The site of the Media Sphera Publishers contains materials intended solely for healthcare professionals.
By closing this message, you confirm that you are a certified medical professional or a student of a medical educational institution.

Login
EN
+7 (495) 482-4118
+7 (495) 482-0604
+8 800 250-18-12
  • (toll-free number for subscriptions)
    Mon-Fri from 10 a.m. to 6 p.m.

  • © 1998-2025
+7 (495) 482-43-29
EN
All journals
Journal
Year
Year
Search result: 0

Petunina N.A.

Kafedra éndokrinologii Pervogo Moskovskogo gosudarstvennogo meditsinskogo universiteta im. I.M. Sechenova

Trukhina L.V.

GBOU VPO "Pervyĭ Moskovskiĭ gosudarstvennyĭ meditsinskiĭ universitet im. I.M. Sechenova" MZ RF

Martirosian N.S.

GBOU VPO "Pervyĭ Moskovskiĭ gosudarstvennyĭ meditsinskiĭ universitet im. I.M. Sechenova" MZ RF

Endocrine ophthalmopathy: state-of-the-art approaches

Authors:

Petunina N.A., Trukhina L.V., Martirosian N.S.

More about the authors

Journal: Problems of Endocrinology. 2012;58(6): 24‑32

Views: 46276

Downloaded: 763

Download PDF (RU)
Contact the author
Table of contents

ENDOCRINE OPHTHALMOPATHY: STATE-OF-THE-ART APPROACHES
ENDOCRINE OPHTHALMOPATHY: STATE-OF-THE-ART APPROACHES

To cite this article:

Petunina NA, Trukhina LV, Martirosian NS. Endocrine ophthalmopathy: state-of-the-art approaches. Problems of Endocrinology. 2012;58(6):24‑32. (In Russ.)

МСФ на ЯМ
Close metadata
Recommended articles:
Glucocorticoid-resistant forms of endo­crine ophthalmopathy. Russian Annals of Ophthalmology. 2024;(6):125-130
Lower eyelid retraction after infe­rior rectus rece­ssion in thyroid eye disease. Russian Annals of Ophthalmology. 2025;(2):101-105

The issues pertaining to etiology, pathogenesis, clinical manifestations, and treatment of endocrine ophthalmopathy (EOP) are discussed. EOP is a heterogeneous autoimmune eye disease most frequently associated with Graves' disease even though it is just as well encountered both in the patients presenting with chronic autoimmune thyroiditis and in the absence of thyroid dysfunction. Although pathogenesis of EOP remains to be elucidated its autoimmune nature with the involvement of sensitized T-lymphocytes and autoantibodies against orbital tissues leaves no doubt. The understanding of mechanisms underlying the development of EOP gave impetus to the creation of new groups of medicines selectively acting on various pathogenic processes associated with this disease. The management of EOP remains a challenging problem requiring a multi-disciplinary approach for its solution.

Keywords:

endocrine ophthalmopathy
Graves' orbitopathy
exophthalmus
rituximab

Authors:

Petunina N.A.

Kafedra éndokrinologii Pervogo Moskovskogo gosudarstvennogo meditsinskogo universiteta im. I.M. Sechenova

Trukhina L.V.

GBOU VPO "Pervyĭ Moskovskiĭ gosudarstvennyĭ meditsinskiĭ universitet im. I.M. Sechenova" MZ RF

Martirosian N.S.

GBOU VPO "Pervyĭ Moskovskiĭ gosudarstvennyĭ meditsinskiĭ universitet im. I.M. Sechenova" MZ RF

List of references:

