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Endokrine Orbitopathie 1998

Graves’ Ophthalmopathy 1998

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Zusammenfassung

□ Hintergrund

Die häufigste extrathyreoidale Manifestation der autoimmunen Thyreopathie ist die endokrine Orbitopathie.

□ Klinisches Bild

Das Charakteristikum dieser Autoimmunerkrankung ist die entzündliche Volumenzunahme des peri- und retrobulbären Gewebes, die zur klinischen Symptomatik nichtinfiltrativer Lidaffektionen, Protrusio bulbi, Augenmuskelparesen und bis hin zum Visusverlust führen kann. Die pathologischen Veränderungen der endokrinen Orbitopathie sind gekennzeichnet durch immunologisch vermittelte Entzündungsreaktionen im Retrobulbärraum, in deren Verlaufes zur lymphozytären Infiltration und Einlagerung von Glykosaminoglykanen in das orbitale Muskel-, Binde- und Fettgewebe kommt.

□ Diagnose und Therapie

Trotz verschiedener neuer diagnostischer Möglichkeiten und therapeutischer Ansätze bietet das adäquate Vorgehen bei der enkokrinen Orbitopathie häufig Schwierigkeiten, vor allem bei rezidivierenden und schweren Verläufen. Mit neuen Erkenntnissen in der Pathogenese und weiteren klinischen Studien sind neue diagnostische und therapeutische Ansätze bei der Behandlung der endokrinen Orbitopathie entstanden.

□ Schlußfolgerung

Eine interdisziplinäre Zusammenarbeit ist für eine effiziente Diagnostik, adäquate Therapie und eine kontinuierliche Nachsorge bei der endokrinen Orbitopathie von entscheidender Bedeutung.

Abstract

□ Background

Ophthalmopathy is the most common extrathyroidal manifestation of Graves’ disease, also called thyroid-associated ophthalmopathy.

□ Clinics

This autoimmune disorder is characterized by a lymphocyte infiltration of the retrobulbar space. Activated T cells react with the target organ and secrete cytokines, leading to accumulation of glycosaminoglycans, interstitial edema of the peri- and retrobulbar tissue and enlargement of the extraocular muscles. During the inflammatory stage, the increased orbital pressure results in the clinical manifestation of the eye disease.

□ Diagnosis and Treatment

Thus, therapeutic immunosuppression is often used initially, and by suppressing inflammatory changes, it can result in subjective and objective improvement of the thyroid eye disease. In recent years, new pathogenetic aspects and clinical randomized trials led to modified therapy concepts.

□ Conclusion

Interdisciplinary management is recommended for rapid diagnosis and effective therapy of patients with thyroid-associated ophthalmopathy.

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Literatur

  1. Bahn RS, Heufelder AE. Pathogenesis of Graves’ ophthalmopathy, N Engl J Med 1993; 329: 1468–75.

    Article  PubMed  CAS  Google Scholar 

  2. Bailey CC, Kabala J, Laitt R, et al. Magnetic resonance imaging in thyroid eye disease. Eye 1996; 10: 617–9.

    PubMed  Google Scholar 

  3. Balazs C, Kiss E, Vamos A, Molnar I, Farid NR. Beneficial effect of pentoxifylline on thyroid associated ophthalmopathy: a pilot study. J Clin Endocrinol Metab 1997; 82: 1999–2002.

    PubMed  CAS  Google Scholar 

  4. Bartalena L, Marcocci C, Pinchera A. Cytokine antagonists: new ideas for the management of Graves’ ophthalmopathy. J Clin Endocrinol Metab 1996; 81: 446–8.

    Article  PubMed  CAS  Google Scholar 

  5. Bartley GB, Fatourechi V, Kadrmas EF, et al. The treatment of Graves’ ophthalmopathy in a incidence cohort. Am J Ophthalmol 1996; 121: 200–6.

