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Multi-Omics-Based Characterization of DNA Methylation Episignatures for Papillary Thyroid Cancer in a Chinese Population. 中国人群乳头状甲状腺癌DNA甲基化特征的多组学分析。
IF 5.8 1区 医学
Thyroid Pub Date : 2025-05-30 DOI: 10.1089/thy.2024.0611
Xianhui Ruan, Feng Yang, Mengling Li, Qiman Dong, Weijing Hao, Wei Zhang, Xinwei Yun, Dapeng Li, Jingzhu Zhao, Xuan Qin, Zihan Rong, Taiyan Guo, Lei Wang, Yi Pan, Ming Gao, Minjie Zhang, Xiangqian Zheng
{"title":"Multi-Omics-Based Characterization of DNA Methylation Episignatures for Papillary Thyroid Cancer in a Chinese Population.","authors":"Xianhui Ruan, Feng Yang, Mengling Li, Qiman Dong, Weijing Hao, Wei Zhang, Xinwei Yun, Dapeng Li, Jingzhu Zhao, Xuan Qin, Zihan Rong, Taiyan Guo, Lei Wang, Yi Pan, Ming Gao, Minjie Zhang, Xiangqian Zheng","doi":"10.1089/thy.2024.0611","DOIUrl":"https://doi.org/10.1089/thy.2024.0611","url":null,"abstract":"<p><p><b><i>Background:</i></b> Thyroid cancer is the most common endocrine malignancy, with papillary thyroid cancer (PTC) accounting for ∼80% of all cases. DNA methylation alterations and gene expression changes in cancer, offer valuable insights into tumor biology and serve as potential clinical biomarkers. However, the functional implications of DNA methylation changes in PTC patients, particularly based on multiomics analysis in the Chinese population, remain insufficiently explored. This study aims to investigate the epigenetic signatures of thyroid cancer and identify the DNA methylation biomarkers for diagnosing PTC in Chinese patients. <b><i>Methods:</i></b> Thyroid cancer tissues (<i>n</i> = 40) and benign thyroid nodule tissues (<i>n</i> = 31) were collected from Chinese patients for global DNA methylation analysis. Gene expression profiles and H3K27ac modifications were also investigated to understand the impacts of epigenetic changes on gene expression. Genome-wide methylation profiling and machine learning methods were employed to differentiate PTC from control samples. <b><i>Results:</i></b> Genome-wide DNA methylation maps revealed significant methylome changes in Chinese PTC tissues. By integrating our data with The Cancer Genome Atlas thyroid cancer methylation profiles, we identified unique hypomethylation patterns associated with thyroid hormone synthesis specifically in Chinese PTC patients. RNA sequencing and H3K27ac modification analysis, along with functional assays, showed that the dysregulated genes in PTC patients are critical for the proliferation, migration, and invasion of thyroid cancer. <b><i>Conclusions:</i></b> Our study provides a comprehensive view of the multi-omics-based, function-guided DNA methylation landscape for Chinese PTC patients. We identified seven functional differentially methylated regions with high sensitivity and specificity for diagnosing thyroid cancer in Chinese patients. Additionally, <i>DHRS3</i> is highlighted as a key player in PTC pathogenesis and shows promise as a valuable biomarker for predicting patient outcomes. This research advances our understanding of DNA methylation in thyroid cancer and underscores the importance of developing population-specific diagnostic tools to improve patient outcomes. However, further validation in larger, independent cohorts is needed to confirm their diagnostic value.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181238","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}
引用次数: 0
Management of Adverse Events During Treatment for Advanced Thyroid Cancer. 晚期甲状腺癌治疗过程中不良事件的处理。
IF 5.8 1区 医学
Thyroid Pub Date : 2025-05-22 DOI: 10.1089/thy.2024.0755
Thomas J Roberts, Lori J Wirth
{"title":"Management of Adverse Events During Treatment for Advanced Thyroid Cancer.","authors":"Thomas J Roberts, Lori J Wirth","doi":"10.1089/thy.2024.0755","DOIUrl":"https://doi.org/10.1089/thy.2024.0755","url":null,"abstract":"<p><p><b><i>Background:</i></b> The management of advanced thyroid cancer has rapidly evolved as several multikinase, and gene-specific inhibitors have substantially improved survival for patients with most types of thyroid cancer. Optimizing management of the treatment-related adverse events (TRAEs) from these medications is important to improve quality of life and outcomes for patients with thyroid cancer. This narrative review discusses common and clinically significant TRAEs of treatments for thyroid cancer and effective management approaches. <b><i>Summary:</i></b> Published