Thyroid最新文献

{"title":"Afirma Xpression Atlas Alteration Status Is Associated with Malignancy Risk in Indeterminate Thyroid Nodules.","authors":"Terrance D Peng, Elena G Hughes, Jiyoon Kim, Chi-Hong Tseng, Stephanie SmookePraw, James X Wu, Michael W Yeh, Masha J Livhits","doi":"10.1177/10507256261484715","DOIUrl":"10.1177/10507256261484715","url":null,"abstract":"<p><strong>Background: </strong>Molecular testing with the Afirma Genomic Sequencing Classifier (GSC) is commonly used to refine the diagnosis of thyroid nodules with indeterminate cytology. The Afirma Xpression Atlas (XA) is a whole-transcriptome RNA-sequencing platform that reports expressed alterations in GSC-suspicious nodules. The clinical implications of XA results have not been clearly defined. This study evaluated the association between XA alteration detection and histopathology outcomes.</p><p><strong>Methods: </strong>A retrospective review was performed of consecutive patients who underwent thyroid fine needle aspiration at a single institution from 3/2020 to 9/2025. All nodules with Bethesda III/IV cytology and GSC-suspicious results with subsequent XA testing that underwent surgical resection were included. Clinicopathologic variables were compared between XA alteration-positive and alteration-negative groups. Nodules were categorized as benign, noninvasive follicular thyroid neoplasm with papillary-like nuclear features, or malignant based on surgical pathology. Subgroup analyses were performed to compare clinicopathologic variables between <i>BRAF</i>-alteration, <i>RAS</i>-alteration, other-alteration, and alteration-negative groups. All analyses involving the other-alteration subgroup were exploratory. Multivariable linear regression was performed to identify independent predictors of 2025 American Thyroid Association (ATA) risk of recurrence category.</p><p><strong>Results: </strong>The study cohort included 192 patients (77.6% female) with a median age of 51 years. Among all 200 nodules, 94 nodules (47.0%) were alteration-positive. Nodule size did not differ between alteration-positive and alteration-negative groups. The malignancy rate was highest in <i>BRAF</i>-alteration nodules (100%; exact 95% Confidence Interval (CI): [71.5%, 100.0%]), followed by other-alteration (67.7%; 95% CI: [48.6%, 83.3%]), <i>RAS</i>-alteration (55.8%; 95% CI: [41.3%, 69.5%]), and alteration-negative nodules (46.2%; 95% CI: [36.5%, 56.2%]) (<i>p</i> < 0.001). Despite a higher malignancy rate, alteration-positive nodules did not demonstrate more aggressive histopathologic features compared with alteration-negative nodules, including rates of extrathyroidal extension, lymphatic invasion, or angioinvasion. On multivariable linear regression, no alteration subgroups or clinical covariates were identified as independent predictors of 2025 ATA risk of recurrence category.</p><p><strong>Conclusions: </strong>Alteration detection by Afirma XA offers incremental malignancy risk stratification beyond GSC-suspicious classification alone in indeterminate thyroid nodules. The substantial malignancy rate in GSC-suspicious alteration-negative nodules, with histopathologic features similar to those of alteration-positive nodules, supports continued consideration of surgical resection in such cases.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"1203-1211"},"PeriodicalIF":6.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841077","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":"Longitudinal Ultrasonographic Analysis of Involutional Changes after Radiofrequency Ablation of Papillary Thyroid Microcarcinoma.","authors":"Taehyuk Ham, Ji Ye Lee, Meesun Lee, Young Hun Jeon, Inpyeong Hwang, Jung Hyo Rhim, Ji-Hoon Kim","doi":"10.1177/10507256261494909","DOIUrl":"10.1177/10507256261494909","url":null,"abstract":"<p><strong>Background: </strong>Radiofrequency ablation (RFA) has emerged as an effective nonsurgical treatment for low-risk papillary thyroid microcarcinoma (PTMC), with widely variable rates of complete disappearance reported. The purpose of our study was to characterize the longitudinal ultrasonographic (US) changes following RFA of PTMC and to propose imaging-based criteria to guide posttreatment surveillance.