FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 329:1468-1475 November 11, 1993 Number 20 Next

	Since this article has no abstract, we have provided an extract of the first 100 words of the full text and any section headings.

	Full Text Purchase this article Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

Ophthalmopathy is a potentially disfiguring and sight-threatening component of Graves' disease. It is clinically evident in 25 to 50 percent of patients with Graves' hyperthyroidism and occurs occasionally in patients with Hashimoto's thyroiditis and in those with Graves' disease but no evident thyroid disease¹. At present, ophthalmopathy is not preventable, and treatment options for established, symptomatic disease are limited. To develop new strategies for the treatment and prevention of Graves' ophthalmopathy, a better understanding of its pathogenesis is necessary. In this paper we review studies aimed at identifying the pathogenic mechanisms that lead to Graves' ophthalmopathy.

Clinical Features

Patients with Graves' . . . [Full Text of this Article]

Histologic Features

Pathogenesis

Humoral Immunity

T-Cell Involvement

Expression of Heat-Shock Proteins

Glycosaminoglycan Production

Possible Role of the Thyrotropin Receptor

Site-Specific Differences between Fibroblasts

Summary of Pathogenesis

Therapeutic Implications

Current Approaches

Future Directions

Source Information

From the Department of Medicine, Division of Endocrinology, Mayo Clinic and Foundation, Rochester, Minn. (R.S.B.), and the Medizinische Klinik, Ludwig-Maximilians University, Munich, Germany (A.E.H.).

Address reprint requests to Dr. Bahn at the Mayo Clinic and Foundation, Division of Endocrinology, 200 First St., S.W., Rochester, MN 55905.

References

This article has been cited by other articles:

