Keywords
Graves ophthalmopathy
Graves’ disease
glucocorticoids
rituximab
radiotherapy
Graves’ disease
glucocorticoids
rituximab
radiotherapy
How to Cite
Gómez, C., Imitola, A., Taboada, L. B., Henao, D. C., Marín, L. F., Camargo, J., Kattath, L., Fonseca, C., Colón, C., & Ascnher, P. (2019). Thyroid orbitopathy: Management protocol based on review of the evidence. Revista Colombiana De Endocrinología, Diabetes &Amp; Metabolismo, 6(3), 210–217. https://doi.org/10.53853/encr.6.3.535
Abstract
Thyroid orbitopathy is a potentially serious condition that may threaten vision. It is the most frequent extrathyroidal manifestation of Graves’ disease and although the prevalence is not yet evaluated in our country, this complication can produce vision loss with catastrophic consequences. Taking this into account, this work was done with the objective of describing its diagnostic and therapeutic approach, based on the best available evidence.
A management protocol applicable in our context was developed. For this, an evaluation and adaptation of the European Group on Graves’ Orbitopathy (EUGOGO) 2016 guideline was done (1). For the evaluation the AGREE II tool was used (2). The GRADE methodology was used to grade the quality of evidence and to formulate recommendations. In addition, a systematic review of the literature was conducted with the objective of evaluating the efficacy of biological therapy in the management of Graves’ orbitopathy.
Throughout the document, recommendations for adequate diagnosis, treatment and follow-up are presented. The importance of having a multidisciplinary team with experience in the management of thyroid orbitopathy (endocrinology, ophthalmology, orbit surgery, radiotherapy and rheumatology) is emphasized, ideally in a third level care center. Adequate classification is essential to determine which patients will benefit from immunosuppressive therapy. If it is managed in a timely manner, a decrease in the appearance of irreversible sequelae can be achieved.
References
1. Bartalena L, Baldeschi L, Boboridis K, Eckstein A, Kahaly GJ, Marcocci C, et al. The 2016 European Thyroid Association/European Group on Graves’ orbitopathy guidelines for the management of graves’ orbitopathy. Eur Thyroid J. 2016;5(1):9-26.
2. Consortium ANS. El Instrumento AGREE II Versión electrónica. 2009. Disponible en: http://www.agreetrust.org.
3. Bahn RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Endocr Pract. 2011;17(3):456-520.
4. Bahn RS. Graves’ ophthalmopathy. New Engl J. 2010;362:726-38.
5. De Leo S, Lee SY, Braverman LE. Hyperthyroidism. Lancet. 2016;116(8):1477-90.
6. Ren Z, Qin L, Wang JQ, Li Y, Li J, Zhang RG. Comparative efficacy of four treatments in patients with Graves’ disease: a network meta-analysis. Exp Clin Endocrinol Diabetes. 2015;123(5):317-22.
7. Tallstedt L, Lundell G, Torring O, Wallin G, Ljunggren JG, Blomgren H, et al. Occurrence of ophthalmopathy after treatment for Graves’ hyperthyroidism. The Thyroid Study Group. N Engl J Med. 1992;326(26):1733-8.
8. Acharya SH, Avenell A, Philip S, Burr J, Bevan JS, Abraham P. Radioiodine therapy (RAI) for Graves’ disease (GD) and the effect on ophthalmopathy: a systematic review. Clin Endocrinol (Oxf). 2008;69(6):943-50.
9. Eckstein AK, Plicht M, Lax H, Neuhauser M, Mann K, Lederbogen S, et al. Thyrotropin receptor autoantibodies are independent risk factors for Graves’ ophthalmopathy and help to predict severity and outcome of the disease. J Clin Endocrinol Metab. 2006;91(9):3464-70.
10. 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. Clin Endocrinol (Oxf). 2000;52(3):267-71.
11. Traisk F, Tallstedt L, Abraham-Nordling M, Andersson T, Berg G, Calissendorff J, et al. Thyroid-associated ophthalmopathy after treatment for Graves’ hyperthyroidism with antithyroid drugs or iodine-131. J Clin Endocrinol Metab. 2009;94(10):3700-7.
12. Vannucchi G, Campi I, Covelli D, Dazzi D, Curro N, Simonetta S, et al. Graves’ orbitopathy activation after radioactive iodine therapy with and without steroid prophylaxis. J Clin Endocrinol Metab. 2009;94(9):3381-6.
13. Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, et al. 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid. 2016;26(10):1343-421.
14. Bartalena L, Martino E, Marcocci C, Bogazzi F, Panicucci M, Velluzzi F, et al. More on smoking habits and Graves’ ophthalmopathy. J Endocrinol Invest. 1989;12(10):733-7.
15. Campi I, Vannucchi G, Salvi M. Therapy of endocrine disease: endocrine dilemma: management of Graves’ orbitopathy. Eur J Endocrinol. 2016;175(3):R117-33.
16. Muller-Forell W, Kahaly GJ. Neuroimaging of Graves’ orbitopathy. Best Pract Res Clin Endocrinol Metab. 2012;26(3):259-71.
17. McKeag D, Lane C, Lazarus JH, Baldeschi L, Boboridis K, Dickinson AJ, et al. Clinical features of dysthyroid optic neuropathy: a European Group on Graves’ Orbitopathy (EUGOGO) survey. Br J Ophthalmol. 2007;91(4):455-8.
18. Vargas-Uricoechea H, Sierra-Torres CH, Meza-Cabrera IA. Tratamiento de la enfermedad de Graves Basedow. Medicina. 2013;35(2):130-49.
19. Khong JJ, McNab A, Ebeling PR, Craig JE, Selva D. Pathogenesis of thyroid eye disease: review and update on molecular mechanisms. Br J Ophthalmol. 2015;100(1):142-50.
20. Vargas-Uricoechea H, Sierra-Torres CH, Meza-Cabrera IA. Enfermedad de Graves-Basedow fisiopatología y diagnóstico. Medicina. 2013;35(1):41-66.
21. Lytton SD, Ponto KA, Kanitz M, Matheis N, Kohn LD, Kahaly GJ. A novel thyroid stimulating immunoglobulin bioassay is a functional indicator of activity and severity of Graves’ orbitopathy. J Clin Endocrinol Metab. 2010;95(5):2123-31.
22. Ponto KA, Kanitz M, Olivo PD, Pitz S, Pfeiffer N, Kahaly GJ. Clinical relevance of thyroid-stimulating immunoglobulins in graves’ ophthalmopathy. Ophthalmology. 2011;118(11):2279-85.
23. Ponto KA, Diana T, Binder H, Matheis N, Pitz S, Pfeiffer N, et al. Thyroidstimulating immunoglobulins indicate the onset of dysthyroid optic neuropathy. J Endocrinol Invest. 2015;38(7):769-77.
24. Barrio-Barrio J, Sabater AL, Bonet-Farriol E, Velázquez-Villoria Á, Galofré JC. Graves’ ophthalmopathy: VISA versus EUGOGO classification, assessment, and management. J Ophthalmol. 2015;2015:249125.
25. Kazim M, Gold KG. A review of surgical techniques to correct upper eyelid retraction associated with thyroid eye disease. Curr Opin Ophthalmol. 2011;22(5):391-3.
26. Marcocci C, Kahaly GJ, Krassas GE, Bartalena L, Prummel M, Stahl M, et al. Selenium and the course of mild Graves’ orbitopathy. N Engl J Med. 2011;364(20):1920-31.
27. Zang S, Ponto KA, Kahaly GJ. Clinical review: intravenous glucocorticoids for Graves’ orbitopathy: efficacy and morbidity. J Clin Endocrinol Metab. 2011;96(2):320-32.
28. Stiebel-Kalish H, Robenshtok E, Hasanreisoglu M, Ezrachi D, Shimon I, Leibovici L. Treatment modalities for Graves’ ophthalmopathy: systematic review and metaanalysis. J Clin Endocrinol Metab. 2009;94(8):2708-16.
29. Marcocci C, Watt T, Altea MA, Rasmussen AK, Feldt-Rasmussen U, Orgiazzi J, et al. Fatal and non-fatal adverse events of glucocorticoid therapy for Graves’ orbitopathy: a questionnaire survey among members of the European Thyroid Association. Eur J Endocrinol. 2012;166(2):247-53.
30. Bartalena L, Burch HB, Burman KD, Kahaly GJ. A 2013 European survey of clinical practice patterns in the management of Graves’ disease. Clin Endocrinol (Oxf). 2016;84(1):115-20.
31. Mou P, Jiang LH, Zhang Y, Li YZ, Lou H, Zeng CC, et al. Common immunosuppressive monotherapy for graves’ ophthalmopathy: a meta-Analysis. PLoS One. 2015;10(10):1-14.