    PubMed  CAS  Google Scholar 

  6. Bartley GB, Fatourechi V, Kadrmas EF, et al. Clinical features of Graves’ ophthalmopathy in an incidence cohort. Am J Ophthalmol 1996; 121: 284–90.

    PubMed  CAS  Google Scholar 

  7. Bartley GB, Fatourechi V, Kadrmas EF, et al. Chronology of Graves’ ophthalmopathy in an incidence cohort. Am J Ophthalmol 1996; 121: 426–34.

    PubMed  CAS  Google Scholar 

  8. Bohuslavizki KH, Oberwohrmann S, Brenner W, et al. 111In-octreotide imaging in patients with long-standing Graves’ ophthalmopathy. Nucl Med Commun 1995; 16: 912–6.

    PubMed  CAS  Google Scholar 

  9. Burch HB, Wartofsky L. Graves’ ophthalmopathy: current concepts regarding pathogenesis and management. Endocr Rev 1993; 14: 747–93.

    PubMed  CAS  Google Scholar 

  10. Burch HB, Sellitti D, Barnes SG, Nagy EV, Bahn RS, Burman KD. Thyrotropin receptor antisera for the detection of immunoreactive protein species in retroocular fibroblasts obtained from patients with Graves’ ophthalmopathy. J Clin Endocrinol Metab 1994; 78: 1384–91.

    Article  PubMed  CAS  Google Scholar 

  11. Classification of eye changes of Graves’ disease. Thyroid 1992; 2: 235–6.

    Google Scholar 

  12. Crisp MS, Lane C, Halliwell M, Wynford-Thomas D, Ludgate M. Thyrotropin receptor transcripts in human adipose tissue. J Clin Endocrinol Metab 1997; 82: 2003–5.

    PubMed  CAS  Google Scholar 

  13. De Bellis A, Bizzarro A, Gattoni A, et al. Behaviour of soluble intercellular adhesion molecule-1 and endothelial-leukocyte adhesion molecule-1 concentrations in patients with Graves’ disease with or without ophthalmopathy and in patients with toxic ademoma. J Clin Endocrinol Metab 1995; 80: 2118–21.

    Article  PubMed  Google Scholar 

  14. De Carli M, D’Elios MM, Mariotti S, et al. Cytolytic T cells with Th1-like cytokine profile predominate in retroorbital lymphocytic infiltrates of Graves’ ophthalmopathy. J Clin Endocrinol Metab 1993; 77: 1120–4.

    Article  PubMed  Google Scholar 

  15. Durak I, Durak H, Ergin M, Yurekli Y, Kaynak S. Somatostatin receptors in the orbits. Clin Nucl Med 1995; 20: 237–42.

    Article  PubMed  CAS  Google Scholar 

  16. Esser J, Sauerwein W, Olbricht T. Corticoid- und Strahlentherapie bei endokriner Orbitopathie. Nuklearmedizin 1995; 18: 163–77.

    Google Scholar 

  17. Feliciello A, Porcellini A, Ciullo I, Bonavolontà G, Avvedimento E, Fenzi G. Expression of thyrotropin-receptor mRNA in healthy and Graves’ disease retro-orbital tissue. Lancet 1993; 342: 337–8.

    Article  PubMed  CAS  Google Scholar 

  18. Förster G, Kahaly G. Rauchen und endokrine Orbitopathie. Dtsch Med Wochenschr 1997; 122: 1060–1.

    Google Scholar 

  19. Förster G, Otto E, Hansen C, Kahaly G. Analysis of orbital T cells recognizing retrobulbar antigens in Graves’ ophthalmopathy. Clin Exp Immunol 1998; 133 (im Druck).

  20. Grubeck-Loebenstein B, Trieb K, Sztanky A, Holter W, Anderl H, Wick G. Retrobulbar T cells from patients with Graves’ ophthalmopathy are CD8+ and specifically recognize autologous fibroblasts. J Clin Invest 1994; 93: 2738–43.

