Introduction
Background
Orbital and ocular changes associated with thyroid dysfunction were first reported by von Basedov in 1840, then Graves in 1935. Thyroid ophthalmopathy currently is recognized as the most common cause of proptosis (protrusion of the globe) in adults (see Image 1).
Severe proptosis and eyelid retraction from thyroid-related orbitopathy. This patient also had optic nerve dysfunction from thyroid related orbitopathy.
Although this patient had mild proptosis, there was also prominent eyelid retraction with temporal flare on the left.
Other clinical features include upper and/or lower eyelid retraction (see Image 2), restrictive myopathy causing diplopia (double vision), compressive optic neuropathy, and exposure keratopathy. Although most patients are clinically hyperthyroid, signs of thyroid ophthalmopathy can be present regardless of thyroid function.1
For excellent patient education resources, visit eMedicine's Endocrine System Center. Also, see eMedicine's patient education article Thyroid Problems.
Pathophysiology
Although not completely understood, the underlying pathophysiology of thyroid ophthalmopathy seems to be an autoimmune reaction directed toward orbital fibroblasts. Thyroglobulin, antithyroglobulin complexes, and other determinants common among orbital and thyroid antigens may initiate hypersensitivity reactions that result in the orbital changes in thyroid ophthalmopathy. Defects in immunoregulation allow B lymphocytes to produce autoantibodies that target extraocular muscles, orbital fat, and the lacrimal gland. Stimulation of orbital fibroblasts in these tissues results in production of hyaluronic acid, which increases the osmotic load of the tissues and results in passive swelling.2,3
Frequency
United States
The incidence of thyroid ophthalmopathy annually is 16 per 100,000 in women and 2.9 per 100,000 in men.
International
Thyroid ophthalmopathy is reported worldwide.
Mortality/Morbidity
Although thyroid ophthalmopathy rarely causes death, its morbidity can be significant.
- Diplopia is often incomitant and difficult to manage. Severe visual loss can occur with compressive optic neuropathy.
- Lagophthalmos and exposure keratopathy can result in corneal epithelial breakdown, increasing the risk of corneal ulceration and perforation.
- Proptosis and eyelid retraction often result in a cosmetically unacceptable appearance. Patients appear wide eyed and startled, regardless of emotional expression.
Race
No racial predilection appears to exist for thyroid ophthalmopathy. Reports of thyroid ophthalmopathy exist worldwide, although exact genetic linkage varies among races.
Sex
Although the male-to-female ratio is 1:4, thyroid ophthalmopathy is more severe in men.
Age
- Thyroid ophthalmopathy typically occurs in those aged 20-50 years.
- Rare cases of thyroid ophthalmopathy have been reported in children and adolescents.
- Thyroid ophthalmopathy is more severe when it occurs in patients older than 50 years.
Anatomy
Thyroid ophthalmopathy causes enlargement of the extraocular muscles and surrounding orbital fat, resulting in proptosis. Muscular enlargement almost always is within the muscle belly, with sparing of the muscle tendon that inserts onto the globe, and often causes diplopia by restricting the globe's movement. Optic nerve compression can occur in the apex of the orbit, where the extraocular muscles originate. Treatment of thyroid ophthalmopathy involves excision of the orbital fat and expansion of orbital volume by fracturing and/or removing the orbital walls. Acute exacerbations of thyroid ophthalmopathy may be treated with either corticosteroids or radiation therapy.
Presentation
Proptosis is the most common sign of thyroid ophthalmopathy and is caused by enlargement of the extraocular muscles, as well as the orbital fat. The most commonly involved extraocular muscles are (from most frequent to least frequent) the inferior rectus, medial rectus, superior rectus, oblique muscles, and lateral rectus. Upper and lower eyelid retraction also is a common feature of thyroid eye disease.
Clinical exacerbations of thyroid ophthalmopathy can occur and are characterized by marked worsening of proptosis, painful myositis, and significant chemosis and vascular engorgement within the orbit. Immediate treatment with corticosteroids often is required to prevent or minimize associated compressive optic neuropathy.
Preferred Examination
Orbital ultrasonography is the most convenient examination for the diagnosis of thyroid ophthalmopathy, because it can be performed quickly and with a high degree of confidence. High reflectivity and enlargement of the extraocular muscles are assessed easily, and serial sonographic examinations can also be used to assess progression or stability of the ophthalmopathy.
Computed tomography (CT) scanning is an excellent imaging modality for the diagnosis of thyroid ophthalmopathy. In addition to allowing visualization of the enlarged extraocular muscles, CT scans provide the surgeon with depictions of the bony anatomy of the orbit when an orbital decompression is required. Magnetic resonance imaging (MRI) also provides excellent imaging of the orbital contents, without the radiation exposure associated with CT scan studies. MRI provides better imaging of the optic nerve, orbital fat, and extraocular muscle, but CT scans provide better views of the bony architecture of the orbit.
