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Ophthalmopathy, Thyroid
Article Last Updated: Oct 26, 2006
AUTHOR AND EDITOR INFORMATION
Section 1 of 12  
Author: Michael T Yen, MD, Associate Professor of Ophthalmology, Department of Ophthalmology, Division of Ophthalmic Plastic, Lacrimal, and Orbital Surgery, Cullen Eye Institute, Baylor College of Medicine
Michael T Yen is a member of the following medical societies: American Academy of Ophthalmology, American Society of Cataract and Refractive Surgery, American Society of Ophthalmic Plastic and Reconstructive Surgery, and Association for Research in Vision and Ophthalmology
Coauthor(s):
Rudolph Lin, MD, Chief of Radiology, Department of Radiology, St. Elizabeth Hospital;
Kimberly G Yen, MD, Assistant Professor of Ophthalmology, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine
Editors: David S Levey, MD, PhD, Orthopedic/Spine MRI TeleRadiologist, Radsource, LLC; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; C Douglas Phillips, MD, Professor, Departments of Radiology, Neurosurgery, and Otolaryngology, University of Virginia Health Sciences Center; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; Eugene C Lin, MD, Consulting Staff, Department of Radiology, Virginia Mason Medical Center
Author and Editor Disclosure
Synonyms and related keywords:
thyroid eye disease, Graves disease, Graves' disease, Graves ophthalmopathy, thyrotoxic ophthalmopathy, thyrotoxic exophthalmos, thyroid-associated ophthalmopathy, endocrine exophthalmos
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). 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. 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.
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.
Clinical Details
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.
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
Findings
Conventional radiographs are not useful in the diagnosis of thyroid ophthalmopathy, because bony abnormalities usually are not associated with the disease.
Degree of Confidence
The degree of confidence is poor. Radiographs cannot determine the amount of extraocular muscle enlargement, degree of optic nerve compression, or presence of other orbital processes that may mimic thyroid ophthalmopathy. Perform orbital ultrasonograpy, CT scanning, or MRI instead.
Findings
CT scanning provides excellent visualization of the extraocular muscles, intraconal fat, as well as the orbital apex. Enlargement of the muscles occurs almost uniformly within the muscle belly (see Images 3-4), and thickening is usually > 4 mm. The tendinous insertion (which is easily visualized in axial sections) usually is not enlarged. Prominent intraconal fat can also result in proptosis (see Image 5). Pay particular attention to the orbital apex to assess for evidence of optic nerve compression, which is identified more readily in coronal sectioning of the orbit. The degree of globe proptosis relative to the lateral orbital rim can be measured with CT scan studies. In addition, scans of the bony architecture of the orbit and adjacent sinuses are available when an orbital decompression is required.
Degree of Confidence
The degree of confidence is high. An additional test rarely is required for the diagnosis of thyroid ophthalmopathy. Orbital ultrasonography also can provide the diagnosis with a high degree of confidence, but cost and convenience considerations make ultrasonography more useful when serial imaging is required.
False Positives/Negatives
Orbital myositis often can mimic the clinical appearance of thyroid ophthalmopathy. This condition most often is unilateral, and the tendinous insertions of the extraocular muscles also are enlarged. Metastatic tumors to the extraocular muscles also may mimic thyroid eye disease, although they are usually associated with other orbital and bony metastases. However, other etiologies should be considered in the presence of isolated lateral rectus muscle enlargement, because this is almost never seen in thyroid orbitopathy.
Findings
Similar to CT scan studies, MRI also provides excellent imaging of the extraocular muscles, their insertions, and the anatomy of the orbital apex (see Image 6). In addition, the amount of fat within the orbit and imaging of the optic nerve can be assessed and localized on MRI better than on CT scans. Typically, however, MRI is not the ideal imaging modality because of the associated increased cost. Because of the significant amount of fat present within the orbit, fat-suppression techniques are utilized in its evaluation, particularly if MRI contrast agents are administered. Fat normally appears bright on both T1-weighted and fast T2-weighted pulse sequences; however, fat suppression significantly reduces the signal from fat, thereby rendering it dark on MRIs. This greatly improves lesion detection by increasing the contrast between the orbital fat and pathologic processes. With MRI contrast administration, enhancing lesions become much more conspicuous with fat suppression during T1-weighted imaging. Likewise, in evaluating tumor or inflammatory processes with higher water content, these abnormalities become easily visible with fat suppression during fast T2-weighted sequences. The MRI signal intensity of the enlarged extraocular muscles is usually isointense on T1-weighted images and isointense to minimally hyperintense on T2-weighted images. High intensity in the extraocular muscle on T1-weighted images is occasionally seen, which is consistent with fatty infiltration. This finding can aid in differentiating thyroid orbitopathy from pseudotumor. Increased T2 signal in the extraocular muscles is likely caused by increased water content. Patients with elevated T2 relaxation times have increased response to anti-inflammatory treatment (this is similar to octreotide accumulation [see Nuclear Medicine section]).