• Chen, M.-H., Liao, S.-L., Chen, M.-H., Tsou, P.-L., Shih, M.-J., Chang, T.-C., Chuang, L.-M. (2008). Lysosome-Related Genes Are Regulated in the Orbital Fat of Patients with Graves' Ophthalmopathy. IOVS 49: 4760-4764 [Abstract] [Full Text]  
• Bunting, H, Creten, O, Muhtaseb, M, Shuttleworth, G (2008). Late reactivation of thyroid associated ophthalmopathy causing optic neuropathy. Postgrad. Med. J. 84: 388-390 [Abstract] [Full Text]  
• Chong, K. K. L., Chiang, S. W. Y., Wong, G. W. K., Tam, P. O. S., Ng, T.-K., Hu, Y.-J., Yam, G. H. F., Lam, D. S. C., Pang, C.-P. (2008). Association of CTLA-4 and IL-13 Gene Polymorphisms with Graves' Disease and Ophthalmopathy in Chinese Children. IOVS 49: 2409-2415 [Abstract] [Full Text]  
• Tsai, C.-C., Kao, S.-C., Cheng, C.-Y., Kau, H.-C., Hsu, W.-M., Lee, C.-F., Wei, Y.-H. (2007). Oxidative Stress Change by Systemic Corticosteroid Treatment Among Patients Having Active Graves Ophthalmopathy. Arch Ophthalmol 125: 1652-1656 [Abstract] [Full Text]  
• Taylor, T., Czarnowski, C. (2007). Asymmetric ophthalmopathy in a hypothyroid patient. cfp 53: 635-638 [Full Text]  
• Cawood, T. J., Moriarty, P., O'Farrelly, C., O'Shea, D. (2007). Smoking and Thyroid-Associated Ophthalmopathy: A Novel Explanation of the Biological Link. J. Clin. Endocrinol. Metab. 92: 59-64 [Abstract] [Full Text]  
• Cawood, T J, Moriarty, P, O'Farrelly, C, O'Shea, D (2006). The effects of tumour necrosis factor-{alpha} and interleukin1 on an in vitro model of thyroid-associated ophthalmopathy; contrasting effects on adipogenesis. Eur J Endocrinol 155: 395-403 [Abstract] [Full Text]  
• Shih, M.-J., Liao, S.-L., Kuo, K.-T., Smith, T. J., Chuang, L.-M. (2006). Molecular Pathology of Muller's Muscle in Graves' Ophthalmopathy. J. Clin. Endocrinol. Metab. 91: 1159-1167 [Abstract] [Full Text]  
• Feldon, S. E., Park, D. J. J., O'Loughlin, C. W., Nguyen, V. T., Landskroner-Eiger, S., Chang, D., Thatcher, T. H., Phipps, R. P. (2005). Autologous T-Lymphocytes Stimulate Proliferation of Orbital Fibroblasts Derived from Patients with Graves' Ophthalmopathy. IOVS 46: 3913-3921 [Abstract] [Full Text]  
• Kubo, Y., Sekiya, S., Ohigashi, M., Takenaka, C., Tamura, K., Nada, S., Nishi, T., Yamamoto, A., Yamaguchi, A. (2005). ABCA5 Resides in Lysosomes, and ABCA5 Knockout Mice Develop Lysosomal Disease-Like Symptoms. Mol. Cell. Biol. 25: 4138-4149 [Abstract] [Full Text]  
• Wemeau, J. L., Caron, P., Beckers, A., Rohmer, V., Orgiazzi, J., Borson-Chazot, F., Nocaudie, M., Perimenis, P., Bisot-Locard, S., Bourdeix, I., Dejager, S. (2005). 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. 90: 841-848 [Abstract] [Full Text]  
• 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. (2004). Double-Blind, Placebo-Controlled Trial of Octreotide Long-Acting Repeatable (LAR) in Thyroid-Associated Ophthalmopathy. J. Clin. Endocrinol. Metab. 89: 5910-5915 [Abstract] [Full Text]  
• Cawood, T., Moriarty, P., O'Shea, D. (2004). Recent developments in thyroid eye disease. BMJ 329: 385-390 [Full Text]  
• Eckstein, A K, Quadbeck, B, Tews, S, Mann, K, Kruger, C, Mohr, C H, Steuhl, K-P, Esser, J, Gieseler, R K (2004). Thyroid associated ophthalmopathy: evidence for CD4+ {gamma}{delta} T cells; de novo differentiation of RFD7+ macrophages, but not of RFD1+ dendritic cells; and loss of {gamma}{delta} and {alpha}{beta} T cell receptor expression. Br J Ophthalmol 88: 803-808 [Abstract] [Full Text]  
• Elner, V. M., Hassan, A. S., Frueh, B. R. (2004). Graded Full-Thickness Anterior Blepharotomy for Upper Eyelid Retraction. Arch Ophthalmol 122: 55-60 [Abstract] [Full Text]  
• Prabhakar, B. S., Bahn, R. S., Smith, T. J. (2003). Current Perspective on the Pathogenesis of Graves' Disease and Ophthalmopathy. Endocr. Rev. 24: 802-835 [Abstract] [Full Text]  
• Bahn, R. S. (2003). Pathophysiology of Graves' Ophthalmopathy: The Cycle of Disease. J. Clin. Endocrinol. Metab. 88: 1939-1946 [Full Text]  
• Ginsberg, J. (2003). Diagnosis and management of Graves' disease. CMAJ 168: 575-585 [Abstract] [Full Text]  
• Krassas, G. E., Pontikides, N., Kaltsas, T., Dumas, A., Frystyk, J., Chen, J. W., Flyvbjerg, A. (2003). Free and Total Insulin-Like Growth Factor (IGF)-I, -II, and IGF Binding Protein-1, -2, and -3 Serum Levels in Patients with Active Thyroid Eye Disease. J. Clin. Endocrinol. Metab. 88: 132-135 [Abstract] [Full Text]  
• Pasquali, D., Notaro, A., Bonavolonta', G., Vassallo, P., Bellastella, A., Sinisi, A. A. (2002). Somatostatin Receptor Genes Are Expressed in Lymphocytes from Retroorbital Tissues in Graves' Disease. J. Clin. Endocrinol. Metab. 87: 5125-5129 [Abstract] [Full Text]  