</p><p><strong>Methods: </strong>This retrospective cohort study included 98 low-risk unifocal PTMC patients (82 females; age range, 27-59 years) who underwent RFA with a median follow-up of 48 months (range, 12-74 months). Comprehensive longitudinal US analysis was performed to characterize temporal changes in the ablation zone and surrounding parenchyma. Factors associated with postablational nodular remnant at 1 year after RFA were also evaluated.</p><p><strong>Results: </strong>All RFA procedures achieved 100% technical success. By 1 year, the volume of the ablation zone had decreased to a median of 0 mL (range, 0-0.41 mL). However, ultrasonography demonstrated complete disappearance in only 70.4% of PTMCs, while 29.6% exhibited postablational nodular remnants despite volumetric resolution. These nodular remnants progressively regressed and eventually disappeared during subsequent follow-up, except for a single case of a tiny macrocalcified residue persisting at 5-year follow-up after RFA. Characteristic postablation US features gradually emerged during the first year after RFA, with incidence at 1 year of capsular retraction, postablational strands, and postablational parenchymal hypoechogenicity reaching 61.2%, 60.2%, and 51.0%, respectively. These findings remained relatively stable through the primary follow-up period of up to 36 months, although postablational strands showed a further significant increase in incidence throughout this period. Without major complications, disease progression occurred in 4.1% (4/98) patients: Three contralateral PTMC cases were treated with additional RFA, and one case with lymph node metastasis underwent surgery. No clinico-radiological or procedural factors were significantly associated with 1-year postablational nodular remnant after RFA.</p><p><strong>Conclusions: </strong>RFA of low-risk PTMC achieves an excellent final complete disappearance rate while frequently inducing characteristic US features, including capsular retraction, postablational strands, and postablational parenchymal hypoechogenicity. Recognition of these US involutional changes is crucial for accurate posttreatment monitoring and for avoiding misinterpretation of benign healing changes as pathological findings, and may inform imaging-based post-RFA surveillance.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"1226-1238"},"PeriodicalIF":6.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128236","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":"Genetic Heterogeneity in Susceptibility to Familial Thyroid Nodular Disease.","authors":"Anne-Sophie Chong, Ralf Paschke, Elisabet Munté, Cristina Rioja, Lilian Bomme Ousager, Anne Marie Jelsig, Daniel Désir, William D Foulkes, Barbara Rivera","doi":"10.1177/10507256261485457","DOIUrl":"10.1177/10507256261485457","url":null,"abstract":"<p><strong>Background: </strong>Nontoxic multinodular goiter (MNG), recently reclassified as thyroid follicular nodular disease (TFND), is a common thyroid disorder with complex and incompletely understood genetic contributors. Although familial aggregation and genetic predisposition have been observed, the underlying molecular mechanisms remain only partially defined.</p><p><strong>Objective: </strong>To identify rare germline genetic variants contributing to familial euthyroid TFND, including families with pedigrees suggestive of autosomal dominant inheritance, using whole-exome sequencing (WES).</p><p><strong>Methods: </strong>WES was performed on germline DNA from 28 affected individuals belonging to eight pedigrees exhibiting TFND. Two analytical approaches were applied, including a cross-pedigree analysis to detect disrupted genes shared across multiple kindreds and kindred-based analyses to identify rare pathogenic variants segregating within individual pedigrees or single affected individuals. Somatic sequencing of four available TFND tissues was also performed to search for second-hit mechanisms or copy number alterations (CNA).</p><p><strong>Results: </strong>Cross-pedigree analysis identified one gene carrying variants of uncertain significance, which did not emerge as definitive candidates. Pedigree-specific analyses revealed a truncating <i>DICER1</i> variant in a kindred previously linked to the MNG-1 locus and associated with early disease onset; a heterozygous <i>SLC26A4</i> variant in only one affected individual from another kindred and loss of heterozygosity in the patient's tissue; and a pathogenic <i>WFS1</i> variant in one kindred, supporting its previously proposed role as a TFND candidate gene, but requiring further validation. Both germline CNA analysis and targeted <i>PLCB1</i> screening in all kindreds yielded negative results.