Thyroid orbitopathy. Tricks for diagnosis and treatment
Abstract Purpose: Thyroid orbitopathy (TO) is an autoimmune disease of unknown etiology. It is a chronic and sometimes subacute or acute edematous and inflammatory disease, the main characteristics of which are eyelid edema, corneal ulcers, ocular hypertension, generally bilateral exophthalmos, restrictive strabismus, diplopia and optic neuropathy. The main purpose of this work is to review and update the current diagnostic and therapeutic approaches. To propose a practical, basic and precocious approach based in the knowledge of the TO. Methods: Literature review and exposition of our experience in the management of TO. Results: TO is an inflammatory orbital disease that probably has an autoimmune origin and most of the time is related to systemic disorders of the thyroid gland. Pathogenesis of the disease is not yet fully understood. Women are more likely to develop TO, and the disease is clearly affected by several factors such as smoking, age, sex and race. It is crucial to determine TO severity and activity for a correct management. Conclusions: Clinical knowledge is essential for the early diagnosis of this disorder, and it is the most important factor for the proper management of the disease. The medical treatment must be initiated promptly and should be aggressive and based in the current phase of the disease, in order to avoid the severe damage that follows TO. The surgical approach must be logical and sequential, but, on the other hand, must be rapid and aggressive in order to return the patient to his/her labour, social and familiar environment.
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Al-Sharif E, Alsuhaibani AH. Fat-removal orbital decompression for thyroid associated orbitopathy: The right procedure for the right patient. Saudi J Ophthalmol. 2017;31:156–61.
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;5:9–26.
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Taylor PN, Zhang L, Lee RWJ, Muller I, Ezra DG, Dayan CM, et al. New insights into the pathogenesis and nonsurgical management of Graves orbitopathy. Nat Rev Endocrinol. 2020;16:104–16.
Ludgate M. Fibrosis in dysthyroid eye disease. Eye. 2020;34:279–84.
Marcinkowski P, Hoyer I, Specker E, Furkert J, Rutz C, Neuenschwander M, et al. A new highly thyrotropin receptor-selective small-molecule antagonist with potential for the treatment of graves’ orbitopathy. Thyroid. 2019;29:111–23.
Smith TJ, Kahaly GJ, Ezra DG, Fleming JC, Dailey RA, Tang RA, et al. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017. https://doi.org/10.1056/NEJMoa1614949.
Perros P, Baldeschi L, Boboridis K, Dickinson AJ, Hullo A, Kahaly GJ, et al. A questionnaire survey on the management of Graves’ orbitopathy in Europe. Eur J Endocrinol. 2006;155:207–11.
Effraimidis G. MANAGEMENT OF ENDOCRINE DISEASE: Predictive scores in autoimmune thyroid disease: are they useful? Eur J Endocrinol. 2019;181:R119–31.
Wiersinga WM, Perros P, Kahaly GJ, Mourits MP, Baldeschi L, Boboridis K, et al. Clinical assessment of patients with Graves’ orbitopathy: The European Group on Graves’ orbitopathy recommendations to generalists, specialists and clinical researchers. Eur J Endocrinol. 2006;155:387–9.
Ramli N, Kala S, Samsudin A, Rahmat K, Zainal Abidin Z. Proptosis - Correlation and Agreement between Hertel Exophthalmometry and Computed Tomography. Orbit. 2015;34:257–62.
Fayers T, Dolman PJ. Validity and reliability of the TED-QOL: A new three-item questionnaire to assess quality of life in thyroid eye disease. Br J Ophthalmol. 2011;95:1670–4.
Nkenke E, Benz M, Maier T, Wiltfang J, Holbach LM, Kramer M, et al. Relative en- and exophthalmometry in zygomatic fractures comparing optical non-contact, non-ionizing 3D imaging to the Hertel instrument and computed tomography. J Cranio-Maxillofacial Surg. 2003;31:362–8.
Negro R, Attanasio R, Grimaldi F, Marcocci C, Guglielmi R, Papini E. A 2016 Italian Survey about the Clinical Use of Selenium in Thyroid Disease. Eur Thyroid J. 2016;5:164–70.
Ventura M, Melo M, Carrilho F. Selenium and thyroid disease: From pathophysiology to treatment. International Journal of Endocrinology. 2017.
