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Bilateral Thyroid Associated Orbitopathy in an Antibody Negative, Euthyroid Patient Moore, M. OMS-III; Patel, J. DO Edward Via College of Osteopathic Medicine-Carolinas, Spartanburg, SC

CBR-20

Introduction Thyroid associated orbitopathy also known as Grave’s disease is an autoimmune mediated disease that affects orbital tissues. (1) We report a patient with clinical features of thyroid associated orbitopathy, including exophthalmos and CT evidence of rectus muscle enlargement who had negative antibody titers and normal thyroid functioning.

While euthyroid thyroid associated orbitopathy with negative antibodies is an atypical and rare presentation, there have been cases in the literature. In one case, hyperthyroidism and antibodies developed 24 months after initial presentation. (4) This suggests a potential progressive relationship between thyroid associated orbitopathy and the development of hyperthyroidism in patients with initial negative antibodies. While there is no official recommendation for how often to monitor patients who are euthyroid and have negative antibody titers, it is important to evaluate for any changes in symptomology or worsening of ophthalmic complaints. These symptoms include palpitations, rapid weight loss, hair thinning and goiter. Ultimately, patients who present with bilateral exophthalmos and other clinical features of thyroid associated orbitopathy can encounter difficult obstacles in treatment. This includes a potential delay in treatment if labs are interpreted as normal and thyroid associated orbitopathy is ruled out. This can lead to the dangerous complications like permanent exophthalmos, scarring and vision loss. (1,5) Thyroid associated orbitopathy must remain in the list of differentials among orbital cavernous hemangioma, orbital inflammatory syndrome, lymphoma, glioma and orbital cellulitis despite these normal lab values. A CT of orbit with contrast is necessary during this evaluation to show the characteristic rectus muscle enlargement. Conclusion

Thyroid function tests were normal:

Thyroid stimulating hormone (TSH) Free T4

Value 1.180 mcIU/mL 0.98 ng/dL

Reference Range 0.358-3.740 mcIU/mL 0.82-1.70 ng/dL 0.0-0.9 IU/mL 0.00-0.55 IU/L

Thyroglobulin antibody <1.0 IU/mL Thyroid stimulating immunoglobulin antibody <0.10 IU/L Table 1: Lab values and reference ranges.

Case Presentation

He was started on a 45-day taper of 10 mg oral Prednisone and 200 mcg Selenium. He was also educated on the harmful health effects of smoking including worsening of his exophthalmos. On his return visit 45-days later, he had improved conjunctival redness and resolved orbital pain. His exophthalmos remained stable and showed no progression. Discussion Thyroid associated orbitopathy has an incidence of 16 cases per 100,000 in women and 3 cases per 100,000 in men. (1) The most common onset of symptoms is between 30-50 years of age. (1) More severe cases tend to occur in male patients and those who are over 50 years of age. (1) Both of these demographics are consistent with our patient and presentation with more severe symptomology. The pathophysiology behind thyroid associated orbitopathy is an immune mediated reaction directed against orbital fibroblasts leading to expansion of orbital tissue. (3) The most common antibody associated is thyroid stimulating immunoglobulin. (1) Approximately less than 5% of patients with thyroid associated orbitopathy are euthyroid and have low antibody titers. (2) The mainstay of treatment for thyroid associated obritopathy include corticosteroids to decrease edema from inflammation and Selenium. (5) Selenium is an antioxidant and its primary mechanism is to to eliminate reactive oxygen species associated with this disease process. (6) If the exophthalmos becomes severe, orbital decompression surgery is a more invasive option. (5)

A 61-year-old male presented with an eight month history of eye lid retraction, exophthalmos, blurred vision and orbital pain. He had no other symptoms of thyroid dysfunction including palpitations, heat intolerance, tremor, fatigue and sweating. He had a history of hypertension controlled on Metoprolol Succinate ER 50 mg and used Olopatadine HCl 0.2% solution as needed for eye irritation. He smoked and continued to smoke one pack of cigarettes per day. On examination, he had bilateral upper and lower eye lid retraction, exophthalmos, bilateral lower lid fat pads and mild conjunctival redness. Visual acuity of right eye was 20/30 and left eye was 20/40. His Grave’s orbitopathy clinical activity score was three. The remainder of his physical examination was normal including fundal examination.

References

1. Edsel Ing. (2019, March 7). Thyroid-Associated Orbitopathy. Retrieved from https://emedicine.medscape.com/article/1218444-overview 2. Nishihara , E. (2013, November 26). Vol 7 Issue 2 p.4-5. Retrieved from https://www.thyroid.org/patient- thyroid-information/ct-for-patients/vol-7-issue-2/vol-7-issue-2-p-4-5/ 3. Pokhrel, B. (2019, June 3). Graves Disease. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK448195/ 4. Tabasum, A., Khan, I., Taylor, P., Das, G., & Okosieme, O. E. (2018, August 5). Thyroid antibody-negative euthyroid Graves' ophthalmopathy in: Endocrinology, Diabetes & Metabolism Case Reports Volume 2016 Issue 1 (2016). Retrieved from https://edm.bioscientifica.com/view/journals/edm/2016/1/EDM16-0008.xml 5. Zheng, H. (2018, September 28). Graves' disease. Retrieved from https://www.mayoclinic.org/diseases- conditions/graves-disease/diagnosis-treatment/drc-20356245 6. Zheng, H., Wei, J., Wang, L., Wang, Q., Zhao, J., Chen, S., & Wei, F. (2018, September 26). Effects of Selenium Supplementation on Graves' Disease: A Systematic Review and Meta-Analysis. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178160/

Image 2: Right eye fundus.

Image 1: Left eye fundus.

CT of orbit with contrast showed mild bilateral enlargement of inferior rectus and medial rectus muscles consistent with thyroid associated orbitopathy. CT head with and without contrast showed mild-moderate atrophy with no acute intracranial event.