Skip to main content
SpringerLink
Log in

Thyroid-Associated Ophthalmopathy and Dermopathy

  • Chapter
Autoimmune Endocrinopathies

Part of the book series: Contemporary Endocrinology ((COE,volume 15))

  • 159 Accesses

Abstract

Various names have been given to the eye signs associated with autoimmune thyroid disease—Graves’ ophthalmopathy, endocrine exophthalmos, ophthalmic Graves’ disease, and so on—but the term thyroid-associated ophthalmopathy (TAO) is now generally accepted as the best, providing recognition that the condition is not always associated with Graves’ disease. The major clinical signs are shown in Table 1 and Fig. 1. Fortunately TAO does not cause problems of diplopia or loss of visual fields in the majority of patients, but the impact of having bulging eyes and periorbital swelling on the patient’s sense of well-being is often underestimated, and even the grittiness and discomfort that are common and among the early features of TAO prove irksome to many patients with Graves’ disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Wartofsky L. (on behalf of various Thyroid Associations). Classification of eye changes of Graves’ disease. Thyroid 1992;2:235–236.

    Google Scholar 

  2. Mourits MPh, Prummel MF, Wiersinga WM, Koorneef L. Clinical activity score as a guide in the management of patients with Graves’ ophthalmopathy. Clin Endocrinol 1997;47:9–14.

    CAS  Google Scholar 

  3. Bartley GB. The epidemiological characteristics and clinical course of ophthalmopathy associated with autoimmune thyroid disease in Olmsted County, Minnesota. Trans Am Ophthalmol Soc 1994; 42:477–588.

    Google Scholar 

  4. Burch HB, Wartofsky L. Graves’ ophthalmopathy: current concepts regarding pathogenesis and management. Endocr Rev 1993;14:747–793.

    PubMed  CAS  Google Scholar 

  5. Villadolid MC, Yokoyama N, Izumi M, Nishikawa T, Kimura H, Ashizawa K, et al. Untreated Graves’ disease patients without clinical ophthalmopathy demonstrate a high frequency of extraocular muscle (EOM) enlargement by magnetic resonance. J Clin Endocrinol Metab 1995;80:2830–2833.

    PubMed  CAS  Google Scholar 

  6. Perros P, Crombie AL, Matthews JNS, Kendall-Taylor P. Age and gender influence the severity of thyroid-associated ophthalmopathy: a study of 101 patients attending a combined thyroid-eye clinic. Clin Endocrinol 1993;38:367–372.

    CAS  Google Scholar 

  7. Prummel MF, Wiersinga WM, Mourits MPh, Koorneef L, Gerghout A, van der Gaag R. Effect of abnormal thyroid function on the severity of Graves’ ophthalmopathy. Arch Intern Med 1990;150: 1098–1101.

    PubMed  CAS  Google Scholar 

  8. Chou P-I, Feldon SE. Late onset dysthyroid optic neuropathy. Thyroid 1994;4:213–216.

    PubMed  CAS  Google Scholar 

  9. Perros P, Crombie AL, Kendall-Taylor P. Natural history of thyroid associated ophthalmopathy. Clin Endocrinol 1995;42:45–50.

    CAS  Google Scholar 

  10. Campbell RJ. Immunology of Graves’ ophthalmopathy: retrobulbar histology and histochemistry. Acta Endocrinol 1989;121(Suppl 2):9–16.

    Google Scholar 

  11. Trokel SL, Jakobiec FA. Correlation of CT scanning and pathological features of ophthalmic Graves’ disease. Ophthalmologica 1981;88:553–564.

    CAS  Google Scholar 

  12. Smith TJ, Bahn RS, Gorman CA. Connective tissue, glycosaminoglycans, and diseases of the thyroid. Endocr Rev 1989;10:366–391.

    PubMed  CAS  Google Scholar 

  13. Tallstedt L, Norberg R. Immunohistochemical staining of normal and Graves’ extraocular muscle. Invest Ophthalmol Vis Sci 1988;29:175–184.

    PubMed  CAS  Google Scholar 

  14. Weetman AP, Cohen S, Gatter KC, Fells P, Shine B. Immunohistochemical analysis of the retrobulbar tissues in Graves’ ophthalmopathy. Clin Exp Immunol 1989;75:222–227.

    PubMed  CAS  Google Scholar 

  15. Heufelder AE, Bahn RS. Elevated expression in situ of selectin and immunoglobulin superfamily type adhesion molecules in retroocular connective tissues from patients with Graves’ ophthalmopathy. Clin Exp Immunol 1993;91:381–389.

    PubMed  CAS  Google Scholar 

  16. 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;108:309–313.

    PubMed  CAS  Google Scholar 

  17. Small RG. Enlargement of levator palpebrae superioris muscle fibers in Graves’ ophthalmopathy. Ophthalmology 1989;96:424–430.

    PubMed  CAS  Google Scholar 

  18. Hudson HL, Levin L, Feldon SE. Graves’ exophthalmos unrelated to extraocular muscle enlargement. Ophthalmology 1991;98:1495–1499.

