The 2024 American Thyroid Association (ATA) Annual Meeting took place from October 30 to November 3 in Chicago, IL. This event is globally recognized as the premier gathering for individuals interested in thyroid diseases and disorders. Attendees had the opportunity to engage in peer-to-peer learning and collaboration through a variety of activities including lectures, interactive discussions, meet-the-professor sessions, and abstract presentations.

One of the key topics of discussion at ATA 2024 was thyroid eye disease (TED). TED is a rare condition characterized by inflammation of the muscles and fatty tissues behind the eye, leading to the protrusion and bulging of the eyes (proptosis). Symptoms of TED can include eye pain, double vision, light sensitivity, and difficulty closing the eyes. While this condition affects a relatively small percentage of the population, it can have a significant impact on those affected.

At ATA 2024, numerous studies were presented with a focus on advancing knowledge and identifying the most effective treatment options for managing TED. The following are concise summaries of these studies, showcasing the latest advancements in the field.

Evaluation of fibroinflammatory activity in thyroid eye disease using 18F-FAPI PET/CT: a prospective study

This study assesses the efficacy of fluorine 18 (18F)-labeled fibroblast activation protein inhibitor (FAPI) PET/CT in evaluating the disease activity of orbital tissue in TED.

The significant uptake of FAPI in the Extraocular Muscles (EOMs) may indicate the activity of TED with a high degree of sensitivity and specificity, demonstrating a positive correlation with pathological fibroinflammation. FAPI PET imaging shows promise as a reliable method for assessing disease activity in TED, potentially surpassing the effectiveness of Clinical Activity Score (CAS) evaluations.

The role and mechanism of gut microbiota in thyroid eye disease

TED is a rare yet serious ocular condition, the complete etiology and pathogenesis of which remain incompletely understood. Recent research suggests that the gut microbiota plays a significant role in both the development and advancement of TED. This study seeks to investigate the specific microbial species and metabolites that may be key factors in the pathophysiology of TED.

The study reveals significant differences in gut microbiota, specifically Clostridium innocuum and Akkermansia muciniphila, as well as metabolites such as oleamide and inosine. These findings suggest that these microbial species and metabolites may impact T cell differentiation, ultimately influencing the onset and progression of TED.

Modeling to inform dose selection for TOUR006, a fully human anti-IL-6 antibody, for treatment of thyroid eye disease: Effect of gender and liver and kidney function on modeling the optimal dose regimen

Interleukin 6 (IL-6) is widely recognized as a pivotal factor in the development of TED, with IL-6 receptor inhibition being utilized off-label in its treatment. TOUR006, previously identified as PF-04236921, is a specific, fully human IgG2 monoclonal antibody that binds to IL-6 with exceptional affinity. Over 400 subjects have received doses of TOUR006 thus far. A Population Pharmacokinetic/Pharmacodynamic model focusing on C-reactive protein (CRP), a marker of IL-6 pathway activity, was employed to determine the most effective dosage regimens of TOUR006 for typical TED patients.

Simulations conducted for 20 mg and 50 mg every 8 weeks subcutaneous doses of TOUR006 indicate that these doses and regimens are likely to achieve a CRP suppression of ≥90% from baseline in the majority of typical TED patients, without the necessity for weight-based adjustments.

Predictive factors and treatment outcomes in intravenous glucocorticoid pulse therapy for active moderate-to-severe thyroid eye disease: Identifying the need for surgical interventions

This retrospective cohort study was conducted with the goal of identifying prognostic factors for treatment success in patients with active, moderate-to-severe TED who were undergoing intravenous glucocorticoid (ivGC) therapy. Treatment success was defined as the absence of the need for orbital decompression and/or strabismus surgery post-treatment. The study also aimed to assess ophthalmological and thyroid-specific outcomes in order to enhance disease management strategies and facilitate the development of more personalized treatment plans.

The findings of this study underscore the significant ophthalmological improvements observed with ivGC treatment, such as improved CAS scores, visual acuity, and reduced diplopia, which may be associated with decreased TRAb levels. Notably, smoking was identified as a strong predictor for surgical interventions, highlighting the importance of addressing this modifiable risk factor in patient management. Additionally, TSH and anti-TPO levels were found to be important predictors, emphasizing the value of tailoring treatment approaches to individual patients.