</p><p><strong>Conclusions: </strong>This study highlights the substantial genetic heterogeneity underlying familial TFND. While most kindreds lacked clear monogenic causes, <i>DICER1</i> explained familial disease in one pedigree, whereas the <i>SLC26A4</i> findings supported a likely somatic second-hit mechanism in a single affected member of another pedigree without accounting for the familial aggregation. The findings support a multifactorial etiology and suggest that TFND represents a phenotypic manifestation within broader hereditary syndromes. Integrating family-based sequencing with functional validation will be critical to fully delineate pathogenic mechanisms and broaden the spectrum of genes implicated in thyroid nodular disease.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"1190-1202"},"PeriodicalIF":6.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931108","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":"Exceptional and Durable Response to Selpercatinib in a Patient with Apparently <i>RET</i>-Negative, <i>HRAS</i>-, and <i>NF1</i>-Mutated Metastatic Medullary Thyroid Carcinoma.","authors":"Ali S Alzahrani, Allianah Benito, Balgees Alghamdi, Ashwag Alqahtani, Hindi Nasser Al-Hindi, Norah Altuwaijri, Wedad Albalawi, Aljoharah AlSaigh, Mohamed H Al-Hamed","doi":"10.1177/10507256261493665","DOIUrl":"10.1177/10507256261493665","url":null,"abstract":"<p><strong>Background: </strong>Selpercatinib is approved for <i>RET</i>-mutated medullary thyroid carcinoma (MTC); its activity in tumors without detectable <i>RET</i> alterations is uncertain.</p><p><strong>Patient findings: </strong>A 50-year-old woman developed rapidly progressive MTC (Ki-67 = 30%) with extensive liver and bone metastases. Because of severe symptomatic progression, selpercatinib was started urgently, off-label, before molecular testing results were available. She had rapid clinical improvement, marked calcitonin and CEA decline, and a remarkable and durable radiographic partial response until the last follow-up (29 months).</p><p><strong>Summary: </strong>Repeated germline and tumor testing [<i>RET</i> Sanger sequencing, germline whole-exome sequencing, tumor DNA/RNA panel testing, <i>RET</i> Multiplex Ligation-Dependent Probe Amplification (MLPA), tumor whole-genome sequencing] identified no pathogenic or actionable <i>RET</i> variant, indel, copy-number alteration, or fusion. The only somatic alterations found were <i>HRAS</i> p.G13S and truncating <i>NF1</i> p.R2450*.</p><p><strong>Conclusions: </strong>This remarkable response to selpercatinib in apparently <i>RET</i>-negative MTC is hypothesis generating and requires confirmation. <i>HRAS</i>/<i>NF1</i> co-alteration supports RAS/MAPK activation but does not explain sensitivity to selective <i>RET</i> inhibition.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"1275-1280"},"PeriodicalIF":6.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115300","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":"Comparative Performance of the 2015 and 2025 American Thyroid Association Initial Recurrence Risk Stratification Systems in Differentiated Thyroid Cancer.","authors":"Weixun Ke, Xuanling Zheng, Liying Wang, Ziyi Xiao, Wenjing Chen, Yang Xu, Najun Ke, Peiying Huang, Tingting Lin, Qingbao Shen, Ruisheng Ke, Kunzhai Huang, Fangsen Xiao","doi":"10.1177/10507256261494916","DOIUrl":"10.1177/10507256261494916","url":null,"abstract":"<p><strong>Background: </strong>The 2025 American Thyroid Association (ATA) guidelines introduced significant modifications to the initial risk stratification system for differentiated thyroid cancer (DTC). However, the real-world prognostic performance and stage migration effects of these updates compared with the 2015 system remain unevaluated.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study at a tertiary referral center in China. Adult patients who underwent initial thyroidectomy for pathologically confirmed DTC between January 2008 and December 2018 were included, with follow-up extending through October 30, 2025. We compared the 2015 and 2025 ATA initial risk stratification systems. The primary outcome was structural disease-free survival (SDFS). Performance was assessed using area under the receiver operating characteristic curve (AUC), reclassification analysis, and decision curve analysis (DCA).