Assessment of disease activity in Graves' orbitopathy

Arnaud Potvin^1*Ioana Catalina Lacraru¹Peter Bisschop²Maartje M.L. de Win³Anja Katrin Eckstein⁴Peerooz Saeed¹

• ¹Department of Ophthalmology, Amsterdam UMC Locatie AMC, Amsterdam, Netherlands
• ²Department of Endocrinology, Amsterdam UMC Locatie AMC, Amsterdam, Netherlands
• ³Department of Radiology and Nuclear Medicine, Amsterdam UMC Locatie AMC, Amsterdam, Netherlands
• ⁴Department of Opthalmology, Universitat Duisburg-Essen Medizinische Fakultat, Essen, Germany

Purpose: Graves' orbitopathy (GO) is the most common extra-thyroidal manifestation of Graves' disease (GD). Clinical disease activity and severity stage at the time of diagnosis is commonly used to determine the optimal treatment. There are still controversies regarding the "gold standard" for establishing disease activity. Although Clinical Activity Score (CAS) is the best evaluated parameter and therefore widely used, it lacks the ability to predict disease progression in all patients, and response to anti-inflammatory treatment. Additional predictors are needed to select the optimal treatment for each individual patient. Methods: We conducted a comprehensive review of the literature on activity assessment in GO. Results: A large variety of parameters are used in studies to assess disease activity, most common clinical activity/severity scores, orbital imaging techniques and serum biomarkers. CAS remains the best validated way for activity scoring. Other promising parameters, including specific MRI imaging sequences (short tau inversion recovery, T2 mapping and diffusion-weighted imaging sequences) and serological biomarkers (Thyroid stimulating immunoglobulin/TSH-binding inhibitor immunoglobulin (TSI/TBII) are starting to prove their utility in quantifying disease activity and in predicting the outcome of GO. TBII and TSI measurements cut off values for prognostic statements are available for almost all routine test systems, and should be used more systematically as biomarkers for GO. Conclusions: CAS is still considered the gold standard for assessing disease activity. Applied alone CAS fails to predict disease progression in all patients. The future assessment is probably a combination of clinical, serological and imaging measurements. Selection of treatment should be tailored to manifestations and main treatment effects of the available drugs. Future studies will need to determine which parameters provide the best predictions for each drug class.