, Kahaly GJ, Baldeschi L, Dayan CM, Eckstein A, Marcocci C, Marinò M, Vaidya B, Wiersinga WM; EUGOGO †. The 2021 European Group on Graves’ orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves’ orbitopathy. European journal of endocrinology 2021; 185(4):G43-G67.
10. 10. Burch HB, Perros P, Bednarczuk T, Cooper DS, Dolman PJ, Leung AM, Mombaerts I, Salvi M, Stan MN. Management of thyroid eye disease: a Consensus Statement by the American Thyroid Association and the European Thyroid Association. European thyroid journal 2022; 11(6): e220189.
11. 11. Mourits MP, Prummel MF, Wiersinga WM, Koornneef L. Clinical activity score as a guide in the management of patients with Graves' ophthalmopathy. Clinical endocrinology 1997; 47(1):9-14.
12. 12. Terwee C, Prummel M, Gerding M, Kahaly G, Dekker F, Wiersinga W. Measuring disease activity to predict therapeutic outcome in Graves’ ophthalmopathy. Clinical Endocrinology 2005; 62(2):145-55.
13. 13. Stiebel-Kalish H, Robenshtok E, Hasanreisoglu M, Ezrachi D, Shimon I, Leibovici L. Treatment modalities for Graves’ ophthalmopathy: systematic review and metaanalysis. The Journal of Clinical Endocrinology & Metabolism 2009; 94(8):2708-16.
14. 14. van Geest RJ , Sasim IV, Koppeschaar HP, Kalmann R, Stravers SN, Bijlsma WR, Mourits MP. Methylprednisolone pulse therapy for patients with moderately severe Graves' orbitopathy: a prospective, randomized, placebo-controlled study. European journal of endocrinology 2008; 158(2):229-37.
15. 15. Zang S, Ponto K, Kahaly G. Intravenous glucocorticoids for Graves' orbitopathy: efficacy and morbidity. The Journal of Clinical Endocrinology & Metabolism 2011; 96(2):320-32.
16. 16. Bartalena L, Baldeschi L, Boboridis K, Eckstein A, Kahaly GJ, Marcocci C, Perros P, Salvi M, Wiersinga WM; European Group on Graves' Orbitopathy (EUGOGO). The 2016 European Thyroid Association/European Group on Graves' orbitopathy guidelines for the management of Graves' orbitopathy. European thyroid journal 2016; 5(1):9-26.
17. 17. Längericht J, Krämer I, Kahaly GJ. Glucocorticoids in Graves’ orbitopathy: mechanisms of action and clinical application. Therapeutic Advances in Endocrinology and Metabolism 2020; 11:2042018820958335.
18. 18. Lee ACH, Kahaly GJ. Novel approaches for immunosuppression in Graves’ hyperthyroidism and associated orbitopathy. European Thyroid Journal 2020; 9 (1_Suppl):17-30.
19. 19. Kahaly GJ, Pitz S, Hommel G, Dittmar M. Randomized, single blind trial of intravenous versus oral steroid monotherapy in Graves’ orbitopathy. The Journal of Clinical Endocrinology & Metabolism 2005; 90(9):5234-40.
20. 20. Marcocci C, Bartalena L, Tanda ML, Manetti L, Dell'Unto E, Rocchi R, Barbesino G, Mazzi B, Bartolomei MP, Lepri P, Cartei F, Nardi M, Pinchera A. 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. The Journal of Clinical Endocrinology & Metabolism 2001; 86(8):3562-7.
21. 21. Sánchez-Ortiga R, Moreno-Pérez O, González Sánchez V, Arias Mendoza N, Mauri Dot M, Alfayate Guerra R, López Macia A, Picó Alfonso A. Treatment of Graves’ ophthalmopathy with high-dose intravenous methylprednisolone: a comparison of two dosing regimens. Endocrinología Y Nutrición 2009; 56(3):118-22.
22. 22. 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. Clinical endocrinology 2000; 52(3):267-71.
23. 23. Lytton S, Ponto K, Kanitz M, Matheis N, Kohn L, Kahaly G. A novel thyroid stimulating immunoglobulin bioassay is a functional indicator of activity and severity of Graves’ orbitopathy. The Journal of Clinical Endocrinology & Metabolism 2010; 95(5):2123-31.
24. 24. Nicolì F, Lanzolla G, Mantuano M, Ionni I, Mazzi B, Leo M, Sframeli A, Posarelli C, Maglionico MN, Figus M, Nardi M, Marcocci C, Marinò M. Correlation between serum anti-TSH receptor autoantibodies (TRAbs) and the clinical feature of Graves’ orbitopathy. Journal of Endocrinological Investigation 2021; 44:581-5.