Thyroid最新文献

{"title":"Identification and Characterization of Highly Potent and Isoenzyme-Selective Inhibitors of Deiodinase Type I via a Nonradioactive High-Throughput Screening Method.","authors":"Rajas Sane, Carola Seyffarth, Sabrina Kleissle, Martin Neuenschwander, Jens Peter von Kries, Caroline Frädrich, Kostja Renko, Eva K Wirth, Josef Köhrle","doi":"10.1089/thy.2025.0036","DOIUrl":"10.1089/thy.2025.0036","url":null,"abstract":"<p><p><b><i>Objective:</i></b> Deiodinase type I (DIO1) is crucial in maintaining thyroid hormone (TH) balance. It converts the prohormone thyroxine (T4) to the active triiodothyronine (T3) and degrades T3 to inactive 3,3'-diiodothyronine (3,3'-T2). It also acts on reverse T3 (rT3) and sulfated TH metabolites, thus contributing to TH elimination. Upregulation of DIO1 is linked to hyperthyroid conditions such as Graves' disease and autonomous thyroid adenoma, making it a promising target for pharmacological intervention. The adverse side effects of the antithyroid drug propylthiouracil (PTU), used in clinics to treat hyperthyroidism due to its thyroid peroxidase- and DIO1-blocking action, highlight the need for novel and potent DIO1-selective inhibitors. <b><i>Methods:</i></b> Using a semiautomatic high-throughput screening (HTS) assay based on the Sandell-Kolthoff (SK) reaction in 384-well plates, we screened 69,344 low-molecular-weight compounds for DIO1-inhibitory effects. Shortlisted hits underwent detailed manual characterization, where we evaluated the potency and isoenzyme specificity by assessing their DIO-inhibitory effects on enzyme preparations from all three DIO isoenzymes, over a wide concentration range (5 nM-20 µM). To evaluate the DIO1 inhibitory effects in intact cells, we applied a novel protocol based on the SK reaction to cell culture supernatants and assessed the intracellular deiodinase activity in DIO1 overexpressing HEK293 cells. <b><i>Results:</i></b> The robust HTS assay flagged 436 (<1%) of the screened compounds as hits, also including known DIO1 inhibitors such as PTU and genistein. Based on a validation screen of 298 compounds, we prioritized 26 compounds to comprehensively characterize their DIO1-selective inhibition. We identified 15 DIO1-selective compounds (IC₅₀ < 1 µM), more potent than the bonafide DIO1-selective inhibitor PTU. Additionally, 8 of the 13 tested compounds were found capable of inhibiting DIO1 in intact cells. <b><i>Conclusions:</i></b> With a successful SK-reaction-based HTS application, we identified novel, potent, and selective inhibitors of DIO1 with nanomolar IC₅₀ values. Furthermore, we successfully showed that some of these compounds were also capable of inhibiting intracellular DIO1 in intact cells. These novel compounds hold immense potential in studying TH modulation, deciphering DIO1 enzyme structure, and developing structure-activity relationships. Furthermore, our novel inhibitors act as lead compounds in developing strategies to combat hyperthyroidism.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"576-589"},"PeriodicalIF":5.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764754","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":"DNA Methylation Dynamics and Prognostic Implications in Metastatic Differentiated Thyroid Cancer.","authors":"Helena Rodríguez-Lloveras, Carles Zafon, Carmela Iglesias, Jennifer Marcos-Ruiz, Joan Gil, Anna Rueda-Pujol, Lorena González, Regina Mayor, Esther N Klein Hesselink, Bettien M van Hemel, Cristina Carrato, Cecília Perelló-Fabregat, Javier Hernández-Losa, Rosa Somoza, Raquel Pluvinet, Jose F Sánchez-Herrero, Lauro Sumoy, Joan Seoane, Garcilaso Riesco-Eizaguirre, Cristina Montero-Conde, Mercedes Robledo, Jorge Hernando, Jaume Capdevila, Jordi L Reverter, Manel Puig-Domingo, Thera P Links, Mireia Jordà","doi":"10.1089/thy.2024.0303","DOIUrl":"10.1089/thy.2024.0303","url":null,"abstract":"<p><p><b><i>Background:</i></b> Distant metastases (DM) are the leading cause of thyroid cancer-related death in patients with differentiated thyroid cancer (DTC). Despite significant progress in understanding DNA methylation in DTC, the methylation landscape of metastatic primary tumors and DM remains unclear. Our primary objective was to investigate DNA methylation dynamics during DTC progression, with a secondary goal of assessing potential clinical implications. <b><i>Materials and Methods:</i></b> We conducted a multicenter retrospective study in patients with DTC who underwent surgery at five university hospitals. We profiled DNA methylation in a discovery series of 97 samples (15 normal tissues, 30 non-metastatic [non-mDTC], and 35 metastatic [mDTC] primary DTC, and 17 paired metastases [lymph nodes and DM]). Results were validated in an independent series of 17 non-mDTC and 13 mDTC. We used receiver operating characteristic curve analysis to evaluate the identified prognostic CpG-signature. <b><i>Results:</i></b> DNA methylation alterations, mostly hypomethylation, increased progressively from primary tumors to DM, both in papillary (PTC) and follicular (FTC) thyroid carcinomas. Compared with normal tissue, non-metastatic primary PTC (non-mPTC) exhibited more hypomethylated than hypermethylated CpGs in contrast to non-metastatic primary FTC (non-mFTC). However, metastatic tumors, both mPTC and mFTC, predominantly exhibited hypomethylated CpGs. The overlap of differentially methylated CpGs (DMe-CpGs) was low between non-mPTC and non-mFTC (14% non-mPTC DMe-CpGs present in non-mFTC) but significantly higher between mPTC and mFTC (60% mPTC DMe-CpGs present in mFTC), underscoring the convergence of epigenetic changes during metastatic progression. The presence of many <i>de novo</i> DMe-CpGs from metastatic primary tumors (83% from mPTC and 40% from mFTC) in DM, including metachronous DM, supports the hypothesis that DM originates from a major subclone of the primary tumor. We identified and validated a 156-CpG signature in primary tumors capable of distinguishing between non-mDTC and mDTC, offering potential prognostic value for DM development regardless of histology. <b><i>Conclusions:</i></b> These results show a progressive increase in DNA methylation alterations, mainly hypomethylation, during PTC and FTC metastatic progression, suggesting a linear model, though the DNA methylation dynamics differs between the two histological types. The analysis of the 156-CpG signature in primary tumors may help identify patients with DTC at high risk for DM, enhancing a more personalized treatment.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"494-507"},"PeriodicalIF":5.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568191","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":"Targeting the Aryl Hydrocarbon Receptor to Attenuate IGF1R Signaling in Thyroid Eye Disease.","authors":"Elisa Roztocil, Farha Husain, Charkira C Patrick, Steven E Feldon, Collynn F Woeller","doi":"10.1089/thy.2024.0529","DOIUrl":"10.1089/thy.2024.0529","url":null,"abstract":"<p><p><b><i>Background:</i></b> Thyroid eye disease (TED) is an autoimmune disorder characterized by proptosis, inflammation, and fibrosis. Elevated insulin-like growth factor 1 receptor (IGF1R) signaling in TED orbital fibroblasts (OFs) drives the proliferation and biosynthesis of hyaluronan, which causes enlargement of orbital tissue volume. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that regulates cellular stress responses, metabolism, and inflammation. Given its important role in regulating cellular responses, we hypothesized that activation of the AHR could limit excessive IGF1R signaling in TED OFs, offering therapeutic potential. <b><i>Methods:</i></b> We measured IGF1R and AHR expression levels in TED, non-TED, and non-OF controls. OF activation was analyzed using proliferation, hyaluronan accumulation, and migration assays. RNA sequencing was used to detect transcriptome-wide changes in IGF1-treated TED OFs. After gene set enrichment analysis, select gene expression changes were validated by quantitative polymerase chain reaction. OFs were treated with the AHR ligands 6-formylindolo[3,2-b]carbazole (FICZ) or tapinarof with or without IGF1. Western blotting evaluated signaling pathways impacted by AHR and IGF1R signaling. <b><i>Results:</i></b> TED OFs showed elevated IGF1R and AHR expression levels compared to controls. IGF1 significantly increased hyaluronan accumulation, proliferation, and migration in TED OFs compared to non-TED OFs. IGF1R signaling altered the expression of hundreds of genes controlling cell migration, proliferation, and metabolism in TED OFs. These genes included <i>TUBA1B</i>, <i>TUBA1C</i>, <i>CRABP2</i> (upregulated), and <i>IRS2</i> and <i>SOD3</i> (downregulated). AHR activation blocked proliferation, migration, hyaluronan production, and gene expression mediated through IGF1R signaling. The AHR inhibited these pathways by reducing phosphorylation of GSK3β, an important mediator of IGF1R/β-catenin mediated signaling. <b><i>Conclusions:</i></b> AHR activation represents a promising therapeutic strategy for mitigating TED progression by inhibiting IGF1R signaling. Through modulation of GSK3β-mediated pathways, AHR activation may target additional pathologically relevant pathways beyond those affected by direct IGF1R inhibitors. This research provides novel insights into TED pathophysiology and offers a potential avenue for developing therapies to improve patient outcomes.