Az endokrin orbitopathia a Graves-kór leggyakoribb extrathyreoidalis manifesztációja. A súlyos – látást veszélyeztető – esetek kezelése a mai napig nem megoldott probléma. A szerzők a közleményben a nemzetközi ajánlásokban is szereplő, elfogadott kezelési módok bemutatása mellett az elmúlt évtizedek terápiás próbálkozásait, a közelmúlt új kezelési lehetőségeit, valamint saját klinikai tapasztalataikat foglalják össze. Kiemelik, hogy az endokrin orbitopathia kezelésében a biológiai terápiák közül elsősorban az anti-CD20 antitesttel végzett terápiával kedvező irodalmi adatok állnak rendelkezésre. A szelén enyhe esetekben egyértelműen pozitív hatású. További, nagyobb esetszámú prospektív vizsgálatok szükségesek a biológiai terápiák alkalmazhatóságáról endokrin orbitopathiában. Orv. Hetil., 2014, 155(33), 1295–1300.
Weetman, A. P.: Graves’ disease. N. Engl. J. Med., 2000, 343(17), 1236–1248.
Brent, G. A.: Graves’ disease. N. Engl. J. Med., 2008, 358(24), 2594–2605.
Bartalena, L., Tanda, M. L.: Graves’ ophthalmopathy. N. Engl. J. Med., 2009, 360(10), 994–1001.
Metcalfe, R. A., Weetman, A. P.: Stimulation of extraocular muscle fibroblasts by citokines and hypoxia: possible role in thyroid-associated ophthalmopathy. Clin. Endocrinol. (Oxf.), 1994, 40(1), 67–72.
Burch, H. B., Lahiri, S., Bahn, R. S., et al.: Superoxide radical production stimulates retroocular fibroblast proliferation in Graves’ ophthalmopathy. Exp. Eye Res., 1997, 65(2), 311–316.
Hofbauer, L. C., Mühlberg, T., König, A., et al.: Soluble interleukin-1-receptor antagonist serum levels in smokers and nonsmokers with Graves’ ophtalmopathy undergoing orbital radiotherapy. J. Clin. Endocrinol. Metab., 1997, 82(7), 2244–2247.
Mengistu, M., Lukes, Y. G., Nagy, E. V., et al.: TSH receptor gene expression in retroocular fibroblasts. J. Endocrinol. Invest., 1994, 17(6), 437–441.
Bahn, R. S.: Thyrotropin receptor expression in orbital adipose/connective tissues from patients with thyroid-associated ophthalmopathy. Thyroid, 2002, 12(3), 193–195.
Prabhakar, B. S., Bahn, R. S., Smith, T. J.: Current perspective on the pathogenesis of Graves’ disease and ophthalmopathy. Endocr. Rev., 2003, 24(6), 802–835.
Bahn, R. S.: Pathophysiology of Graves’ ophthalmopathy: the cycle of disease. J. Clin. Endocrinol. Metab., 2003, 88(5), 1939–1946.
Mourits, M. P., Prummel, M. F., Wiersinga, W. M., et al.: Clinical activity score as a guide in the management of patients with Graves’ ophthalmopathy. Clin. Endocrinol., 1997, 47(1), 9–14.
Galuska, L., Leovey, A., Szucs-Farkas, Z., et al.: Imaging of disease activity in Graves’ orbitopathy with different methods: comparison of (99m)Tc-DTPA and (99m)Tc-depreotide single photon emission tomography, magnetic resonance imaging and clinical activity scores. Nucl. Med. Commun., 2005, 26(5), 407–414.
Ujhelyi, B., Erdei, A., Galuska, L., et al.: Retrobulbar 99mTc-diethylenetriamine-pentaacetic-acid uptake may predict the effectiveness of immunosuppressive therapy in Graves’ ophtalmopathy. Thyroid, 2009, 19(4), 375–380.
Bartalena, L., Baldeschi, L., Dickinson, A., et al.: Consensus statement of European Group on Graves’ orbitopathy (EUGOGO) on management of GO. Eur. J. Endocrinol., 2008, 158(3), 273–285.
Bartalena, L., Pinchera, A., Marcocci, C.: Management of Graves ophthalmopathy: reality and perspectives. Endocr. Rev., 2000, 21(2), 168–199.
Bartalena, L.: Prevention of Graves’ ophthalmopathy. Best Pract. Res. Clin. Endocrinol. Metab., 2012, 26(3), 371–379.
Lazarus, J. H., Bartalena, L., Marcocci, C., et al.: Glucocorticoid administration for Graves’ hyperthyroidism treated by radioiodine. A questionnaire survey among members of the European Thyroid Association. J. Endocrinol. Invest., 2010, 33(6), 409–413.
Leövey, A., Bakó, G., Szabó, J., et al.: Combined cyclosporin-A and methylprednisolone treatment of Graves’ ophthalmopathy. Acta Med. Hung., 1992–1993, 49(3–4), 179–185.
Prummel, M. F., Mourits, M. P., Berghout, A., et al.: Prednisone and cyclosporine in the treatment of severe Graves’ ophtalmopathy. N. Engl. J. Med., 1989, 321(20), 1353–1359.
Chang, T. C., Yao, W. C., Chang, C. C.: Octreotide and urinary glucosaminoglycan in Graves’ disease. Br. Med. J., 1992, 304(6839), 1444.
Dickinson, A. J., Vaidya, B., Miller, M., et al.: Double-blind, placebo-controlled trial of octreotide long-acting repeatable (LAR) in thyroid-associated ophtalmopathy. J. Clin. Endocrinol. Metab., 2004, 89(12), 5910–5915.
