Endocrine orbitopathy: the present view of a clinical endocrinologist

Czech version

Authors: Jan Jiskra
Authors‘ workplace: III. interní klinika 1. LF UK a VFN v Praze
Published in: Vnitř Lék 2017; 63(10): 690-696
Category: Reviews

Overview

Graves’ orbitopathy (GO) occurs in 25–50 % cases of Graves’ disease. Only in 5 % of patients the eye threatening GO is present. About 5–10 % and 10 % cases are present in euthyroid and hypothyroid patients respectively. All patients with GO should be assessed for activity (clinical activity score – CAS) and severity of the disease. Basic preconditions of the treatment are maintenance of euthyroidism, an effort to stop smoking, and referring of patients with moderate to severe and sight threatening GO to specialized thyroid eye centers. The first line treatment includes maintenance of wet eye (lubricants), supplementation of selenium deficiency, intravenous glucocorticoids, radiotherapy and surgery. Cases with moderate to severe GO should be treated with intravenous glucocorticoids in thyroid eye centers, however, the risk/benefit ratio in all cases should be considered. Cases with sight threatening GO should be immediately referred to thyroid eye centers, high-dose intravenous glucocorticoids are administered, and when the clinical response is absent within 2 weeks, surgical orbital decompression is recommended. Other immunosuppressive drugs (cyclosporine, mycophenolate mofetil) or biological therapy (teprotumumab) are not routinely recommended because of lack of evidence obtained by randomized controlled trials.

Key words:
clinical activity score – dysthyroid optic neuropathy – Graves’ orbitopathy – intravenous glucocorticoids – mycophenolate mofetil

Sources

1. Alkawas AA, Hussein AM, Shahien EA. Orbital steroid injection versus oral steroid therapy in management of thyroid-related ophthalmopathy. Clin Exp Ophthalmol 2010; 38(7): 692–697. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1442–9071.2010.02332.x>.

2. Antonelli A, Saracino A, Alberti B et al. Highose intravenous immunoglobulin treatment in Graves’ ophthalmopathy. Acta Endocrinol (Copenh) 1992; 126(1): 13–23.

3. Bahn Chair RS, Burch HB, Cooper DS et al. [American Thyroid Association; American Association of Clinical Endocrinologists]. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid 2011; 21(6): 593–646. Dostupné z DOI: <http://dx.doi.org/10.1089/thy.2010.0417>.

4. Bahn RS. Graves’ ophthalmopathy. N Engl J Med 2010; 362(8): 726–738. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMra0905750>.

5. Bartalena L, Baldeschi L, Boboridis K et al. [European Group on Graves‘ Orbitopathy (EUGOGO)]. 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. Dostupné z DOI: <http://dx.doi.org/10.1159/000443828>.

6. Bartalena L, Baldeschi L, Dickinson A et al. [European Group on Graves‘ Orbitopathy (EUGOGO)]. Consensus statement of the European Group on Graves‘ orbitopathy (EUGOGO) on management of GO. Eur J Endocrinol 2008; 158(3): 273–285. Dostupné z DOI: <http://dx.doi.org/10.1530/EJE-07–0666>.

7. Bartalena L, Marcocci C, Bogazzi F et al. Relation between therapy for hyperthyroidism and the course of Graves’ ophthalmopathy. N Engl J Med 1998; 338(2): 73–78.

8. Dickinson AJ, Vaidya B, Miller M et al. Double-blind, placebo-controlled trial of octreotide longacting repeatable (LAR) in thyroid-associated ophthalmopathy. J Clin Endocrinol Metab 2004; 89(12): 5910–5915.

9. Ebner R, Devoto MH, Weil D et al. Treatment of thyroid associated ophthalmopathy with periocular injections of triamcinolone. Br J Ophthalmol 2004; 88(11): 1380–1386.

10. Eckstein AK, Plicht M, Lax H 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): 3464–3470.

11. Finamor FE, Martins JR, Nakanami D et al. Pentoxifylline (PTX) – an alternative treatment in Graves‘ ophthalmopathy (inactive phase): assessment by a disease specific quality of life questionnaire and by exophthalmometry in a prospective randomized trial. Eur J Ophthalmol 2004; 14(4): 277–283. Dostupné z DOI: <http://dx.doi.org/10.5301/EJO.2008.5017>.

12. Forbes G, Gorman CA, Brennan MD et al. Ophthalmopathy of Graves’ disease: computerized volume measurements of the orbital fat and muscle. Am J Neuroradiol 1986; 7(4): 651–656.

13. Gerding MN, van der Meer JW, Broenink M et al. Association of thyrotrophin receptor antibodies with the clinical features of Graves’ ophthalmopathy. Clin Endocrinol (Oxf) 2000; 52(3): 267–271.

14. Kahaly G, Schrezenmeir J, Krause U et al. Ciclosporin and prednisone v. prednisone in treatment of Graves‘ ophthalmopathy: a controlled, randomized and prospective study. Eur J Clin Invest 1986; 16(5): 415–422.