literature was reviewed to summarize available information on the incidence of TRAEs with medications used to treat thyroid cancer and management approaches for these TRAEs. There are common TRAEs across many treatments for advanced thyroid cancer including fatigue, hypertension, gastrointestinal toxicities, rashes, and hand-foot syndrome. Additionally, several other TRAEs with thyroid cancer treatments are significant because of their frequency with specific medications (e.g., pyrexia syndrome) or their severity (e.g., thromboembolic events and cardiac impairment). Data from clinical trials and real-world data along with expert guidelines and insights from experienced clinicians can guide management approaches for many of these TRAEs. <b><i>Conclusions:</i></b> The toxicity profiles are well established for treatments for advanced thyroid cancer, there are evidence-based management approaches for many commonly encountered scenarios. Following these approaches to optimizing management of TRAEs can improve the quality of life and outcomes for patients with thyroid cancer.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120611","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}
引用次数: 0
Letter: "High Rates of Unnecessary Surgery for Indeterminate Thyroid Nodules in the Absence of Molecular Test and the Cost-Effectiveness of Utilizing Molecular Test in an Asian Population: A Decision Analysis" by Fung et al. 致编辑的信:Fung等人的“在没有分子检测的情况下,不确定甲状腺结节的高不必要手术率和在亚洲人群中使用分子检测的成本效益:决策分析”。
IF 5.8 1区 医学
Thyroid Pub Date : 2025-05-01 Epub Date: 2025-03-25 DOI: 10.1089/thy.2025.0072
Kennichi Kakudo, Andrey Bychkov, Jen-Fan Hang, Mitsuyoshi Hirokawa, Somboon Keelawat, Zhiyan Liu, Radhika Srinivasan, Chan Kwon Jung
{"title":"<i>Letter:</i> \"High Rates of Unnecessary Surgery for Indeterminate Thyroid Nodules in the Absence of Molecular Test and the Cost-Effectiveness of Utilizing Molecular Test in an Asian Population: A Decision Analysis\" by Fung et al.","authors":"Kennichi Kakudo, Andrey Bychkov, Jen-Fan Hang, Mitsuyoshi Hirokawa, Somboon Keelawat, Zhiyan Liu, Radhika Srinivasan, Chan Kwon Jung","doi":"10.1089/thy.2025.0072","DOIUrl":"10.1089/thy.2025.0072","url":null,"abstract":"","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"595-596"},"PeriodicalIF":5.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701640","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}
引用次数: 0
The 2024 World Medical Association Declaration of Helsinki and Its Importance for Thyroidology. 2024年世界医学协会赫尔辛基宣言及其对甲状腺学的重要性。
IF 5.8 1区 医学
Thyroid Pub Date : 2025-05-01 Epub Date: 2025-05-02 DOI: 10.1089/thy.2025.0181
Joseph Tobias, Megan K Applewhite, Peter Angelos
{"title":"The 2024 World Medical Association Declaration of Helsinki and Its Importance for Thyroidology.","authors":"Joseph Tobias, Megan K Applewhite, Peter Angelos","doi":"10.1089/thy.2025.0181","DOIUrl":"10.1089/thy.2025.0181","url":null,"abstract":"","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"457-459"},"PeriodicalIF":5.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015458","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}
引用次数: 0
Development of a Nomogram to Integrate Molecular Testing and Clinical Variables to Improve Malignancy Risk Assessment Among Cytologically Indeterminate Thyroid Nodules. 一种结合分子检测和临床变量的Nomogram方法的发展,以改善细胞学上不确定的甲状腺结节的恶性肿瘤风险评估。
IF 5.8 1区 医学
Thyroid Pub Date : 2025-05-01 Epub Date: 2025-03-05 DOI: 10.1089/thy.2024.0481
Jiahui Wu, Paul Stewardson, Markus Eszlinger, Moosa Khalil, Sana Ghaznavi, Erik Nohr, Adrian Box, Ralf Paschke
{"title":"Development of a Nomogram to Integrate Molecular Testing and Clinical Variables to Improve Malignancy Risk Assessment Among Cytologically Indeterminate Thyroid Nodules.","authors":"Jiahui Wu, Paul Stewardson, Markus Eszlinger, Moosa Khalil, Sana Ghaznavi, Erik Nohr, Adrian Box, Ralf Paschke","doi":"10.1089/thy.2024.0481","DOIUrl":"10.1089/thy.2024.0481","url":null,"abstract":"<p><p><b><i>Background:</i></b> The introduction of molecular testing (MT) of cytologically indeterminate thyroid nodules (ITNs) alone has not impacted thyroidectomy rates. Due to this, we evaluated the incremental diagnostic value of various clinical variables in addition to MT results, in predicting the risk of malignancy (ROM) among ITNs. <b><i>Methods:</i></b> This prospective observational study included 1024 consecutive ITNs that underwent reflexive ThyroSPEC MT