Thyroid最新文献

{"title":"Progastrin-Releasing Peptide and Procalcitonin as Additional Markers in the Diagnostic Workup for Medullary Thyroid Carcinoma.","authors":"Leonoor E Schonebaum, Sjoerd A A van den Berg, Mathé van Balkum, W Edward Visser, Luca Giovanella, Robin P Peeters","doi":"10.1089/thy.2024.0293","DOIUrl":"10.1089/thy.2024.0293","url":null,"abstract":"<p><p><b><i>Background:</i></b> Calcitonin (CT), a well-established tumor marker for medullary thyroid carcinoma (MTC), is limited by a high rate of false positives in the diagnostic phase. Potential new markers for MTC are procalcitonin (PCT) and progastrin-releasing peptide (proGRP). Where literature has proven noninferiority for PCT, evidence is lacking for proGRP. Therefore, the present study prospectively evaluated the clinical performance of proGRP and PCT in a multicohort study of patients with MTC compared with other thyroid diseases. <b><i>Methods:</i></b> Adult patients undergoing thyroid surgery for thyroid nodular disease diagnosed in a tertiary center from the Netherlands (discovery cohort) between 2013 and 2025 were prospectively included. Serum samples were collected preoperatively. Diagnostic performance of CT, PCT, proGRP, and carcinoembryonic antigen was calculated separately. A two-step approach, combining different markers, was investigated. Analyses were repeated in a validation cohort from Switzerland. <b><i>Results:</i></b> The discovery and validation cohorts consisted of 335 and 61 patients, respectively. Patients had benign disease (<i>n</i> = 166), other thyroid carcinomas (non-MTC, <i>n</i> = 186), or MTC (<i>n</i> = 44). Median proGRP and PCT levels were significantly higher in MTC compared with benign disease and non-MTC. ProGRP had a low sensitivity (69.2% [CI 48.2-85.7]), while PCT performed similarly to CT (100.0% [CI 89.1-100.0] and 100.0% [CI 88.8-100.0], respectively). The combination of CT and PCT, both in the individual cohorts and when combining the two cohorts, showed the best diagnostic performance with a sensitivity of 100% [CI 91.8-100.0] and negative predictive value of 100% [CI 98.9-100.0] and specificity and positive predictive value of 99.7% [CI 98.4-100.0] and 97.7% [CI 88.0-99.9], respectively. <b><i>Conclusions:</i></b> ProGRP alone or with CT does not have additional value as a diagnostic marker for MTC. A two-step approach combining the use of CT and PCT measurement, in the CT concentration range between 10 and 100 pg/mL, is a promising method to diagnose MTC in patients with thyroid nodules with high diagnostic accuracy.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"1030-1038"},"PeriodicalIF":6.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144508385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thyroxine Treatment after Traumatic Brain Injury Suppresses Astrogliosis and Enhances Neuronal Recovery in Mice.","authors":"Yan-Yun Liu, Wenling Chen, Paola Aguiari, Kiyomi Abe, Anna Milanesi, Gregory A Brent","doi":"10.1177/10507256251372171","DOIUrl":"10.1177/10507256251372171","url":null,"abstract":"<p><p><b><i>Background:</i></b> Traumatic brain injury (TBI) disrupts blood supply, damages neurons and glial cells, and reduces local activation of the prohormone thyroxine (T4) to the active form, triiodothyronine. We treated mice with T4 post-TBI to evaluate the role of thyroid hormone in neural cell protection and injury recovery after TBI, especially the effects on neuroglial cells. <b><i>Materials and Methods:</i></b> A T4 dose was given 1 hour after controlled cortical injury, and in some groups, an additional T4 dose was given 5 days post-TBI. We analyzed the reactive astrocytes and activated microglia in the ipsilateral cortex. We assessed cortical gliogenesis, with or without T4 treatment, in live animals using 5-ethynyl 2'-deoxyuridine-labeling. Finally, learning and spatial memory retention were tested using the