    PubMed  CAS  Google Scholar 

  19. Hesse RJ. Graves’ exophthalmos without muscle involvement. Ophthalmology 1992;99:645 (letter).

    Google Scholar 

  20. Birchall D, Goodall KL, Noble JL, Jackson A. Graves’ ophthalmopathy: intracranial fat prolapse on CT images as an indicator of optic nerve compression. Radiology 1996;200:123–127.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  22. Sergott RC, Felberg NT, Savino PJ, Blizzard JJ, Schatz NJ, Sanford CA. Association of HLA antigen BW35 with severe Graves’ ophthalmopathy. Invest Ophthalmol Vis Sci 1983;24:124–127.

    PubMed  CAS  Google Scholar 

  23. Kendall-Taylor P, Stephenson A, Stratton A, Papiha SS, Perros P, Roberts DF. Differentiation of autoimmune ophthalmopathy from Graves’ hyperthyroidism by analysis of genetic markers. Clin Endocrinol 1988;28:601–610.

    CAS  Google Scholar 

  24. Frecker M, Stenszky V, Balazs C, Kozma L, Kraszits E, Farid NR. Genetic factors in Graves’ ophthalmopathy. Clin Endocrinol 1986;25:479–485.

    CAS  Google Scholar 

  25. Frecker M, Mercer G, Skanes VM, Farid NR. Major histocompatibility complex (MHC) factors predisposing to and protecting against Graves’ eye disease. Autoimmunity 1988;1:307–315

    PubMed  CAS  Google Scholar 

  26. Weetman AP, So AK, Warner CA, Foroni L, Fells P, Shine B. Immunogenetics of Graves’ ophthalmopathy. Clin Endocrinol 1988;28:619–628.

    CAS  Google Scholar 

  27. Weetman AP, Zhang L, Webb S, Shine B. Analysis of HLA-DQB and HLA-DPB alleles in Graves’ disease by oligonucleotide probing of enzymatically amplified DNA. Clin Endocrinol 1990;33:65–71.

    CAS  Google Scholar 

  28. Inoue D, Sato K, Enomoto T, Sugawa H, Maeda M, Inoko H, et al. Correlation of HLA types and clinical findings in Japanese patients with hyperthyroid Graves’ disease: evidence indicating the existence of four subpopulations. Clin Endocrinol 1992;36:75–82.

    CAS  Google Scholar 

  29. Weetman AP, Poole J. Failure to find an association of blood group P1 with thyroid-associated ophthalmopathy. Clin Endocrinol 1992;37:423–425.

    CAS  Google Scholar 

  30. 30. Tellez M, Cooper J, Edmonds C. Graves’ ophthalmopathy in relation to cigarette smoking and ethnic origin. Clin Endocrinol 1992;36:291–294.

    Google Scholar 

  31. Hagg E, Asplund K. Is endocrine ophthalmopathy related to smoking? Br Med J 1987;295:634–365.

    CAS  Google Scholar 

  32. Bartalena L, Bogazzi F, Tanda ML, Manetti L, Dell’Unto E, Martino E. Cigarette smoking and the thyroid. Eur J Endocrinol 1995;133:507–512.

    PubMed  CAS  Google Scholar 

  33. Pfeilschifter J, Ziegler R. Smoking and endocrine ophthalmopathy: impact of smoking severity and current vs lifetime cigarette consumption. Clin Endocrinol 1996;45:477–481.

    CAS  Google Scholar 

  34. 34. Weetman AP. Thyroid-associated eye disease: pathophysiology. Lancet 1991;358:25–28.

    Google Scholar 

  35. Bahn RS, Heufelder AE. Pathogenesis of Graves’ ophthalmopathy. N Engl J Med 1993;329:1468–1475.

    PubMed  CAS  Google Scholar 

  36. McLachlan SM, Bahn RS, Rapoport B. Endocrine ophthalmopathy: a re-evaluation of the association with thyroid autoantibodies. Autoimmunity 1992;14:143–148.

    PubMed  CAS  Google Scholar 

  37. Kuroki T, Ruf J, Whelan L, Miller A, Wall JR. Antithyroglobulin monoclonal and autoantibodies cross-react with an orbital connective tissue membrane antigen: a possible mechanism for the association of ophthalmopathy with autoimmune thyroid disorders. Clin Exp Immunol 1985;62:361–370.

    PubMed  CAS  Google Scholar 

  38. Tao T-W, Cheng P-J, Pham H, Leu S-L, Kriss JS. Monoclonal antithyroglobulin antibodies derived from immunizations of mice with human eye muscle and thyroid membranes. J Clin Endocrinol Metab 1986;63:577–582.

    PubMed  CAS  Google Scholar 

  39. Ludgate M, Dong Q, Dreyfus PA, Taylor P, Vassart G, Soreq H. Definition, at the molecular level, of a thyroglobulin-acetylcholinesterase shared epitope: study of its pathophysiological significance in patients with Graves’ disease. Autoimmunity 1989;3:167–176.

    PubMed  CAS  Google Scholar 

  40. Weetman AP, Tse CK, Randall WR, Tsim KWK, Barnard EA. Acetylcholinesterase antibodies and thyroid autoimmunity. Clin Exp Immunol 1988;71:96–99.

