Case Presentation: A 41-year-old female smoker with no known past medical history presented with gradual onset dry eyes and blurry vision that progressively worsened over the course of 3 months. She developed right eye bulging with pain and diplopia. She denied other symptoms of thyroid dysfunction. Examination showed right eye proptosis, superior eyelid retraction, mild redness, and tearing. The left eye showed mild proptosis but was otherwise normal. The thyroid was normal in size and texture. The rest of the examination was within normal limits. Laboratory workup was significant for elevated TSI 370 and TRAB 8.03 with normal range TSH and free T4 and T3. Contrast-enhanced CT of the orbits showed asymmetric enlargement of the right inferior and medial rectus muscles. MRI of the orbits showed unilateral thickening, edema and prominent enhancement of the right inferior, medial and lateral rectus muscles, most suggestive of idiopathic orbital inflammation. Left ocular muscles were of normal thickness without edema. She received a prolonged, high-dose prednisone taper over 2 months with symptomatic improvement. She was also counseled on smoking cessation. Since diagnosis, she was found to remain clinically and biochemically euthyroid.
Discussion: Euthyroid Graves’ disease is defined as infiltrative orbitopathy occurring in the absence of past/present clinical or biochemical thyroid abnormalities without any antithyroid treatment. It presents a diagnostic dilemma due to asymmetrical manifestations and the occurrence of thyroid dysfunction 15-45 months after the onset of ophthalmopathy in 8-25% of patients. Treatment options remain the same as in Graves’ disease. Cigarette smoking has a strong correlation with Graves’ ophthalmopathy with smokers having more severe disease and less responsive to immunosuppressive therapies. Systematic reviews have shown a prevalence of 7.9% for euthyroidism, 10.36% for hypothyroidism, and 86.2% for hyperthyroidism in thyroid-associated ophthalmopathy. This diversity in the clinical phenotype of Graves’ disease is suspected secondary to the heterogeneity of antithyroid receptor antibodies and their signaling cascades. Delineation of this functional heterogeneity may elucidate new approaches to therapy. In general, patients with euthyroid Graves’ ophthalmopathy have a better response to treatment secondary to milder ophthalmic symptoms and lower clinical activity scores. Frequent longitudinal thyroid exams, thyroid function testing, and monitoring for signs and symptoms of thyroid dysfunction are crucial in these patients.
Conclusions: With Graves’ ophthalmic features occurring in absence of clinical or biochemical thyroid abnormalities, it is imperative to screen and monitor for thyroid dysfunction, given that approximately 5-10% of patients with Graves’ ophthalmopathy are found to be euthyroid with low titers of anti-thyrotropin receptor antibodies.