    Article  PubMed  CAS  Google Scholar 

  21. Hansen C, Fraiture B, Rouhi R, Otto E, Förster G, Kahaly G. HPLC glycosaminoglycan analysis in patients with Graves’ disease. Clin Sci 1997; 92: 511–7.

    PubMed  CAS  Google Scholar 

  22. Heufelder AE, Dutton CM, Sarkar G, Donovan KA, Bahn RS. Detection of TSH receptor RNA in cultured fibroblasts from patients with Graves’ ophthalmopathy and pretibial dermopathy. Thyroid 1993; 3: 297–300.

    Article  PubMed  CAS  Google Scholar 

  23. Heufelder AE, Bahn RS. Soluble intercellular adhesion molecule-1 (sICAM-1) in sera of patients with Graves’ ophthalmopathy and thyroid disease. Clin Exp Immunol 1993; 92: 296–302.

    PubMed  CAS  Google Scholar 

  24. Heufelder AE, Bahn RS. Modulation of Graves’ orbital fibroblast proliferation by cytokines and glucocorticoid receptor agonists. Invest Ophthalmol Vis Sci 1994; 35: 120–7.

    PubMed  CAS  Google Scholar 

  25. Heufelder AE, Herterich S, Ernst G, Bahn RS, Scriba PC. Analysis of retroorbital T cell antigen receptor variable region gene usage in patients with Graves’ ophthalmopathy. Eur J Endocrinol 1995; 132: 266–77.

    Article  PubMed  CAS  Google Scholar 

  26. Heufelder AE, Scriba PC. Characterization of adhesion receptors on cultured microvascular endothelial cells derived from the retroorbital connective tissue of patients with Graves’ ophthalmopathy. Eur J Endocrinol 1996; 134: 51–60.

    Article  PubMed  CAS  Google Scholar 

  27. Heufelder AE, Wenzel BE, Scriba PC. Antigen receptor variable region repertoires expressed by T cells infiltrating thyroid, retroorbital, and pretibial tissue in Graves’ disease. J Clin Endocrinol Metab 1996; 81: 3733–9.

    Article  PubMed  CAS  Google Scholar 

  28. Hiromatsu Y, Tanaka K, Sato M, et al. Intravenous methylprednisolone pulse therapy for Graves’ ophthalmopathy. Endocr J 1993; 40: 63–72.

    Article  PubMed  CAS  Google Scholar 

  29. Hiromatsu Y, Sato M, Inoue Y, et al. Localization and clinical significance of thyrotropin receptor mRNA expression in orbital fat and eye muscle tissue from patients with thyroid-associated ophthalmopathy. Thyroid 1996; 6: 553–62.

    Article  PubMed  CAS  Google Scholar 

  30. Hosojima H, Uchida K. Availability of an anti platelet aggregation inhibitor, ticlopidine, in the treatment of Graves’ ophthalmopathy. J Drug Dev Clin Pract 1996; 8: 129–33.

    CAS  Google Scholar 

  31. Kahaly G, Böckmann H, Beyer J, Bischoff S. Longterm observation of endocrine ophthalmopathy and retrospective appraisal of therapeutic measures. J Endocrinol Invest 1990; 13: 287–92.

    PubMed  CAS  Google Scholar 

  32. Kahaly G, Stover C, Otto E, Beyer J, Schuler M. Glycosaminoglycans in thyroid-associated ophthalmopathy. Autoimmunity 1992; 13: 81–8.

    Article  PubMed  CAS  Google Scholar 

  33. Kahaly G, Hansen C, Felke B, Dienes HP. Immunohistochemical staining of retrobulbar adipose tissue in Graves’ ophthalmopathy. Clin Immunol Immunopathol 1994; 73: 53–62.

    Article  PubMed  CAS  Google Scholar 

  34. Kahaly G, Hansen C, Beyer J, Winand R. Plasma glycosaminoglycans in endocrine ophthalmopathy. J Endocrinol Invest 1994; 17: 45–50.

