TED is an unpredictable autoimmune inflammatory disease that can be sight-threatening, debilitating, and disfiguring. Although most TED patients are hyperthyroid, in at least 10% of cases TED occurs in the setting of euthyroidism or hypothyroidism. While the overall TED prevalence is about 40% in Graves patients, subclinical extraocular muscle enlargement can occur in nearly 70% of adult patients with Graves hyperthyroidism. The majority of patients have mild, self-limited TED, 20% to 30% of patients experience moderate/severe disease, and 3% to 5% may develop sight-threatening disease, such as CON or exposure keratopathy. In a recent study of newly diagnosed Graves patients, the prevalence of concurrent mild, moderate-severe, and sight-threatening disease was 20%, 5.8%, and 0.3%, respectively. Leading risk factors for TED include cigarette smoking, thyroid dysfunction, radioactive iodine treatment, female sex, and increasing age.[6,7]
The heterogeneous presentation of TED, including the timing of onset, activity, and severity, can lead to delays in accurate diagnosis, with the average time to diagnosis from symptom onset being 9 months. The disease is commonly initially misdiagnosed, up to 58% of the time in a recent UK survey. Finally, the varied temporal relationship between onset of TED and Graves disease (GD) can add to the challenge in diagnosis because in 23% of patients, GD develops after the diagnosis of TED.
TED begins with an acute inflammatory/active phase that can last from 6 to 36 months, with symptoms including dry eyes, orbital or ocular surface pain, periorbital swelling, and eyelid retraction. Some patients develop disfiguring proptosis, diplopia, and vision loss. Over time, the inflammation subsides and the patient enters a chronic phase characterized by fibrosis, which can be accompanied by permanent disfigurement and functional vision loss. Theoretically, the optimal time to initiate therapy is during the active phase, as intervention then limits disease progression and visual morbidity and may decrease the need for reconstructive surgery.
Treatment of TED lends itself to a multidisciplinary approach, since it involves significant input of both endocrinology and oculoplastic orbital surgeons. Significant advances in treatment have occurred in recent years. Discussion of the various therapeutic considerations is the focus of this manuscript. We will first review the pathophysiology of TED and its clinical assessment, then we will discuss therapeutic options for TED.
J Endo Soc. 2021;5(5) © 2021 Endocrine Society