</p><p><strong>Results: </strong>Among 1508 patients (median age 43 years, interquartile range [IQR] = 33-53; 1147 [76.1%] female), 120 (8.0%) developed events during a median follow-up of 8.9 years (IQR = 7.56-10.80). The 2025 ATA system demonstrated superior discrimination compared with the 2015 system (ΔAUC 0.0455 [confidence interval or CI: 0.0147-0.0764], <i>p</i> = 0.004), although both systems showed significant risk stratification (log-rank <i>p</i> < 0.001). Reclassification analysis revealed that the 2025 system reassigned 41.7% of patients with recurrence to higher-risk categories but also reassigned 38.8% of recurrence-free patients to higher-risk categories. Multivariable analyses identified the revised multifocality criteria and the presence of two or more low-to-intermediate risk features as the major contributors to this reclassification (risk inflation). Conversely, refined compartment-based lymph node stratification was associated with improved classification accuracy. DCA demonstrated greater net clinical benefit for the 2025 system across clinically relevant threshold probabilities.</p><p><strong>Conclusions: </strong>The 2025 ATA initial risk stratification system significantly improves prognostic discrimination compared with the 2015 system. However, the enhanced sensitivity comes with a specificity trade-off, leading to substantial upward risk reclassification for recurrence-free patients. These real-world findings provide critical insights for clinicians to balance intensified surveillance against the potential for overtreatment under the new guidelines.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"1169-1177"},"PeriodicalIF":6.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128212","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":"<i>RET</i> Variant Reclassification across Demographic Sub-Groups in a Large-Scale Clinical Population.","authors":"Kirkpatrick B Fergus, Marcy E Richardson, Elad Ziv, Julie Ann Sosa, Elizabeth G Grubbs","doi":"10.1177/10507256261493762","DOIUrl":"10.1177/10507256261493762","url":null,"abstract":"<p><strong>Background: </strong>The expanded use of germline testing panels that include the <i>RET</i> proto-oncogene has identified many variants of uncertain significance (VUSs). It remains poorly understood how many <i>RET</i> VUSs are returned in clinical practice, how many are ultimately reclassified, and which patient populations are affected most.</p><p><strong>Methods: </strong>We conducted a nationwide retrospective cohort study of individuals tested for <i>RET</i> germline variants between 2017 and 2024 as part of routine clinical diagnostic testing at Ambry Genetics. Samples underwent next-generation sequencing, and variants were reported with their associated five-tier pathogenicity classification. Variant reclassification was measured as a change between initial and updated classification status on a per-variant and per-person basis. Test requisition forms, pedigrees, and clinic notes were used to associate genetic test results with demographic and clinical patient characteristics.</p><p><strong>Results: </strong>Among 616,077 individuals who underwent <i>RET</i> germline genetic testing that included <i>RET</i>, 969 (0.2%) had a <i>RET</i> PV, and 5516 (0.9%) had a <i>RET</i> VUS. A total of 1607 (29%) individuals with initial <i>RET</i> VUSs were reclassified. Most variants (164/166; 98.8%) and individuals (1605/1607; 99.9%) were reclassified as benign. The prevalence of VUS on initial classification was significantly higher in individuals self-reporting as Asian (1.5%), Black (1.3%), and Hispanic (1%) compared with those self-reporting as White (0.8%). Reclassification reduced the proportion of VUSs within race and ethnicity groups, but relative differences remained statistically significant.</p><p><strong>Conclusions: </strong>The expansion of <i>RET</i> germline testing coincided with substantial reclassification of VUSs, highlighting the importance of periodic laboratory reassessment. Most reclassifications were benign, which is cautiously reassuring for clinical counseling of patients. Both further characterization of RET variants and society guidance on clinical management of VUS test results are needed as genetic testing continues to expand.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"1258-1266"},"PeriodicalIF":6.