  1. Braverman L.E., Utiger R.D. The thyroid: a Fundamental and clinical text. 9th ed Phylodelphia: Lippicott Williams Wilkins 2005; 474-485.
  2. Enzmann D.R., Donaldson S.S., Kriss J.P. Appearance of Graves' disease on orbital computed tomography. J Comput Ass Tomogr 1979; 3: 815-819.
  3. Wiersinga W.M., Bartalena L. Epidemiology and prevention of Graves' ophthalmopathy. Thyroid 2002; 12: 855-860.
  4. Wiersinga W.M., Smith T., van der Gaag R., Koornneef L. Temporal relationship between onset of Graves' ophthalmopathy and onset of thyroidal Graves' disease. J Endocrinol Invest 1988; 11: 615-619.
  5. Bartley G.B. 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.
  6. Bahn R.S. Graves' ophthalmopathy. N Engl J Med 2010; 362: 8: 726-738.
  7. Wakelkamp I.M., Bakker O., Baldeschi L., Wiersinga W.M., Prummel M.F. TSH-R expression and cytokine profile in orbital tissue of active vs. inactive Graves' ophthalmopathy patients. Clin Endocrinol (Oxford) 2003; 58: 280-287.
  8. Balabolkin M.I., Klebanova E.M., Kreminskaya V.M. Fundamental'naya i klinicheskaya tiroidologiya: Uchebnoe posobie. M: Meditsina 2007; 441-492.
  9. Petunina N.A. Prognosticheskie faktory i optimizatsiya metodov lecheniya diffuznogo toksicheskogo zoba: Avtoref. dis. ... d-ra med. nauk. M 2004.
  10. Eckstein A.K., Plicht M., Lax H., Neuhäuser M., Mann K., Lederbogen S., Heckmann C., Esser J., Morgenthaler N.G. 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. Gerding M.N., van der Meer J.W., Broenink M., Bakker O., Wiersinga W.M., Prummel M.F. Association of thyrotrophin receptor antibodies with the clinical features of Graves' ophthalmopathy. Clin Endocrinol (Oxford) 2000; 52: 267-271.
  12. Smith T.J. The putative role of fibroblasts in the pathogenesis of Graves' disease: evidence for the involvement of the insulin-like growth factor-1 receptor in fibroblast activation. Autoimmunity 2003; 36: 409-415.
  13. Gopinath B., Musselman R., Adams C.L., Tani J., Beard N., Wall J.R. Study of serum antibodies against three eye muscle antigens and the connective tissueantigen collagen XIII in patients with Graves' disease with and without ophthalmopathy: correlation with clinical features. Thyroid 2006; 16: 10: 967-974.
  14. Gopinath B., Musselman R., Beard N., El-Kaissi S., Tani J., Adams C.L., Wall J.R. Antibodies targeting the calcium binding skeletal muscle protein calsequestrin are specific markers of ophthalmopathy and sensitive indicators of ocular myopathy in patients with Graves' disease. Clin Exp Immunol 2006; 145: 1: 56-62.
  15. Prummel M.F., van Pareren Y., Bakker O., Wiersinga W.M. Anti-heat shock protein (hsp)72 antibodies are present in patients with Graves' disease (GD) and in smoking control subjects. Clin Exp Immunol 1997; 110: 292-295.
  16. Heufelder A.E., Wenzel B.E., Bahn R.S. Enhanced induction of a 72 kDa heat shock protein in cultured retroocular fibroblasts. Invest Ophthalmol Vis Sci 1992; 33: 2: 466-470.
  17. Bahn R.S. Clinical review 157: pathophysiology of Graves' ophthalmopathy: the cycle of disease. J Clin Endocrinol Metab 2003; 88: 1939-1946.
  18. Prabhakar B.S., Bahn R.S., Smith T.J. Current perspective on the pathogenesis of Graves' disease and ophthalmopathy. Endocr Rev 2003; 24: 802-835.
  19. Khoo T.K., Coenen M.J., Schiefer A.R., Kumar S., Bahn R.S. Evidence for enhanced Thy1 (CD90) expression in orbital fibroblasts of patients with Graves' ophthalmopathy. Thyroid 2008; 18: 12: 1291-1296.
  20. Smith T.J., Koumas L., Gagnon A., Bell A., Sempowski G.D., Phipps R.P., Sorisky A. Orbital fibroblast heterogeneity may determine the clinical presentation of thyroid-associated ophthalmopathy. J Clin Endocrinol Metab 2002; 87: 1: 385-392.
  21. Sorisky A., Pardasani D., Gagnon A., Smith T.J. Evidence of adipocyte differentiation in human orbital fibroblasts in primary culture. J Clin Endocrinol Metab 1996; 81: 3428-3431.