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"527-542"},"PeriodicalIF":5.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033118","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":"Residential Greenness Is Associated with Lower Thyroid Nodule Prevalence: A Nationwide Study in China.","authors":"Siying Liu, Cihang Lu, Yongze Li, Lili Zhu, Zhongyan Shan, Weiping Teng, Tingting Liu","doi":"10.1089/thy.2024.0616","DOIUrl":"10.1089/thy.2024.0616","url":null,"abstract":"<p><p><b><i>Background:</i></b> The prevalence of thyroid nodules is increasing globally. This study explored the association between residential greenness and thyroid nodule prevalence. <b><i>Methods:</i></b> Data were collected from a national cross-sectional survey of 73,728 participants across 31 provinces in mainland China. Residential greenness was assessed with the normalized difference vegetation index (NDVI) and the enhanced vegetation index (EVI). Thyroid nodules >10 mm in diameter were diagnosed via ultrasound. We used quartile comparisons of the NDVI and EVI to compare nodule prevalence and employed logistic regression and restricted cubic spline analyses to examine nodules' associations with greenness. Interaction and sensitivity analyses were performed to test robustness. <b><i>Results:</i></b> A total of 73,728 participants were included in this study. The prevalence of 10 mm thyroid nodules decreased across NDVI500 quartiles: Q1: 7.99% (7.59-8.39%), Q2: 10.04% (9.60-10.48%), Q3: 6.59% (6.23-6.95%), and Q4: 5.20% (4.88-5.52%) (<i>p</i> for trend <0.001). The prevalence was 5.25% (95% confidence interval [CI]: 5.02-5.49%) in males and 9.09% (CI: 8.80-9.39%) in females. Logistic regression analysis showed that greater residential greenness was associated with a lower prevalence of thyroid nodules after adjusting for all covariates. This association was observed for both continuous greenness measures (NDVI500: odds ratio [OR] = 0.20, CI: 0.16-0.25; EVI500: OR = 0.08, CI: 0.06-0.12) and across quartiles (NDVI500 Q4: OR = 0.53, CI: 0.48-0.58; EVI500 Q4: OR = 0.55, CI: 0.51-0.60; both compared to Q1). Multiple sensitivity analyses confirmed this negative association, including the use of an alternative thyroid nodule definition (5 mm threshold), exclusion of individuals with cysts on ultrasound, and subgroup analyses excluding individuals with autoimmune thyroid antibody positivity, goiter, or both. In all these sensitivity analyses, NDVI and EVI data were assessed using both 500 m and 1000 m buffers. <b><i>Conclusion:</i></b> Our study is the first to identify an association between higher levels of residential greenness and a lower prevalence of thyroid nodules.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"543-552"},"PeriodicalIF":5.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011383","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":"Is There a Better Way to Estimate Levothyroxine Doses for Hypothyroid Patients?","authors":"Mary H Samuels","doi":"10.1089/thy.2025.0176","DOIUrl":"10.1089/thy.2025.0176","url":null,"abstract":"","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"460-461"},"PeriodicalIF":5.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998718","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":"Multimodality Ultrasound Utilizing Microvascular Flow Imaging and Shear Wave Elastography to Guide Fine-Needle Aspiration of Thyroid Lesions: A Prospective Study Validating Pattern-Based Microvascular Classification.","authors":"Jiamin Chen, Jing Zhong, Yu Zhuang, Bixue Deng, Jiayi Hong, Yuhong Lin, Zhongzhen Su, Xin Wen","doi":"10.1089/thy.2024.0586","DOIUrl":"10.1089/thy.2024.0586","url":null,"abstract":"<p><p><b><i>Background:</i></b> Most current guidelines recommend fine-needle aspiration (FNA) biopsy of thyroid nodules based on grayscale ultrasound (GUS) features, but the biopsy rate for benign nodules remains high. Our aim was to construct a new pattern-based microvascular classification (PBMC) for thyroid nodules to develop and validate predictive multimodality US models based on GUS, microvascular flow imaging, and shear wave elastography, and compare FNA decision accuracy with the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS). <b><i>Methods:</i></b> This prospective study included consecutive patients with thyroid nodules who underwent multimodality US examinations from September 2022 to