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127720","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":"Zingiberen Newsaponin Enhances Antitumor Immunity in Anaplastic Thyroid Carcinoma Via Induction of Autophagy-Dependent Pyroptosis.","authors":"Qing-Xuan Wang, Tong-Xin Zou, Zi-Yan Chen, Xin-Yue Wang, Quan Li, Jun-Hao Zhang, Ye-Feng Cai, Jie You, En-Dong Chen, Gang Chen, Jin-Miao Qu","doi":"10.1177/10507256261493805","DOIUrl":"10.1177/10507256261493805","url":null,"abstract":"<p><strong>Background: </strong>Anaplastic thyroid carcinoma (ATC) is a lethal malignancy with a dismal prognosis and limited therapeutic options. Although immunotherapy has revolutionized the oncological landscape, the efficacy of Programmed Cell Death Protein 1 (PD-1) blockade as a monotherapy remains underwhelming in ATC. Consequently, identifying novel agents capable of triggering immunogenic cell death (ICD) to sensitize ATC to immune checkpoint inhibitors is a critical clinical priority.</p><p><strong>Materials and methods: </strong>Through high-throughput screening of 3200 compounds, Zingiberen newsaponin (ZN) was identified as a lead anti-ATC agent. Its therapeutic efficacy was evaluated using ATC cell lines, patient-derived organoids, and xenograft models. Mechanistic investigations were conducted via pharmacological inhibition, genetic knockout, and Western blotting to examine the autophagy-pyroptosis axis. Furthermore, an immunocompetent murine ATC model was employed to assess the synergistic effects of ZN and anti-PD-1 therapy on the tumor immune microenvironment through immunohistochemical analysis of T-cell infiltration.</p><p><strong>Results: </strong>ZN exhibited potent antiproliferative activity against ATC cells with half-maximal inhibitory concentration values ranging from 1.95 to 2.98 μM. Morphological assessment and biochemical assays (Lactate dehydrogenase, interleukin-1 beta, and high mobility group box 1 release) confirmed that ZN induces Gasdermin E (GSDME)-mediated pyroptosis via the activation of caspase-3 and caspase-8. Importantly, genetic knockout of GSDME significantly attenuated the pyroptotic phenotype, corroborating the central role of GSDME in ZN-induced pyroptosis. Mechanistically, ZN-induced pyroptosis was found to be autophagy-dependent, as pharmacological inhibition of autophagy with chloroquine significantly reversed GSDME cleavage and cell death both <i>in vitro</i> and <i>in vivo</i>. Consistently, ATG5 knockdown markedly rescued ZN-induced cell pyroptosis. Furthermore, ZN functioned as a potent inducer of ICD. In immunocompetent murine models, ZN treatment remodeled the tumor immune microenvironment by significantly increasing the infiltration of CD8⁺ T cells. Notably, the combination of ZN and anti-PD-1 therapy demonstrated superior synergistic antitumor efficacy compared with monotherapy.</p><p><strong>Conclusions: </strong>Our study identifies ZN as a novel inducer of autophagy-mediated GSDME pyroptosis in ATC. By triggering ICD and recruiting CD8⁺ T cells, ZN sensitizes ATC to PD-1 blockade, offering a promising therapeutic strategy for this lethal disease.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"1212-1225"},"PeriodicalIF":6.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128164","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":"What Happens after an Incidental Thyroid Nodule? Patterns of Thyroid Ultrasound Use and Downstream Evaluation.","authors":"Felipe Larios, Luis Vilatuna Andrango, Mariana Borras-Osorio, Megan E Branda, David Toro-Tobon, Yuqi Wu, Esteban Cabezas, Ricardo Loor-Torres, Maria Mateo Chavez, Ana Gabriela Claros, Maria Lizarazo Jimenez, Ivan Mateo Alzamora, Marcelo Montero, Esteban Gomez-Alvarez, Misk Al Zahidy, Cristian Soto Jacome, Jungwei W Fan, Oscar Josue Ponce-Ponte, Naykky M Singh Ospina, Juan P Brito","doi":"10.1177/10507256261493769","DOIUrl":"10.1177/10507256261493769","url":null,"abstract":"<p><strong>Background: </strong>Incidental thyroid nodules (ITNs) detected on nonthyroid imaging contribute to thyroid cancer overdiagnosis, largely through downstream evaluation initiated by thyroid ultrasound (TUS). However, TUS follow-up rates for ITNs and their drivers in routine practice remain unclear. We quantified TUS utilization after ITN detection and identified patient, imaging, nodule, and reporting factors associated with this first step in the diagnostic cascade.