  22. Starkey K.J., Janezic A., Jones G., Jordan N., Baker G., Ludgate M. Adipose thyrotrophin receptor expression is elevated in Graves' and thyroid eye diseases ex vivo and indicates adipogenesis in progress in vivo. J Mol Endocrinol 2003; 30: 369-380.
  23. Valyasevi R.W., Erickson D.Z., Harteneck D.A. et al. Differentiation of human orbital preadipocyte fibroblasts induces expression of functional thyrotropin receptor. J Clin Endocrinol Metab 1999; 84: 2557-2562.
  24. Grewal I.S., Flavell R.A. The role of CD40 ligand in costimulation and T-cell activation. Immunol Rev 1996; 153: 85-106.
  25. Dorkhan M., Lantz M., Frid A., Groop L., Hallengren B. Treatment with a thiazolidinedione increases eye protrusion in a subgroup of patients with type 2 diabetes. Clin Endocrinol (Oxford) 2006; 65: 35-39.
  26. Lu M., Lin R.Y. TSH stimulates adipogenesis in mouse embryonic stem cells. J Endocrinol 2008; 196: 159-169.
  27. Kroll A.J., Kuwabara T. Dysthyroid ocular myopathy: anatomy, histology, and electron microscopy. Arch Ophthalmol 1966; 76: 244-247.
  28. Aniszewski J.P., Valyasevi R.W., Bahn R.S. Relationship between disease duration and predominant orbital T cell subset in Graves' ophthalmopathy. J Clin Endocrinol Metab 2000; 85: 776-780.
  29. Kumar S., Bahn R.S. Relative overexpression of macrophage-derived cytokines in orbital adipose tissue from patients with graves' ophthalmopathy. J Clin Endocrinol Metab 2003; 88: 9: 4246-4250.
  30. Bartalena L., Baldeschi L., Dickinson A., Eckstein A., Kendall-Taylor P., Marcocci C., Mourits M., Perros P., Boboridis K., Boschi A., Currò N., Daumerie C., Kahaly G.J., Krassas G.E., Lane C.M., Lazarus J.H., Marinò M., Nardi M., Neoh C., Orgiazzi J., Pearce S., Pinchera A., Pitz S., Salvi M., Sivelli P., Stahl M., von Arx G., Wiersinga W.M., 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.
  31. Prummel M.F., Wiersinga W.M. Smoking and risk of Graves' disease. JAMA 1993; 269: 4: 479-482.
  32. Thornton J., Kelly S.P., Harrison R.A., Edwards R. Cigarette smoking and thyroid eye disease: a systematic review. Eye 2006; 20: 1-11.
  33. Bartalena L., Tanda M.L., Piantanida E., Lai A., Pinchera A. Relationship between management of hyperthyroidism and course of the ophthalmopathy. J Endocrinol Invest 2004; 27: 3: 288-294.
  34. Costenbader K.H., Karlson E.W. Cigarette smoking and autoimmune disease: what can we learn from epidemiology? Lupus 2006; 15: 737-745.
  35. Cawood T.J., Moriarty P., O'Farrelly C. et al. Smoking and thyroid-associated ophthalmopathy: A novel explanation of the biological link. J Clin Endocrinol Metab 2007; 92: 59-64.
  36. Prummel M.F., Wiersinga W.M., Mourits M.P., Koornneef L., Berghout A., van der Gaag R. Effect of abnormal thyroid function on the severity of Graves' ophthalmopathy. Arch Intern Med 1990; 150: 5: 1098-1101.
  37. Tallstedt L., Lundell G., Terring O., Wallin G., Ljunggren J.G., Blomgren H., Taube A., Thyroid Study Group. Occurrence of ophthalmopathy after treatment for Graves' hyperthyroidism. New Engl J Med 1992; 326: 1733-1738.
  38. Gianoukakis A.G., Khadavi N., Smith T.J. Cytokines, Graves' disease, and thyroid-associated ophthalmopathy. Thyroid 2008; 18: 9: 953-958.
  39. Griepentrog G.J., Garrity J.A. Update on the medical treatment of Graves' ophthalmopathy. Int J Gen Med 2009; 2: 263-269.
  40. Naik V.M., Naik M.N., Goldberg R.A., Smith T.J., Douglas R.S. Immunopathogenesis of thyroid eye disease: emerging paradigms. Surv Ophthalmol 2010; 55: 3: 215-226.
  41. Rundle F.F., Wilson C.W. Development and course of exophthalmos and ophthalmoplegia in Graves' disease with special reference to the effect of thyroidectomy. Clin Sci 1945; 5: 177-194.
  42. Wiersinga W.M., Smit T., van der Gaag R., Mourits M., Koornneef L. Clinical presentation of Graves' ophthalmopathy. Ophthal Res 1989; 21: 73-82.
  43. Fatourechi V. Pretibial myxedema: pathophysiology and treatment options. Am J Clin Dermatol 2005; 6: 295-309.
  44. Brovkina A.F. Bolezni orbity. M 1993.