    PubMed  CAS  Google Scholar 

  41. Mappouras DG, Philippou G, Haralambous S, Tzartos SJ, Balafas A, Souvatzoglou A, et al. Antibodies to acetylcholinesterase cross-reacting with thyroglobulin in myasthenia gravis and Graves’ disease. Clin Exp Immunol 1995;100:336–343.

    PubMed  CAS  Google Scholar 

  42. Brimijoin S, Lennon VA. Autoimmune preganglionic sympathectomy induced by acetylcholinesterase antibodies. Proc Natl Acad Sci USA 1990;87:9630–9634.

    PubMed  CAS  Google Scholar 

  43. Heufelder AE. Involvement of orbital fibroblast and TSH receptor in the pathogenesis of Graves’ ophthalmopathy. Thyroid 1995;5:331–340.

    PubMed  CAS  Google Scholar 

  44. Wall JR, Strakosch CR, Fang SL, Ingbar SH, Braverman LE. Thyroid binding antibodies and other immunological abnormalities in patients with Graves’ ophthalmopathy: effect of treatment with cyclophosphamide. Clin Endocrinol 1979;10:78–91.

    Google Scholar 

  45. Nishikawa M, Yoshimura M, Toyoda N, Masaki H, Yonemoto T, Gondou A, et al. Correlation of orbital muscle changes evaluated by magnetic resonance imaging and thyroid-stimulating antibody in patients with Graves’ ophthalmopathy. Acta Endocrinol 1993;129:213–219.

    PubMed  CAS  Google Scholar 

  46. Shokeir MO, Pudek MR, Katz S, Rootman J, Kendler DL. The relationship of thyrotropin receptor antibody levels to the severity of thyroid orbitopathy. Clin Biochem 1996;29:187–189.

    PubMed  CAS  Google Scholar 

  47. Kasagi K, Hidaka A, Nakamura H, Takeuchi R, Misaki T, Iida Y, et al. Thyrotropin receptor antibodies in hypothyroid Graves’ disease. J Clin Endocrinol Metab 1993;76:504–508.

    PubMed  CAS  Google Scholar 

  48. 48. Atkinson S, Holcombe M, Kendall-Taylor P. Ophthalmopathic immunoglobulin in patients with Graves’ ophthalmopathy. Lancet 1984;ii:374–376.

    Google Scholar 

  49. Kadluboswki M, Irvine WJ, Rowland AC. The lack of specificity of ophthalmic immunoglobulins in Graves’ disease. J Clin Endocrinol Metab 1986;63:990–995.

    Google Scholar 

  50. Ahmann A, Baker JR, Weetman AP, Wartofsky L, Nutman TB, Burman KD. Antibodies to porcine eye muscle in patients with Graves’ ophthalmopathy; identification of serum immunoglobulins directed against unique determinants by immunoblotting and enzyme-linked immunosorbent assay. J Clin Endocrinol Metab 1987;64:454–460.

    PubMed  CAS  Google Scholar 

  51. Schifferdecker E, Ketzler-Sasse U, Boehm BO, Ronsheimer HB, Scherbaum WA, Schoffling K. Re-evaluation of eye muscle autoantibody determination in Graves’ ophthalmopathy: failure to detect a specific antigen by use of enzyme-linked immunosorbent assay, indirect immunofluorescence, and immunoblotting techniques. Acta Endocrinol 1989;121:643–650.

    PubMed  CAS  Google Scholar 

  52. Salvi M, Hiromatsu Y, Bernard N, How J, Wall JR. Human orbital tissue and thyroid membrane express a 64kDa protein which is recognised by autoantibodies in serum of patients with thyroidassociated ophthalmopathy. FEBS Lett 1988;232:135–139.

    PubMed  CAS  Google Scholar 

  53. Weightman D, Kendall-Taylor P. Cross-reaction of eye muscle antibodies with thyroid tissue in thyroid-associated ophthalmopathy. J Endocrinol 1989;122:201–206.

    PubMed  CAS  Google Scholar 

  54. Kendler DL, Huber GK, Rootman J, Davies TF. A 64kDa membrane antigen is a recurrent epitope for natural autoantibodies in patients with Graves’ thyroid and ophthalmic diseases. Clin Endocrinol 1991;35:539–547.

    CAS  Google Scholar 

  55. Salvi M, Bernard N, Miller A, Zhang Z, Gardini E, Wall JR. Presence of antibodies reactive with a 64kDa eye muscle membrane antigen in thyroid-associated ophthalmopathy. Thyroid 1991;1:207–213.

    PubMed  CAS  Google Scholar 

  56. Chang TC, Chang TJ, Huang YS, Huang KM, Su RJ, Kao SCS. Identification of autoantigen recognized by autoimmune ophthalmopathy sera with immunoblotting correlated with orbital computed tomographv. Clin Immunol Immunopathol 1992;65:161–166.

    PubMed  CAS  Google Scholar 

  57. Hiromatsu Y, Sato M, Tanaka K, Shoji S, Nonaka K, Chinami M, et al. Significance of anti-eye muscle antibody in patients with thyroid-associated ophthalmopathy by quantitative Western blot. Autoimmunity 1992;14:9–16.