    PubMed  CAS  Google Scholar 

  35. Kahaly G, Diaz M, Hahn K, Beyer J, Bockisch A. Indium-111-pentetreotide scintigraphy in Graves’ ophthalmopathy. J Nucl Med 1995; 36: 550–4.

    PubMed  CAS  Google Scholar 

  36. Kahaly G, Diaz M, Just M, Beyer J, Lieb W. Role of octreoscan and correlation with MR imaging in Graves’ ophthalmopathy. Thyroid 1995; 5: 107–11.

    Article  PubMed  CAS  Google Scholar 

  37. Kahaly G, Pitz S, Müller-Forell W, Hommel G. Randomized trial of intravenous immunoglobulins versus prednisolone in Graves’ ophthalmopathy. Clin Exp Immunol 1996; 106: 197–202.

    Article  PubMed  CAS  Google Scholar 

  38. Kahaly G, Rösler HP, Köhler B, et al. Randomised trial comparing three irradiation protocols for endocrine orbitopathy (EO). Exp Clin Endocrinol Diab 1997; (Suppl) 1, 31.

    Google Scholar 

  39. Kahaly G, Förster G, Pitz S, Rösler H-P, Mann W. Aktuelle interdisziplinäre Diagnostik und Therapie der endokrinen Orbitopathie. Dtsch Med Wochenschr 1997; 122: 27–32.

    Article  PubMed  CAS  Google Scholar 

  40. Kalmann R, Mourits MP, van der Pol JP, Koorneef L. Coronal approach for rehabilitative orbital decompression in Graves’ ophthalmopathy. Br J Ophthalmol 1997; 81; 41–5.

    Article  PubMed  CAS  Google Scholar 

  41. Krassas GE, Dumas A, Pontikides N, Kaltsas T. Somatostatin receptor scintigraphy and octreotide treatment in patients with thyroid eye disease. Clin Endocrinol (Oxf) 1995; 42: 571–80.

    Article  CAS  Google Scholar 

  42. Krassas GE, Kaltsas T, Dumas A, Pontikides N, Tolis G. Lanreotide in the treatment of patients with thyroid eye disease. Eur J Endocrinol 1997; 136: 416–22.

    Article  PubMed  CAS  Google Scholar 

  43. Krenning EP, Kwekkeboom DJ, Bakker WH, et al. Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe]- and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 1000 patients. Eur J Nucl Med 1993; 20: 716–31.

    Article  PubMed  CAS  Google Scholar 

  44. Kung AW, Michon J, Tai KS, Chan FL. The effect of somatostatin versus corticosteroid in the treatment of Graves’ ophthalmopathy. Thyroid 1996; 6: 381–4.

    Article  PubMed  CAS  Google Scholar 

  45. Major BJ, Cures A, Frauman AG. The full length and splice variant thyrotropin receptor is expressed exclusively in skeletal muscle of extraocular origin: a link to the pathogenesis of Graves’ ophthalmopathy. Biochem Biophys Res Commun 1997; 230: 493–6.

    Article  PubMed  CAS  Google Scholar 

  46. Mann W, Kahaly G, Lieb W, Amedee R. Orbital decompression for endocrine ophthalmopathy: the endonasal approach. Am J Rhinol 1994; 8: 123–7.

    Article  Google Scholar 

  47. McLachlan SM, Prummel MF, Rapoport B. Cell-mediated or humoral immunity in Graves’ ophthalmopathy? Profiles of T-cell cytokines amplified by polymerase chain reaction from orbital tissue. J Clin Endocrinol Metab 1994; 78: 1070–4.

    Article  PubMed  CAS  Google Scholar 

  48. McMab AA. Orbital decompression for thyroid orbitopathy. Aust NZJ Ophthalmol 1997; 25: 55–61.

    Article  Google Scholar 

  49. Metcalfe RA, Weetman AP. Stimulation of extraocular muscle fibroblasts by cytokines and hypoxia: possible role in thyroid-associated ophthalmopathy. Clin Endocrinol (Oxf) 1994; 40: 67–72.