Xu N, Cui Y, Xie T, Zheng M. Comparative Efficacy of Medical Treatments for Thyroid Eye Disease: A Network Meta-Analysis. J Ophthalmol. 2018. https://doi.org/10.1155/2018/7184163.
Bartalena L, Kahaly GJ, Baldeschi L, Dayan CM, Eckstein A, Marcocci C, et al. The 2021 European Group on Graves’ orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves’ orbitopathy. Eur J Endocrinol. 2021;185:G43–67.
Lehman JS, Kalaaji AN. Role of primary prophylaxis for pneumocystis pneumonia in patients treated with systemic corticosteroids or other immunosuppressive agents for immune-mediated dermatologic conditions. J Am Acad Dermatol. 2010;63:815–23.
Nieto-Ríos JF, Zuluaga-Quintero M, Aristizábal-Alzate A, Ocampo-Kohn C, Serna-Higuita LM, Ramírez-Sánchez IC, et al. Insuficiencia respiratoria hipoxémica grave por Pneumocystis jirovecii después de trasplante renal. Biomedica. 2018;38:32–6.
Calero-Bernal ML, Martin-Garrido I, Donazar-Ezcurra M, Limper AH, Carmona EM. Intermittent Courses of Corticosteroids Also Present a Risk for Pneumocystis Pneumonia in Non-HIV Patients. Can Respir J. 2016;2016.
Bartalena L. What to do for moderate-to-severe and active Graves’ orbitopathy if glucocorticoids fail? Clin Endocrinol (Oxf). 2010;73:149–52.
Viani GA, Boin AC, De Fendi LI, Fonseca EC, Stefano EJ, de Paula JS. Radiation therapy for graves’ ophthalmopathy: A systematic review and meta-analysis of randomized controlled trials. Arq Bras Oftalmol. 2012;75:324–32.
Dolman PJ, Rath S. Orbital radiotherapy for thyroid eye disease. Current Opinion in Ophthalmology. 2012.
Kahaly G, Yuan JP, Krause U, Hülbusch K, Beyer J. Ciclosporin and thyroid-stimulating immunoglobulins in endocrine orbitopathy. Res Exp Med. 1989. https://doi.org/10.1007/BF01855041.
Perros P, Weightman DR, Crombie AL, Kendall-Taylor P. Azathioprine in the treatment of thyroid-associated ophthalmopathy. Acta Endocrinol (Copenh). 1990;122:8–12.
Chalvatzis NT, Tzamalis AK, Kalantzis GK, El-Hindy N DS& PM. Safety and efficacy of combined immunosuppression and orbital radiotherapy in thyroid-related restrictive myopathy: two- center experience.itle. Eur J Ophthalmol 2. 2014.
Rajendram R, Lee RW, Potts MJ, Rose GE, Jain R, Olver JM, et al. Protocol for the combined immunosuppression & radiotherapy in thyroid eye disease (CIRTED) trial: A multi-centre, double-masked, factorial randomised controlled trial. Trials. 2008;9:1–17.
Strianese D. Efficacy and Safety of Immunosuppressive Agents for Thyroid Eye Disease. Ophthalmic plastic and reconstructive surgery. 2018.
Patel A, Yang H, Douglas RS. A New Era in the Treatment of Thyroid Eye Disease. Am J Ophthalmol. 2019;208:281–8.
Pérez-Moreiras JV, Álvarez-López A, Gómez EC. Treatment of active corticosteroid-resistant Graves’ orbitopathy. Ophthal Plast Reconstr Surg. 2014. https://doi.org/10.1097/IOP.0000000000000037.
Zhao LQ, Yu DY, Cheng JW. Intravenous glucocorticoids therapy in the treatment of Graves’ ophthalmopathy: A systematic review and Metaanalysis. Int J Ophthalmol. 2019;12:1177–86.
Salvi M, Vannucchi G, Currò 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;100:422–31.
Campi I, Vannucchi G, Muller I, Lazzaroni E, Currò N, Dainese M, et al. Therapy With Different Dose Regimens of Rituximab in Patients With Active Moderate-To-Severe Graves’ Orbitopathy. Front Endocrinol (Lausanne). 2022;12 January:1–9.
Burch HB, Perros P, Bednarczuk T, Cooper DS, Dolman PJ, Leung AM, et al. Management of thyroid eye disease: a Consensus Statement by the American Thyroid Association and the European Thyroid Association. Eur Thyroid J. 2022;11.
Szucs-Farkas Z, Toth J, Kollar J, Galuska L, Burman KD, Boda J, et al. Volume changes in intra- and extraorbital compartments in patients with Graves’ ophthalmopathy: Effect of smoking. Thyroid. 2005. https://doi.org/10.1089/thy.2005.15.146.
Li Z, Cestari DM, Fortin E. Thyroid eye disease: what is new to know? Curr Opin Ophthalmol. 2018;29:528–34.
Al-Sharif E, Alsuhaibani AH. Fat-removal orbital decompression for thyroid associated orbitopathy: The right procedure for the right patient. Saudi J Ophthalmol. 2017;31:156–61.
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;5:9–26.
Bartalena L, Baldeschi L, Dickinson A, Eckstein A, Kendall-Taylor P, Marcocci C, et al. Consensus statement of the European Group on Graves’ orbitopathy (EUGOGO) on management of GO. Eur J Endocrinol. 2008;158:273–85.
Taylor PN, Zhang L, Lee RWJ, Muller I, Ezra DG, Dayan CM, et al. New insights into the pathogenesis and nonsurgical management of Graves orbitopathy. Nat Rev Endocrinol. 2020;16:104–16.
Ludgate M. Fibrosis in dysthyroid eye disease. Eye. 2020;34:279–84.
Marcinkowski P, Hoyer I, Specker E, Furkert J, Rutz C, Neuenschwander M, et al. A new highly thyrotropin receptor-selective small-molecule antagonist with potential for the treatment of graves’ orbitopathy. Thyroid. 2019;29:111–23.
Smith TJ, Kahaly GJ, Ezra DG, Fleming JC, Dailey RA, Tang RA, et al. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017. https://doi.org/10.1056/NEJMoa1614949.
Perros P, Baldeschi L, Boboridis K, Dickinson AJ, Hullo A, Kahaly GJ, et al. A questionnaire survey on the management of Graves’ orbitopathy in Europe. Eur J Endocrinol. 2006;155:207–11.
Effraimidis G. MANAGEMENT OF ENDOCRINE DISEASE: Predictive scores in autoimmune thyroid disease: are they useful? Eur J Endocrinol. 2019;181:R119–31.
Wiersinga WM, Perros P, Kahaly GJ, Mourits MP, Baldeschi L, Boboridis K, et al. Clinical assessment of patients with Graves’ orbitopathy: The European Group on Graves’ orbitopathy recommendations to generalists, specialists and clinical researchers. Eur J Endocrinol. 2006;155:387–9.
Ramli N, Kala S, Samsudin A, Rahmat K, Zainal Abidin Z. Proptosis - Correlation and Agreement between Hertel Exophthalmometry and Computed Tomography. Orbit. 2015;34:257–62.
Fayers T, Dolman PJ. Validity and reliability of the TED-QOL: A new three-item questionnaire to assess quality of life in thyroid eye disease. Br J Ophthalmol. 2011;95:1670–4.
Nkenke E, Benz M, Maier T, Wiltfang J, Holbach LM, Kramer M, et al. Relative en- and exophthalmometry in zygomatic fractures comparing optical non-contact, non-ionizing 3D imaging to the Hertel instrument and computed tomography. J Cranio-Maxillofacial Surg. 2003;31:362–8.
Negro R, Attanasio R, Grimaldi F, Marcocci C, Guglielmi R, Papini E. A 2016 Italian Survey about the Clinical Use of Selenium in Thyroid Disease. Eur Thyroid J. 2016;5:164–70.
Ventura M, Melo M, Carrilho F. Selenium and thyroid disease: From pathophysiology to treatment. International Journal of Endocrinology. 2017.
Xu N, Cui Y, Xie T, Zheng M. Comparative Efficacy of Medical Treatments for Thyroid Eye Disease: A Network Meta-Analysis. J Ophthalmol. 2018. https://doi.org/10.1155/2018/7184163.
Bartalena L, Kahaly GJ, Baldeschi L, Dayan CM, Eckstein A, Marcocci C, et al. The 2021 European Group on Graves’ orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves’ orbitopathy. Eur J Endocrinol. 2021;185:G43–67.
Lehman JS, Kalaaji AN. Role of primary prophylaxis for pneumocystis pneumonia in patients treated with systemic corticosteroids or other immunosuppressive agents for immune-mediated dermatologic conditions. J Am Acad Dermatol. 2010;63:815–23.