December 2023. Using PBMC, lesions were divided into three categories: malignant signs (convergence sign, piercing sign, and spoke wheel sign), benign signs (ring sign), and other vascular patterns. Univariate and multivariable logistic regression analyses were conducted to determine the odds ratios (ORs) of US features, including vascular signs, and construct predictive models based on multimodality US. Multimodality US models were validated with internal cross-validation and evaluated based on discrimination, calibration, and decision curve analyses. <b><i>Results:</i></b> Overall, 793 thyroid nodules confirmed using pathological analysis (248 benign and 545 malignant) in 599 participants (mean age, 43 years ±11 [SD]) were included. In univariate logistic regression analyses, malignant vascular signs showed a positive association with malignant nodules (OR: 10.43, 95% confidence interval [CI]: 5.76, 18.88; <i>p</i> < 0.01), whereas benign vascular signs were inversely associated with malignancy (OR: 0.10, 95% CI: 0.06, 0.16; <i>p</i> < 0.01). Four multivariable models incorporated GUS features, Young's modulus, and PBMC. The highest area under the receiver operating characteristic curve (AUC) was 0.95 (95% CI: 0.82, 0.97) for the multimodality US model, and the lowest AUC was 0.62 (95% CI: 0.57, 0.66) for ACR TI-RADS based on GUS (<i>p</i> < 0.001). At a 71% risk threshold, multimodality US avoided 27% (95% CI: 21, 34) of FNA procedures, compared with 13% (95% CI: 0, 38) with TI-RADS (<i>p</i> < 0.001). <b><i>Conclusion:</i></b> Visual assessment of microvascular morphology patterns may improve differentiation of benign and malignant thyroid nodules and potentially reduce the risk of unnecessary biopsy of benign thyroid nodules.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"516-526"},"PeriodicalIF":5.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039082","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":"Combining Ultrasound Imaging and Molecular Testing in a Multimodal Deep Learning Model for Risk Stratification of Indeterminate Thyroid Nodules.","authors":"Shreeram Athreya, Andrew Melehy, Sujit Silas Armstrong Suthahar, Vedrana Ivezić, Ashwath Radhachandran, Vivek R Sant, Chace Moleta, Henry Zheng, Maitraya Patel, Rinat Masamed, Masha Livhits, Michael Yeh, Corey W Arnold, William Speier","doi":"10.1089/thy.2024.0584","DOIUrl":"10.1089/thy.2024.0584","url":null,"abstract":"<p><p><b><i>Objective:</i></b> Indeterminate cytology (Bethesda III and IV) represents 15-30% of biopsied thyroid nodules and require additional diagnostic testing. Molecular testing (MT) is a commonly used diagnostic tool that evaluatesmalignancy risk through next generation sequencing of fine needle aspiration (FNA) samples. While MT achieves high sensitivity (97-100%) in ruling out malignancy, its specificity and positive predictive value (PPV) remain relatively low. This study proposes a multimodal deep learning model that integrates ultrasound (US) imaging with MT to improve risk stratification by enhancing PPV while maintaining high sensitivity. Combining these modalities leverages complementary information from both molecular and imaging data, addressing limitations in current approaches and offering a robust framework for evaluating indeterminate nodules. <b><i>Methods:</i></b> We retrospectively analyzed 333 patients with indeterminate thyroid nodules (259 benign, 74 malignant) at UCLA Medical Center between 2016 and 2022. We evaluated four configurations: whole frame US images, 256 × 256 patches, 128 × 128 patches, and an ensemble model combining the first three configurations. The clinical baseline consisted of Bethesda cytology and MT results. Models were assessed using five fold cross validation stratified by surgical outcomes. <b><i>Results:</i></b> The clinical baseline (Bethesda + MT) achieved an AUROC of 0.728 [0.68, 0.78] with sensitivity of 0.946 [0.88, 1.00], specificity of 0.664 [0.60, 0.73], and PPV of 0.448 [0.41, 0.48]. The proposed ensemble model demonstrated improved performance, achieving an AUROC of 0.831 [0.77, 0.89] with a sensitivity of 0.946 [0.88, 1.00], specificity of 0.703 [0.66, 0.75], and PPV of 0.477 [0.46, 0.50]. These improvements were statistically significant (<i>p</i> = 0.0008). <b><i>Conclusion:</i></b> Our multimodal model enhances MT performance by providing statistically significant improvements in PPV and specificity while maintaining high sensitivity. Our framework could be leveraged to reduce the number of benign thyroid resections in patients with indeterminate nodules. However, this study is limited by its single center dataset, lack of external validation, and the use of binarized MT outputs rather than granular malignancy risk probabilities. Future work should validate these findings across diverse populations and larger external datasets for more comprehensive risk stratification.