15. Kahaly GJ, Rosler HP, Pitz S et al. Low- versus high-dose radiotherapy for Graves’ ophthalmopathy: a randomized, single blind trial. J Clin Endocrinol Metab 2000; 85(1): 102–108.

16. Krassas GE, Stafilidou A, Boboridis KG. Failure of rituximab treatment in a case of severe thyroid ophthalmopathy unresponsive to steroids. Clin Endocrinol (Oxf) 2010; 72(6): 853–855. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1365–2265.2009.03762.x>.

17. Lee SJ, Rim TH, Jang SY et al. Treatment of upper eyelid retraction related to thyroid-associated ophthalmopathy using subconjunctival triamcinolone injections. Graefes Arch Clin Exp Ophthalmol 2013; 251(1): 261–270. Dostupné z DOI: <http://dx.doi.org/10.1007/s00417–012–2153-y>.

18. Lendorf ME, Rasmussen AK, Fledelius HC et al. Cardiovascular and cerebrovascular events in temporal relationship to intravenous glucocorticoid pulse therapy in patients with severe endocrine ophthalmopathy. Thyroid 2009; 19(12): 1431–1432. Dostupné z DOI: <http://dx.doi.org/10.1089/thy.2009.0069>.

19. Lipman LM, Green DE, Snyder NJ et al. Relationship of long-acting thyroid stimulator to the clinical features and course of Graves’ disease. Am J Med 1967; 43(4): 486–498.

20. Marcocci C, Bartalena L, Bogazzi F et al. Orbital radiotheraphy combined with high-dose systemic glucocorticoids for Graves’ ophthalmopathy is more effective than orbital radiotherapy alone: results of a prospective study. J Endocrinol Invest 1991; 14(10): 853–860.

21. Marcocci C, Kahaly GJ, Krassas GE et al. [European Group on Graves‘ Orbitopathy]. Selenium and the course of mild Graves‘ orbitopathy. N Engl J Med 2011; 364(20): 1920–1931. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1012985>.

22. Mourits MP, Koornneef L, Wiersinga WM et al. Clinical criteria for the assessment of disease activity in Graves’ ophthalmopathy: a novel approach. Br J Ophthalmol 1989; 73(8): 639–644.

23. Mourits MP, van Kempen-Harteveld ML, Garcia MB et al. Radiotherapy for Graves’ orbitopathy: randomised placebo-controlled study. Lancet 2000; 355(9214): 1505–1509.

24. Paridaens D, van den Bosch WA, van der Loos TL et al. The effect of etanercept on Graves’ ophthalmopathy: a pilot study. Eye 2005; 19(12): 1286–1289.

25. Prummel MF, Mourits MP, Berghout A et al. Prednisone and cyclosporine in the treatment of severe Graves’ ophthalmopathy. N Engl J Med 1989; 321(20): 1353–1359.

26. Prummel MF, Terwee CB, Gerding MN et al. A randomized controlled trial of orbital radiotherapy versus sham irradiation in patients with mild Graves’ ophthalmopathy. J Clin Endocrinol Metab 2004; 89(1): 15–20.

27. Ross DS, Burch HB, Cooper DS et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid 2016; 26(10): 1343–1421.

28. Salvi M, Vannucchi G, Campi I et al. Rituximab treatment in a patient with severe thyroid-associated ophthalmopathy: effects on orbital lymphocytic infiltrates. Clin Immunol 2009; 131(2): 360–365. <http://dx.doi.org/10.1016/j.clim.2008.12.005>.

29. Salvi M, Vannucchi G, Campi I et al. Treatment of Graves’ disease and associated ophthalmopathy with the anti-CD20 monoclonal antibody rituximab: an open study. Eur J Endocrinol 2007; 156(1): 33–40.

30. Smith TJ, Kahaly GJ, Ezra DG et al. Teprotumumab for Thyroid-Associated Ophthalmopathy. N Engl J Med 2017; 376(18): 1748–1761. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1614949>.

31. Soeters MR, van Zeijl CJJ, Boelen A et al. Optimal management of graves orbitopathy: a multidisciplinary approach. Neth J Med 2011; 69(7): 302–308.

32. Stan MN, Garrity JA, Carranza Leon BG et al. Randomized controlled trial of rituximab in patients with Graves‘ orbitopathy. J Clin Endocrinol Metab 2015; 100(2): 432–441. Dostupné z DOI: <http://dx.doi.org/10.1210/jc.2014–2572>.

33. Werner SC. Modification of the classification of the eye changes of Grave’s disease. Am J Ophthalmol 1977; 83(5): 725–7257.

34. Ye X, Bo X, Hu X et al. Efficacy and safety of mycophenolate mofetil in patients with active moderate-to-severe Graves‘ orbitopathy. Clin Endocrinol (Oxf) 2017; 86(2): 247–255. Dostupné z DOI: <http://dx.doi.org/10.1111/cen.13170>.

35. Zang S, Ponto KA, Kahaly GJ. Intravenous Glucocorticoids for Graves’ Orbitopathy: Efficacy and Morbidity. J Clin Endocrinol Metab 2011; 96(2): 320–332. Dostupné z DOI: <http://dx.doi.org/10.1210/jc.2010–1962>.