    PubMed  CAS  Google Scholar 

  58. Tandon N, Yan SL, Arnold K, Metcalfe RA, Weetman AP. Immunoglobulin class and subclass distribution of eye muscle and fibroblast antibodies in patients with thyroid-associated ophthalmopathy. Clin Endocrinol 1994;40:629–639.

    CAS  Google Scholar 

  59. Kadlubowski M, Irvine WJ, Rowland AC. Anti-muscle antibodies in Graves’ ophthalmopathy. J Clin Lab Immuno1 1987;24:105–111.

    CAS  Google Scholar 

  60. Dong Q, Ludgate M, Vassart G. Cloning and sequencing of a novel 64kDa antoantigen recognized by patients with autoimmune thyroid disease. J Clin Endocrinol Metab 1991;72:1375–1381.

    PubMed  CAS  Google Scholar 

  61. Bernard NF, Nygen TN, Tyutunikov A, Stolarski C, Scalise D, Genovese C, et al. Antibodies against 1D, a recombinant 64kDa membrane protein, are associated with ophthalmopathy in patients with thyroid autoimmunity. Clin Immunol Immunopathol 1994;70:225–233.

    PubMed  CAS  Google Scholar 

  62. Ross PV, Koenig RJ, Arscott P, Ludgate M, Waier M, Nelson CC, et al. Tissue specificity and serologic reactivity of an autoantigen associated with autoimmune thyroid disease. J Clin Endocrinol Metab 1993;77:433–438.

    PubMed  CAS  Google Scholar 

  63. Barsouk A, Wengrowicz S, Scalise D, Stolarski C, Nebes V, Sato M. et al. New assays for the measurement of serum antibodies reactive with eye muscle membrane antigens confirm their significance in thyroid-associated ophthalmopathy. Thyroid 1995;5:195–200.

    PubMed  CAS  Google Scholar 

  64. Wall JR, Hayes M, Scalise D, Stolarski C, Nebes V, Kiljanski J, et al. Native gel electrophoresis and isoelectric focusing of a 64-kilodalton eye muscle protein shows that it is an important target for serum autoantibodies in patients with thyroid-associated ophthalmopathy and not expressed in other skeletal muscle. J Clin Endocrinol Metab 1995;80:1226–1232.

    PubMed  CAS  Google Scholar 

  65. Bahn RS, Gorman CA, Johnson CM, Smith TJ. Presence of antibodies in the sera of patients with Graves’ disease recognizing a 23 kilodalton fibroblast protein. J Clin Endocrinol Metab 1989;69:622–628.

    PubMed  CAS  Google Scholar 

  66. Arnold K, Metcalfe RA, Weetman AP. Immunoglobulin A class fibroblast antibodies in patients with Graves’ disease and pretibial myxedema. J Clin Endocrinol Metab 1995;80:3430–3437.

    PubMed  CAS  Google Scholar 

  67. Molnár I, Balázs CS. Comparative study on IgG and IgA antibodies against human thyroid and eyemuscle antigens in Graves’ ophthalmopathy. Acta Med Hungarica 1991;48:13–21.

    Google Scholar 

  68. Stover C, Otto E, Beyer J, Kahaly G. Humoral immunity and retrobulbar fibroblasts in endocrine ophthalmopathy. Acta Endocrinol 1992;126:394–398.

    PubMed  CAS  Google Scholar 

  69. Dillon J, Zhang Z-Q, Hiromatsu N, Bernard M, Salvi M, Wall JR. Failure to detect complementmediated antibody-dependent cytotoxicity against human orbital tissue cells in the serum of patients with thyroid-associated ophthalmopathy. Autoimmunity 1989;5:125–132.

    PubMed  CAS  Google Scholar 

  70. Ringel MD, Taylor T, Barsouk A, Wall JR, Freter CE, Howard RS, et al. Hodgkin’s disease treated with neck radiation is associated with increased antibody-dependent cellular cytotoxicity against human extraocular muscle cells. Thyroid 1997;7:425–432.

    PubMed  CAS  Google Scholar 

  71. Perros P, Kendall-Taylor P. Biological activity of autoantibodies from patients with thyroid-associated ophthalmopathy: in vitro effects of porcine extraocular myoblasts. Q J Med 1992;305:691–706.

    Google Scholar 

  72. Weightman DR, Perros P, Sherif IH, Kendall-Taylor P. Autoantibodies to IGF-1 binding sites in thyroid associated ophthalmopathy. Autoimmunity 1993;16:251–257.

    PubMed  CAS  Google Scholar 

  73. Jaume JC, Portolano S, Prummel MF, McLachlan SM, Rapoport B. Molecular cloning and characterization of genes for antibodies generated by orbital tissue-infiltrating B-cells in Graves’ ophthalmopathy. J Clin Endocrinol Metab 1994;78:348–352.

