Doença de Graves

O hipertireoidismo pode causar perda mineral óssea e o grau dessa perda tem relação com o tempo em que o hipertireoidismo ficou sem tratamento.[174]Flynn RW, Bonellie SR, Jung RT, et al. Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on long-term thyroxine therapy. J Clin Endocrinol Metab. 2010 Jan;95(1):186-93. http://www.ncbi.nlm.nih.gov/pubmed/19906785?tool=bestpractice.com Esse tempo precisaria ser longo para causar osteoporose definitiva.

Osteoporose

A orbitopatia de Graves ocorre em cerca de 25% dos casos e é geralmente leve.[1]Tanda ML, Piantanida E, Liparulo L, et al. Prevalence and natural history of Graves' orbitopathy in a large series of patients with newly diagnosed graves' hyperthyroidism seen at a single center. J Clin Endocrinol Metab. 2013 Apr;98(4):1443-9. https://academic.oup.com/jcem/article/98/4/1443/2536784 http://www.ncbi.nlm.nih.gov/pubmed/23408569?tool=bestpractice.com ​ É importante avaliar e classificar a atividade e a gravidade da orbitopatia para ajudar a orientar o tratamento.[58]Bartalena L, Kahaly GJ, Baldeschi L, et al. The 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' orbitopathy. Eur J Endocrinol. 2021 Aug 27;185(4):G43-G67. https://www.doi.org/10.1530/EJE-21-0479 http://www.ncbi.nlm.nih.gov/pubmed/34297684?tool=bestpractice.com [155]Burch HB, Perros P, Bednarczuk T, et al. Management of thyroid eye disease: a consensus statement by the American Thyroid Association and the European Thyroid Association. Thyroid. 2022 Dec;32(12):1439-70. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9807259 http://www.ncbi.nlm.nih.gov/pubmed/36480280?tool=bestpractice.com ​​ Foram publicadas diretrizes que fornecem recomendações sobre a avaliação e o tratamento iniciais.[58]Bartalena L, Kahaly GJ, Baldeschi L, et al. The 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' orbitopathy. Eur J Endocrinol. 2021 Aug 27;185(4):G43-G67. https://www.doi.org/10.1530/EJE-21-0479 http://www.ncbi.nlm.nih.gov/pubmed/34297684?tool=bestpractice.com [155]Burch HB, Perros P, Bednarczuk T, et al. Management of thyroid eye disease: a consensus statement by the American Thyroid Association and the European Thyroid Association. Thyroid. 2022 Dec;32(12):1439-70. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9807259 http://www.ncbi.nlm.nih.gov/pubmed/36480280?tool=bestpractice.com ​[156]Perros P, Dayan CM, Dickinson AJ, et al. Management of patients with Graves' orbitopathy: initial assessment, management outside specialised centres and referral pathways. Clin Med (Lond). 2015 Apr;15(2):173-8. https://www.rcpjournals.org/content/clinmedicine/15/2/173 http://www.ncbi.nlm.nih.gov/pubmed/25824071?tool=bestpractice.com ​

Nas crianças a orbitopatia é geralmente leve e, muitas vezes, regride uma vez que se restaure o estado eutireoidiano. Uma estratégia de "esperar para ver" pode ser apropriada.

Os fatores de risco devem ser abordados para prevenir a progressão da orbitopatia de Graves, incluindo a garantia de um controle adequado da disfunção tireoidiana e o suporte aos pacientes que fumam para abandonarem o hábito de fumar.[58]Bartalena L, Kahaly GJ, Baldeschi L, et al. The 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' orbitopathy. Eur J Endocrinol. 2021 Aug 27;185(4):G43-G67. https://www.doi.org/10.1530/EJE-21-0479 http://www.ncbi.nlm.nih.gov/pubmed/34297684?tool=bestpractice.com

