Citations

Background: Pretibial dermopathy (PTD) is a rare, disfiguring manifestation of Graves’ disease. The shared pathophysiology with thyroid eye disease (TED), centered on fibroblast activation via a thyroid-stimulating hormone receptor and insulin-like growth factor-1 receptor (IGF-1R) complex, provides a strong rationale for using the IGF-1R inhibitor, teprotumumab. Methods: We present a case series of five patients with severe PTD and concomitant TED who were treated with teprotumumab. A review of reported cases in the literature was also conducted. Results: All patients experienced significant clinical improvement, including regression of skin thickening as well as enhanced functional capacity. Side effects included mild hearing loss, muscle cramps, and fatigue. One patient experienced a severe gastrointestinal event requiring treatment discontinuation, while those experiencing a recurrence of PTD, responded to a second course of therapy. Conclusions: Teprotumumab showed promising efficacy in the treatment of PTD. Further studies are needed to confirm its durability and safety.

Abstract Graves’ disease (GD) is an autoimmune entity that had an unchanged treatment paradigm for more than half a century with radioactive iodine, antithyroid drugs (ATDs), and surgery representing the mainstay of therapy, with variation in their use over time and geographic location. Hypothyroidism has been an accepted tradeoff in many cases, though recently there are increased concerns about altered quality of life in these patients. Fortunately, the last decade has seen an intense pursuit of GD's immunological mechanisms and a recalibration of classic treatment modalities focusing on thyroid preservation, as reflected in the preference for ATD as primary therapy, including its use in long-term protocols. The immune targets currently explored aim to address this gap by intervening in the TRAb lifecycle: minimizing production (eg, B-cell targeting), enhancing clearance (eg, neonatal Fc receptor inhibitors), or neutralizing its target—the TSH receptor (eg, receptor blockade). While these approaches are going through the necessary clinical trials evaluation, we are starting to see the potential for technology and artificial intelligence to make an impact on how we identify, treat, and monitor patients with GD. The combination of these approaches will likely lead to a significant individualization of GD management that will take us from the goal of normalization of thyroid levels to that of inducing long-term remission and prevention of the associated autoimmune phenomena that GD is associated with. While time is needed for these aspects to mature, the future looks bright for our GD patients and maybe soon these lessons will open new doors for our patients with Hashimoto's thyroiditis as well.

Abstract Disclosure: S. Saad-Omer: None. M. Stan: None. M.R. Castro: None. J. Brito: None. J.E. Hallanger-Johnson: None. M.M. Ryder: None. Background: Thyroid fine needle aspiration (FNA) is a widely utilized diagnostic tool for evaluating thyroid nodules. The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) provides a standardized framework for classifying cytologic findings and guiding management. This study retrospectively reviews thyroid FNA cases at a large academic institution to analyze the distribution of Bethesda classifications.Methods: A retrospective review was conducted of all thyroid FNA cases done in the department of Endocrinology at a large academic institution performed from January 1st 2019 to October 3rd 2023. Thyroid FNA results were divided into categories according to the Bethesda classification system, such as benign, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), follicular neoplasm (FN), suspicious for malignancy, malignancy and non-diagnostic. FNA results that were not able to be classified were labelled as other.Results: A total of 3,291 thyroid FNA cases were included in the analysis. The distribution of cases across the Bethesda categories revealed a significant proportion of benign findings, with 73.6% classified as benign. This was followed by 8.1% follicular neoplasm, 6.56% Papillary Thyroid Cancer, 6.62% Non-diagnostic, 2.4% Atypical, and 2.3% Suspicious. 0.5% of FNA results were classified as other.Conclusion: Overall our cohort was found to have similar findings in terms of benign and confirmed PTC nodules compared to recent literature; however, the rate of atypical and non-diagnostic nodules was found to be lower. Presentation: Monday, July 14, 2025