Morris water maze (MWM). <b><i>Results:</i></b> T4 treatment 1-hour post-TBI significantly reduced the number of reactive astrocytes and activated microglia in the ipsilateral cortical area. An additional dose of T4 on day 5 post-TBI further reduced the number and size of reactive astrocytes. T4 treatment induced gliogenesis 2.6-fold greater than with saline treatment. T4 treatment induced neuron-glia antigen 2-expressing glial cell proliferation but not astrocytes. Mice treated with T4 post-TBI had improved MWM performance, better escape latency, and better spatial memory compared with saline-treated mice. <b><i>Conclusion:</i></b> Our data indicate that T4 treatment shortly after TBI significantly reduced acute astroglial cell activation and improved recovery of neurons and brain function.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"1083-1094"},"PeriodicalIF":6.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Thyrotropin Receptor Antibody Reactome Determines Thyroid and Retro-orbital Responsiveness.","authors":"Pingping Xiang, Rauf Latif, Terry F Davies","doi":"10.1177/10507256251359557","DOIUrl":"10.1177/10507256251359557","url":null,"abstract":"<p><p><b><i>Background:</i></b> The roles of different thyrotropin (TSH) receptor (TSHR) antibodies in Graves' disease (GD) and thyroid eye disease (TED) remain unclear, and animal models have been used to try and clarify. While several models have been developed using different TSHR antigens, they have failed to robustly replicate the complexities of human disease, regardless of mouse strain, immunization method, or TSHR antigen used, and often overlook the complete TSHR reactome. In this study, we evaluated a mouse model of GD, focusing on TSHR antibodies with different bioactivities. <b><i>Methods:</i></b> Female Balb/c mice were immunized intramuscularly with an adenovirus expressing residues 1-289 of the human TSHR (Ad-TSHR 289) or control vector (Ad-Lacz) with 10 injections at 3-week intervals. Thyroid function was assessed by total thyroxine (T4) and TSH levels. The presence of TSHR binding antibodies as well as stimulating TSHR antibodies (TSAb) and TSH-blocking TSHR antibodies (TBAb) was evaluated using flow cytometry and a transcriptional-based luciferase cell bioassay. We also conducted thyroid ultrasound and histology, micro-magnetic resonance imaging (micro-MRI) for orbital changes, and histological analysis of orbital tissue after 30 weeks of immunization to assess immunopathological changes. <b><i>Results:</i></b> Out of a total of 16 mice, 9 became hyperthyroid-characterized by decreased TSH levels, increased T4 levels, and diffuse enlargement of the thyroid glands. All mice developed TSHR antibodies when assessed by flow cytometry. 8/9 of the hyperthyroid mice had TSAb but mostly at low levels, while 7 showed only TBAb but without hypothyroidism. Only 2 mice had detectable linear antibodies. Five hyperthyroid mice showed eye signs, including conjunctival redness and eyelid thickening. Micro-MRI and histology revealed mild retrobulbar adipose and muscle enlargement with macrophage infiltration. <b><i>Conclusions:</i></b> Hyperthyroidism occurred in 56% (9/16) of mice, despite all developing TSHR antibodies. The detected TSAbs were of low-level despite their high levels by flow cytometry, suggesting that the simultaneous presence of TBAbs may explain the weak stimulating activity. In the mice with TBAbs, there was no hypothyroidism, suggesting they were not highly effective due to simultaneous TSAb activity and may indeed have prevented hyperthyroidism. These findings highlight the importance of considering the full TSHR antibody reactome in GD mouse models, as it ultimately determines thyroid outcomes.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"1063-1073"},"PeriodicalIF":6.