ТИРОНЕТ – все о щитовидной железе Для специалистов Журнал Тиронет Архив журнала 2006 год № 1

Современные концепции диагностики и лечения эндокринной офтальмопатии

Герасимос Крассас1, Вильмар Вирсинга2
Department of Endocrinology, Diabetes and Metabolism, Panagia General Hospital, Thessaloniki, Greece
Department of Endocrinology, Academic Medical Centre, University of Amsterdam, The Netherlands
Thyroid international 4 — 2005 (перевод В.В. Фадеева)


  1. Wiersinga WM, Prummel MF. Pathogenesis of Graves' ophthalmopathy — current understanding. J Clin Endocrinol Metab 2001; 86:501-503.^
  2. Burch HB, Wartofsky L. Graves' ophthalmopathy: current concepts regarding pathogenesis and management. Endocr Rev 1993; 14:747-793.^
  3. Shine B, Fells P, Edwards OM, Weetman AP. Association between Graves' ophthalmopathy and smoking. Lancet 1990; 335:1261-1263.^
  4. Prummel MF, Wiersinga WM. Smoking and risk of Graves' disease. JAMA 1993; 269:479-482.^
  5. Krassas GE, Heufelder AE. Immunosuppressive therapy in patients with thyroid eye disease: an overview of current concepts. Eur J Endocrinol 2001; 144:311- 318. ^
  6. Bartley GB. The epidemiologic characteristics and clinical course of ophthalmopathy associated with autoimmune thyroid disease in Olmsted County, Minnesota. Trans Am Ophthalmol Soc 1994; 92:477-588. ^
  7. Perros P, Crombie AL, Matthews JN, 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 (Oxf) 1993; 38:367-372.^
  8. Kendall-Taylor P, Perros P. Clinical presentation of thyroid associated orbitopathy. Thyroid 1998; 8:427-428. ^
  9. Marcocci C, Bartalena L, Bogazzi F, et al. Studies on the occurrence of ophthalmopathy in Graves' disease. Acta Endocrinol (Copenh) 1989; 120:473-478.^
  10. Pappa A, Jackson P, Stone J, et al. An ultrastructural and systemic analysis of glycosaminoglycans in thyroid-associated ophthalmopathy. Eye 1998; 12 ( Pt 2):237-244. ^
  11. Hansen C, Rouhi R, Forster G, Kahaly GJ. Increased sulfatation of orbital glycosaminoglycans in Graves' ophthalmopathy. J Clin Endocrinol Metab 1999; 84:1409-1413. ^
  12. Valyasevi RW, Erickson DZ, Harteneck DA, et al. Differentiation of human orbital preadipocyte fibroblasts induces expression of functional thyrotropin receptor. J Clin Endocrinol Metab 1999; 84:2557-2562.^
  13. Khoo DH, Ho SC, Seah LL, et al. The combination of absent thyroid peroxidase antibodies and high thyroid-stimulating immunoglobulin levels in Graves' disease identifies a group at markedly increased risk of ophthalmopathy. Thyroid 1999; 9:1175-1180.^
  14. 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; 52:267-271.^
  15. Akamizu T, Kohn LD, Hiratani H, et al. Hashimoto's thyroiditis with heterogeneous antithyrotropin receptor antibodies: unique epitopes may contribute to the regulation of thyroid function by the antibodies. J Clin Endocrinol Metab 2000; 85:2116-2121.^
  16. Perros P, Dickinson AJ, Kendall-Taylor P. Clinical presentation and natural history of Graves’ ophthalmopathy. In Bahn R (Ed) Thyroid Eye Disease. Kluwer  Academic Publishers, Boston 2001 pp119-38.^
  17. Perros P, Dickinson AJ. Ophthalmopathy. In Braverman LE, Utiger RD (Eds) Werner and Ingbar’s The Thyroid. A fundamental and clinical text, 9th Ed. Lippincott Williams & Wilkins, Boston 2005 pp474-87.^
  18. Dickinson AJ, Perros P. Controversies in the clinical evaluation of active thyroid-associated orbitopathy: use of a detailed protocol with comparative photographs for objective assessment. Clin Endocrinol (Oxf) 2001; 55:283-303.^
  19. Gorman CA. Temporal relationship between onset of Graves' ophthalmopathy and diagnosis of thyrotoxicosis. Mayo Clin Proc 1983; 58:515-519.^