32. Kahaly GJ, Pitz S, Hommel G, Dittmar M. Randomized, single blind trial of intravenous versus oral steroid monotherapy in Graves’ orbitopathy. J Clin Endocrinol Metab. 2005;90(9):5234-40.
33. Zhu W, Ye L, Shen L, Jiao Q, Huang F, Han R, et al. A prospective, randomized trial of intravenous glucocorticoids therapy with different protocols for patients with graves’ ophthalmopathy. J Clin Endocrinol Metab. 2014;99(6):1999-2007.
34. Bartalena L, Krassas GE, Wiersinga W, Marcocci C, Salvi M, Daumerie C, et al. Efficacy and safety of three different cumulative doses of intravenous methylprednisolone for moderate to severe and active Graves’ orbitopathy. J Clin Endocrinol Metab. 2012;97(12):4454-63.
35. Vargas-Uricoechea H, Maya-Ruiz DE. Eficacia del tratamiento con esteroides para la oftalmopatía tiroidea. Rev Venez Endocrinol Metab. 2014;12(3):157-66.
36. Farach A, Carpenter LS. Radiation therapy for orbitopathy of thyroid eye disease. Int Ophthalmol Clin. 2016;56(1):81-93.
37. Sisti E, Menconi F, Leo M, Profilo MA, Mautone T, Mazzi B, et al. Long-term outcome of Graves’ orbitopathy following high-dose intravenous glucocorticoids and orbital radiotherapy. J Endocrinol Invest. 2015;38(6):661-8.
38. Rajendram R, Bunce C, Lee RWJ, Morley AMS. Orbital radiotherapy for adult thyroid eye disease. Cochrane Database Syst Rev. 2012;(7):CD007114.
39. Viani GA, Boin ACAC, De Fendi LI, Fonseca EC, Stefano EJ, Paula JS. Radiation therapy for graves’ ophthalmopathy: a systematic review and meta-analysis of randomized controlled trials. Arq Bras Oftalmol. 2012;75(5):324-32.
40. Salvi M. Immunotherapy for Graves’ ophthalmopathy. Curr Opin Endocrinol Diabetes Obes. 2014;21(5):409-14.
41. Perez-Moreiras JV, Gomez-Reino JJ, Maneiro JR, et al. Efficacy of Tocilizumab in Patients With Moderate-to-Severe Corticosteroid-Resistant Graves Orbitopathy: A Randomized Clinical Trial. Am J Ophthalmol. 2018;195:181-90.
42. Salvi M, Vannucchi G, Curro 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;100(2):422-31.
43. Stan MN, Garrity JA, Carranza Leon BG, Prabin T, Bradley EA, Bahn RS. Randomized controlled trial of rituximab in patients with Graves’ orbitopathy. J Clin Endocrinol Metab. 2015;100(2):432-41.
44. Smith TJ, Kahaly GJ, Ezra DG, Fleming JC, Dailey RA, Tang RA, et al. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017;376(18):1748-61.
45. Prummel MF, Mourits MP, Berghout A, Krenning EP, van der Gaag R, Koornneef L, et al. Prednisone and cyclosporine in the treatment of severe Graves’ ophthalmopathy. N Engl J Med. 1989;321(20):1353-9.
2. Consortium ANS. El Instrumento AGREE II Versión electrónica. 2009. Disponible en: http://www.agreetrust.org.
3. Bahn RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Endocr Pract. 2011;17(3):456-520.
4. Bahn RS. Graves’ ophthalmopathy. New Engl J. 2010;362:726-38.
5. De Leo S, Lee SY, Braverman LE. Hyperthyroidism. Lancet. 2016;116(8):1477-90.
6. Ren Z, Qin L, Wang JQ, Li Y, Li J, Zhang RG. Comparative efficacy of four treatments in patients with Graves’ disease: a network meta-analysis. Exp Clin Endocrinol Diabetes. 2015;123(5):317-22.
7. Tallstedt L, Lundell G, Torring O, Wallin G, Ljunggren JG, Blomgren H, et al. Occurrence of ophthalmopathy after treatment for Graves’ hyperthyroidism. The Thyroid Study Group. N Engl J Med. 1992;326(26):1733-8.
8. Acharya SH, Avenell A, Philip S, Burr J, Bevan JS, Abraham P. Radioiodine therapy (RAI) for Graves’ disease (GD) and the effect on ophthalmopathy: a systematic review. Clin Endocrinol (Oxf). 2008;69(6):943-50.