    PubMed  CAS  Google Scholar 

  74. McLachlan SM, Prummel MF, Jaume JC, Rapoport B. Immunoglobulin A in Graves’ orbital tissue: Deoxyribonucleic acid amplification by polymerase chain reaction. J Endocrinol Invest 1994;17: 247–252.

    PubMed  CAS  Google Scholar 

  75. Felberg NT, Sergott RC, Savino PJ, Blizzard JJ, Schatz NJ, Amsel J. Lymphocyte subpopulations in Graves’ ophthalmopathy. Arch Ophthalmol 1985;103:656–659.

    PubMed  CAS  Google Scholar 

  76. Tyutyunikov A, Raikow RB, Kennerdell JS, Kazim M, Dalbow MH, Scalise D. Re-examination of peripheral blood T cell subsets in dysthyroid orbitopathy. Invest Ophthalmol Vis Sci 1992;33: 2299–2303.

    PubMed  CAS  Google Scholar 

  77. Pedersen BK, Perrild H, Feldt-Rasmussen U, Christensen T, Klarlund K, Hansen JM. Suppressed natural killer cell activity in patients with euthyroid Graves’ ophthalmopathy. Autoimmunity 1989;2: 291–298.

    PubMed  CAS  Google Scholar 

  78. Prummel MF, Wiersinga WM, van der Gaag R, Mourits MP, Koornneef L. Soluble IL-2 receptor levels in patients with Graves’ ophthalmopathy. Clin Exp Immunol 1992;88:405–409.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  80. Hofbauer LC, Mühlberg T, Konig A, Heufelder G, Schworm H-D, Heufelder AE. Soluble interleukin1 receptor antagonist serum levels in smokers and non-smokers with Graves’ ophthalmopathy undergoing orbital radiotherapy. J Clin Endocrinol Metab 1997;82:2244–2247.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  82. Arnold K, Tandon N, McIntosh RS, Elisei R, Ludgate M, Weetman AP. T cell responses to orbital antigens in thyroid-associated ophthalmopathy. Clin Exp Immunol 1994;96:329–334.

    PubMed  CAS  Google Scholar 

  83. Stover C, Otto E, Beyer J, Kahaly G. Cellular immunity and retrobulbar fibroblasts in Graves’ ophthalmopathy. Thyroid 1994;4:161–165.

    PubMed  CAS  Google Scholar 

  84. Grubeck-Loebenstein B, Trieb K, Sztankay 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;93:2738–2743.

    PubMed  CAS  Google Scholar 

  85. De Carli M, D’Elios MM, Mariotti S, Marcocci C, Pinchera A, Ricci M, et al. Cytolytic T cells with Th1-like cytokine profile predominate in retroorbital lymphocytic infiltrates of Graves’ ophthalmopathy. J Clin Endocrinol Metab 1993;77:1120–1124.

    PubMed  CAS  Google Scholar 

  86. Otto EA, Ochs K, Hansen C, Wall JR, Kahaly GJ. Orbital tissue-derived T lymphocytes from patients with Graves’ ophthalmopathy recognize autologous orbital antigens. J Clin Endocrinol Metab 1996; 81:3045–3050.

    PubMed  CAS  Google Scholar 

  87. Pappa A, Calder V, Ajjan R, Fells P, Ludgate M, Weetman AP, Lightman S. Analysis of extraocular muscle-infiltrating T cells in thyroid-associated ophthalmopathy (TAO). Clin Exp Immunol 1997; 109:362–369.

    PubMed  CAS  Google Scholar 

  88. 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;132:266–277.

    PubMed  CAS  Google Scholar 

  89. 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 81:1996;3733–3739.

    PubMed  CAS  Google Scholar 

  90. Heufelder AE, Bahn RS. Detection and localization of cytokine immunoreactivity in retro-ocular connective tissue in Graves’ ophthalmopathy. Eur J Clin Invest 1993;23:10–17.

    PubMed  CAS  Google Scholar 

  91. 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;78:1070–1074.

    PubMed  CAS  Google Scholar 

  92. Korducki JM, Loftus SJ, Bahn RS. Stimulation of glycosaminoglycan production in cultured human retroocular fibroblasts. Invest Ophthalmol Vis Sci 1992;33:2037–2042.

    PubMed  CAS  Google Scholar 

  93. Smith TJ, Bahn RS, Gorman CA, Cheavens M. Stimulation of glycosaminoglycan accumulation by interferon gamma in cultured human retroocular fibroblasts. J Clin Endocrinol Metab 1991;72: 1169–1171.

    PubMed  CAS  Google Scholar 

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

    CAS  Google Scholar 

  95. Hansson HA, Petruson B, Skottner A. Somatomedin C in pathogenesis of malignant exophthalmos of endocrine origin. Lancet 1986;I:218–219.

    Google Scholar 

  96. Smith TJ, Wang H-S, Hogg MG, Henrikson RC, Keese CR, Giaever I. Prostaglandin E2 elicits a morphological change in cultured orbital fibroblasts from patients with Graves’ ophthalmopathy. Proc Natl Acad. Sci USA 1994;91:5094–5098.