  20. Kendler DL, Lippa J, Rootman J. The initial clinical characteristics of Graves' orbitopathy vary with age and sex. Arch Ophthalmol 1993; 111:197-201.^
  21. DeGroot LJ, Gorman CA, Pinchera A, et al. Therapeutic controversies, Retro-orbital radiation and radioactive iodine ablation of the thyroid may be good for Graves’ ophthalmopathy. J Clin Endocrinol Metab 1995; 80:339-340.^
  22. Bartley GB, Fatourechi V, Kadrmas EF, et al. Long-term followup of Graves ophthalmopathy in an incidence cohort. Ophthalmology 1996; 103:958-962.^
  23. Hales IB, Rundle FF. Ocular changes in Graves' disease. A longterm follow-up study. Q J Med 1960; 29:113-126. ^
  24. Rundle FF, Wilson CW. Development and course of exophthalmos and ophthalmoplegia in Graves’ disease with special reference to the effect of thyroidectomy. Clin Science 1945; 5:177-194.^
  25. Perros P, Crombie AL, Kendall-Taylor P. Natural history of thyroid associated ophthalmopathy. Clin Endocrinol (Oxf) 1995; 42:45-50.^
  26. McKinnon SG, Gentry LR. Systemic diseases involving the orbit. Semin Ultrasound CT MR. 1998; 19:292-308. ^
  27. Marino M, Barbesino G, Pinchera A, et al. Increased frequency of euthyroid ophthalmopathy in patients with Graves' disease associated with myasthenia gravis. Thyroid 2000; 10:799-802. ^
  28. Byrne SF, Gendron EK, Glaser JS, et al. Diameter of normal extraocular recti muscles with echography. Am J Ophthalmol 1991; 112:706-713.^
  29. Erickson BA, Harris GJ, Lewandowski MF, et al. Echographic monitoring of response of extraocular muscles to irradiation in Graves' ophthalmopathy. Int J Radiat Oncol Biol Phys 1995; 31:651-660.^
  30. Prummel MF, Suttorp-Schulten MS, Wiersinga WM, et al. New ultrasonographic method to detect disease activity and predict response to immunosuppressive treatment in Graves ophthalmopathy. Ophthalmology 1993; 100:556-561.^
  31. Nugent RA, Belkin RI, Neigel JM, et al. Graves orbitopathy: correlation of CT and clinical findings. Radiology 1990; 177:675-682.^
  32. Forbes G, Gorman CA, Gehring D, Baker HL Jr. Computer analysis of orbital fat and muscle volumes in Graves ophthalmopathy. AJNR Am J Neuroradiol 1983; 4:737-740. ^
  33. Forbes G, Gehring DG, Gorman CA, et al. Volume measurements of normal orbital structures by computed tomographic analysis. AJNR Am J Neuroradiol 1985; 6:419-424.^
  34. Forbes G, Gorman CA, Brennan MD, et al. Ophthalmopathy of Graves' disease: computerized volume measurements of the orbital fat and muscle. AJNR Am J Neuroradiol 1986; 7:651-656.^
  35. Enzmann DR, Donaldson SS, Kriss JP. Appearance of Graves' disease on orbital computed tomography. J Comput Assist Tomogr 1979; 3:815-819.^
  36. Yoshikawa K, Higashide T, Nakase Y, et al. Role of rectus muscle enlargement in clinical profile of dysthyroid ophthalmopathy. Jpn J Ophthalmol 1991; 35:175-181. ^
  37. Feldon SE, Lee CP, Muramatsu SK, Weiner JM. Quantitative computed tomography of Graves' ophthalmopathy. Extraocular muscle and orbital fat in development of optic neuropathy. Arch Ophthalmol 1985; 103:213-215.^
  38. Hosten N, Sander B, Cordes M, et al. Graves ophthalmopathy: MR imaging of the orbits. Radiology 1989; 172: 759-762.^
  39. Just M, Kahaly G, Higer HP, et al. Graves ophthalmopathy: role of MR imaging in radiation therapy. Radiology 1991; 179:187- 190.^
  40. Hiromatsu Y, Kojima K, Ishisaka N, et al. Role of magnetic resonance imaging in thyroid-associated ophthalmopathy: its predictive value for therapeutic outcome of immunosuppressive therapy. Thyroid 1992; 2:299-305. ^
  41. Ohnishi T, Noguchi S, Murakami N, et al. Extraocular muscles in Graves ophthalmopathy: usefulness of T2 relaxation time measurements. Radiology 1994; 190:857-862. ^