9. Eckstein AK, Plicht M, Lax H, Neuhauser M, Mann K, Lederbogen S, et al. Thyrotropin receptor autoantibodies are independent risk factors for Graves’ ophthalmopathy and help to predict severity and outcome of the disease. J Clin Endocrinol Metab. 2006;91(9):3464-70.
10. 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. Clin Endocrinol (Oxf). 2000;52(3):267-71.
11. Traisk F, Tallstedt L, Abraham-Nordling M, Andersson T, Berg G, Calissendorff J, et al. Thyroid-associated ophthalmopathy after treatment for Graves’ hyperthyroidism with antithyroid drugs or iodine-131. J Clin Endocrinol Metab. 2009;94(10):3700-7.
12. Vannucchi G, Campi I, Covelli D, Dazzi D, Curro N, Simonetta S, et al. Graves’ orbitopathy activation after radioactive iodine therapy with and without steroid prophylaxis. J Clin Endocrinol Metab. 2009;94(9):3381-6.
13. Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, et al. 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid. 2016;26(10):1343-421.
14. Bartalena L, Martino E, Marcocci C, Bogazzi F, Panicucci M, Velluzzi F, et al. More on smoking habits and Graves’ ophthalmopathy. J Endocrinol Invest. 1989;12(10):733-7.
15. Campi I, Vannucchi G, Salvi M. Therapy of endocrine disease: endocrine dilemma: management of Graves’ orbitopathy. Eur J Endocrinol. 2016;175(3):R117-33.
16. Muller-Forell W, Kahaly GJ. Neuroimaging of Graves’ orbitopathy. Best Pract Res Clin Endocrinol Metab. 2012;26(3):259-71.
17. McKeag D, Lane C, Lazarus JH, Baldeschi L, Boboridis K, Dickinson AJ, et al. Clinical features of dysthyroid optic neuropathy: a European Group on Graves’ Orbitopathy (EUGOGO) survey. Br J Ophthalmol. 2007;91(4):455-8.
18. Vargas-Uricoechea H, Sierra-Torres CH, Meza-Cabrera IA. Tratamiento de la enfermedad de Graves Basedow. Medicina. 2013;35(2):130-49.
19. Khong JJ, McNab A, Ebeling PR, Craig JE, Selva D. Pathogenesis of thyroid eye disease: review and update on molecular mechanisms. Br J Ophthalmol. 2015;100(1):142-50.
20. Vargas-Uricoechea H, Sierra-Torres CH, Meza-Cabrera IA. Enfermedad de Graves-Basedow fisiopatología y diagnóstico. Medicina. 2013;35(1):41-66.
21. Lytton SD, Ponto KA, Kanitz M, Matheis N, Kohn LD, Kahaly GJ. A novel thyroid stimulating immunoglobulin bioassay is a functional indicator of activity and severity of Graves’ orbitopathy. J Clin Endocrinol Metab. 2010;95(5):2123-31.
22. Ponto KA, Kanitz M, Olivo PD, Pitz S, Pfeiffer N, Kahaly GJ. Clinical relevance of thyroid-stimulating immunoglobulins in graves’ ophthalmopathy. Ophthalmology. 2011;118(11):2279-85.
23. Ponto KA, Diana T, Binder H, Matheis N, Pitz S, Pfeiffer N, et al. Thyroidstimulating immunoglobulins indicate the onset of dysthyroid optic neuropathy. J Endocrinol Invest. 2015;38(7):769-77.
24. Barrio-Barrio J, Sabater AL, Bonet-Farriol E, Velázquez-Villoria Á, Galofré JC. Graves’ ophthalmopathy: VISA versus EUGOGO classification, assessment, and management. J Ophthalmol. 2015;2015:249125.
25. Kazim M, Gold KG. A review of surgical techniques to correct upper eyelid retraction associated with thyroid eye disease. Curr Opin Ophthalmol. 2011;22(5):391-3.
26. Marcocci C, Kahaly GJ, Krassas GE, Bartalena L, Prummel M, Stahl M, et al. Selenium and the course of mild Graves’ orbitopathy. N Engl J Med. 2011;364(20):1920-31.
27. Zang S, Ponto KA, Kahaly GJ. Clinical review: intravenous glucocorticoids for Graves’ orbitopathy: efficacy and morbidity. J Clin Endocrinol Metab. 2011;96(2):320-32.