    CAS  Google Scholar 

  97. Smith TJ, Bahn RS, Gorman CA. Hormonal regulations of hyaluronate synthesis in cultured human fibroblasts: Evidence for differences between retroocular and dermal fibroblasts. J Clin Endocrinol Metab 1989;69:1019–1023.

    PubMed  CAS  Google Scholar 

  98. Berenson CS, Smith TJ. Human orbital fibroblasts in culture express ganglioside profiles distinct from those in dermal fibroblasts. J Clin Endocrinol Metab 1995;80:2668–2674.

    PubMed  CAS  Google Scholar 

  99. Heufelder AE, Wenzel BE, Gorman CA, Bahn RS. Detection, cellular localization, and modulation of heat shock proteins in cultured fibroblasts from patients with extrathyroidal manifestations of Graves’ disease. J Clin Endocrinol Metab 1991;73:739–745.

    PubMed  CAS  Google Scholar 

  100. Heufelder AE, Smith TJ, Gorman CA, Bahn RS. Increased induction of HLA-DR by interferon-y in cultured fibroblasts derived from patients with Graves’ ophthalmopathy and pretibial dermopathy. J Clin Endocrinol Metab 1991;73:307–313.

    PubMed  CAS  Google Scholar 

  101. Tanaka K, Hiromatsu Y, Sato M, Inoue Y, Nonaka K. Localization of heat shock protein in orbital tissue from patients with Graves’ ophthalmopathy using in situ hybridization. Life Sci 1993;54:355–359.

    Google Scholar 

  102. 102. Hiromatsu Y, Tanaka K, Ishisaka N, Kamachi J, Kuroki T, Hoshino T, et al. Human histocompatibility leukocyte antigen-DR and heat shock protein-70 expression in eye muscle tissue in thyroid-associated ophthalmopathy. J Clin Endocrinol Metab 1995;80:685–691.

    Google Scholar 

  103. Salmon M, Scheel-Toellner D, Hulssoon AP, Pilling D, Shamsadeen N, Hyde H, et al. Inhibition of T cell apoptosis in the rheumatoid synovium. J Clin Invest 1997;99:439–446.

    PubMed  CAS  Google Scholar 

  104. 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.

    PubMed  CAS  Google Scholar 

  105. Rotella CM, Zonefrati R, Toccafondi R, Valente WA, Kohn LD. Ability of monoclonal antibodies to the thyrotropin receptor to increase collagen synthesis in human fibroblasts: an assay which appears to measure exophthalmogenic immunoglobulins in Graves’ sera. J Clin Endocrinol Metab 1986; 62:357–367.

    PubMed  CAS  Google Scholar 

  106. Tao T-W, Leu S-L, Kriss JP. Biological activity of autoantibodies associated with Graves’ dermopathy. J Clin Endocrinol Metab 1989;69:90–99.

    PubMed  CAS  Google Scholar 

  107. Metcalfe RA, Davies R, Weetman AP. Analysis of fibroblast-stimulating activity in IgG from patients with Graves’ dermopathy. Thyroid 1993;3:207–212.

    PubMed  CAS  Google Scholar 

  108. Paschke R, Metcalfe A, Alcalde L, Vassart G, Weetman AP, Ludgate M. Presence of nonfunctional thyrotropin receptor variant transcripts in retroocular and other tissues. J Clin Endocrinol Metab 1994; 79:1234–1238.

    PubMed  CAS  Google Scholar 

  109. 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; 42:565–569.

    CAS  Google Scholar 

  110. Endo T, Ohta K, Haraguchi K, Onaya T. Cloning and functional expression of a thyrotropin receptor cDNA from rat fat cells. J Biol Chem 1995;270:10,833–10,837.

    Google Scholar 

  111. Crisp MS, Lane C, Halliwell M, Wynford-Thomas D, Ludgate M. Thyrotropin receptor transcripts in human adipose tissue. J Clin Endocrinol Metab 1997;82:2003–2005.

    PubMed  CAS  Google Scholar 

  112. Feliciello A, Porcellini A, Ciullo I, Bonavolontà G, Avvedimento EV, Fenzi G. Expression of thyrotropin-receptor mRNA in healthy and Graves’ disease retro-orbital tissue. Lancet 1993;342:337–338.

    PubMed  CAS  Google Scholar 

  113. 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.

    PubMed  CAS  Google Scholar 

  114. Mengistu M, Lukes YG, Nagy EV, Burch HB, Carr FE, Lahiri S, et al. TSH receptor gene expression in retro-ocular fibroblasts. J Endocrinol Invest 1994;17:437–441.

    PubMed  CAS  Google Scholar 

  115. 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;230:493–496.

    PubMed  CAS  Google Scholar 

  116. Hiromatsu Y, Sato M, Inoue Y, Koga M, Miyake I, Kameo J, et al. Localization and clinical significance of thyrotropin receptor mRNA expression in orbital fat and eye muscle tissues from patients with thyroid-associated ophthalmopathy. Thyroid 1996;6:553–562.

    PubMed  CAS  Google Scholar 

  117. 117. Aust G, Ludgate M, Weetman AP, Scherbaum WA, Paschke R. Illegitimate transcription of thyroid autoantigens. 10th International Congress. Endocrinology, San Francisco, USA 1996 (Abstract P3–989).