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Teprotumumab Treatment in Patients with Steroid and Surgery-Resistant Dysthyroid Optic Neuropathy: A Case Series.","authors":"Anna Lucia Carretti, Gauthier Kielwasser, Françoise Borson-Chazot, Mathilde Peiffert, Teodora Bogaciu, Kim Thia-Soui-Tchong, Caroline Froment Tilikete, Gérald Raverot, Emmanuel Jouanneau, Hélène Lasolle, Solene Castellnou, Romain Manet, Juliette Abeillon-du Payrat","doi":"10.1177/10507256251372194","DOIUrl":"10.1177/10507256251372194","url":null,"abstract":"<p><p><b><i>Background:</i></b> Dysthyroid optic neuropathy (DON) is a rare but serious complication of Graves' orbitopathy (GO) that can lead to permanent vision loss. In a previous study, medical and surgical treatment of DON according to EUGOGO guidelines resulted in partial or no recovery in 30% of patients. Insulin growth factor-1 receptor inhibitor teprotumumab has shown significant improvement of GO symptoms, but little is known about its effect on DON. The aim of this study was to evaluate the efficacy of teprotumumab in treating steroid- and surgery-resistant DON. <b><i>Methods:</i></b> This retrospective case series included 6 patients (8 eyes; median age 58 years) with confirmed DON resistant to steroids and orbital decompression (median duration of DON 2 months, interquartile range [IQR 2.0-6.5]) treated at the Hospices Civils de Lyon. Median time from the end of first-line treatment was 34.5 days (IQR: 8.0-61.7). The treatment protocol was 8 intravenous infusions of teprotumumab administered every 3 weeks. Definition of DON recovery was based on changes in best-corrected visual acuity (BCVA) and visual field mean deviation (VF-MD). <b><i>Results:</i></b> At the end of teprotumumab treatment, DON recovered in 7/8 (87.5%) of affected eyes, with BCVA improvement in all patients (median 0.30 logMAR [0.24-0.42], <i>p</i> = 0.004) and a median VF-MD improvement of 66% (46-90) (<i>p</i> = 0.024). In 3/6 patients, DON improved after one infusion. All patients showed improvements in clinical activity score and proptosis. Improvements persisted over the follow-up (median from first infusion, 73.8 weeks), with no DON relapse but inflammatory relapse in two patients. Due to adverse events, two patients did not complete all infusions. <b><i>Conclusions:</i></b> The data suggest teprotumumab as a promising treatment for steroid- and surgery-resistant DON with rapid symptom improvement and long-lasting recovery. However, these only preliminary results need to be better evaluated by specific clinical trials.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Representation and Bias in Artificial Intelligence Models for Thyroid Cancer: A Systematic Review.","authors":"Rashi Ramchandani, Eddie Guo, Sanaz G Biglou, Sami G Sabbah, Michael Mostowy, Donya Mahiny, Christian Hurtubise, Gift Anicho-Okereke, Risa Shorr, Lisa Caulley, Evan J Propst, Nikolaus E Wolter, Jonathan D Wasserman, Antoine Eskander, Jennifer M Siu","doi":"10.1177/10507256251372175","DOIUrl":"https://doi.org/10.1177/10507256251372175","url":null,"abstract":"<p><p><b><i>Background:</i></b> There has been growing interest in the application of artificial intelligence (AI) in thyroid cancer care, given its potential to enhance diagnostic accuracy, predict patient outcomes, and personalize treatment plans. However, bias introduced during the development of AI algorithms used for thyroid cancer care poses a significant challenge, as biased datasets can lead to disparities in diagnosis and treatment recommendations, particularly in underrepresented populations. This systematic review evaluates the current landscape of AI models for thyroid cancer, focusing on demographic representation and potential biases. <b><i>Methods:</i></b> This systematic review was registered on PROSPERO (ID: CRD42024519238) and conducted in accordance with the Cochrane handbook and reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A literature search was performed