A orbitopatia levemente ativa é tratada com colírios e pomadas lubrificantes, ou óculos de sol para sintomas superficiais, ou prismas para diplopia.[155]Burch HB, Perros P, Bednarczuk T, et al. Management of thyroid eye disease: a consensus statement by the American Thyroid Association and the European Thyroid Association. Thyroid. 2022 Dec;32(12):1439-70. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9807259 http://www.ncbi.nlm.nih.gov/pubmed/36480280?tool=bestpractice.com ​ Alguns pacientes com orbitopatia de Graves leve de curta duração podem se beneficiar de um ciclo de 6 meses de suplementos de selênio.[157]Marcocci C, Kahaly GJ, Krassas GE, et al. Selenium and the course of mild Graves' orbitopathy. N Engl J Med. 2011 May 19;364(20):1920-31. http://www.nejm.org/doi/full/10.1056/NEJMoa1012985#t=article http://www.ncbi.nlm.nih.gov/pubmed/21591944?tool=bestpractice.com [158]Bednarczuk T, Schomburg L. Challenges and perspectives of selenium supplementation in Graves' disease and orbitopathy. Hormones (Athens). 2020 Mar;19(1):31-9. https://www.doi.org/10.1007/s42000-019-00133-5 http://www.ncbi.nlm.nih.gov/pubmed/31721133?tool=bestpractice.com