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"590-594"},"PeriodicalIF":5.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045016","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":"Risk Factors for Thyroid Function Test Abnormalities During Pregnancy: A Systematic Review of the Literature to Validate Current Risk Factors and Identify Novel Ones.","authors":"Yindi Liu, Joris A J Osinga, Spyridoula Maraka, Sofie Bliddal, Erik K Alexander, Chrysoula Dosiou, Kristien Boelaert, Gabriela Brenta, Elise Krabbendam, Jennifer L Eaton, Haixia Guan, Sun Y Lee, Lilah F Morris-Wiseman, Caroline T Nguyen, Zhongyan Shan, Rima K Dhillon-Smith, Elizabeth N Pearce, Robin P Peeters, Angela M Leung, Tim I M Korevaar","doi":"10.1089/thy.2024.0743","DOIUrl":"10.1089/thy.2024.0743","url":null,"abstract":"<p><p><b><i>Background:</i></b> International guidelines recommend that the indication to perform thyroid function testing during pregnancy is based on the presence of risk factors for thyroid function test abnormalities. However, the discriminative ability of currently recommended risk factors is questionable. To inform on an update of the American Thyroid Association Guidelines for the Diagnosis and Management of Thyroid Disease in Preconception, Pregnancy, and the Postpartum, we aimed to systematically review the literature to evaluate evidence for current risk factors and potential novel ones for thyroid function test abnormalities in pregnancy. <b><i>Methods:</i></b> A systematic literature search was performed on Embase, Medline Ovid, and the Cochrane Library from inception to October 17, 2024, to identify articles on the associations of any candidate variables with thyroid function test abnormalities, thyroid antibody positivity, or results of continuous thyroid function tests in pregnancy. Additional records were identified through citation searching. Study quality was assessed using the Newcastle-Ottawa Scale. We summarized the results using a narrative synthesis. <b><i>Results:</i></b> A total of 81 articles were included, describing 36 candidate variables. Thyroid antibody positivity was associated with a higher risk of overt or subclinical hypothyroidism compared with antibody negativity (absolute risks: 2.4-7.0% vs. 0.1-0.2% for overt hypothyroidism and 1.9-29.0% vs. 2.0-5.7% for subclinical hypothyroidism). In cases of iodine deficiency, sufficiency, and intake above pregnancy requirements or excess, the absolute risks for subclinical hypothyroidism were 2.2-42.6%, 1.42-16.0%, and 3.8-24.3%, respectively. A limited number of studies were available for history of autoimmune diseases, family history of thyroid disease, symptoms of hypothyroidism, and history of pregnancy loss, preterm delivery, or infertility. There was little or no association of current risk factors with isolated hypothyroxinemia or (subclinical) hyperthyroidism. We did not identify novel risk factors for thyroid function test abnormalities. <b><i>Conclusions:</i></b> Evidence for most currently recommended risk factors remains limited and heterogeneous, and no novel risk factor was identified. While risk factors can help guide thyroid function testing in pregnancy, a clinical risk assessment cannot be replaced. Future studies are needed to detect novel risk factors that can improve the accuracy and efficiency of identifying pregnant women at high risk of thyroid function test abnormalities, in particular, overt hypothyroidism.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"553-575"},"PeriodicalIF":5.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049182","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":"Utility of Ultrasound Surveillance for Thyroid Cancer in Children.","authors":"Sanjay Rao, Mary C Frates, Carol B Benson, Christine E Cherella, Jessica R Smith, Ari J Wassner","doi":"10.1089/thy.2024.0624","DOIUrl":"10.1089/thy.2024.0624","url":null,"abstract":"<p><p><b><i>Background:</i></b> Differentiated thyroid cancer (DTC) is the most common pediatric endocrine malignancy. The utility of ultrasound (US) surveillance after initial treatment has not been clearly delineated. We sought to evaluate the clinical utility of US for the detection of residual or recurrent disease in pediatric patients with thyroid cancer beginning 1 year after initial therapy. <b><i>Methods:</i></b> This