on EMBASE, PubMed, and Google Scholar up to January 2024. Studies were included if they involved AI models for thyroid cancer management and provided demographic details. Data extraction and risk-of-bias assessments were conducted by two independent reviewers. <b><i>Results:</i></b> A total of 197 studies were included in the review, with the majority focusing on diagnosis (<i>n</i> = 133) and prediction/prognosis (<i>n</i> = 47). Most studies predominantly involved participants from China (<i>n</i> = 124) and the United States (<i>n</i> = 26), with more female participants (<i>n</i> = 12,410) than males (<i>n</i> = 4222). Ethnicity data from 197 studies (248,896 participants) revealed a significant underrepresentation of East Asians (14.6%) compared with their global thyroid cancer prevalence (18.7%), while White (26.8%) and Black participants (26.8%) were overrepresented relative to their global prevalence (20.7% and 11.3%, respectively). Socioeconomic factors, marital status, and race/ethnicity were less frequently considered in the models. <b><i>Conclusion:</i></b> The findings highlight significant gaps in the diversity and representativeness of data used in thyroid cancer AI models. Current models align with epidemiological trends but lack comprehensive demographic inclusion. As such, more representative AI models are required that account for all aspects of a patient's demographics and sociocultural background. Future research should focus on developing and validating more equitable AI models to improve thyroid cancer care across diverse populations.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interobserver Agreement Among Thyroid Ultrasound Operators in Defining Thyroid Nodules as Subcapsular.","authors":"Pierpaolo Trimboli, Enrico Papini, Jörg Bojunga, Chiara Camponovo, Maurilio Deandrea, Antonio Giangregorio, Lauro Gianola, Giorgio Grani, Rinaldo Guglielmi, Andrea Frasoldati, Fabian Pitoia, Gilles Russ, Cosimo Durante, Andrea Leoncini","doi":"10.1177/10507256251372649","DOIUrl":"https://doi.org/10.1177/10507256251372649","url":null,"abstract":"<p><p><b><i>Background:</i></b> Ultrasound (US) examination is the pivotal test to assess the risk of cancer and the indication for fine needle aspiration cytology (FNAC) in thyroid nodules (TNs). The subcapsular location of a TN may strengthen the indication for FNAC as, in TN resulting malignant at cytology may favor surgery rather than active surveillance. However, the definition of a subcapsular TN remains unclear. This study aimed to evaluate the interobserver agreement (IOA) among thyroid US experts in classifying TNs as subcapsular or not. <b><i>Methods:</i></b> Twelve raters received an electronic link to a file containing static US images and were asked to assess 60 TNs for subcapsular location, blinded to all other TN characteristics. The overall IOA was calculated, and the TN US features were subsequently analyzed to evaluate their potential influence on interobserver variability. The raters had high or very high thyroid US experience. Two experienced operators preliminarily selected the case series and analyzed the findings. All cases were derived from patients undergoing surgery and histological diagnosis. The IOA was calculated according to Fleiss' kappa, ranging from 0.0 (no agreement) to 1.0 (perfect agreement). <b><i>Results:</i></b> The overall IOA was fair (κ = 0.34), with a slightly better result in the subgroup of raters with higher experience (κ = 0.39). A higher IOA value (κ = 0.38) was observed in TNs of medium size. Following multiple sub-analyses, the highest κ value (0.46) was observed in the subgroup of TNs that were categorized as EU-TIRADS 5 and were smaller than 2 cm. <b><i>Conclusions:</i></b> The overall IOA among US experts when assessing TNs as subcapsular was unsatisfactory. A clear and standardized definition of subcapsular position is needed to improve clinical decision-making. Future guidelines should address this issue to ensure consistent assessment and management of subcapsular TNs.