SPECT/CT imaging in thyroid eye disease: an emerging role in assessing sub-clinical activity

Thyroid eye disease (TED) diagnosis is made based on the presence of a constellation of clinical, laboratory, and radiologic findings. Currently, computed tomography (CT) and magnetic resonance imaging (MRI) are the most commonly used imaging modalities; however, they provide indirect indicators of underlying inflammation, resulting in limited specificity. Our narrative review explored the role of Single Photon Emission Computed Tomography (SPECT)/CT in TED with the goal of enhancing our ability to correlate structure with function in TED. A non-systematic narrative search of major electronic databases was conducted to identify literature on SPECT/CT in TED, using targeted selection and thematic narrative synthesis to analyze the findings. Technetium-99m diethylenetriaminepentaacetic acid (^99mTc-DTPA) is the most common tracer used in SPECT/CT and it undergoes extravasation in the presence of inflammatory mediators. The uptake ratio (UR) of this tracer in orbital tissues can be calculated and compared with a reference tissue to provide a way of direct spatial visualization of function and corresponding structure. The UR was consistently higher in patients with a clinical activity score (CAS) ≥ 3. The UR was also consistently elevated in those identified as having active TED on MRI, indicating good correspondence. Lastly, the UR was reduced in the extraocular muscle after introducing triamcinolone injection, highlighting the usefulness of SPECT/CT in identifying anatomic disease activity and guiding treatment among a cohort of CAS-negative patients. While the quantitative calculation of the ^99mTc-DTPA UR provides an objective metric for evaluating active disease, its clinical use in TED is still limited by substantial inter-study variability and intrinsic technical limitations. Monitoring UR may be better suited for monitoring each patient's progression within the same institution.