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study of adults without prior thyroid disease who underwent imaging that incidentally captured the thyroid at Mayo Clinic sites (2017-2023). A validated natural language processing pipeline identified ITNs and extracted nodule characteristics from radiology reports across multiple imaging modalities. The main outcome was the rate of TUS within 180 days after ITN detection. Clinical outcomes, including thyroid biopsy, thyroidectomy, and thyroid cancer diagnosis, were compared between patients who underwent TUS and those who did not. Factors associated with TUS utilization were assessed using multivariable logistic regression with penalized variable selection.</p><p><strong>Results: </strong>Among 115,683 patients who underwent thyroid-capturing imaging, 8426 (7.3%) had an ITN. These patients were predominantly female (64.6%) and White (89.7%), with a mean age of 61.7 years (standard deviation 15.2). Most nodules were detected on computed tomography (80.8%), most commonly from chest imaging (52.3%). Overall, 1677 patients with ITNs (19.9%) underwent TUS. In multivariable analysis, TUS use was independently associated with higher body mass index (odds ratio [OR], 1.20 per 10-unit increase; confidence interval [CI] [1.08-1.33]), nodule size ≥1.5 cm (OR, 1.79; CI [1.52-2.10]), and a radiologist recommendation (OR, 2.51; CI [2.12-2.98]), whereas older age was associated with lower odds of TUS (OR, 0.89 per 10-year increase; CI [0.84-0.93]). Patients undergoing TUS had higher rates of thyroid biopsy, partial thyroidectomy, and total thyroidectomy compared with those without it. All detected thyroid cancers (103 cases) occurred in the TUS group, representing 6.1% of that cohort.</p><p><strong>Conclusions: </strong>One in five patients with ITNs underwent TUS, representing a critical gateway to downstream diagnostic procedures and thyroid cancer detection. Factors associated with TUS utilization highlight opportunities to better define appropriateness of ultrasound after incidental nodule detection and to reduce unnecessary testing and treatment.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"1239-1246"},"PeriodicalIF":6.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149082125","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":"Locoregional Control and Toxicity of Neck Radiation with Field Reduction in Advanced Differentiated Thyroid Carcinoma: A Retrospective Cohort Study.","authors":"Justin Choi, Shuai Wang, Eric J Sherman, Edward Christopher Dee, Zhigang Zhang, Achraf Shamseddine, Yao Yu, Jennifer Ma, Nadeem Riaz, Sean McBride, Zeinab Abou Yehia, Alan L Ho, Lara Dunn, Winston Wong, R Michael Tuttle, James A Fagin, Mona Sabra, Stephanie Fish, Jennifer R Cracchiolo, Ian Ganly, Ashok R Shaha, Richard J Wong, Nancy Y Lee","doi":"10.1177/10507256261493011","DOIUrl":"10.1177/10507256261493011","url":null,"abstract":"<p><strong>Background: </strong>External beam radiotherapy (RT) is indicated for high-risk, gross residual, unresected, or recurrent differentiated thyroid cancer (DTC) when further surgery is not recommended. Although RT improves time to locoregional control (LRC), head and neck toxicities remain a significant concern. Whether field reduction can lessen toxicity while maintaining tumor control in advanced DTC remains undefined.</p><p><strong>Methods: </strong>In this retrospective cohort study, detailed RT plans were available for 284 of 327 consecutive nonanaplastic, nonmedullary DTC patients treated from 1999 to 2023 at a single tertiary center. Treatment fields were classified as: comprehensive (bilateral central compartment and bilateral necks), ipsilateral (central compartment plus ipsilateral neck), or central (central compartment only). Acute toxicities were defined as the worst grade within 90 days of RT start (CTCAE) and late toxicities thereafter (RTOG). Time to locoregional recurrence (LRR) was assessed using cumulative incidence functions, treating death without LRR as a competing risk. Overall median follow-up was 8.9 years (interquartile range 5.3-12.7 years).</p><p><strong>Results: </strong>Among 284 patients, 103 (36%) received comprehensive, 116 (41%) ipsilateral, and 65 (23%) central fields. Group differences in acute grade ≥ 2 toxicities were observed in xerostomia (36% comprehensive, 17% ipsilateral, 16% central, <i>p</i> = 0.002), dysphagia (58% comprehensive, 48% ipsilateral, 36% central, <i>p</i> = 0.02), voice changes (39% comprehensive, 22% ipsilateral, 28% central, <i>p</i> = 0.02) and fatigue (41% comprehensive, 28% ipsilateral, 22% central, <i>p</i> = 0.02). Also differing was late grade ≥ 2 dysphagia (23% comprehensive, 6% ipsilateral, 8% central, <i>p</i> = 0.0004). Percutaneous endoscopic gastrostomy tube placement was higher in comprehensive versus central (<i>p</i> = 0.0003) and ipsilateral (<i>p</i> = 0.019) fields. In-field failure rates were 11/103 (10.7%) for comprehensive, 11/116 (9.5%) for ipsilateral, and 5/65 (7.7%) for central fields, with no difference in LRC across groups (<i>p</i> = 0.88). Six patients with central RT developed out-of-field lateral neck recurrences, all successfully salvaged with surgery.</p><p><strong>Conclusions: </strong>Progressive RT field reduction in appropriately selected DTC patients was associated with significantly lower rates of acute and late toxicities without compromising LRC. These findings support individualized field selection and highlight the potential role of RT field de-escalation in this population. Prospective multicenter studies are needed to confirm these findings.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"1178-1189"},"PeriodicalIF":6.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137833","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":"TSH-Lowering Levothyroxine Therapy Is Associated with Higher rT3 and Stable fT3 Levels in Euthyroid Patients with Papillary Thyroid Microcarcinoma During Active Surveillance.","authors":"Yoshiki Furumura, Akira Miyauchi, Mitsuru Ito, Mitsushige Nishikawa, Nozomi Yamasaki, Hideyuki Iwayama, Masumi Iwasa, Masashi Yamamoto, Makoto Fujishima, Yasuhiro Ito, Takashi Akamizu","doi":"10.1177/10507256261484710","DOIUrl":"10.1177/10507256261484710","url":null,"abstract":"<p><strong>Background: </strong>We previously reported that lowering serum thyrotropin (TSH) levels with levothyroxine (LT4) during active surveillance (AS) of papillary thyroid microcarcinoma (PTMC) was associated with a trend toward a lower rate of disease progression. In euthyroid patients with PTMC managed with mild TSH-lowering therapy, free thyroxine (fT4) levels increased, whereas free triiodothyronine (fT3) levels remained unchanged overall, thereby raising questions regarding thyroid hormone metabolism. We therefore investigated thyroid hormone balance, with particular focus on thyroxine (T4) metabolism, including serum reverse triiodothyronine (rT3).</p><p><strong>Methods: </strong>This retrospective study included patients with PTMC undergoing AS who were initially euthyroid and treated with LT4. At the final follow-up, patients were classified according to the detailed TSH score: 209 in the low normal group (lower half of the reference range) and 110 in the high subnormal group (mildly subnormal range). Age- and sex-matched controls were selected from euthyroid PTMC patients undergoing AS who had not received LT4. TSH, fT4, fT3, triiodothyronine (T3), and rT3 levels were analyzed. TSH, fT4, and fT3 were measured using an electrochemiluminescence immunoassay, and T3 and rT3 were measured using liquid chromatography-tandem mass spectrometry.</p><p><strong>Results: </strong>Compared with matched controls, both the low normal and high subnormal groups showed significantly higher fT4 levels (<i>p</i> < 0.001), while fT3 levels did not differ significantly. The fT3/fT4 ratio was significantly lower, whereas the rT3 levels and the rT3/T3 ratio were significantly higher in both the low normal and high subnormal groups (all <i>p</i> < 0.001). In analyses combining the low normal and high subnormal groups, rT3 levels were significantly and positively correlated with fT4 (<i>r</i> = 0.51, <i>p</i> < 0.001), whereas no significant correlations were observed with TSH, fT3, or T3.</p><p><strong>Conclusions: </strong>In euthyroid patients with PTMC undergoing AS, LT4 therapy aimed at maintaining TSH within the lower half of the reference range or within the mildly subnormal range was associated with higher rT3 and stable fT3 levels. These findings raise the possibility of a compensatory buffering mechanism in thyroid hormone metabolism.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"1161-1168"},"PeriodicalIF":6.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866648","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}