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disease-Specific and Histological Outcomes of Preoperative TERT Promoter Mutation Detected in Isolation or in Combination with Other Mutations in Thyroid Neoplasms.","authors":"Michael Calcaterra, Alaa Sada, Esra Karslioglu-French, Elena M Morariu, Kelly L McCoy, Kimberly M Ramonell, Saba Kurtom, N Paul Ohori, Simion I Chiosea, Raja R Seethala, Sally E Carty, Marina N Nikiforova, Yuri E Nikiforov, Linwah Yip","doi":"10.1177/10507256251370304","DOIUrl":"https://doi.org/10.1177/10507256251370304","url":null,"abstract":"<p><p><b><i>Background:</i></b> <i>TERT</i> promoter mutations in thyroid cancer are associated with aggressive disease, including recurrence, distant metastasis, and disease-related mortality. We aim to assess histological and disease-related outcomes when <i>TERT</i> mutation is detected alone or with other alterations during preoperative testing. <b><i>Methods:</i></b> A retrospective, single-institution study was performed, including all adult patients undergoing initial diagnostic thyroid nodule evaluation with <i>TERT</i> promoter mutation (C228T/C250T) detected in preoperative thyroid fine needle aspiration samples using TSv3 testing. <b><i>Results:</i></b> Of 70 thyroid nodules, 18 (26%) were isolated (iTERT), and 52 (74%) were associated with ≥1 concurrently detected mutation (TERT+). The most common additional abnormalities were <i>BRAF^V600E</i> (23, 44%), RAS (19, 37%), and copy number alterations (CNA; 15, 29%). Patients with iTERT were older than those with TERT+ nodules (<i>p</i> = 0.007). While nodule size was similar between the two groups (mean size 3.2 cm, <i>p</i> = 0.18), Bethesda III/IV cytology was more likely with iTERT (94% vs. Bethesda V/VI 56%, <i>p</i> = 0.007). Histology was available for 9 (50%) iTERT and 51 (98%) TERT+ nodules and malignancy was higher with preoperative detection of TERT+ compared with iTERT (96% vs. 67%, <i>p</i> = 0.02). Poorly differentiated or anaplastic cancers were diagnosed in 33% of the malignancies at an equivalent rate in both cohorts. At median follow-up of 13.1 months (interquartile range 26.2, 7.2-33.4), distant metastasis occurred in 32.7% of patients including 17% (1/6) with iTERT versus 33% of patients with TERT+ (<i>p</i> = 0.65). None of the iTERT patients had locoregional recurrence as compared with 25% of TERT+ patients (<i>p</i> = 0.31). <b><i>Conclusions:</i></b> When preoperatively detected, <i>TERT</i> promoter mutations are more often seen in association with additional driver mutations or other genetic alterations such as CNA, but when present, carries a very high risk of malignancy (93%). Up to 1/3 are poorly differentiated or anaplastic thyroid cancer, and this likelihood is equivalent when <i>TERT</i> is present in isolation or in combination with other mutation. Thus, surgery should be strongly considered in iTERT nodules, and total thyroidectomy should be favored when TERT+ is identified.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-Reported Tolerability of Selpercatinib Compared to Cabozantinib/Vandetanib: A Secondary Analysis of the LIBRETTO-531 Randomized-Controlled Trial in <i>RET</i>-Mutant Medullary Thyroid Cancer.","authors":"Rossella Elisei, Lori J Wirth, Jaume Capdevila, Ana Oliveira Hoff, Makoto Tahara, Eric J Sherman, Mimi I Hu, Ming-Hua Ge, Jonathan Wadsley, Fernanda Vaisman, Katerina Kopeckova, Jolanta Krajewska, Dinorath Olvera, Collin Churchill, Patricia Maeda, Adrienne M Gilligan, Yan Lin, Nalin Payakachat, Bruce Robinson, Julien Hadoux, Marcia S Brose","doi":"10.1177/10507256251367352","DOIUrl":"10.1177/10507256251367352","url":null,"abstract":"<p><p><b><i>Background:</i></b> Progression-free survival (PFS) may not fully capture