  45. Baranov V.G., Potin V.V. Bolezni shchitovidnoi zhelezy. Rukovodstvo po klinicheskoi endokrinologii. L: Meditsina 1977; 8: 375-377.
  46. Werner S.C. Modification of the classification of the eye changes of Graves' disease. Am J Ophthalmol 1977; 83: 5: 725-727.
  47. Mourits M.P., Prummel M.F., Wiersinga W.M., Koornneef L. Clinical activity score as a guide in the management of patients with Graves' ophthalmopathy. Clin Endocrinol (Oxford) 1997; 47: 1: 9-14.
  48. Mourits M.P., Koornneef L., Wiersinga W.M., Prummel M.F., 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: 8: 639-644.
  49. Terwee C.B., Gerding M.N., Dekker F.W., Prummel M.F., Wiersinga W.M. Development of disease specific quality of life questionnaire for patients with Graves' ophthalmopathy: the GO-QoL. Br J Ophthalmol 1998; 82: 773-779.
  50. Bartalena L., Marcocci C., Tanda M.L., Manetti L., Dell'Unto E., Bartolomei M.P. et al. Cigarette smoking and treatment outcomes in Graves ophthalmopathy. Ann Intern Med 1998; 129: 8: 632-635.
  51. Terwee C.B., Prummel M.F., Gerding M.N., Kahaly G.J., Dekker F.W., Wiersinga W.M. Measuring disease activity to predict therapeutic outcome in Graves' ophthalmopathy. Clin Endocrinol (Oxford) 2005; 62: 2: 145-155.
  52. Marcocci C., Kahaly G.J., Krassas G.E. et al. Selenium and the Course of Mild Graves' Orbitopathy. N Engl J Med 2011; 364: 1920-1931.
  53. Kahaly G.J., Pitz S., Muller-Forell W., Hommel G. Randomized trial of intravenous immunoglobulins versus prednisolone in Graves' ophthalmopathy. Clin Exp Immunol 1996; 106: 197-202.
  54. Kahaly G., Schrezenmeir J., Krause U., Schwikert B., Meuer S., Muller W., Dennebaum R., Beyer J. Ciclosporin and prednisone vs. prednisone in treatment of Graves' ophthalmopathy: a controlled, randomized and prospective study. Eur J Clin Invest 1986; 16: 415-422.
  55. Kung A.W., Michon J., Tai K.S., Chan F.L. The effect of somatostatin versus corticosteroids in the treatment of Graves' ophthalmopathy.Thyroid 1996; 6: 381-384.
  56. Prummel M.F., Mourits M.P., Berghout A., Krenning E.P., van der Gaag R., Koornneef L., Wiersinga W.M. Prednisone and cyclosporine in the treatment of severe Graves' ophthalmopathy. New Engl J Med 1989; 321: 1353-1359.
  57. Prummel M.F., Mourits M.P., Blank L., Berghout L., Koornneef L., Wiersinga W.M. Randomised double-blind trial of prednisone versus radiotherapy in Graves' ophthalmopathy. Lancet 1993; 342: 949-954.
  58. Marcocci C., Bartalena L., Panicucci M., Marconcini C., Cartei F., Cavallacci G., Laddaga M., Campobasso G., Baschieri L., Pinchera A. Orbital cobalt irradiation combined with retrobulbar or systemic corticosteroids for Graves' ophthalmopathy: a comparative study. Clin Endocrinol 1987; 27: 33-42.
  59. Kahaly G.J., Pitz S., Hommel G., Dittmar M. Randomized, single-blind trial of intravenous versus oral steroid monotherapy in Graves' orbitopathy. J Clin Endocrinol Metabol 2005; 90: 5234-5240.
  60. Kauppinen-Makelin R., Karmi A., Leinonen E., Loyttyniemi E., Salonen O., Sane T., Setala K., Viikari J., Heufelder A., Valimaki M. High dose intravenous methylprednisolone pulse therapy versus oral prednisone for thyroid-associated ophthalmopathy. Acta Ophthalmol Scand 2002; 80: 316-321.
  61. Macchia P.E., Bagattini M., Lupoli G., Vitale M., Vitale G., Fenzi G. High-dose intravenous corticosteroid therapy for Graves' ophthalmopathy. J Endocrinol Invest 2001; 24: 152-158.
  62. Marcocci C., Bartalena L., Tanda M.L., Manetti L., Dell'Unto E., Rocchi E., Barbesino G., Mazzi B., Bartolomei M.P., Lepri P., Cartei F., Nardi M., Pinchera A. 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 Metabol 2001; 86: 8: 3562-3567.
  63. Tambe K., Bhargava J., Tripathi A., Gregory M., Burns J., Sampath R. The role of intravenous methylprednisolone immunosuppression in the management of active thyroid eye disease. Orbit 2010; 29: 5: 227-231.
  64. Antonelli A., Saracino A., Alberti B., Canapicchi R., Cartei F., Lepri A. et al. High-dose intravenous immunoglobulin treatment in Graves' ophthalmopathy. Acta Endocrinol (Copenhagen) 1992; 126: 1: 13-23.