    Google Scholar 

  118. 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;78:1384–1391.

    PubMed  CAS  Google Scholar 

  119. Spitzweg C, Joba W, Hunt N, Heufelder AE. Analysis of human thyrotropin receptor gene expression and immunoreactivity in human orbital tissue. Eur J Endocrinol 1997;136:599–607.

    PubMed  CAS  Google Scholar 

  120. Stadlmayr W, Spitzweb C, Bichlmair A-M, Heufelder AE. TSH receptor transcripts and TSH receptorlike immunoreactivity in orbital and pretibial fibroblasts of patients with Graves’ ophthalmopathy and pretibial myxedema. Thyroid 1997;7:3–12.

    PubMed  CAS  Google Scholar 

  121. Bartalena L, Marcocci C, Bogazzi F, Panicucci M, Lepri A, Pinchera A. Use of corticosteroids to prevent progression of Graves’ ophthalmopathy after radioiodine therapy for hyperthyroidism. N Engl J Med 1989;321:1349–1352.

    PubMed  CAS  Google Scholar 

  122. Tallstedt L, Lundell G, TØrring O, Wallin G, Ljunggren J-G, Blomgren H, et al. Occurrence of ophthalmopathy after treatment for Graves’ hyperthyroidism. N Engl J Med 1992;326:1733–1738.

    PubMed  CAS  Google Scholar 

  123. Kung AWC, Cheng A. The incidence of ophthalmopathy after radioiodine therapy for Graves’ disease: prognostic factors and the role of methimazole. J Clin Endocrinol Metab 1994;79:542–546.

    PubMed  CAS  Google Scholar 

  124. DeGroot LJ, Gorman CA, Pinchera A, Bartalena L, Marocci C, Wiersinga WM, et al. Radiation and Graves’ ophthalmopathy. J Clin Endocrinol Metab 1995;80:339–349.

    PubMed  CAS  Google Scholar 

  125. Winsa B, Rastad J, Akerstrom G, Johansson H, Westermark K, Karlsson FA. Retrospective evaluation of subtotal and total thyroidectomy in Graves’ disease with and without endocrine ophthalmopathy. Eur J Endocrinol 1995;132:406–412.

    PubMed  CAS  Google Scholar 

  126. 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;81:449–452.

    PubMed  CAS  Google Scholar 

  127. Weetman AP, Wiersinga W. Current management of thyroid-associated ophthalmopathy in Europe. Results of an international survey. Clin Endocrinol 1998;49:21–28.

    CAS  Google Scholar 

  128. Prummel MF, Mourits MPh, Blank L, Berghout A, Koornneef L, Wiersinga WM. Randomised doubleblind trial of prednisone versus radiotherapy in Graves’ ophthalmopathy. Lancet 1993;342:949–954.

    PubMed  CAS  Google Scholar 

  129. Wiersinga WM. Immunosuppressive treatment of Graves’ ophthalmopathy. Thyroid 1992;2:229–233.

    PubMed  CAS  Google Scholar 

  130. Bartley GB, Fatourechi V, Kadrmas EF, Jacobsen SJ, Ilstrup DM, Garrity JA, et al. The treatment of Graves’ ophthalmopathy in an incidence cohort. Am J Ophthalmol 1996;121:200–206.

    PubMed  CAS  Google Scholar 

  131. Wilson WB, Prochoda M. Radiotherapy for thyroid orbitopathy. Effects on extraocular muscle balance. Arch Ophthalmol 1995;113:1420–1425.

    PubMed  CAS  Google Scholar 

  132. Snijders-Keilholz A, De Keizer RJW, Goslings BM, Van Dam EWCM, Jansen JThM, Broerse JJ. Probable risk of tumour induction after retro-orbital irradiation for Graves’ ophthalmopathy. Radiother Oncol 1996;38:69–71.

    PubMed  CAS  Google Scholar 

  133. Blank LECM, Barendsen GW, Prummel MF, Stalpers L, Wiersinga W, Koornneef L. Probable risk of tumor induction after retro-orbital irradiation for Graves’ ophthalmopathy. Radiother Oncol 1996; 40:187–189.

    PubMed  CAS  Google Scholar 

  134. Prummel MF, Mourits MPh, Berghout A, Krenning EP, van der Gaag R, Koornneef L, et al. Prednisone and cyclosporine in the treatment of severe Graves’ ophthalmopathy. N Engl J Med 1989;321:1353–1359.

    PubMed  CAS  Google Scholar 

  135. 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.

    PubMed  CAS  Google Scholar 

  136. Baschieri L, Antonelli A, Nardi S, Alberti B, Lepri A, Canapicchi R, et al. Intravenous immunoglobulin versus corticosteroid in treatment of Graves’ ophthalmopathy. Thyroid 1997;7:579–585.

    PubMed  CAS  Google Scholar 

  137. Kung AWC, Michon J, Tai KS, Chan FL. The effect of somatostatin versus corticosteroid in the treatment of Graves’ ophthalmopathy. Thyroid 1996;6:381–384.