Os pacientes com orbitopatia ativa moderada a grave devem ser tratados por uma equipe multidisciplinar especializada, composta por oftalmologistas e endocrinologistas; o tratamento de primeira linha é a terapia com pulsoterapia de corticosteroides intravenosos (por exemplo, metilprednisolona).[155]Burch HB, Perros P, Bednarczuk T, et al. Management of thyroid eye disease: a consensus statement by the American Thyroid Association and the European Thyroid Association. Thyroid. 2022 Dec;32(12):1439-70. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9807259 http://www.ncbi.nlm.nih.gov/pubmed/36480280?tool=bestpractice.com [159]Zang S, Ponto KA, Kahaly GJ. Clinical review: intravenous glucocorticoids for Graves' orbitopathy: efficacy and morbidity. J Clin Endocrinol Metab. 2011 Feb;96(2):320-32. http://www.ncbi.nlm.nih.gov/pubmed/21239515?tool=bestpractice.com [160]Bartalena L, Krassas GE, Wiersinga W, 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 Dec;97(12):4454-63. https://academic.oup.com/jcem/article/97/12/4454/2536457 http://www.ncbi.nlm.nih.gov/pubmed/23038682?tool=bestpractice.com ​​​ O uso de outros agentes, incluindo uma combinação de um corticosteroide associado a micofenolato, ou imunoterapia direcionada (por exemplo, teprotumumabe) é recomendado em alguns países.[58]Bartalena L, Kahaly GJ, Baldeschi L, et al. The 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' orbitopathy. Eur J Endocrinol. 2021 Aug 27;185(4):G43-G67. https://www.doi.org/10.1530/EJE-21-0479 http://www.ncbi.nlm.nih.gov/pubmed/34297684?tool=bestpractice.com [155]Burch HB, Perros P, Bednarczuk T, et al. Management of thyroid eye disease: a consensus statement by the American Thyroid Association and the European Thyroid Association. Thyroid. 2022 Dec;32(12):1439-70. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9807259 http://www.ncbi.nlm.nih.gov/pubmed/36480280?tool=bestpractice.com ​​[161]American Academy of Ophthalmology. Thyroid eye disease. Jul 2024 [internet publication]. https://eyewiki.org/Thyroid_Eye_Disease [162]Men CJ, Kossler AL, Wester ST. Updates on the understanding and management of thyroid eye disease. Ther Adv Ophthalmol. 2021 Jan-Dec;13:25158414211027760. https://www.doi.org/10.1177/25158414211027760 http://www.ncbi.nlm.nih.gov/pubmed/34263138?tool=bestpractice.com [163]Smith TJ, Kahaly GJ, Ezra DG, et al. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017 May 4;376(18):1748-1761. https://www.doi.org/10.1056/NEJMoa1614949 http://www.ncbi.nlm.nih.gov/pubmed/28467880?tool=bestpractice.com [164]Douglas RS, Kahaly GJ, Patel A, et al. Teprotumumab for the treatment of active thyroid eye disease. N Engl J Med. 2020 Jan 23;382(4):341-352. https://www.doi.org/10.1056/NEJMoa1910434 http://www.ncbi.nlm.nih.gov/pubmed/31971679?tool=bestpractice.com ​​​​​[165]Kahaly GJ, Douglas RS, Holt RJ, et al. Teprotumumab for patients with active thyroid eye disease: a pooled data analysis, subgroup analyses, and off-treatment follow-up results from two randomised, double-masked, placebo-controlled, multicentre trials. Lancet Diabetes Endocrinol. 2021 Jun;9(6):360-72. https://www.doi.org/10.1016/S2213-8587(21)00056-5 http://www.ncbi.nlm.nih.gov/pubmed/33865501?tool=bestpractice.com [166]Feng W, Hu Y, Zhang C, et al. Efficacy and safety of mycophenolate mofetil in the treatment of moderate to severe Graves' orbitopathy: a meta-analysis. Bioengineered. 2022 Jun;13(6):14719-29. https://www.tandfonline.com/doi/full/10.1080/21655979.2022.2101191#d1e361 http://www.ncbi.nlm.nih.gov/pubmed/35959915?tool=bestpractice.com ​​​ Os efeitos adversos associados ao teprotumumabe incluem doença inflamatória intestinal, sintomas otológicos, incluindo perda auditiva, e hiperglicemia.[165]Kahaly GJ, Douglas RS, Holt RJ, et al. Teprotumumab for patients with active thyroid eye disease: a pooled data analysis, subgroup analyses, and off-treatment follow-up results from two randomised, double-masked, placebo-controlled, multicentre trials. Lancet Diabetes Endocrinol. 2021 Jun;9(6):360-72. https://www.doi.org/10.1016/S2213-8587(21)00056-5 http://www.ncbi.nlm.nih.gov/pubmed/33865501?tool=bestpractice.com [167]Kossler AL, Douglas R, Dosiou C. Teprotumumab and the evolving therapeutic landscape in thyroid eye disease. J Clin Endocrinol Metab. 2022 Aug 8;107(suppl_1):S36-46. https://academic.oup.com/jcem/article/107/Supplement_1/S36/6658346 http://www.ncbi.nlm.nih.gov/pubmed/36346685?tool=bestpractice.com ​ As terapias com anticorpos monoclonais (por exemplo, rituximabe e tocilizumabe) mostraram resultados mistos e são consideradas opções de segunda ou terceira linhas.[155]Burch HB, Perros P, Bednarczuk T, et al. Management of thyroid eye disease: a consensus statement by the American Thyroid Association and the European Thyroid Association. Thyroid. 2022 Dec;32(12):1439-70. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9807259 http://www.ncbi.nlm.nih.gov/pubmed/36480280?tool=bestpractice.com [168]Salvi M, Vannucchi G, Currò N, 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 Feb;100(2):422-31. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4318899 http://www.ncbi.nlm.nih.gov/pubmed/25494967?tool=bestpractice.com [169]Stan MN, Garrity JA, Carranza Leon BG, et al. Randomized controlled trial of rituximab in patients with Graves' orbitopathy. J Clin Endocrinol Metab. 2015 Feb;100(2):432-41. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4318907 http://www.ncbi.nlm.nih.gov/pubmed/25343233?tool=bestpractice.com [170]Kang S, Hamed Azzam S, Minakaran N, et al. Rituximab for thyroid-associated ophthalmopathy. Cochrane Database Syst Rev. 2022 Jun 16;6(6):CD009226. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD009226.pub3/full http://www.ncbi.nlm.nih.gov/pubmed/35709102?tool=bestpractice.com