  65. Stan M.N., Garrity J.A., Bradley E.A., Woog J.J., Bahn M.M., Brennan M.D., Bryant S.C., Achenbach S.J., Bahn R.S. Randomized, double-blind, placebo-controlled trial of long-acting release octreotide for treatment of Graves' ophthalmopathy. J Clin Endocrinol Metab 2006; 91: 12: 4817-4824.
  66. Wémeau J.L., Caron P., Beckers A., Rohmer V., Orgiazzi J., Borson-Chazot F., Nocaudie M., Perimenis P., Bisot-Locard S., Bourdeix I., Dejager S. 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: 2: 841-848.
  67. Dickinson A.J., Vaidya B., Miller M., Coulthard A., Perros P., Baister E., Andrews C.D., Hesse L., Heverhagen J.T., Heufelder A.E., Kendall-Taylor P. Double-blind, placebo-controlled trial of octreotide long-acting repeatable (LAR) in thyroid-associated ophthalmopathy. J Clin Endocrinol Metab 2004; 89: 12: 5910-5915.
  68. Marcocci C., Bartalena L., Bogazzi F., Bruno-Bossio G., Lepri A., Pinchera A. 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: 853-860.
  69. Mirna Abboud, Asma Arabi, Ibrahim Salti, Fady Geara. Outcome of thyroid associated ophthalmopathy treated by radiation therapy. Radiat Oncol 2011; 6: 46.
  70. Bartalena L., Marcocci C., Tanda M.L., Rocchi R., Mazzi B., Barbesino G., Pinchera A. Orbital radiotherapy for Graves' ophthalmopathy. Thyroid 2002; 12: 245-250.
  71. Kahaly G.J., Rosler H.P., Pitz S., Hommel G. Low- versus high-dose radiotherapy for Graves' ophthalmopathy: a randomized, single blind trial. J Clin Endocrinol Metabol 2000; 85: 102-108.
  72. Marcocci C., Bartalena L., Rocchi R., Marinò M., Menconi F., Morabito E., Mazzi B., Mazzeo S., Sartini M.S., Nardi M., Cartei F., Cionini L., Pinchera A. Long-term safety of orbital radiotherapy for Graves' ophthalmopathy. J Clin Endocrinol Metab 2003; 88: 8: 3561-3566.
  73. Khanna D., Chong K.K., Afifiyan N.F., Hwang C.J., Lee D.K., Garneau H.C. et al. Rituximab treatment of patients with severe, corticosteroid-resistant thyroid-associated ophthalmopathy. Ophthalmology 2010; 117: 1: 133-139.
  74. 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: 33-40.
  75. Paridaens D., van den Bosch W.A., Krenning E. The effect of etanercept on Graves' ophthalmopathy: a pilot study. Eye 2005; 19: 1286-1289.
  76. Durrani O.M., Reuser T.Q., Murray P.I. Infliximab: a novel treatment for sight-threatening thyroid associated ophthalmopathy. Orbit 2005; 24: 117-119.
  77. Wakelkamp I.M., Baldeschi L., Saeed P., Mourits M.P., Prummel M.F., Wiersinga W.M. Surgical or medical decompression as a first-line treatment of optic neuropathy in Graves' ophthalmopathy? A randomized controlled trial. Clin Endocrinol (Oxford) 2005; 63: 3: 323-328.

Close metadata

Contact the author
Email
Message
The publishing house "Media Sphere" does not provide treatment services, does not give recommendations on contacting medical institutions and specific specialists, on the prescription of medicines and dietary supplements.

Email Confirmation

An email was sent to test@gmail.com with a confirmation link. Follow the link from the letter to complete the registration on the site.

Email Confirmation

Contact us
If you have any questions, complaints or suggestions, please use this feedback form.
Email
Message
The publishing house "Media Sphere" does not provide treatment services, does not give recommendations on contacting medical institutions and specific specialists, on the prescription of medicines and dietary supplements.
Submit Application

You can become an author of one of our magazines, send a request and we will consider it in during the day.

Name
Phone
E-mail
Message
Login
Registration
E-mail
Password
Forgot Password?

Log in to the site using your account in one of the services

Password recovery
E-mail
Login
Register

We use cооkies to improve the performance of the site. By staying on our site, you agree to the terms of use of cооkies. To view our Privacy and Cookie Policy, please. click here.