Abstract Disclosure: Y. Ahmed: None. S.M. Saad-Omer: None. R.M. Castro: None. M. Rivera: None. M.N. Stan: None. Background: Fine-needle aspiration (FNA) is a cornerstone in the evaluation of thyroid nodules. Its accuracy during long term follow up is not well established though. Our project aims to address that. Objective: To assess long-term accuracy of FNA results at Mayo Clinic Rochester including diagnostic classifications, procedural and cytologic variables, and concordance with surgical pathology. Methods: We conducted a retrospective cohort study of patients who underwent thyroid FNA at Mayo Clinic Rochester in 2014, to allow for the long-term follow-up. Descriptive statistics summarized patient demographics, nodule characteristics, and procedural factors. Cross-tabulation was used to evaluate concordance between FNA cytology and surgical pathology. This is an interim analysis. Results: Among 199 patients (from 741 FNAs that year), the mean age was 58.6 ± 14.1 years, and 73.7% were female. The average BMI was 29.6 ± 6.4 kg/m². Most had non-toxic multinodular goiter (69.3%) or non-toxic solitary nodules (27.6%). Nodules were 45% solid, 8% cystic, and 47% mixed, with a mean size of 2.3 cm. FNA results were predominantly benign (Bethesda II, 80%), followed by malignant (Bethesda VI, 8%), suspicious for follicular neoplasm (Bethesda IV, 7.5% ), non-diagnostic (Bethesda I, 3%), and suspicious for malignancy (Bethesda V,1%). There were no cases read as Bethesda III (AUS) in 2014. Of the 16 Bethesda VI cases, 15 had surgery; 14 were confirmed malignant, and 1 was benign (Hurthle cell adenoma). Both Bethesda V cases that underwent surgery were benign. Of the 15 Bethesda IV cases, 12 had surgery; 11 were benign and 1 was malignant and 3 had long term follow up (2 benign, and one malignant based on the available data). Overall the malignancy rate for Bethesda IV was 13.3%. Surgery was performed in 12 Bethesda II cases, with final pathology available for 11; 9 were confirmed benign, while 2 were malignant. In the other 147 cases of benign FNAs that didn’t undergo surgery we have not identified any indication of necessity for surgery during the mean of 9 years of follow-up, presumably indicating their benign character. Overall malignancy rate for this group was 1.3%. We had only 6 non diagnostic FNAs (Bethesda I), with all of them during follow up proven benign (2 by surgery, 2 by repeat FNA and 2 by long term follow up). Conclusion: Long term follow up data (over 9 years) support the continued reliability of Bethesda II and VI , while conversely raising questions about the significance of the Bethesda V classification. The malignancy rate in Bethesda IV (likely including the Bethesda III category at the time) is consistent with our institutional data, although it remains lower than that reported by other institutions. We’re currently enriching our cohort to verify and strengthen our conclusions. Presentation: Monday, July 14, 2025

Abstract Disclosure: D. Hamadi: None. A. Algeciras-Schimnich: None. M. Stan: None. Background: Thyroid hormone-binding proteins (TBPs)—thyroxine-binding globulin (TBG), transthyretin, and albumin—play a critical role in transporting thyroid hormones in the bloodstream. Rare genetic alterations in these proteins can lead to discordant thyroid function test (TFT) results, potentially mimicking thyroid dysfunction despite a clinically euthyroid state. This study retrospectively evaluates the clinical scenarios that warrant TBP testing. Methods: Data was extracted from the electronic medical record (EMR) at the Mayo Clinic in Rochester, MN. The study included patients who had Thyroid-binding protein electrophoresis (TBPE) ordered between 2016 to 2023. Results: A total of 138 patients were included (53% female; median age: 58 years) of which 42% had TBP abnormalities. TBP testing was frequently ordered by endocrinology (33%), followed by cardiology (9%) and family medicine (7%). Discrepancies between thyroid-stimulating hormone (TSH) and total T4 (TT4) were identified in 41 patients of which 75% had abnormal TBP. Among these, eleven were diagnosed with familial dysalbuminemic hyperthyroxinemia (FDH), including one with a known family history. Additionally, five patients were diagnosed with thyroid hormone resistance—one of whom had previously been misdiagnosed with Graves’ disease. Three patients were found to have TSH-secreting tumors, and three were receiving infusion therapy with patisiran with resulting TBP abnormalities. The remaining cases involved binding protein abnormalities, most commonly presenting as elevated TBG. Conclusion: This study identified varied clinical utilization for TBP testing, from very appropriate indications to cases of doubtful clinical utility. TBP abnormalities were clinically meaningful in 22% of cases, supporting the utility of testing in select scenarios. Specifically, TBP testing should be reserved for situations with a clear discrepancy between clinical presentation and TFT results—particularly discordant TSH and total T4 levels. In such contexts, TBP assessment is valuable in preventing misdiagnoses and avoiding unnecessary treatments, especially since individuals with TBP mutations are typically clinically euthyroid. Presentation: Sunday, July 13, 2025

Abstract Thyroid eye disease (TED) is a complex ocular autoimmune disorder primarily associated with Graves’ disease. It leads to significant morbidity due to orbital inflammation, fibrosis, and tissue expansion. While corticosteroids have been the traditional mainstay of therapy, recent advancements in understanding TED pathophysiology have driven the development of targeted treatments. Notably, inhibition of the insulin-like growth factor-1 receptor with teprotumumab has revolutionized TED management, demonstrating efficacy in reducing proptosis and disease severity. Additional emerging therapies, including neonatal Fc receptor inhibitors, thyroid-stimulating hormone receptor blockers, and interleukin-6 receptor antagonists, offer promising alternatives for patients with active and refractory disease. Despite these advancements, challenges remain in disease classification and outcome assessment. As the landscape of TED management continues to evolve, this review provides a comprehensive overview of current and emerging therapies for TED, critically examines gaps in disease evaluation, and highlights the evolving paradigm of patient-centered care. Future efforts should focus on optimizing therapeutic algorithms, refining risk stratification models, guiding personalized treatment, and promoting a multidisciplinary approach, which remain essential in improving outcomes and quality of life for affected individuals.