between Jul 30, 2020, and Oct 30, 2023. A multivariable logistic regression model was built to assess the relationship between histology outcomes and clinical variables, including nodule discovery by palpation, ultrasound risk categories, maximum nodule size, Bethesda category, Bethesda atypia, and ThyroSPEC categories. A total of 332 out of 1024 patients who underwent surgery and had complete data for all variables were included in the model. A nomogram was subsequently developed based on the model. <b><i>Results:</i></b> The model achieved a cross-validated AUC of 0.831 (95% confidence intervals: 0.787-0.874). Patients with high-risk mutations or malignant molecular markers exhibited significantly higher odds (152.79 times) of malignancy compared to those with mutation-negative or benign molecular marker results. Patients with maximum nodule size >5 cm have 4.34 times higher odds of malignancy than those 0-2 cm. The presence of nuclear atypia increased the odds of malignancy by 4.26 times, while ultrasound malignancy risk category 5 increased the odds of malignancy by 2.89 times compared to categories 1-3. Positive palpation discovery increased the odds by 1.83 times. The integrated ROM estimated from the regression model is significantly associated with the surgery type (<i>p</i> < 0.001). In the low (0-30%) and intermediate ROM (31-70%) categories, lobectomy alone is the most common surgery (61% and 70%, respectively), while in the high ROM (>70%) category, total thyroidectomy dominates (62%). <b><i>Conclusions:</i></b> Although MT alone played an important role in decision-making regarding surveillance versus surgery in our study population, integrating MT results with additional clinical variables improved the malignancy risk prediction for ITNs. Our results highlight the importance of contextualizing MT results within an integrated interdisciplinary thyroid nodule diagnostic pathway.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"508-515"},"PeriodicalIF":5.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557359","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}
引用次数: 0
Evaluation of the Current State of Thyroid Hormone Testing in Human Serum-Results of the Free Thyroxine and Thyrotropin Interlaboratory Comparison Study. 人血清甲状腺激素检测现状评价——游离甲状腺素与促甲状腺素实验室间比较研究结果。
IF 5.8 1区 医学
Thyroid Pub Date : 2025-05-01 Epub Date: 2025-05-07 DOI: 10.1089/thy.2024.0728
Ashley Ribera, Otoe Sugahara, Tatiana Buchannan, Norma Vazquez, Alicia N Lyle, Li Zhang, Uliana I Danilenko, Hubert W Vesper
{"title":"Evaluation of the Current State of Thyroid Hormone Testing in Human Serum-Results of the Free Thyroxine and Thyrotropin Interlaboratory Comparison Study.","authors":"Ashley Ribera, Otoe Sugahara, Tatiana Buchannan, Norma Vazquez, Alicia N Lyle, Li Zhang, Uliana I Danilenko, Hubert W Vesper","doi":"10.1089/thy.2024.0728","DOIUrl":"10.1089/thy.2024.0728","url":null,"abstract":"<p><p><b><i>Background:</i></b> Performance of thyroid function assays can vary significantly. To address this issue, the Centers for Disease Control and Prevention (CDC) Clinical Standardization Programs conducted an interlaboratory comparison of free thyroxine (fT4) immunoassays (IAs) and laboratory-developed tests (LDTs). This assessment aimed to determine the current performance characteristics of these assays as a first step toward measurement standardization. Thyrotropin (TSH) IAs were also evaluated. <b><i>Methods:</i></b> Assays measured 41 blinded individual-donor sera, including a sample from a pregnant woman (for fT4 analysis only) and three serum pools, with 11.3-32.1 pmol/L (0.881-2.49 ng/dL) fT4 and 0.337-21.6 mIU/L TSH in duplicate over 2 days. Passing-Bablok regression analysis performed pre-recalibration compared assays performance to the CDC fT4 reference measurement procedure (RMP) or TSH all-lab mean (ALM). Additionally, the impact of linear regression-based recalibration of assays to the CDC fT4 RMP or TSH ALM was estimated. Inter-assay agreement of sample classification according to the assay-specific reference interval (RI) was assessed pre- and post-recalibration. <b><i>Results:</i></b> A total of 21 fT4 and 17 TSH assays participated. Pre-recalibration, median biases of TSH measurements to the ALM were -1.2% [confidence interval or CI -1.8% to -0.4%], and good classification agreement among TSH assays was observed. fT4 assays all showed a negative median bias to the RMP, with higher bias among IAs (median: -20.3%, CI [-21.5% to -19.4%]) than LDTs (median: -4.5%, [CI -6.1% to -3.2%]). Of the individual-donor sera, only 21 out of 40 samples were classified uniformly by all fT4 assays, indicating poor inter-assay agreement. Post-recalibration, agreement improved to 33 out of 40 individual-donor sera correctly classified by all tested IAs and LDTs. Similar improvement in post-recalibration median percent bias was observed for fT4 IAs (median: -0.2, [CI -1.2% to 0.6%]) and LDTs (median: -0.3%, [CI -2.5% to 1.4%]). <b><i>Conclusions:</i></b> The comparison among fT4 assays emphasizes the need for measurement standardization to improve accuracy and comparability. This and previous studies demonstrate the possibility to develop common fT4 RIs via standardization, enabling the use of evidence-based clinical guidelines universally in patient care. Recalibration can effectively address high variability in fT4 assays, ensuring consistent diagnostic classification.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"471-484"},"PeriodicalIF":5.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998713","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}
引用次数: 0
Response to Kakudo et al.: "High Rates of Unnecessary Surgery for Indeterminate Thyroid Nodules in the Absence of Molecular Test and the Cost-Effectiveness of Utilizing Molecular Test in an Asian Population: A Decision Analysis". 对Kakudo等人发表的“在没有分子检测的情况下,不确定甲状腺结节的高不必要手术率和在亚洲人群中使用分子检测的成本效益:决策分析”的回应。
IF 5.8 1区 医学
Thyroid Pub Date : 2025-05-01 Epub Date: 2025-04-29 DOI: 10.1089/thy.2025.0150
Man Him Matrix Fung, Ching Tang, Gin Wai Kwok, Tin Ho Chan, Yan Luk, David Tak Wai Lui, Carlos King Ho Wong, Brian Hung Hin Lang
{"title":"Response to Kakudo et al.: \"High Rates of Unnecessary Surgery for Indeterminate Thyroid Nodules in the Absence of Molecular Test and the Cost-Effectiveness of Utilizing Molecular Test in an Asian Population: A Decision Analysis\".","authors":"Man Him Matrix Fung, Ching Tang, Gin Wai Kwok, Tin Ho Chan, Yan Luk, David Tak Wai Lui, Carlos King Ho Wong, Brian Hung Hin Lang","doi":"10.1089/thy.2025.0150","DOIUrl":"10.1089/thy.2025.0150","url":null,"abstract":"","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"597-598"},"PeriodicalIF":5.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027994","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}
引用次数: 0
Reimagining the Therapeutic Approach for Anaplastic Thyroid Cancer: The Roadmap to a Cure. 重新构想间变性甲状腺癌的治疗方法:治愈的路线图。
IF 5.8 1区 医学
Thyroid Pub Date : 2025-05-01 DOI: 10.1089/thy.2025.0044
Maria E Cabanillas, Neal Akhave, Victoria Banuchi, Naifa Busaidy, Ramona Dadu, Renata Ferrarotto, Gary B Gunn, Sarah Hamidi, Marie-Claude Hofmann, S Mohsen Hosseini, Priyanka C Iyer, Stephen Y Lai, Anna Lee, Anastasios Maniakas, Matthew S Ning, Michael Spiotto, Jennifer R Wang, Michelle D Williams, Mark Zafereo
{"title":"Reimagining the Therapeutic Approach for Anaplastic Thyroid Cancer: The Roadmap to a Cure.","authors":"Maria E Cabanillas, Neal Akhave, Victoria Banuchi, Naifa Busaidy, Ramona Dadu, Renata Ferrarotto, Gary B Gunn, Sarah Hamidi, Marie-Claude Hofmann, S Mohsen Hosseini, Priyanka C Iyer, Stephen Y Lai, Anna Lee, Anastasios Maniakas, Matthew S Ning, Michael Spiotto, Jennifer R Wang, Michelle D Williams, Mark Zafereo","doi":"10.1089/thy.2025.0044","DOIUrl":"https://doi.org/10.1089/thy.2025.0044","url":null,"abstract":"<p><p><b><i>Background:</i></b> Anaplastic thyroid cancer (ATC) is an aggressive cancer that leads to rapid death if left untreated. However, recent advances in ATC treatment have dramatically changed the prognosis in a select group of patients with BRAF<sup>V600E</sup> mutations. In these patients, BRAF/MEK inhibitors have been shown to dramatically and rapidly shrink tumors. Yet, these responses are short-lived unless additional treatment modalities are applied. In patients without a BRAF<sup>V600E</sup> mutation, the current available therapies are far less effective. <b><i>Summary:</i></b> In this article, we review the relevant literature and propose applying the \"Total Therapy\" approach used since the 1960s for another deadly but curable disease, acute lymphocytic leukemia, to ATC. We have adapted the concepts of Induction, Consolidation, and Maintenance, applying them to ATC. This regimen integrates the treatments we have found to be successful in ATC: combination systemic therapy using targeted therapy plus immunotherapy, surgery, radiation, and continuation of the systemic therapy for several years, thereby attempting to eradicate all residual ATC cells. <b><i>Conclusions:</i></b> There has been a renewed interest in understanding the genomics of ATC and treating these patients with urgency rather than just providing palliative care. This shift has led to significant improvements in the prognosis of ATC. With the right tools and a clear roadmap to guide us, we now aim to take on the challenge of curing these patients.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":"35 5","pages":"462-470"},"PeriodicalIF":5.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102077","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}
引用次数: 0
Sex Differences in Risk for Iatrogenic Thyrotoxicosis Among Older Adults: An Analysis from Real-World Clinical Data. 老年人医源性甲状腺毒症风险的性别差异:来自真实世界临床数据的分析。
IF 5.8 1区 医学
Thyroid Pub Date : 2025-05-01 Epub Date: 2025-03-21 DOI: 10.1089/thy.2024.0604
Roy Adams, Jennifer Sophie Mammen
{"title":"Sex Differences in Risk for Iatrogenic Thyrotoxicosis Among Older Adults: An Analysis from Real-World Clinical Data.","authors":"Roy Adams, Jennifer Sophie Mammen","doi":"10.1089/thy.2024.0604","DOIUrl":"10.1089/thy.2024.0604","url":null,"abstract":"<p><p><b><i>Background:</i></b> Overtreatment with thyroid hormone is common and is associated with multiple adverse health outcomes, especially in older adults. Higher overtreatment rates have been reported among women. Understanding this sex difference could lead to better clinical utilization of therapy in at-risk populations. <b><i>Methods:</i></b> We performed a retrospective cohort study to examine the relationship between iatrogenic thyrotoxicosis and patient sex, adjusting for demographics, comorbidities, body composition, and thyroid hormone dosing using electronic health records for adults age 50 and older in a large community health system in the United States. <b><i>Results:</i></b> A total of 20,724 patients met all inclusion criteria, of whom 77% were female and 23% non-White. Women were more likely to have a low thyrotropin (TSH) compared to men (36.7% vs. 23.9%; unadjusted hazard ratio [HR] = 1.67 [95% confidence interval {CI} 1.56-1.79]). Many covariates varied by sex, including rates of several comorbidities, and there was a small but statistically significant difference in the median daily levothyroxine dose per actual body mass: 1.1 μg/kg in male patients compared with 1.2 μg/kg in female patients (<i>p</i> < 0.001). Adjusting for covariates other than dose did not significantly change the sex-related risk of iatrogenic thyrotoxicosis. In fully adjusted Cox models including dose per actual body mass, the female versus male HR = 1.50 [CI 1.34-1.69] was also not different from models which did not account for dose (<i>p</i> = 0.422). However, the association between female sex and thyrotoxicosis risk was partially mediated when adjusting for dose per ideal body mass (HR = 1.30 [CI: 1.16-1.46]; <i>p</i> < 0.001) and was fully mediated by dose calculated using lean body mass (HR = 1.06 [CI: 0.95-1.19]; <i>p</i> < 0.001). That is, women had higher risk of iatrogenic thyrotoxicosis compared to men receiving similar actual body mass doses, whereas women and men receiving comparable lean body mass doses had comparable risk. <b><i>Conclusions:</i></b> Mediation analysis demonstrates that the increased risk of iatrogenic thyrotoxicosis in older women may be attributable to differences in body composition between men and women. The use of ideal or lean body weight-based dose calculators in place of actual body weight dosing could reduce this potential source of iatrogenic thyrotoxicosis risk in older women.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"485-493"},"PeriodicalIF":5.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674576","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}
引用次数: 0
Identification and Characterization of Highly Potent and Isoenzyme-Selective Inhibitors of Deiodinase Type I via a Nonradioactive High-Throughput Screening Method. 通过非放射性高通量筛选方法鉴定高效和同工酶选择性I型脱碘酶抑制剂。
IF 5.8 1区 医学
Thyroid Pub Date : 2025-05-01 Epub Date: 2025-04-02 DOI: 10.1089/thy.2025.0036
Rajas Sane, Carola Seyffarth, Sabrina Kleissle, Martin Neuenschwander, Jens Peter von Kries, Caroline Frädrich, Kostja Renko, Eva K Wirth, Josef Köhrle
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