A irradiação orbital, com ou sem corticosteroides, também é usada em casos de orbitopatia ativa moderada a grave; há evidências limitadas para que se possa sugerir a radiação orbital como forma de prevenção da neuropatia óptica compressiva.[171]Chundury RV, Weber AC, Perry JD. Orbital radiation therapy in thyroid eye disease. Ophthal Plast Reconstr Surg. 2016 Mar-Apr;32(2):83-9. http://www.ncbi.nlm.nih.gov/pubmed/26325378?tool=bestpractice.com [172]Rajendram R, Bunce C, Lee RW, et al. Orbital radiotherapy for adult thyroid eye disease. Cochrane Database Syst Rev. 2012 Jul 11;(7):CD007114. http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007114.pub2/full http://www.ncbi.nlm.nih.gov/pubmed/22786503?tool=bestpractice.com [173]Tanda ML, Bartalena L. Efficacy and safety of orbital radiotherapy for Graves' orbitopathy. J Clin Endocrinol Metab. 2012 Nov;97(11):3857-65. http://www.ncbi.nlm.nih.gov/pubmed/22962421?tool=bestpractice.com ​​​ A cirurgia de reabilitação tem um papel importante na orbitopatia moderada a grave quando a doença está estável e inativa.

A fibrilação atrial pode ocorrer após os 40 anos e pode ser o sintoma manifesto mesmo no hipertireoidismo subclínico. A fibrilação atrial pode resultar em complicações tromboembólicas e acidente vascular cerebral (AVC).[2]Smith TJ, Hegedüs L. Graves' disease. N Engl J Med. 2016 Oct 20;375(16):1552-65. http://www.ncbi.nlm.nih.gov/pubmed/27797318?tool=bestpractice.com

Fibrilação atrial aguda

A insuficiência congestiva ou de alto débito pode ocorrer nos casos graves, especialmente em idosos.[2]Smith TJ, Hegedüs L. Graves' disease. N Engl J Med. 2016 Oct 20;375(16):1552-65. http://www.ncbi.nlm.nih.gov/pubmed/27797318?tool=bestpractice.com

Exacerbação aguda de insuficiência cardíaca congestiva

A orbitopatia com ameaça à visão geralmente ocorre no primeiro ano após o diagnóstico de hipertireoidismo, mas pode ocorrer antes desse diagnóstico ou, em alguns casos, anos mais tarde. Tais complicações são raras e incluem úlceras da córnea e neuropatia óptica.

A neuropatia óptica deve ser tratada urgentemente com doses muito altas de corticosteroides intravenosos.[58]Bartalena L, Kahaly GJ, Baldeschi L, et al. The 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' orbitopathy. Eur J Endocrinol. 2021 Aug 27;185(4):G43-G67. https://www.doi.org/10.1530/EJE-21-0479 http://www.ncbi.nlm.nih.gov/pubmed/34297684?tool=bestpractice.com ​ Os pacientes que respondem bem ao tratamento inicial com corticosteroides podem trocar para a terapia com pulsoterapia de corticosteroides intravenosos. A descompressão orbital cirúrgica é recomendada se os corticosteroides falharem.[58]Bartalena L, Kahaly GJ, Baldeschi L, et al. The 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' orbitopathy. Eur J Endocrinol. 2021 Aug 27;185(4):G43-G67. https://www.doi.org/10.1530/EJE-21-0479 http://www.ncbi.nlm.nih.gov/pubmed/34297684?tool=bestpractice.com [155]Burch HB, Perros P, Bednarczuk T, et al. Management of thyroid eye disease: a consensus statement by the American Thyroid Association and the European Thyroid Association. Thyroid. 2022 Dec;32(12):1439-70. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9807259 http://www.ncbi.nlm.nih.gov/pubmed/36480280?tool=bestpractice.com ​​[175]Boboridis KG, Bunce C. Surgical orbital decompression for thyroid eye disease. Cochrane Database Syst Rev. 2011 Dec 7;(12):CD007630. http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007630.pub2/full http://www.ncbi.nlm.nih.gov/pubmed/22161415?tool=bestpractice.com A cirurgia de reabilitação (para reduzir a proptose e corrigir a diplopia) e a cirurgia das pálpebras também podem ser necessárias quando a orbitopatia estiver estável e inativa.[10]Bartley GB, Fatourechi V, Kadrmas EF, et al. Clinical features of Graves' ophthalmopathy in an incidence cohort. Am J Ophthalmol. 1996 Mar;121(3):284-90. http://www.ncbi.nlm.nih.gov/pubmed/8597271?tool=bestpractice.com [118]Fatourechi V. Medical treatment of Graves' ophthalmopathy. Ophthalmol Clin North Am. 2000;13:683-91.[176]Soares-Welch CV, Fatourechi V, Bartley GB, et al. Optic neuropathy of Graves disease: results of transantral orbital decompression and long-term follow-up in 215 patients. Am J Ophthalmol. 2003 Sep;136(3):433-41. http://www.ncbi.nlm.nih.gov/pubmed/12967795?tool=bestpractice.com