    Article  CAS  Google Scholar 

  50. Molnar I, Balazs C. High circulating IL-6 levels in Graves’ ophthalmopathy. Autoimmunity 1997; 25: 91–6.

    Article  PubMed  CAS  Google Scholar 

  51. Mourits MP, Koorneef L, Wiersinga WM, Prummel MF, Berghout A, van der Gaag R. Clinical criteria for the assessment of disease activity in Graves’ ophthalmopathy: a novel approach. Br J Ophthalmol 1989; 73: 639–44.

    Article  PubMed  CAS  Google Scholar 

  52. Nakahara H, Noguchi S, Murakami N, et al. Graves’ ophthalmopathy: MR evaluation of 10-Gy versus 24-Gy irradiation combined with systemic corticosteroids. Radiology 1995; 196: 857–62.

    PubMed  CAS  Google Scholar 

  53. Otto AJ, Koorneef L, Mourits MP, Deen van Leewen L. Retrobulbar pressures measured during surgical decompression of the orbit. Br J Ophthalmol 1996; 80: 1042–5.

    Article  PubMed  CAS  Google Scholar 

  54. Otto E, Ochs K, Hansen C, Wall J, Kahaly G. Orbital tissue-derived T lymphocytes from patients with Graves’ ophthalmopathy recognize autologous orbital antigens. J Clin Endocrinol Metab 1996; 81: 3045–50.

    Article  PubMed  CAS  Google Scholar 

  55. Otto E, Förster G, Kuhlemann K, Hansen C, Kahaly G. TSH receptor in endocrine autoimmunity. Clin Exp Rheumatol 1996: 14: 77–84.

    Google Scholar 

  56. Ozata M, Bolu E, Sengul A, et al. Soluble intercellular adhesion molecule-1 concentrations in patients with subacute thyroiditis and in patients with Graves’ disease with or without ophthalmopathy. Endocr J 1996; 43: 517–25.

    Article  PubMed  CAS  Google Scholar 

  57. Ozata M, Bolu E, Sengul A, et al. Effects of octreotide treatment on Graves’ ophthalmopathy and circulating sICAM-1 levels. Thyroid 1996; 6: 283–8.

    Article  PubMed  CAS  Google Scholar 

  58. Pappa A, Calder V, Fells P, Lightman S. Adhesion molecule expression in vivo on extraocular muscles (EOM) in thyroid associated ophthalmopathy (TAO). Clin Exp Immunol 1997; 108: 309–13.

    Article  PubMed  CAS  Google Scholar 

  59. Paschke R, Vassart G, Ludgate M. Current evidence for and against the TSH receptor being the common antigen in Graves’ disease and thyroid associated ophthalmopathy. Clin Endocrinol 1995; 42: 565–9.

    Article  CAS  Google Scholar 

  60. Pfeilschifter J, Ziegler R. Smoking and endocrine ophthalmopathy: impact of smoking severity and current vs lifetime cigarette consumption. Clin Endocrinol (Oxf) 1996; 45: 477–81.

    Article  CAS  Google Scholar 

  61. Prummel MF, Mourits MP, Berghout A, et al. Prednisone and Cyclosporine in the treatment of severe Graves’ ophthalmopathy. N Engl J Med 1989; 321: 215–22

    Article  Google Scholar 

  62. Prummel MF, Mourits MP, Blank L, Berghout A, Koornneef L, Wiersinga WM. Randomized double-blind trial of prednisone versus radiotherapy in Graves’ ophthalmopathy. Lancet 1993; 342: 949–54.

    Article  PubMed  CAS  Google Scholar 

  63. Prummel MF, Wiersinga WM. Medical management of Graves’ ophthalmopathy. Thyroid 1995; 5: 231–4.

    PubMed  CAS  Google Scholar 

  64. Saber E, McDonnell J, Zimmermann KM, Yugar JE, Feldon SE. Extraocular muscle changes in experimental orbital venous stasis: some similarities to Graves’ orbitopathy. Graefes Arch Clin Exp Ophthalmol 1996; 234: 331–6.