is a retrospective cohort study of pediatric patients (<19 years) diagnosed with DTC between 1998 and 2022 whose response to therapy (RTT) one year after initial treatment (thyroidectomy ± radioactive iodine) was excellent or indeterminate. We evaluated the association between sonographic and biochemical findings (thyroglobulin [Tg] and Tg antibodies [TgAb]) at one year with the subsequent diagnosis of residual/recurrent structural disease in the neck (SDN). <b><i>Results:</i></b> In total, 112 patients had 1-year RTT that was excellent (<i>n</i> = 61, 54.5%) or indeterminate (<i>n</i> = 51, 45.5%). Median length of subsequent follow-up was 6.4 (interquartile range 3.8-8.9) years. Overall, 683 surveillance neck US were performed, with a mean ± standard deviation of 1.0 ± 0.4 US per patient per year. Of 61 patients with excellent RTT, none developed SDN during follow-up. Eighteen patients (29.5%) had a false-positive indeterminate or abnormal US finding. Of 51 patients with indeterminate RTT, 9 (17.6%) developed SDN during follow-up. SDN was detected by US in 7/9 cases (77.8%). SDN was detected by I-123 scan, but not by US, in two cases (22.2%), both with abnormal Tg/TgAb. 7/9 (77.8%) cases of SDN were detectable by Tg/TgAb. Overall, fine-needle aspiration (FNA) was performed in 17/112 (15.2%) patients and diagnosed SDN in six patients. Overall, 11/112 patients (9.8%) underwent FNA but were not diagnosed with SDN. <b><i>Conclusions:</i></b> In pediatric DTC patients with excellent response to initial therapy, the utility of serial US surveillance is limited by the low risk of SDN and frequent false-positive US findings. In children with indeterminate RTT, SDN occurs in a significant proportion and may be detected by US or by abnormal Tg/TgAb levels. These patients may benefit from the combination of US and biochemical surveillance.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"406-414"},"PeriodicalIF":5.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068077","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":"Association Between Maternal Thyroid Hormone Concentration with Normal Thyroid Function During Pregnancy and Preschoolers' Glycolipid Metabolism: A Birth Cohort Study.","authors":"Wenjin Cai, Lu Chen, Manyu Zhang, Jiajun Ouyang, Penggui Wu, Juan Tong, Guopeng Gao, Shuangqin Yan, Fangbiao Tao, Kun Huang","doi":"10.1089/thy.2024.0334","DOIUrl":"10.1089/thy.2024.0334","url":null,"abstract":"<p><p><b><i>Background:</i></b> Thyroid hormones (THs) are essential endocrine hormones that play key roles in individual's growth and development. There is limited knowledge about the association between maternal TH concentrations variations with normal thyroid function during pregnancy and offspring's glycolipid metabolism. <b><i>Methods:</i></b> A total of 1130 mother-child pairs from the Ma'anshan birth cohort were included in this prospective study. Maternal TH levels and thyroid peroxidase antibodies were measured in the 1st, 2nd, and 3rd trimesters of pregnancy during the childhood follow-up period. Fasting venous blood was collected from children at 4-6 years of age and glycolipid metabolic indicators were assayed. Analyses were performed using Binary logistic regression models, linear regression models, and Generalized linear regression model. <b><i>Results:</i></b> Maternal TH trajectories were fitted via latent category growth models. During the 1st trimester of pregnancy, maternal T3 and free thyroxine (fT4) levels were positively associated with children's blood glucose levels (β = 0.007 [CI 0.028-0.181]; β = 0.022 [CI 0.004-0.040]), whereas high levels of fT4 may be associated with decreased risk of children's hypercholesterolemia (OR = 0.870 [CI 0.768-0.986]). Maternal T4 concentrations during the 3rd trimester of pregnancy were negatively associated with children's cholesterol levels (β = -0.002 [CI -0.003-0.00]). High maternal TH levels were associated with high fasting glucose level and low low-density lipoprotein concentrations in children. <b><i>Conclusions:</i></b> Maternal TH dynamic variations may be associated with glycolipid metabolism in preschoolers, even when women do not have clinically diagnosed thyroid disorders. The exact associations between maternal THs in specific trimesters of pregnancy under normal thyroid function conditions and glycolipid metabolism in offspring require further investigation.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"444-456"},"PeriodicalIF":5.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575991","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}