the impact of treatment on patients, especially in cancers with longer natural histories and thus, could be complemented by robust measures of patient-reported tolerability (PRT). We report the use of a novel, quantifiable PRT metric as a multiplicity-controlled endpoint to support regulatory and clinical decision-making for selpercatinib use. Comparative PRT was assessed in LIBRETTO-531 (NCT04211337), a randomized phase 3 trial of selpercatinib versus vandetanib/cabozantinib (control) in advanced <i>RET</i>-mutant medullary thyroid cancer (MTC). <b><i>Patients and Methods:</i></b> Patients were self-administered the single Functional Assessment of Cancer Therapy item GP5: \"I am bothered by side effects\" weekly, and scores were dichotomized into \"low\" (0-2) and \"high\" (3-4) side-effect burden. PRT measured the proportion of time on treatment (PTT) with \"high\" side-effect burden for each patient. Comparative PRT was tested at a two-sided significance level of 0.05, conditional on achieving significance for efficacy endpoints. Complementary patient-reported outcomes included health-related quality of life (HRQoL) and symptomatic adverse events self-administered at baseline and at different intervals post-baseline during treatment period. <b><i>Results:</i></b> In the tolerability evaluable population (N = 242; selpercatinib n = 161 and control n = 81 [56 received cabozantinib, 25 received vandetanib]), patients on selpercatinib had significantly better PRT with lower PTT with \"high side-effect burden\" than control (8% vs. 24%, <i>p</i> < 0.0001). Post-baseline compliance rates for PRO questionnaires were generally greater than 80% in both treatment groups. Patients on selpercatinib reported significantly less PTT with HRQoL impairment across physical (36% vs. 52%), role (2% vs. 11%), cognitive (4% vs. 8%), emotional (6% vs. 11%), and social (2% vs. 8%) function (all <i>p</i> < 0.01); and significantly less PTT with severe diarrhea (5% vs. 38%), fatigue (6% vs. 21%), taste change (3% vs. 15%), decreased appetite (2% vs. 15%), and hand-foot syndrome (2% vs. 9%) (all <i>p</i> < 0.001). <b><i>Conclusion:</i></b> This study demonstrated superior PRT for selpercatinib compared with control in patients with <i>RET</i>-mutant MTC, further supporting selpercatinib use as the first-line treatment for patients with advanced <i>RET</i>-mutant MTC. Comparative PRT deserves further adoption as a complement to traditional endpoints in future randomized-controlled trials.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant Therapy with Multikinase Inhibitors for Locally Advanced Differentiated Thyroid Cancer: A Systematic Review.","authors":"Justin Bauzon, Guillermo Ponce de Leon-Ballesteros, Eddy Lincango, Heriberto Medina-Franco, Rafael Perez-Soto, Ossama Lashin, Jessica L Geiger, Christian Nasr, Joyce Shin, Allan Siperstein, Gustavo Romero-Velez","doi":"10.1177/10507256251367286","DOIUrl":"https://doi.org/10.1177/10507256251367286","url":null,"abstract":"<p><p><b><i>Background:</i></b> The use of multikinase inhibitors (MKIs) in thyroid cancer has been established to downsize and facilitate resection of poorly differentiated, differentiated high-grade, anaplastic, and medullary thyroid cancer. Case reports and case series have suggested the potential use of MKIs as neoadjuvant therapies for locally advanced differentiated thyroid cancer (DTC). Our objective was to review available studies and assess if neoadjuvant therapy with MKI can improve surgical and oncological outcomes in patients with locally advanced DTC. <b><i>Methods:</i></b> A systematic search of four different databases (PubMed, Cochrane Library, Scopus, and EMBASE) with no time restrictions was performed to identify relevant observational studies evaluating patients with locally advanced DTC who received neoadjuvant therapy before surgery with MKI (PROSPERO ID: CRD420251012812). <b><i>Results:</i></b> A total of 119 participants from 23 observational studies (12 case reports, 9 case series, and 2 prospective phase II studies) were included. Lenvatinib was the most frequently used MKI, followed by sorafenib. Tumor volume reduction ranged from 25% to 87%, and partial response rates ranged between 33.3% and 76.9%, whereas progressive disease was described only in seven cases. Of 114 patients with inoperable or potentially resectable tumors with associated high perioperative morbidity, 95 (83.3%) were able to undergo surgery. <b><i>Conclusions:</i></b> Neoadjuvant MKIs in locally advanced DTC may improve resection rates. The overall low quality of evidence prompts further prospective studies to confirm these findings.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Features of Chinese Patients with Thyroid Eye Disease: A Multicenter Retrospective Study.","authors":"Chaoyu Lei, Xukun Lyu, Yujie Ren, Dingwei Wei, Siyuan Zhang, Yuwei Zhang, Liu Wang, Libin Liu, Junping Wen, Xiaowei Liu, Chaobin Lin, Wei Lu, Jian Liu, Runchuan Li, Shuo Zhang, Xuefei Song, Zhangsheng Yu, Rebecca S Bahn, Huifang Zhou","doi":"10.1177/10507256251359559","DOIUrl":"10.1177/10507256251359559","url":null,"abstract":"<p><p><b><i>Background:</i></b> Thyroid eye disease (TED) is a debilitating autoimmune disorder linked to thyroid dysfunction. There is limited knowledge of TED in Asian populations. This multicenter study characterizes the clinical features and treatment response of TED in a large Chinese cohort. <b><i>Methods:</i></b> A retrospective multicenter study included 4157 patients with TED from nine Chinese hospitals from February 2016 to July 2023. Disease severity and activity were evaluated according to the European Group on Graves' Orbitopathy standards. We examined associations of variables including sex, age, smoking status, I¹³¹ treatment, consultation department, and geographical region with clinical outcomes. Logistic regression and nomogram models were developed to examine associations with sight-threatening TED and, in a subgroup analysis (<i>n</i> = 126), patients' responsiveness to intravenous glucocorticoid (IVGC) therapy. <b><i>Results:</i></b> We included 4157 patients with mean age and standard deviation (SD) 45.96 ± 16.44 years. Of these, 63.6% (<i>n</i> = 2644) were females. Over half (55.6%, <i>n</i> = 2310) of participants were in the inactive phase, with a mean clinical activity score of 2.19 ± 1.61 (SD) for all patients. TED severity was categorized as mild (9.3%, <i>n</i> = 385), moderate-to-severe (82.5%, <i>n</i> = 3428), and sight-threatening (8.2%, <i>n</i> = 344). The average degree of exophthalmos was 20.04 ± 5.27 mm, and 48.8% (<i>n</i> = 2029) of patients had diplopia. Patients treated with I¹³¹ had higher disease activity (47.5%, <i>n</i> = 468, vs. 43.5%, <i>n</i> = 1379, <i>p</i> < 0.05). Coastal region patients exhibited more severe TED (sight-threatening cases: 10.1%, <i>n</i> = 195, vs. 7.2%, <i>n</i> = 147) and higher diplopia scores (1.00 ± 1.10 vs. 0.86 ± 1.09, <i>p</i> < 0.001) than inland counterparts. TED severity was also greater in patients treated in Ophthalmology departments (mild cases: 6.0%, <i>n</i> = 213; moderate-to-severe cases: 85.6%, <i>n</i> = 3055) compared with Endocrinology departments (mild cases: 29.3%, <i>n</i> = 172; moderate-to-severe cases: 63.5%, <i>n</i> = 373). Nomograms had an area under the receiver operating curve of 0.742 (confidence interval [CI] 0.716-0.768) for sight-threatening TED and 0.759 (CI 0.674-0.843) for IVGC therapy responsiveness. <b><i>Conclusions:</i></b> We characterized the clinical features and treatment response of TED in a large Chinese cohort. These findings offer valuable insights informing TED risk stratification in Asian patients and forming a foundation for future prospective studies.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}