    Article  PubMed  CAS  Google Scholar 

  65. Salvi M, Spaggiari E, Neri F, et al. The study of visual evoked potentials in patients with thyroid-associated ophthalmopathy identifies asymptomatic optic nerve involvement. J Clin Endocrinol Metab 1997; 82: 1027–30.

    Article  PubMed  CAS  Google Scholar 

  66. Seppel T, Schlaghecke R, Becker A, Engelbrecht V, Feldkamp J, Kornely E. High-dose intravenous therapy with 7S immunoglobulins in autoimmune endocrine ophthalmopathy. Clin Exp Reumatol 1996; 14: 109–14.

    Google Scholar 

  67. Sorsky A, Pardasani D, Gagnon A, Smith TJ. Evidence of adipocyte differentiation in human orbital fibroblasts in primary culture. J Clin Endocrinol Metab 1996; 81: 3428–31.

    Article  Google Scholar 

  68. Stark B, Olivari N. Treatment of exophthalmus by orbital fat removal. Clin Plast Surg 1993; 20: 285–9.

    PubMed  CAS  Google Scholar 

  69. Stover C, Otto E, Beyer J, Kahaly G. Cellular immunity and retrobulbar fibroblasts in Graves’ ophthalmopathy. Thyroid 1994; 4: 161–5.

    Article  PubMed  CAS  Google Scholar 

  70. Tagami T, Tanaka K, Sugawa H, et al. High dose intravenous steroid pulse therapy in thyroid associated ophthalmopathy. Endocr J 1996; 43: 689–99.

    Article  PubMed  CAS  Google Scholar 

  71. Tallstedt L, Lundell G. Radioiodine treatment, ablation, and ophthalmopathy: a balanced perspective. Thyroid 1997; 7: 241–5.

    Article  PubMed  CAS  Google Scholar 

  72. Tan GH, Dutton CM, Bahn RS. Interleukin-1 (IL-1) receptor antagonist and soluble IL-1 receptor inhibit IL-1-induced glycosaminoglycan production in cultured human orbital fibroblasts from patients with Graves’ ophthalmopathy. J Clin Endocrinol Metab 1996; 81: 449–52.

    Article  PubMed  CAS  Google Scholar 

  73. Wall JR, Kennerdell JS. Progress in thyroid-associated ophthalmopathy. Autoimmunity 1995; 22: 191–5.

    Article  PubMed  CAS  Google Scholar 

  74. Wall JR, Hayes M, Scalise D, et al. Native gel electrophoresis and isoelectric focusing of a 64-kilodalton eye muscle protein shows that it is an important target for serum antibodies in patients with thyroid-associated ophthalmopathy and not expressed in other skeletal muscle. J Clin Endocrinol Metab 1995; 80: 1226–32.

    Article  PubMed  CAS  Google Scholar 

  75. Weetman AP. The role of T lymphocytes in thyroid-associated ophthalmopathy. Autoimmunity 1992; 13: 69–73.

    Article  PubMed  CAS  Google Scholar 

  76. Zhang ZG, JR Wall, Bernard NF. Tissue distribution and quantitation of a gene expressing a 64-kDa antigen associated with thyroid-associated ophthalmopathy. Clin Immunol Immunopathol 1996; 80: 236–44.

    Article  PubMed  CAS  Google Scholar 

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  1. Klinlk und Poliklinik Innere Medizin, Schwerpunkt Endokrinologie und Stoffwechselerkrankungen, Klinikum der Johannes-Gutenberg-Universität Mainz, Langenbeckstraße 1, D-55101, Mainz

    Gregor Förster & George Kahaly

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  1. Gregor Förster
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Förster, G., Kahaly, G. Endokrine Orbitopathie 1998. Med Klin 93, 365–373 (1998). https://doi.org/10.1007/BF03044681

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