    PubMed  CAS  Google Scholar 

  138. Krassas GE, Dumas A, Pontikides N, Kaltsas Th. Somatostatin receptor scintigraphy and octreotide treatment in paitents with thyroid eye disease. Clin Endocrinol 1995;42:571–580.

    CAS  Google Scholar 

  139. Imai Y, Odajima R, Inoue Y, Shishiba Y. Effect of growth factors on hyaluronan and proteoglycan synthesis by retroocular tissue fibroblasts of Graves’ ophthalmopathy in culture. Acta Endocrinol 1992;126:541–552.

    PubMed  CAS  Google Scholar 

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

    Google Scholar 

  141. Chang C-C, Chang T-C, Kao SCS, Kuo Y-F, Chien L-F. Pentoxifylline inhibits the proliferation and glycosaminoglycan synthesis of cultured fibroblasts derived from patients with Graves’ ophthalmopathy and pretibial myxoedema. Acta Endocrinol 1993;129:322–327.

    PubMed  CAS  Google Scholar 

  142. Fatourechi V, Pajouhi M, Fransway AF. Dermopathy of Graves’ disease (pretibial myxedema). Review of 150 cases. Medicine 1994;73:1–7.

    PubMed  CAS  Google Scholar 

  143. Wortsman J, Dietrich J, Traycoff RB, Stone S. Pretibial myxedema in thyroid disease. Arch Dermatol 1981;117:635–638.

    PubMed  CAS  Google Scholar 

  144. Peacey SP, Flemming L, Messenger A, Weetman AP. Is Graves’ dermopathy a generalized disorder? Thyroid 1996;6:1–4.

    Google Scholar 

  145. Somiach SC, Helm TN, Lawlor KB, Bergfeld WF, Bass J. Pretibial mucin. Histologic patterns and clinical correlation. Arch Dermatol 1993;129:1152–1155.

    Google Scholar 

  146. Matsuoka LY, Wortsman J, Uitto J, Hashimoto K, Kupehella CE, Eng AM, et al. Altered skin elastic fibers in hypothyroid myxedema and pretibial myxedema. Arch Intern Med 1985;145:117–121.

    PubMed  CAS  Google Scholar 

  147. Heufelder AE, Bahn RS, Scriba PC. Analysis of T cell antigen receptor variable region gene usage in patients with thyroid-related pretibial dermopathy. J Invest Dermatol 1995;105:372–378.

    PubMed  CAS  Google Scholar 

  148. Shishiba Y, Imai Y, Odajima R, Ozawa Y, Shimizu T. Immunoglobulin G of patients with circumscribed pretibial myxedema of Graves’ disease stimulates proteoglycan synthesis in human skin fibroblasts in culture. Acta Endocrinol 1992;127:44–51.

    PubMed  CAS  Google Scholar 

  149. Bahn RS, Dutton CM, Heufelder AE, Sarkar G. A genomic point mutation in the extracellular domain of the thyrotropin receptor in patients with Graves’ ophthalmopathy. J Clin Endocrinol Metab 1994; 78:256–260.

    PubMed  CAS  Google Scholar 

  150. Watson PF, French A, Pickerill AP, McIntosh RS, Weetman AP. Lack of association between a polymorphism in the coding region of the thyrotropin receptor gene and Graves’ disease. J Clin Endocrinol Metab 1995;80:1032–1035.

    PubMed  CAS  Google Scholar 

  151. Chang T-C, Wu S-L, Hsiao Y-L, Kuo S-T, Chien L-F, Kuo Y-F, et al. TSH and TSH receptor antibodybinding sites in fibroblasts of pretibial myxedema are related to the extracellular domain of entire TSH receptor. Clin Immunol Immunopathol 1994;71:113–120.

    PubMed  CAS  Google Scholar 

  152. Wu S-L, Chang T-C, Chang T-J, Kuo Y-F, Hsiao Y-L, Chang C-C. Cloning and sequencing of complete thyrotropin receptor transcripts in pretibial fibroblast culture cells. J Endocrinol Invest 1996; 19:365–370.

    PubMed  CAS  Google Scholar 

  153. Chang T-C, Kao SCS, Huang KM. Octreotide and Graves’ ophthalmopathy and pretibial myxoedema. Br Med J 1992;304:158.

    CAS  Google Scholar 

  154. Kuyvenhoven JPh, van der Pijl JW, Goslings BM, Wiersinga WM. Graves’ dermopathy: does octreotide scintigraphy predict the response to octreotide treatment? Thyroid 1996;6:385–389.

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. Anthony P. Weetman MD, DSc
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Division of Endocrinology, Department of Medicine, The Wellesley Hospital, University of Toronto, Toronto, Ontario, Canada

    Robert Volpé MD, FRCP(C), FACP, FRCP

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer Science+Business Media New York

About this chapter

Cite this chapter

Weetman, A.P. (1999). Thyroid-Associated Ophthalmopathy and Dermopathy. In: Volpé, R. (eds) Autoimmune Endocrinopathies. Contemporary Endocrinology, vol 15. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-704-8_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-704-8_10

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4757-4572-6

  • Online ISBN: 978-1-59259-704-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation