ThyroidPub Date : 2025-01-31DOI: 10.1089/thy.2024.0624
Sanjay Rao, Mary C Frates, Carol B Benson, Christine E Cherella, Jessica R Smith, Ari J Wassner
{"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":"https://doi.org/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":""},"PeriodicalIF":5.8,"publicationDate":"2025-01-31","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}
ThyroidPub Date : 2025-01-27DOI: 10.1089/thy.2024.0595
Alexander Papachristos, Lydia Zhou, Amy Sheen, Mark Sywak, Bruce Robinson, Roderick Clifton-Bligh, Stan Sidhu, Anthony J Gill
{"title":"Tumor-Infiltrating Lymphocytes Assessed Using the International TILs Working Group System Are Not Prognostic in Medullary Thyroid Cancer.","authors":"Alexander Papachristos, Lydia Zhou, Amy Sheen, Mark Sywak, Bruce Robinson, Roderick Clifton-Bligh, Stan Sidhu, Anthony J Gill","doi":"10.1089/thy.2024.0595","DOIUrl":"https://doi.org/10.1089/thy.2024.0595","url":null,"abstract":"<p><p><b><i>Background:</i></b> Tumor-infiltrating lymphocytes (TILs) are a protective prognostic factor in several solid tumors and predict response to immune checkpoint inhibitor therapy. The prognostic impact of TILs in medullary thyroid cancer (MTC) is poorly understood. <b><i>Materials and Methods:</i></b> In this retrospective cohort study, we assessed the TILs profile of primary MTC tumors using the International TILs Working Group system and correlated this with clinicopathological prognostic variables, including the International Medullary Thyroid Cancer Grading System (IMTCGS) grade and survival outcomes. <b><i>Results:</i></b> We identified 71 patients with primary MTC tumors who were treated surgically between 1995 and 2016 at the Royal North Shore Hospital in Sydney, Australia. The median (interquartile range) duration of follow-up was 69 (90) months. Using the ITWG system, all patients with MTC had low TILs, with a median (range) of 3% (0-10%). This group was further subdivided into \"very low\" (0-4%) and \"low\" (5-10%), and on Cox regression analysis, increasing TILs were associated with increased local recurrence (log-rank <i>p</i> = 0.022, odds ratio [OR] 1.94 [confidence interval or CI 0.61-6.16], <i>p</i> = 0.26), reduced disease-specific survival (log-rank <i>p</i> = 0.015, OR 5.11 [CI 1.01-26.0], <i>p</i> = 0.049), and a trend to decreased distant metastasis-free survival (log-rank <i>p</i> = 0.14). When examining the association between TILs and other prognostic factors, only \"high IMTCGS grade\" was significantly associated with increased TILs (OR 7.29 [CI 1.21-43.90], <i>p</i> = 0.015). In the multivariable logistic regression analysis, there was no significant association between TILs and local recurrence or disease-specific survival. <b><i>Conclusions:</i></b> In our study, the prognostic value of TILs in MTC was limited. Even high-grade MTC can be considered an immune quiescent tumor, and the adverse prognostic factors associated with higher grade tumors outweigh the marginal increase in immune recognition associated with a slight increase in TILs. The low level of TILs in MTC and their lack of correlation with survival suggest that immune checkpoint inhibitor therapy may not be effective.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047899","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}
ThyroidPub Date : 2025-01-27DOI: 10.1089/thy.2024.0266
Hyunjong Byun, Han Sai Lee, Young Shin Song, Young Joo Park
{"title":"Transcriptome of Anaplastic Thyroid Cancer Reveals Two Molecular Subtypes with Distinct Tumor Microenvironment and Prognosis.","authors":"Hyunjong Byun, Han Sai Lee, Young Shin Song, Young Joo Park","doi":"10.1089/thy.2024.0266","DOIUrl":"https://doi.org/10.1089/thy.2024.0266","url":null,"abstract":"<p><p><b><i>Background:</i></b> Although patients with anaplastic thyroid cancer (ATC) generally have a poor prognosis and there are currently no effective treatment options, survival and response to therapy vary between patients. Genomic and transcriptomic profiles of ATC have been reported; however, a comprehensive study of the tumor microenvironment (TME) of ATC is still lacking. This study aimed to elucidate the TME characteristics associated with ATC and their prognostic implications. <b><i>Methods:</i></b> We analyzed bulk RNA transcriptomic data from 1,634 samples-including 476 normal thyroid tissues, 25 benign thyroid adenomas, 340 <i>RAS</i>-like and 719 <i>BRAF</i><sup>V600E</sup>-like differentiated thyroid cancers (DTC-R and DTC-B, respectively), and 74 ATCs. We assessed the TME and molecular characteristics of these thyroid cancer subtypes using deconvolution analysis. <b><i>Results:</i></b> The