Abstract The therapeutic landscape of Graves’ hyperthyroidism has been rapidly evolving in the past few years. There has been a shift worldwide toward antithyroid drugs as the preferred first-line therapy with significant interest in thyroid function preservation, even if it requires more than 2 years of antithyroid drug treatment. This approach, long term antithyroid drug therapy, has gained traction as a therapeutic option after it has been shown to be safe and associated with significantly higher rates of remission than the traditional 18-month course of medical treatment. In parallel, we see, after 80 years of antithyroid drugs as the only medical therapy available for Graves’ disease, a strong interest in new drug development that follows more closely the pathophysiology of the disease. These approaches span the spectrum of targeting antigen presentation, B cell activation, TSHR antibody cycle and TSHR signaling. Separately, advances in wearable devices and artificial intelligence models present new opportunities for more timely diagnosis, monitoring, and treatment of patients with Graves’ disease. Finally, new therapies will pose novel challenges in the management of patients that will necessitate adjustments to our clinical practices and development of guidelines suited for these new therapeutic options.

Abstract The use of radiofrequency ablation (RFA) of benign, symptomatic thyroid nodules is growing in clinical practice. Objective outcomes of symptom relief are needed to support the use of this treatment. Thus, a previously established thyroid nodule symptom scoring system was prospectively administered to patients prior to RFA of symptomatic thyroid nodules and then at 1, 3, 6, and 12 months following ablation. A total of 38 patients of mean age 57 years were treated with RFA between August 2022 and January 2024 and completed at least 1 follow-up survey. Five of these patients underwent simultaneous ablation of 2 thyroid nodules; the remainder had a single nodule treated. Mean modified symptom score prior to RFA was 3.5 (SD 1.6) with higher scores correlating with increasing baseline nodule volume (R = 0.46, P = 0.0038). Patient symptom scores decreased at the first 1-month survey (mean 1.2; SD 1.3) and 3-month survey (mean 0.9; SD 1.3) with durable response in those patients with more extended follow-up. In those patients with imaging follow-up, decreasing nodule size was shown to correlate with decreasing symptoms. The early results of this study show that RFA of benign, symptomatic thyroid nodules results in quantifiable symptom relief within 3 months of treatment. Such objective measures of symptom relief may be used to measure long-term durability of treatment.

Background Orbital decompression is an essential tool for reducing proptosis in thyroid eye disease (TED), yet the impact of surgical approach and preoperative factors on outcomes remains uncertain. Objective To compare proptosis reduction following different orbital decompression techniques, identify additional risk factors that may play a role in surgical orbital decompression outcomes, and develop clinical decision-making recommendations based on these results. Methods A retrospective analysis was performed on TED patients who underwent endoscopic medial wall, orbital floor, and/or open lateral wall decompression. We evaluated the influence of preoperative comorbidities, anatomic and laboratory values, and surgical approach on postdecompression Hertel exophthalmometry outcomes. Results Analysis encompassed 130 orbits from 80 patients, 83% female, 48 with preoperative diplopia, and mean age of 54.4 years. Preoperative Hertel measurement was predictive of extent of proptosis reduction ( P < .0001), indicating that higher initial Hertel measurement predicts greater absolute reduction following surgical intervention. Surgical technique correlated with outcome on univariate analysis ( P = .04), but not multivariate ( P = .13) analyses. When categorized into preoperative Hertel ranges, combined endoscopic medial and open lateral wall decompression resulted in mean proptosis reduction of 3.13 mm for range 20.01 to 24 mm and 3.85 mm for range 24.01 to 28 mm. Three-wall decompression resulted in mean proptosis reduction of 2.49 mm for and 3.84 mm for these ranges, respectively. Variables such as smoking, body mass index, orbital wall height, and TRAb level, did not affect outcomes. Nine patients had new onset diplopia. Conclusions Preoperative Hertel exophthalmometry is the strongest predictor of proptosis reduction following orbital decompression in TED. Surgical technique appears to be less impactful on outcome than expected. Surgical decision making should be individualized based on patient goals; these findings can be used to achieve proptosis reduction and limit the risk of new onset diplopia.

Abstract Imaging-guided percutaneous core needle biopsy is currently the most common technique for the investigation of potentially malignant bone lesions. It allows precise needle placement and better visual guidance, leading to improved diagnostic accuracy. Needle tract seeding (NTS) is a rare complication of biopsies in general, and its true incidence remains unknown. This study aimed to assess the risk of NTS in patients with thyroid cancer who underwent bone biopsy. For our cohort, we extracted data from the electronic medical record at the Mayo Clinic in Rochester (Minnesota, USA). Inclusion criteria included patients with a history of thyroid cancer who underwent biopsy for bone metastasis between 1/1/2014 and 10/1/2023. We identified a cohort of 20 patients that fit our inclusion criteria. Of these 20 patients, 2 patients developed NTS after CT-guided bone biopsy. Cases of seeding had a larger tumor size, a more aggressive histopathological presentation, a significantly shorter duration between cancer diagnosis and bone metastasis, and underwent more tumor manipulation procedures, such as biopsy and radiofrequency ablation, in contrast to those without seeding. In conclusion, our study identified NTS to have an incidence of 10% after biopsies of bone metastasis related to thyroid carcinoma. These are likely the result of an interplay of risk factors, including tumor biology, penetrated tissues and procedural technical details. Further studies with larger sample sizes are needed to confirm our findings and identify strategies to mitigate NTS.