28. Stiebel-Kalish H, Robenshtok E, Hasanreisoglu M, Ezrachi D, Shimon I, Leibovici L. Treatment modalities for Graves’ ophthalmopathy: systematic review and metaanalysis. J Clin Endocrinol Metab. 2009;94(8):2708-16.
29. Marcocci C, Watt T, Altea MA, Rasmussen AK, Feldt-Rasmussen U, Orgiazzi J, et al. Fatal and non-fatal adverse events of glucocorticoid therapy for Graves’ orbitopathy: a questionnaire survey among members of the European Thyroid Association. Eur J Endocrinol. 2012;166(2):247-53.
30. Bartalena L, Burch HB, Burman KD, Kahaly GJ. A 2013 European survey of clinical practice patterns in the management of Graves’ disease. Clin Endocrinol (Oxf). 2016;84(1):115-20.
31. Mou P, Jiang LH, Zhang Y, Li YZ, Lou H, Zeng CC, et al. Common immunosuppressive monotherapy for graves’ ophthalmopathy: a meta-Analysis. PLoS One. 2015;10(10):1-14.
32. Kahaly GJ, Pitz S, Hommel G, Dittmar M. Randomized, single blind trial of intravenous versus oral steroid monotherapy in Graves’ orbitopathy. J Clin Endocrinol Metab. 2005;90(9):5234-40.
33. Zhu W, Ye L, Shen L, Jiao Q, Huang F, Han R, et al. A prospective, randomized trial of intravenous glucocorticoids therapy with different protocols for patients with graves’ ophthalmopathy. J Clin Endocrinol Metab. 2014;99(6):1999-2007.
34. Bartalena L, Krassas GE, Wiersinga W, Marcocci C, Salvi M, Daumerie C, et al. Efficacy and safety of three different cumulative doses of intravenous methylprednisolone for moderate to severe and active Graves’ orbitopathy. J Clin Endocrinol Metab. 2012;97(12):4454-63.
35. Vargas-Uricoechea H, Maya-Ruiz DE. Eficacia del tratamiento con esteroides para la oftalmopatía tiroidea. Rev Venez Endocrinol Metab. 2014;12(3):157-66.
36. Farach A, Carpenter LS. Radiation therapy for orbitopathy of thyroid eye disease. Int Ophthalmol Clin. 2016;56(1):81-93.
37. Sisti E, Menconi F, Leo M, Profilo MA, Mautone T, Mazzi B, et al. Long-term outcome of Graves’ orbitopathy following high-dose intravenous glucocorticoids and orbital radiotherapy. J Endocrinol Invest. 2015;38(6):661-8.
38. Rajendram R, Bunce C, Lee RWJ, Morley AMS. Orbital radiotherapy for adult thyroid eye disease. Cochrane Database Syst Rev. 2012;(7):CD007114.
39. Viani GA, Boin ACAC, De Fendi LI, Fonseca EC, Stefano EJ, Paula JS. Radiation therapy for graves’ ophthalmopathy: a systematic review and meta-analysis of randomized controlled trials. Arq Bras Oftalmol. 2012;75(5):324-32.
40. Salvi M. Immunotherapy for Graves’ ophthalmopathy. Curr Opin Endocrinol Diabetes Obes. 2014;21(5):409-14.
41. Perez-Moreiras JV, Gomez-Reino JJ, Maneiro JR, et al. Efficacy of Tocilizumab in Patients With Moderate-to-Severe Corticosteroid-Resistant Graves Orbitopathy: A Randomized Clinical Trial. Am J Ophthalmol. 2018;195:181-90.
42. Salvi M, Vannucchi G, Curro 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;100(2):422-31.
43. Stan MN, Garrity JA, Carranza Leon BG, Prabin T, Bradley EA, Bahn RS. Randomized controlled trial of rituximab in patients with Graves’ orbitopathy. J Clin Endocrinol Metab. 2015;100(2):432-41.
44. Smith TJ, Kahaly GJ, Ezra DG, Fleming JC, Dailey RA, Tang RA, et al. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017;376(18):1748-61.
45. Prummel MF, Mourits MP, Berghout A, Krenning EP, van der Gaag R, Koornneef L, et al. Prednisone and cyclosporine in the treatment of severe Graves’ ophthalmopathy. N Engl J Med. 1989;321(20):1353-9.
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