Comparison of efficacy of tocilizumab to intravenous glucocorticoids in the treatment of thyroid eye disease

TED presents a significant challenge as an autoimmune disorder, with some patients demonstrating poor responses to steroid therapy. Tocilizumab (TCZ) has emerged as a promising treatment option for steroid-resistant TED patients. However, its effectiveness in patients who have not received prior steroid treatment remains largely unexplored. The objective of this study is to compare the efficacy of TCZ with intravenous glucocorticoids in the treatment of TED. TCZ has demonstrated potential in improving clinical activity scores (CAS), reducing proptosis (eye bulging), decreasing DTPA uptake, and lowering TRAb levels. Additionally, TCZ has shown superior efficacy in alleviating proptosis compared to traditional steroid therapy.

This research aims to provide valuable insights into the effectiveness of TCZ as a treatment option for TED, particularly in patients who have not previously undergone steroid therapy. By comparing the outcomes of TCZ with intravenous glucocorticoids, we hope to contribute to the advancement of treatment strategies for this challenging autoimmune disorder.

Proteome-wide mendelian randomization study identifies potential novel drug targets for thyroid eye disease

The treatment of TED remains a challenge, highlighting the necessity for the identification of safe and effective drugs. Genetic evidence from protein quantitative trait loci (pQTLs) data presents an opportunity to discover new therapeutic targets. As such, we conducted a thorough proteome-wide Mendelian randomization (MR) analysis to investigate potential targets for TED.

Through the proteome-wide MR analysis and colocalization, we identified 9 potential drug targets for TED. External validation further confirmed FCRL1 and BDNF as promising targets. These findings offer hope for the development of effective treatments for TED and underscore the importance of additional clinical research in this area.

Audiologic adverse effects secondary to teprotumumab: a single academic center historical cohort

Teprotumumab, an IGF-1R antagonist approved for the treatment of TED, has been associated with audiologic adverse effects. This study was conducted to explore audiometric screening and characterize the pattern of audiologic adverse effects in real-world settings.

Although it is established that teprotumumab can lead to hearing loss, tinnitus, and other audiologic symptoms, the specific patterns and monitoring guidelines have not been clearly defined. The findings from this case series suggest that hearing loss associated with teprotumumab treatment may not be limited to the high frequency range, as observed with other ototoxic medications. Therefore, it is recommended that patients undergo serial audiometric monitoring both before starting teprotumumab therapy and throughout the course of treatment.

Preliminary safety and efficacy of subcutaneous lonigutamab (anti–IGF-1R) from a phase 1/2 proof-of-concept study in patients with thyroid eye disease

The efficacy of subcutaneous lonigutamab (anti–IGF-1R) in patients with active TED was evaluated in a recent study (NCT05683496). These findings represent the first reported proof-of-concept results of a subcutaneous anti–IGF-1R in patients with TED.

Patients in the study demonstrated early clinical responses that were sustained over time, even at week 12 (off-treatment), indicating the potential for longer dosing intervals. Evidence from Cohort 1 suggests that lonigutamab was well-tolerated and showed clinical efficacy responses. These findings were further supported by data from Cohort 2. Overall, the results of this study provide valuable insights into the potential benefits of subcutaneous lonigutamab for patients with active TED. Further research and clinical trials are warranted to confirm and build upon these promising findings.

Is teprotumumab associated with decreasing heart rate?

TED is an autoimmune condition associated with thyroid autoimmunity that greatly impacts the quality of life of affected individuals. Teprotumumab, an inhibitor of the insulin-like growth factor-1 receptor (IGF-1R), has demonstrated efficacy in treating TED. However, there is limited data on the impact of Teprotumumab on heart rate. This study aims to investigate whether there is a correlation between Teprotumumab use and changes in heart rate.

A notable number of patients experienced a significant reduction in heart rate while undergoing Teprotumumab therapy. Although the clinical significance of this finding is not yet fully understood, healthcare providers should take note of these results when evaluating patients who may be at risk of developing symptomatic bradycardia. Further research is necessary to determine the potential causality and clinical implications of this phenomenon.

Thank you for joining us for this recap of the ATA 2024. We recommend visiting this link to explore all the posters presented at the event, including ongoing trials. We look forward to seeing you at ATA 2025!

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