Nieto-Ríos JF, Zuluaga-Quintero M, Aristizábal-Alzate A, Ocampo-Kohn C, Serna-Higuita LM, Ramírez-Sánchez IC, et al. Insuficiencia respiratoria hipoxémica grave por Pneumocystis jirovecii después de trasplante renal. Biomedica. 2018;38:32–6.
Calero-Bernal ML, Martin-Garrido I, Donazar-Ezcurra M, Limper AH, Carmona EM. Intermittent Courses of Corticosteroids Also Present a Risk for Pneumocystis Pneumonia in Non-HIV Patients. Can Respir J. 2016;2016.
Bartalena L. What to do for moderate-to-severe and active Graves’ orbitopathy if glucocorticoids fail? Clin Endocrinol (Oxf). 2010;73:149–52.
Viani GA, Boin AC, De Fendi LI, Fonseca EC, Stefano EJ, de Paula JS. Radiation therapy for graves’ ophthalmopathy: A systematic review and meta-analysis of randomized controlled trials. Arq Bras Oftalmol. 2012;75:324–32.
Dolman PJ, Rath S. Orbital radiotherapy for thyroid eye disease. Current Opinion in Ophthalmology. 2012.
Kahaly G, Yuan JP, Krause U, Hülbusch K, Beyer J. Ciclosporin and thyroid-stimulating immunoglobulins in endocrine orbitopathy. Res Exp Med. 1989. https://doi.org/10.1007/BF01855041.
Perros P, Weightman DR, Crombie AL, Kendall-Taylor P. Azathioprine in the treatment of thyroid-associated ophthalmopathy. Acta Endocrinol (Copenh). 1990;122:8–12.
Chalvatzis NT, Tzamalis AK, Kalantzis GK, El-Hindy N DS& PM. Safety and efficacy of combined immunosuppression and orbital radiotherapy in thyroid-related restrictive myopathy: two- center experience.itle. Eur J Ophthalmol 2. 2014.
Rajendram R, Lee RW, Potts MJ, Rose GE, Jain R, Olver JM, et al. Protocol for the combined immunosuppression & radiotherapy in thyroid eye disease (CIRTED) trial: A multi-centre, double-masked, factorial randomised controlled trial. Trials. 2008;9:1–17.
Strianese D. Efficacy and Safety of Immunosuppressive Agents for Thyroid Eye Disease. Ophthalmic plastic and reconstructive surgery. 2018.
Patel A, Yang H, Douglas RS. A New Era in the Treatment of Thyroid Eye Disease. Am J Ophthalmol. 2019;208:281–8.
Pérez-Moreiras JV, Álvarez-López A, Gómez EC. Treatment of active corticosteroid-resistant Graves’ orbitopathy. Ophthal Plast Reconstr Surg. 2014. https://doi.org/10.1097/IOP.0000000000000037.
Zhao LQ, Yu DY, Cheng JW. Intravenous glucocorticoids therapy in the treatment of Graves’ ophthalmopathy: A systematic review and Metaanalysis. Int J Ophthalmol. 2019;12:1177–86.
Salvi M, Vannucchi G, Currò 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;100:422–31.
Campi I, Vannucchi G, Muller I, Lazzaroni E, Currò N, Dainese M, et al. Therapy With Different Dose Regimens of Rituximab in Patients With Active Moderate-To-Severe Graves’ Orbitopathy. Front Endocrinol (Lausanne). 2022;12 January:1–9.
Burch HB, Perros P, Bednarczuk T, Cooper DS, Dolman PJ, Leung AM, et al. Management of thyroid eye disease: a Consensus Statement by the American Thyroid Association and the European Thyroid Association. Eur Thyroid J. 2022;11.
Szucs-Farkas Z, Toth J, Kollar J, Galuska L, Burman KD, Boda J, et al. Volume changes in intra- and extraorbital compartments in patients with Graves’ ophthalmopathy: Effect of smoking. Thyroid. 2005. https://doi.org/10.1089/thy.2005.15.146.
Marqués-Fernández, V. E., Galindo-Ferreiro, A., Palacios-Mures, J. M., & Villacorta-Martín, M. del M. (2023). Thyroid orbitopathy. Tricks for diagnosis and treatment. Revista ORL, 14(4), e30933. https://doi.org/10.14201/orl.30933
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