Degree of Confidence
The degree of confidence is high. Similar to CT scanning, MRI usually can provide the diagnosis of thyroid ophthalmopathy with or without optic nerve compression. Additional testing usually is not required if an MRI study already has been obtained.
False Positives/Negatives
MRI may be better than CT scanning in identifying other causes of proptosis, such as orbital tumors.
Findings
Orbital ultrasonography is excellent for the diagnosis of thyroid ophthalmopathy, and medium to high internal reflectivity of the extraocular muscles, as well as enlargement of the muscle belly, is characteristic. The tendinous insertion of the extraocular muscle also can be visualized easily. Patients with thyroid ophthalmopathy show lower peak-systolic and end-diastolic velocities that may be appreciated with Doppler imaging. Visualization of the orbital apex is difficult with orbital ultrasonography, and CT scanning or MRI may be preferred when compression of the optic nerve is suspected.
Degree of Confidence
The degree of confidence is high. Additional examinations to diagnose thyroid ophthalmopathy are not needed if the characteristic high reflectivity and enlargement of the extraocular muscles with sparing of the tendinous insertion are present on sonograms. However, to better visualize the apex of the orbit for evidence of optic nerve compression, CT scanning or MRI may be required if warranted by the clinical presentation.
False Positives/Negatives
Orbital myositis is characterized by high reflectivity and enlarged extraocular muscle bellies when examined with ultrasonography. However, in orbital myositis, the tendinous insertion is enlarged, which differentiates this condition from thyroid ophthalmopathy.
Findings
Although not clinically useful in the diagnosis of thyroid ophthalmopathy, functional studies such as positron emission tomography (PET) scans or somatostatin-receptor scintigraphy (SRS) may assess disease activity. Orbital infiltration with mononuclear cells in thyroid ophthalmopathy can be identified by receptor imaging with octreotide, a radiolabeled somatostatin analogue. Patients with active thyroid ophthalmopathy show higher octreotide uptake and may respond better to treatments such as corticosteroids or radiation therapy. Patients with inactive disease,however, do not respond to these treatments. In the future, nuclear medicine testing may determine whether stability of the orbital disease has been achieved before proceeding to surgical decompression.
Degree of Confidence
Patients with thyroid ophthalmopathy often present when their disease is no longer active. PET scans or SRS in these patients is not informative, and alternative imaging methods (ultrasonography or CT scanning) are required.
False Positives/Negatives
Other orbital inflammatory processes also may result in increased uptake during functional imaging.
Findings
Angiography typically is not used in the diagnosis or management of thyroid ophthalmopathy. Enlarged orbital vessels with increased blood-flow velocities may be present.
No radiologic intervention exists.
Medical/Legal Pitfalls
- Failure to make the diagnosis in a timely manner (This may result in claims against the radiologist.)
- Failure to perform orbital ultrasonography with particular attention to internal reflectivity, which may aid in differentiating between metastatic disease and thyroid ophthalmopathy
- Failure to consider biopsy when findings are suggestive of metastatic disease
Special Concerns
- Isolated metastasis to the extraocular muscle, which may cause enlargement of the extraocular muscle
| Media file 1:
Severe proptosis and eyelid retraction from thyroid-related orbitopathy. This patient also had optic nerve dysfunction from thyroid related orbitopathy. |
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Although this patient had mild proptosis, there was also prominent eyelid retraction with temporal flare on the left. |
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| Media file 3:
Computed tomography axial image demonstrates the enlarged bellies of the extraocular muscle without involvement of the tendinous insertion to the globe. |
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Computed tomography coronal section through the orbit demonstrates enlargement of multiple muscles within the orbit. |
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Prominent intraconal fat can also result in proptosis and straightening of the optic nerve. In addition, this patient has mild enlargement of the extraocular muscles. |
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Computed tomography axial section of the orbit. Note the enlargement of the muscle bellies that spare the tendinous insertion on the globe. |
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Computed tomography axial section demonstrates enlarged inferior rectus muscles. |
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Computed tomography coronal section of the same patient as in Image 7. The extraocular muscle bellies, especially the inferior rectus muscle on the right, are enlarged. |
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Computed tomography coronal section deeper in the orbit near the apex demonstrates crowding of the optic nerve by the enlarged extraocular muscles. |
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B-scan ultrasonography reveals enlargement of the extraocular muscle belly. The tendinous insertion of the extraocular muscle at the globe is not thickened, which is characteristic of thyroid-related orbitopathy. |
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A-scan ultrasonography reveals medium to high internal reflectivity of the extraocular muscle belly. |
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Ophthalmopathy, Thyroid excerpt Article Last Updated: Oct 26, 2006
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