Limitations of Techniques
The primary limitations of orbital ultrasonography are lack of visualization of the bony orbital architecture and inability to image the orbital apex. CT scanning provides excellent studies; however, cost and radiation exposure limit their use for serial examinations. MRI can assess the amount of fat within the orbit, but CT scans provide better views of the bony anatomy and are less expensive.
Differential Diagnoses
Other Problems to Be Considered
Orbital myositis (inflammatory pseudotumor of the orbit)
Cavernous sinus thrombosis
Histiocytosis X
Lacrimal gland tumor
Orbital varices
Cavernous hemangioma of the orbit
More on Ophthalmopathy, Thyroid |
 Overview: Ophthalmopathy, Thyroid |
| Imaging: Ophthalmopathy, Thyroid |
| Follow-up: Ophthalmopathy, Thyroid |
| Multimedia: Ophthalmopathy, Thyroid |
| References |
| Further Reading |
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References
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Khoo TK, Bahn RS. Pathogenesis of Graves' ophthalmopathy: the role of autoantibodies. Thyroid. Oct 2007;17(10):1013-8. [Medline].
Mayer EJ, Fox DL, Herdman G, et al. Signal intensity, clinical activity and cross-sectional areas on MRI scans in thyroid eye disease. Eur J Radiol. Oct 2005;56(1):20-4.
Taoka T, Sakamoto M, Nakagawa H, et al. Evaluation of extraocular muscles using dynamic contrast enhanced MRI in patients with chronic thyroid orbitopathy. J Comput Assist Tomogr. Jan-Feb 2005;29(1):115-20.
Dodds NI, Atcha AW, Birchall D, Jackson A. Use of high-resolution MRI of the optic nerve in Graves' ophthalmopathy. Br J Radiol. Jan 5 2009;[Medline].
Volpe NJ, Sbarbaro JA, Gendron Livingston K, et al. Occult thyroid eye disease in patients with unexplained ocular misalignment identified by standardized orbital echography. Am J Ophthalmol. Jul 2006;142(1):75-81.
Kuo PH, Monchamp T, Deol P. Imaging of inflammation in Graves'' ophthalmopathy by positron emission tomography/computed tomography. Thyroid. Apr 2006;16(4):419-20.
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Bartley GB, Fatourechi V, Kadrmas EF, et al. Clinical features of Graves'' ophthalmopathy in an incidence cohort. Am J Ophthalmol. Mar 1996;121(3):284-90. [Medline].
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Byrne SF, Gendron EK, Glaser JS, et al. Diameter of normal extraocular recti muscles with echography. Am J Ophthalmol. Dec 15 1991;112(6):706-13. [Medline].
Day RM, Carroll FD. Corticosteroids in the treatment of optic nerve involvement associated with thyroid dysfunction. Arch Ophthalmol. Mar 1968;79(3):279-82. [Medline].
Forrester JV, Sutherland GR, McDougall IR. Dysthyroid ophthalmopathy: orbital evaluation with B-scan ultrasonography. J Clin Endocrinol Metab. Aug 1977;45(2):221-4. [Medline].
Gerding MN, van der Zant FM, van Royen EA, et al. Octreotide-scintigraphy is a disease-activity parameter in Graves'' ophthalmopathy. Clin Endocrinol (Oxf). Mar 1999;50(3):373-9. [Medline].
Hall R, Kirkham K, Doniach D, el-Kabir D. Ophthalmic Graves'' disease. Diagnosis and pathogenesis. Lancet. Feb 21 1970;1(7643):375-8. [Medline].
Kahaly GJ. Imaging in thyroid-associated orbitopathy. Eur J Endocrinol. (Aug) 2001;145(2):107-18.
Nunery WR. Ophthalmic Grave's disease: a dual theory of pathogenesis. Ophthalmol Clin North Am. 1991;4:73-87.
Ozgen A, Alp MN, Ariyurek M, et al. Quantitative CT of the orbit in Graves'' disease. Br J Radiol. Aug 1999;72(860):757-62. [Medline].
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Shammas HJ, Minckler DS, Ogden C. Ultrasound in early thyroid orbitopathy. Arch Ophthalmol. Feb 1980;98(2):277-9. [Medline].
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Further Reading
Related eMedicine topics
Thyroid Ophthalmopathy (from Ophthalmology)
Thyroid Disease
Hyperthyroidism (from Endocrinology)
Hyperthyroidism (from Pediatrics: General Medicine)
Hyperthyroidism, Thyroid Storm, and Graves Disease
Clinical guidelines
ACR Appropriateness Criteria Orbits, Vision, and Visual Loss
Screening for Thyroid Disease: Recommendation Statement
Clinical trials
Thyroid-Associated Ophthalmopathy Subtypes and Orbital Antibodies
Rituximab in the Treatment of Graves' Disease
Keywords
thyroid ophthalmopathy, thyroid eye disease, Graves disease, Graves' disease, Graves ophthalmopathy, thyrotoxic ophthalmopathy, thyrotoxic exophthalmos, thyroid-associated ophthalmopathy, endocrine exophthalmos