TME of ATC was characterized by a high abundance of immune cells and fibroblasts and a low abundance of epithelial cells compared to other thyroid histologies. During its malignant evolution, ATC exhibited an ecotype more closely related to DTC-B than <i>RAS</i>-like DTC (DTC-R). Furthermore, we identified two distinct molecular subtypes within ATC with significant differences in their TMEs. We termed the subtype with increased immune cells and fibroblasts as ATC-immune-fibroblast (ATC-IF) and the subtype with elevated epithelial and endothelial cells as ATC-epithelial-endothelial (ATC-E). The ATC-IF group had worse disease-specific survival (log-rank <i>p</i> = 0.035), higher ERK scores, and lower thyroid differentiation scores than the ATC-E group. While both ATC subtypes had elevated immune cells and fibroblasts compared to DTC-R and DTC-B, this increase was more pronounced in ATC-IF, with a marked rise in myeloid lineage cells and promigratory fibroblasts. Immune checkpoint gene expression and epithelial-mesenchymal transition scores were significantly higher in the ATC-IF group than in the ATC-E group. <b><i>Conclusion:</i></b> ATC shows a TME distinct from that of DTC and can be further divided into two molecular subtypes-each with its own unique TME. The ATC-IF group, with a poorer prognosis and higher ERK score, is enriched in immune cells and fibroblasts, which may represent potential therapeutic targets.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047888","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}
ThyroidPub Date : 2025-01-01Epub Date: 2025-01-08DOI: 10.1089/thy.2024.0690
David Toro-Tobon, Naykky Singh Ospina, Juan P Brito
{"title":"Thyroid Cancer Risk with GLP-1 Receptor Agonists: Evidence, Knowledge Gaps, and the Path Forward.","authors":"David Toro-Tobon, Naykky Singh Ospina, Juan P Brito","doi":"10.1089/thy.2024.0690","DOIUrl":"10.1089/thy.2024.0690","url":null,"abstract":"","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"3-5"},"PeriodicalIF":5.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955425","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}
ThyroidPub Date : 2025-01-01Epub Date: 2024-12-04DOI: 10.1089/thy.2024.0495
Sarah Hamidi, Sireesha Yedururi, Mimi I Hu, Naifa L Busaidy, Steven I Sherman, Camilo Jimenez, Elizabeth G Grubbs, Anastasios Maniakas, Mark E Zafereo, Vivek Subbiah, Steven G Waguespack
{"title":"Efficacy and Safety of Selective RET Inhibitors in Patients with Advanced Hereditary Medullary Thyroid Carcinoma.","authors":"Sarah Hamidi, Sireesha Yedururi, Mimi I Hu, Naifa L Busaidy, Steven I Sherman, Camilo Jimenez, Elizabeth G Grubbs, Anastasios Maniakas, Mark E Zafereo, Vivek Subbiah, Steven G Waguespack","doi":"10.1089/thy.2024.0495","DOIUrl":"10.1089/thy.2024.0495","url":null,"abstract":"<p><p><b><i>Background:</i></b> Two selective RET inhibitors (RETis) are effective in treating <i><u>RE</u>arranged during <u>T</u>ransfection</i> (<i>RET</i>)-altered medullary thyroid carcinoma (MTC), but clinical trials did not distinguish responses between hereditary MTC (hMTC) and sporadic MTC (sMTC) cases. We reviewed our single-center experience using a RETi to treat advanced hMTC. <b><i>Methods:</i></b> We conducted a retrospective cohort study of patients with hMTC treated with a selective RETi at a tertiary cancer center. The primary outcome was overall response rate using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary end points included overall survival (OS), progression-free survival (PFS), biochemical response rate, and safety. <b><i>Results:</i></b> We identified 23 evaluable patients as follows: 15 (65%) multiple endocrine neoplasia (MEN)2A and 8 (35%) MEN2B. Median age at start of RETi was 51 years (range, 15-79). All patients had distant metastases, and 52% (12/23) had received prior systemic therapy (median = 1, range, 0-3). Patients were treated with selpercatinib (<i>n</i> = 13) or pralsetinib (<i>n</i> = 10), 57% (13/23) within a clinical trial. Median duration of RETi was 25 months (range, 3-72) with 11/23 (48%) patients remaining on drug at data cutoff due to an ongoing response. Median duration of follow-up was 49 months (range, 9-72). Best radiographical response was partial response in 18 (78%) and stable disease in 5 (22%) patients. Median OS was 51 months (confidence interval, 40.5-61.3); median PFS was not reached. Most common adverse events (AEs) were increased alanine aminotransferase (ALT) (48%) and aspartate aminotransferase (26%), dry mouth (39%), QT interval prolongation (39%), fatigue (35%), and hypertension (26%). AEs led to dose reductions in eight (35%) patients. No grade 5 treatment-related AEs occurred. While the germline nature of the <i>RET</i> pathogenic variant in hMTC could hypothetically result in increased drug-related toxicity, the incidence of most AEs, other than grade 1-2 ALT elevation and QT interval prolongation, was comparable to published clinical trials. <b><i>Conclusions:</i></b> In patients with advanced hMTC, selective RETis appear safe and effective with outcomes similar to clinical trial cohorts, which mostly comprised patients with sMTC. Duration of response and AE profile was similar to sMTC, although longer follow-up and larger patient numbers are needed to confirm this.