  42. Utech CI, Khatibnia U, Winter PF, Wulle KG. MR T2 relaxation time for the assessment of retrobulbar inflammation in Graves' ophthalmopathy. Thyroid 1995; 5:185-193. ^
  43. Kahaly G, Diaz M, Just M, et al. Role of octreoscan and correlation with MR imaging in Graves' ophthalmopathy. Thyroid 1995; 5:107-111. ^
  44. Krassas GE, Kahaly GJ. The role of octreoscan in thyroid eye disease. Eur J Endocrinol 1999; 140:373-375. ^
  45. Wiersinga WM, Prummel MF, Terwee CB. Effects of Graves' ophthalmopathy on quality of life. J Endocrinol Invest 2004; 27:259-264.^
  46. Terwee CB, Gerding M. Quality of life measurement in patients with Graves’ ophthalmopathy. In Bahn RS (Ed) Thyroid eye disease. Kluwer Academic Publishers, Boston 2001 pp163-83. ^
  47. Jaeschke R, Singer J, Guyatt GH. Measurement of health status. Ascertaining the minimal clinically important difference. Control Clin Trials 1989; 10:407-415.^
  48. Terwee C, Wakelkamp I, Tan S, et al. Long-term effects of Graves' ophthalmopathy on healthrelated quality of life. Eur J Endocrinol 2002 146:751-757. ^
  49. Terwee CB, Dekker FW, Mourits MP, et al. Interpretation and validity of changes in scores on the Graves' ophthalmopathy quality of life questionnaire (GO-QOL) after different treatments. Clin Endocrinol (Oxf) 2001; 54:391-398.^
  50. Sprangers MA, de Regt EB, Andries F, et al. Which chronic conditions are associated with better or poorer quality of life? J Clin Epidemiol 2000; 53:895-907.^
  51. Fayers P, Bjordal K. Should quality-of-life needs influence resource allocation? Lancet 2001; 357:978. ^
  52. Bartalena L, Pinchera A, Marcocci C. Management of Graves' ophthalmopathy: reality and perspectives. Endocr Rev 2000; 21:168-199. ^
  53. Marcocci C, Bartalena L, Tanda ML, et al. Comparison of the effectiveness and tolerability of intravenous or oral glucocorticoids associated with orbital radiotherapy in the management of severe Graves' ophthalmopathy: results of a prospective, single-blind, randomized study. J Clin Endocrinol Metab 2001; 86:3562-3567. ^
  54. Marino M, Morabito E, Brunetto MR, et al. Acute and severe liver damage associated with intravenous glucocorticoid pulse therapy in patients with Graves' ophthalmopathy. Thyroid 2004; 14:403-406.^
  55. Weissel M, Hauff W. Fatal liver failure after high-dose glucocorticoid pulse therapy in a patient with severe thyroid eye disease. Thyroid 2000; 10:521.^
  56. Dourakis SP, Sevastianos VA, Kalipi P. Acute severe steathoepatitis related to prednisolone therapy. Am J Gastroenterol 2002; 97:1074-1075. ^
  57. Kahaly GJ, Rosler HP, Pitz S, Hommel G. Low- versus highdose radiotherapy for Graves' ophthalmopathy: a randomized, single blind trial. J Clin Endocrinol Metab 2000; 85:102-108. ^
  58. Perros P, Krassas GE. Orbital irradiation for thyroid-associated orbitopathy: conventional dose, low dose or no dose? Clin Endocrinol (Oxf) 2002; 56:689-691. ^
  59. Gorman CA, Garrity JA, Fatourechi V, et al. A prospective, randomized, double-blind, placebo-controlled study of orbital radiotherapy for Graves' ophthalmopathy. Ophthalmology. 2001; 108:1523-1534. ^
  60. Gorman CA, Garrity JA, Fatourechi V, et al. The aftermath of orbital radiotherapy for graves' ophthalmopathy. Ophthalmology 2002; 109:2100-2107.^
  61. Steinsapir KD, Goldberg RA. Orbital radiation therapy for Graves' ophthalmopathy. Ophthalmology 2003; 110:451-452. ^
  62. Mourits MP, van Kempen-Harteveld ML, Garcia MB, et al. Radiotherapy for Graves' orbitopathy: randomised placebo-controlled study. Lancet 2000; 355:1505-1509. ^
  63. 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; 89:15-20.^
  64. Bartalena L, Marcocci C, Gorman CA, et al. Orbital radiotherapy for Graves' ophthalmopathy: useful or useless? Safe or dangerous? J Endocrinol Invest 2003; 26:5-16. ^