Os fatores que impõem risco à visão (por exemplo, neuropatia óptica, rompimento da córnea) são uma complicação ocasional nas crianças e podem exigir intervenção cirúrgica imediata. É necessário um envolvimento multidisciplinar (que inclua endocrinologia e oftalmologia pediátricas).[177]Szczapa-Jagustyn J, Gotz-Więckowska A, Kocięcki J. An update on thyroid-associated ophthalmopathy in children and adolescents. J Pediatr Endocrinol Metab. 2016 Oct 1;29(10):1115-22. https://www.degruyter.com/view/j/jpem.2016.29.issue-10/jpem-2016-0122/jpem-2016-0122.xml http://www.ncbi.nlm.nih.gov/pubmed/27682712?tool=bestpractice.com [Figure caption and citation for the preceding image starts]: Orbitopatia e elefantíaseCedida pelo Dr. Vahab Fatourechi [Citation ends].

A dermopatia geralmente ocorre 1 ano após a orbitopatia. A dermopatia (mixedema pré-tibial) ocorre em 10% a 20% dos pacientes com orbitopatia moderada a grave. Ela geralmente é leve e apresenta resolução espontânea, ou com corticoterapia de uso local.[18]Fatourechi V. Pretibial myxedema: pathophysiology and treatment options. Am J Clin Dermatol. 2005;6(5):295-309. http://www.ncbi.nlm.nih.gov/pubmed/16252929?tool=bestpractice.com [178]Vannucchi G, Campi I, Covelli D, et al. Treatment of pretibial myxedema with dexamethazone injected subcutaneously by mesotherapy needles. Thyroid. 2013 May;23(5):626-32. http://www.ncbi.nlm.nih.gov/pubmed/23397966?tool=bestpractice.com ​​ Um dermatologista deve ser consultado se a dermopatia for persistente, extensa e/ou problemática. Nos casos graves com orbitopatia moderada a grave associada, a terapia com corticosteroide sistêmico pode ser benéfica, embora faltem evidências de longo prazo.[18]Fatourechi V. Pretibial myxedema: pathophysiology and treatment options. Am J Clin Dermatol. 2005;6(5):295-309. http://www.ncbi.nlm.nih.gov/pubmed/16252929?tool=bestpractice.com ​ Atualmente não há tratamentos para a acropaquia. A elefantíase ocorre em 5% dos casos de dermopatia e é de difícil tratamento. A elefantíase pode gerar problemas estéticos e funcionais.[18]Fatourechi V. Pretibial myxedema: pathophysiology and treatment options. Am J Clin Dermatol. 2005;6(5):295-309. http://www.ncbi.nlm.nih.gov/pubmed/16252929?tool=bestpractice.com [59]Schwartz KM, Fatourechi V, Ahmed DD, et al. Dermopathy of Graves' disease (pretibial myxedema): long-term outcome. J Clin Endocrinol Metab. 2002 Feb;87(2):438-46. http://www.ncbi.nlm.nih.gov/pubmed/11836263?tool=bestpractice.com [179]Rose Jr JG, Burkat CN, Boxrud CA. Diagnosis and management of thyroid orbitopathy. Otolaryngol Clin North Am. 2005 Oct;38(5):1043-74. http://www.ncbi.nlm.nih.gov/pubmed/16214573?tool=bestpractice.com [Figure caption and citation for the preceding image starts]: ElefantíaseCedida pelo Dr. Vahab Fatourechi [Citation ends].