Seppel, T., Schlaghecke, R., Becker, A., et al.: High dose intravenous therapy with 7S immunoglobulins in autoimmune endocrine ophthalmopathy. Clin. Exp. Rheumatol., 1996, 14(Suppl. 15), S109–S114.
Kahaly, G., Pitz, S., Müller-Forell, W., et al.: Randomized trial of intravenous immunoglobulins versus prednisolone in Graves’ ophtalmopathy. Clin. Exp. Immunol., 1996, 106(2), 197–202.
Bouzas, E. A., Karadimas, P., Mastorakos, G., et al.: Antioxidant agents in the treatment of Graves’ ophthalmopathy. Am. J. Ophthalmol., 2000, 129(5), 618–622.
Balázs, C., Kiss, E., Vamos, A., et al.: Beneficial effect of pentoxiphylline on thyroid associated ophtalmopathy (TAO): a pilot study. J. Clin. Endocinol. Metab., 1997, 82(6), 1999–2002.
Pescovitz, M. D.: Rituximab, an anti-CD20 monoclonal antibody: history and mechanism of action. Am. J. Transplant., 2006, 6(5 Pt 1), 859–866.
Nadler, L. M., Ritz, J., Hardy, R., et al.: An unique cell surface antigen identifying lymphoid malignancies of B cell origin. J. Clin. Invest., 1981, 67(1), 134–140.
Maloney, D. G., Smith, B., Appelbaum, F. R.: The anti-tumor effect of monoclonal anti-CD20 antibody (mAb) therapy includes direct anti-proliferative activity and induction of apoptosis in CD20 positive non-Hodgkin’s lymphoma (NHL) cell lines. Blood, 1996, 88(Suppl. 1), 637a.
Salvi, M., Vannucchi, G., Campi, I., et al.: Efficacy of rituximab treatment for thyroid-associated ophthalmopathy as a result of intraorbital B-cell depletion in one patient unresponsive to steroid immunosuppression. Eur. J. Endocrinol., 2006, 154(4), 511–517.
El Fassi, D., Nielsen, C. H., Hasselbalch, H. C., et al.: Treatment-resistant severe, active Graves’ ophthalmopathy successfully treated with B lymphocyte depletion. Thyroid, 2006, 16(7), 709–710.
El Fassi, D., Clemmensen, O., Nielsen, C. H., et al.: Evidence of intrathyroidal B-lymphocyte depletion after rituximab therapy in a patient with Graves’ disease. J. Clin. Endocrinol. Metab., 2007, 92(10), 3762–3763.
El Fassi, D., Nielsen, C. H., Bonnema, S. J., et al.: B lymphocyte depletion with the monoclonal antibody rituximab in Graves’ disease: a controlled pilot study. J. Clin. Endocrinol. Metab., 2007, 92(5), 1769–1772.
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.
Datta, S. K.: Anti-CD20 antibody is an efficient therapeutic tool for the selective removal of autoreactive T cells. Nat. Clin. Pract. Rheumatol., 2009, 5(2), 80–82.
Heemstra, K. A., Toes, R. E., Sepers, J., et al.: Rituximab in relapsing Graves’ disease, a phase II study. Eur. J. Endocrinol., 2008, 159(5), 609–615.
El Fassi, D., Banga, J. P., Gilbert, J. A., et al.: Treatment of Graves’ disease with rituximab specifically reduces the production of thyroid stimulating autoantibodies. Clin. Immunol., 2009, 130(3), 252–258.
Khanna, D., Chong, K. K., Afifiyan, N. F., et al.: Rituximab treatment of patients with severe, corticosteroid-resistant thyroid-associated ophthalmopathy. Ophtalmology, 2010, 117(1), 133–139.e2.
Mitchell, A. L., Gan, E. H., Morris, M., et al.: The effect of B cell depletion therapy on anti-TSH receptor antibodies and clinical outcome in glucocorticoid-refractory Graves’ orbitopathy. Clin. Endocrinol., 2013, 79(3), 437–442.
Savino, G., Balia, L., Colucci, D., et al.: Intraorbital injection of rituximab: a new approach for active thyroid-associated orbitopathy, a prospective case series. Minerva Endocrinol., 2013, 38(2), 173–179.
Stan, M. N., Garrity, J. A., Thapa, P., et al.: Randomized double-blind placebo-controlled trial of rituximab for treatment of Graves’ ophtalmopathy. Thyroid, 2013, 23(Suppl. 1), A13–A14.
Durrani, O. M., Reuser, T. Q., Murray, P. I.: Infliximab: a novel treatment for sight-threatening thyroid associated ophthalmopathy. Orbit, 2005, 24(2), 117–119.
Komorowski, J., Jankiewicz-Wika, J., Siejka, A., et al.: Monoclonal anti-TNF-alpha antibody (infliximab) in the treatment of patient with thyroid associated ophthalmopathy. Klin. Oczna, 2007, 109(10–12), 457–460.
Paridaens, D., van den Bosch, W. A., van der Loos, T. L., et al.: The effect of etanercept on Graves ophtalmopathy: a pilot study. Eye, 2005, 19(12), 1286–1289.
Smith, T. J., Hegedüs, L., Douglas, R. S.: Role of insulin-like growth factor-1 (IGF-1) pathway in the pathogenesis of Graves’ orbitopathy. Best Pract. Res. Clin. Endocrinol. Metab., 2012, 26(3), 291–302.
Marcocci, C., Kahaly, G. J., Krassas, G. E., et al.: Selenium and the course of mild Graves’ orbitopathy. N. Engl. J. Med., 2011, 364(20), 1920–1931.