• Marcocci, C., Bartalena, L., Tanda, M. L., Manetti, L., Dell'Unto, E., Rocchi, R., Barbesino, G., Mazzi, B., Bartolomei, M. P., Lepri, P., Cartei, F., Nardi, M., Pinchera, A. (2001). 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. 86: 3562-3567 [Abstract] [Full Text]  
• Busuttil, B. E., Frauman, A. G. (2001). Extrathyroidal Manifestations of Graves' Disease: The Thyrotropin Receptor Is Expressed in Extraocular, But Not Cardiac, Muscle Tissues. J. Clin. Endocrinol. Metab. 86: 2315-2319 [Abstract] [Full Text]  
• Valyasevi, R. W., Jyonouchi, S. C., Dutton, C. M., Munsakul, N., Bahn, R. S. (2001). Effect of Tumor Necrosis Factor-{{alpha}}, Interferon-{{gamma}}, and Transforming Growth Factor-{beta} on Adipogenesis and Expression of Thyrotropin Receptor in Human Orbital Preadipocyte Fibroblasts. J. Clin. Endocrinol. Metab. 86: 903-908 [Abstract] [Full Text]  
• Weetman, A. P. (2000). Graves' Disease. NEJM 343: 1236-1248 [Full Text]  
• Bartalena, L., Pinchera, A., Marcocci, C. (2000). Management of Graves' Ophthalmopathy: Reality and Perspectives. Endocr. Rev. 21: 168-199 [Abstract] [Full Text]  
• Hiromatsu, Y., Yang, D., Bednarczuk, T., Miyake, I., Nonaka, K., Inoue, Y. (2000). Cytokine Profiles in Eye Muscle Tissue and Orbital Fat Tissue from Patients with Thyroid-Associated Ophthalmopathy. J. Clin. Endocrinol. Metab. 85: 1194-1199 [Abstract] [Full Text]  
• Mühlberg, T., Joba, W., Spitzweg, C., Schworm, H.-D., Heberling, H.-J., Heufelder, A. E. (2000). Interleukin-1 Receptor Antagonist Ribonucleic Acid and Protein Expression by Cultured Graves' and Normal Orbital Fibroblasts Is Differentially Modulated by Dexamethasone and Irradiation. J. Clin. Endocrinol. Metab. 85: 734-742 [Abstract] [Full Text]  
• Aniszewski, J. P., Valyasevi, R. W., Bahn, R. S. (2000). Relationship between Disease Duration and Predominant Orbital T Cell Subset in Graves' Ophthalmopathy. J. Clin. Endocrinol. Metab. 85: 776-780 [Abstract] [Full Text]  
• Kahaly, G. J., Rösler, H.-P., Pitz, S., Hommel, G. (2000). Low- Versus High-Dose Radiotherapy for Graves' Ophthalmopathy: A Randomized, Single Blind Trial. J. Clin. Endocrinol. Metab. 85: 102-108 [Abstract] [Full Text]  
• Valyasevi, R. W., Erickson, D. Z., Harteneck, D. A., Dutton, C. M., Heufelder, A. E., Jyonouchi, S. C., Bahn, R. S. (1999). Differentiation of Human Orbital Preadipocyte Fibroblasts Induces Expression of Functional Thyrotropin Receptor. J. Clin. Endocrinol. Metab. 84: 2557-2562 [Abstract] [Full Text]  
• Many, M.-C., Costagliola, S., Detrait, M., Denef, J.-F., Vassart, G., Ludgate, M. (1999). Development of an Animal Model of Autoimmune Thyroid Eye Disease. J. Immunol. 162: 4966-4974 [Abstract] [Full Text]  
• Hansen, C., Rouhi, R., Förster, G., Kahaly, G. J. (1999). Increased Sulfatation of Orbital Glycosaminoglycans in Graves' Ophthalmopathy. J. Clin. Endocrinol. Metab. 84: 1409-1413 [Abstract] [Full Text]  
• Colao, A., Lastoria, S., Ferone, D., Pivonello, R., Macchia, P. E., Vassallo, P., BonavolontÁ, G., Muto, P., Lombardi, G., Fenzi, G. (1998). Orbital Scintigraphy with [111In-Diethylenetriamine Pentaacetic Acid-D-Phe1]-Octreotide Predicts the Clinical Response to Corticosteroid Therapy in Patients with Graves' Ophthalmopathy. J. Clin. Endocrinol. Metab. 83: 3790-3794 [Abstract] [Full Text]  
• De Bellis, A., Di Martino, S., Fiordelisi, F., Muccitelli, V. I., Sinisi, A. A., Abbate, G. F., Gargano, D., Bellastella, A., Bizzarro, A. (1998). Soluble Intercellular Adhesion Molecule-1 (sICAM-1) Concentrations in Graves' Disease Patients Followed Up for Development of Ophthalmopathy. J. Clin. Endocrinol. Metab. 83: 1222-1225 [Abstract] [Full Text]  
• Bahn, R. S., Dutton, C. M., Natt, N., Joba, W., Spitzweg, C., Heufelder, A. E. (1998). Thyrotropin Receptor Expression in Graves' Orbital Adipose/Connective Tissues: Potential Autoantigen in Graves' Ophthalmopathy. J. Clin. Endocrinol. Metab. 83: 998-1002 [Abstract] [Full Text]  
• Grossmann, M., Weintraub, B. D., Szkudlinski, M. W. (1997). Novel Insights into the Molecular Mechanisms of Human Thyrotropin Action: Structural, Physiological, and Therapeutic Implications for the Glycoprotein Hormone Family. Endocr. Rev. 18: 476-501 [Abstract] [Full Text]  
• Hofbauer, L. C., Muhlberg, T., Konig, A., Heufelder, G., Schworm, H.-D., Heufelder, A. E. (1997). Soluble Interleukin-1 Receptor Antagonist Serum Levels in Smokers and Nonsmokers with Graves' Ophthalmopathy Undergoing Orbital Radiotherapy. J. Clin. Endocrinol. Metab. 82: 2244-2247 [Abstract] [Full Text]