  65. Marcocci C, Bartalena L, Marino M, et al. Current medical management of Graves ophthalmopathy. Ophthal Plast Reconstr Surg 2002; 18:402-408.^
  66. Marcocci C, Bartalena L, Rocchi R, et al. Long-term safety of orbital radiotherapy for Graves' ophthalmopathy. J Clin Endocrinol Metab 2003; 88:3561-3566. ^
  67. Taurog A, Dorris M, Doerge DR. Evidence for a radical mechanism in peroxidase-catalyzed coupling. I. Steady-state experiments with various peroxidases. Arch Biochem Biophys 1994; 315:82-89.^
  68. Venditti P, Balestrieri M, Di Meo S, De Leo T. Effect of thyroid state on lipid peroxidation, antioxidant defences, and susceptibility to oxidative stress in rat tissues. J Endocrinol 1997; 155:151-157.^
  69. Bouzas EA, Karadimas P, Mastorakos G, Koutras DA. Antioxidant agents in the treatment of Graves' ophthalmopathy. Am J Ophthalmol 2000; 129:618-622.^
  70. Bartalena L, Marcocci C, Pinchera A. Cytokine antagonists: new ideas for the management of Graves' ophthalmopathy. J Clin Endocrinol Metab 1996; 81:446-448. ^
  71. Raza A. Anti-TNF therapies in rheumatoid arthritis, Crohn's disease, sepsis, and myelodysplastic syndromes. Microsc Res Tech 2000; 50:229-235.^
  72. Balazs C, Kiss E, Vamos A, et al. Beneficial effect of pentoxyfilline on thyroid-associated ophthalmopathy. J Clin Endocrinol Metab 1998; 82:1999-2002.^
  73. Krassas GE. Somatostatin analogs: a new tool for the management of Graves' ophthalmopathy. J Endocrinol Invest 2004; 27:281-287.^
  74. Dickinson AJ, Vaidya B, Miller M, et al. Double-blind, placebo-controlled trial of octreotide long-acting repeatable (LAR) in thyroid-associated ophthalmopathy. J Clin Endocrinol Metab 2004; 89:5910-5915.^
  75. Wemeau JL, Caron P, Beckers A, et al. Octreotide (long-acting release formulation) treatment in patients with graves' orbitopathy: clinical results of a four-month, randomized, placebo-controlled, double-blind study. J Clin Endocrinol Metab 2005; 90:841-848. ^
  76. Bradley EA, Bartley GB, Garrity JA. Surgical management of Graves’ ophthalmopathy. In Bahn RS (Ed) Thyroid Eye Disease. Kluwer Academic Publishers Boston 2001 pp219-34. ^
  77. Kennerdell JS, Maroon JC, Buerger GF. Comprehensive surgical management of proptosis in dysthyroid orbitopathy. Orbit 1987; 6:153-158.^
  78. Trokel S, Kazim M, Moore S. Orbital fat removal. Decompression for Graves orbitopathy. Ophthalmology 1993; 100:674-682.^
  79. Bartley GB. The eyelids in Graves’ ophthalmopathy. In Boshiak S (Ed) Principles and Practice of Ophthalmic Plastic and Reconstructive Surgery. W.B. Saunders, Philadelphia 1996 pp514-24. ^
  80. Fletcher RH, Fletcher SW, Wagner EH. In Clinical Epidemiology. The Essentials, 2nd ed. Williams & Wilkins, Baltimore 1988 pp157-71.^
  81. Wiersinga WM, Bartalena L. Epidemiology and prevention of Graves' ophthalmopathy. Thyroid 2002; 12:855-860. ^
  82. Gamblin GT, Harper DG, Galentine P, et al. Prevalence of increased intraocular pressure in Graves' disease-evidence of frequent subclinical ophthalmopathy. N Engl J Med 1983; 308:420-424.^
  83. Bartalena L, Marcocci C, Pinchera A. Graves' ophthalmopathy: a preventable disease? Eur J Endocrinol 2002; 146:457-461. ^
  84. Hagg E, Asplund K. Is endocrine ophthalmopathy related to smoking? Br Med J (Clin Res Ed) 1987; 295:634-635. ^
  85. Bartalena L, Bogazzi F, Tanda ML, et al. Cigarette smoking and the thyroid. Eur J Endocrinol 1995; 133:507-512.^
  86. Bartalena L, Martino E, Marcocci C, et al. More on smoking habits and Graves' ophthalmopathy. J Endocrinol Invest 1989; 12:733-737.^
  87. Prummel MF, Wiersinga WM. Smoking and risk of Graves' disease. JAMA 1993; 269:479-482. ^
