Thyroid orbitopathy, also known as thyroid eye disease, thyroid ophthalmopathy and Graves’ eye disease, is an autoimmune process that affects the soft tissue and fat of the orbit. Its prevalence is more common in females than males. It most commonly occurs concurrently in the setting of thyroid disease and less frequently precedes and follows thyroid disease.
Thyroid orbitopathy has the highest association with Graves’ disease, an autoimmune process that causes hyperthyroidism. However, it can occur less commonly in hypothyroid and euthyroid states.
Traditionally, the disease activity of the orbitopathy and the disease activity of the thyroid are thought to be distinct. However, recent research has shown that the thyroid tissue and orbital tissue share similar antigens that may be important in the activity of the orbitopathy.
The actual immune process is understood to be T-cell- and antibody-mediated. Inflammatory cells that lead to lipogenesis and fibrosis infiltrate orbital tissue. Both lead to increased orbital volume, which impede venous return and can cause compression of the optic nerve.
Jenny Y. Yu
Recent research has shown specific antigens and antibodies that may help in targeted treatment of the disease; however, much clarification is still needed to fully understand the correlation between the two-disease process of the thyroid and the orbitopathy.
The presentation of thyroid orbitopathy varies considerably. Clinical signs of inflammation such as lid edema, conjunctival/caruncular chemosis and dry eye symptoms can be the first presentation of the disease. Due to the vagueness of such signs, early stages of thyroid orbitopathy can easily be missed. Proptosis, lateral flare, lid retraction and lid lag on down gaze occur later in the disease process and make diagnosis of thyroid orbitopathy a bit easier.
Clinical diagnosis is not always straightforward, as various other disease processes of the orbit can mimic the signs and symptoms of thyroid orbitopathy. Computed tomography and/or magnetic resonance imaging of the orbit can be useful in such situations, as characteristic tendon-sparing muscle belly enlargement and/or increased fat volume can help make the diagnosis.
The diagnosis of thyroid orbitopathy remains a clinical one. Abnormal thyroid hormone levels and the presence of antibodies such as anti-thyroglobulin, anti-microsomal or anti-thyrotropin receptor can aid in the diagnosis. Several small sample size studies have attempted to show a correlation between circulating autoantibodies such as thyroid-stimulating immunoglobulins and disease activity. Clinically, elevated thyroid-stimulating immunoglobulins can be seen in patients with active thyroid orbitopathy. However, large randomized trials are needed before any conclusions can be made in regard to using these blood markers in part of the clinical diagnosis.
Clinical activity scales exist to help classify the disease severity. The most often used clinical activity scale is the one established by Mourits et al in 1997 that has since been modified by the European Group on Graves’ Orbitopathy (EUGOGO). Using the clinical activity and severity scales, disease process can be stratified into mild, moderate-to-
severe and sight-threatening.
Most cases spontaneously remit without intervention, with 3% to 5% of patients developing significant disease. Rundle’s curve describes the typical course of the disease without intervention to be an average of 18 months of active disease that then plateaus to a cicatricial phase of the tissue. Cigarette smoking, which has been linked to many autoimmune diseases, increases incidence. A dose–response relationship between the number of cigarettes smoked per day and the probability of developing Graves’ orbitopathy has been demonstrated.
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In part 2 of this column, Yu describes treatment options.
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For more information:
Jenny Y. Yu, MD, is an assistant professor of Ophthalmology at UPMC and the University of Pittsburgh and can be reached at 203 Lothrop Street, Pittsburgh, PA 15213; 412-605-1451; email: firstname.lastname@example.org
Disclosure: Yu has no relevant financial disclosures.