  88. Pfeilschifter J, Ziegler R. Smoking and endocrine ophthalmopathy: impact of smoking severity and current vs lifetime cigarette consumption. Clin Endocrinol (Oxf) 1996; 45:477-481. ^
  89. Bartalena L, Marcocci C, Tanda ML, et al. Cigarette smoking and treatment outcomes in Graves ophthalmopathy. Ann Intern Med 1998; 129:632-635.^
  90. Prummel MF, Wiersinga WM, Mourits MP. Amelioration of eye changes of Graves' ophthalmopathy by achieving euthyroidism. Acta Endocrinol 1989; 121 (Suppl. 2):185-189. ^
  91. Prummel MF, Wiersinga WM, Mourits MP, et al. Effect of abnormal thyroid function on the severity of Graves' ophthalmopathy. Arch Intern Med 1990; 150:1098-1101.^
  92. Bartalena L, Marcocci C, Bogazzi F, et al. Relation between therapy for hyperthyroidism and the course of Graves' ophthalmopathy. N Engl J Med 1998; 338:73-78. ^
  93. Marcocci C, Bruno-Bossio G, Manetti L, et al. The course of Graves' ophthalmopathy is not influenced by near total thyroidectomy: a case-control study. Clin Endocrinol (Oxf) 1999; 51: 503-508.^
  94. Wiersinga WM. Preventing Graves' ophthalmopathy. N Engl J Med 1998; 338:121-122. ^
  95. Tallstedt L, Lundell G, Torring O, et al. Occurrence of ophthalmopathy after treatment for Graves' hyperthyroidism. The Thyroid Study Group. N Engl J Med 1992; 326:1733-1738. ^
  96. Gorman CA. Therapeutic controversies. Radioiodine therapy does not aggravate Graves' ophthalmopathy. J Clin Endocrinol Metab 1995; 80:340-342.^
  97. Marcocci C, Bartalena L, Bogazzi F, et al. Relationship between Graves' ophthalmopathy and type of treatment of Graves' hyperthyroidism. Thyroid 1992; 2:171- 178.^
  98. Prummel MF, Bakker A, Wiersinga WM, et al. Multi-centre study on the characteristics and treatment strategies of patients with Graves' orbitopathy: the first European Group on Graves' Orbitopathy experience. Eur J Endocrinol 2003; 148:491-495.^
  99. Chang TC, Kao SC, Huang KM. Octreotide and Graves’ ophthalmopathy and pretibial myxoedema. BMJ 1992, 304: 158. ^
  100. 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. ^
  101. 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.^
  102. Khoo DHC, Tan YT, Fok ACK, Tan CE. Octreotide in the management of Graves’ ophthalmopathy — changes in insulin-like growth factor 1 levels do not predict clinical response. Am J Clin Res 1995, 4: 33-42.^
  103. 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. ^
  104. Uysal AR, Corapcioglu D, Tonyukuk VC. et al. Effect of octreotide treatment on Graves’ ophthalmopathy. Endocr J 1999, 46: 573-7.^
  105. Durak I, Durak H, Ergin M, et al. Somatostatin receptors in the orbits. Clin Nucl Med 1995, 20: 237-42. ^
  106. Krassas GE, Kaltsas T, Dumas A, et al. Lanreotide in the treatment of patients with thyroid eye disease. Eur J Endocrinol 1997, 136: 416-22. ^
  107. Krassas GE, Doumas A, Kaltsas T, et al. Somatostatin receptor scintigraphy before and after treatment with somatostatin analogues in patients with thyroid eye disease. Thyroid 1999; 9:47-52.^
  108. Krassas GE. Thyroid eye disease in children and adolescentsnew therapeutic approaches. J Pediatr Endocrinol Metab 2001; 14:97-100.^
  109. Krassas GE, Pontikides N, Dumas A, et al. The effect of long-term somatostatin analogue treatment on free and total insulin-like growth factor (IGF) — I, -II and IGF binding protein -1, -2 and -3 serum levels in euthyroid patients with active thyroid eye disease. Hormones 2004; 3:191-197.^
  110. DeGroot LJ, Gorman CA, Pinchera A, et al. Therapeutic controversies. Retro-orbital radiation and radioactive iodide ablation of the thyroid may be good for Graves' ophthalmopathy. J Clin Endocrinol Metab 1995; 80:339-340.