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"6-17"},"PeriodicalIF":5.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781047","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}
ThyroidPub Date : 2025-01-01Epub Date: 2024-12-19DOI: 10.1089/thy.2024.0312
Marina Kunstreich, Cecile M Ronckers, Kerstin Lorenz, Saskia H Wolf, Lienhard Lessel, Tilman R Rohrer, Christian Vokuhl, Kurt W Schmid, Markus Luster, Michael C Frühwald, Peter Vorwerk, Antje Redlich, Michaela Kuhlen
{"title":"Subsequent Thyroid Carcinomas in Children and Adolescents Registered in the German MET Consortium (1997-2023).","authors":"Marina Kunstreich, Cecile M Ronckers, Kerstin Lorenz, Saskia H Wolf, Lienhard Lessel, Tilman R Rohrer, Christian Vokuhl, Kurt W Schmid, Markus Luster, Michael C Frühwald, Peter Vorwerk, Antje Redlich, Michaela Kuhlen","doi":"10.1089/thy.2024.0312","DOIUrl":"10.1089/thy.2024.0312","url":null,"abstract":"<p><p><b><i>Introduction:</i></b> Among childhood cancer survivors, the cumulative incidence rate of differentiated thyroid carcinomas (DTCs) is estimated to be 8-11%. Although the association of DTC with prior radiotherapy is well-studied, the association with chemotherapy remains less understood. Most studies focused on young adults, leaving a knowledge gap on subsequent DTC occurring in childhood and adolescence. <b><i>Methods:</i></b> In this retrospective cohort study, we analyzed DTCs in children and adolescents under 18 years of age who were registered with the national multicenter Malignant Endocrine Tumor studies in Germany (1997-2023). We compared patients with first primary DTC to those with subsequent DTC that developed after a history of childhood cancer or hematopoietic stem cell transplantation (HSCT). In the subsequent DTC subgroup, we compared DTCs following chemotherapy only to those following chemo- and radiotherapy. <b><i>Results:</i></b> Of 505 patients with DTCs, 66 (13.1%) (38 male, 28 female) were subsequent DTCs. The median age at subsequent DTC diagnosis was 12.7 years (range, 5.1-17.9), with a median latency of 7.3 years (range, 2.2-15.6) from the first malignancy or HSCT. The 5-year overall survival (OS) and thyroid-related adverse event-free survival (EFS) estimates from the diagnoses of a subsequent DTC were 100.0% and 82.5%, respectively. Prior treatment included chemotherapy in 64 patients, with 18 receiving chemotherapy alone. In all, 46 subsequent DTC patients had a history of external radiotherapy, including 2 treated with radiotherapy only and 14 with total body irradiation. Two patients received <sup>131</sup>I-metaiodobenzylguanidine treatment. Subsequent DTCs versus first DTCs were smaller in size but more frequently multifocal. Subsequent DTCs following chemotherapy only, compared with chemo- and radiotherapy, developed after a shorter latency (median 6.2 vs. 7.8 years), and were larger (median 1.86 vs. 1.18 cm). Patients with subsequent DTCs following chemotherapy only were younger at diagnosis (median 11.5 vs. 13.7 years). No differences were observed for OS and EFS. <b><i>Conclusions:</i></b> Presenting features of subsequent DTCs differ from primary counterparts, although the prognosis is not significantly different. Subsequent DTCs following chemotherapy only versus chemo- and radiotherapy DTCs were larger and diagnosed in younger patients after a shorter latency. More research is needed to identify risk factors and mechanisms potentially contributing to thyroid tumorigenesis post-chemotherapy.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"18-30"},"PeriodicalIF":5.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855453","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}
ThyroidPub Date : 2025-01-01Epub Date: 2025-01-08DOI: 10.1089/thy.2024.0387
Sarah M Baxter, Lars Christian Lund, Jacob H Andersen, Thomas H Brix, Laszlo Hegedüs, Miyuki Hsing-Chun Hsieh, Chris Tzu-Ting Su, Michael Chun-Yuan Cheng, Zoe Chi-Jui Chang, Edward Chia-Cheng Lai, Swaleh Hussain, Cherry Chu, Tara Gomes, Tony Antoniou, Antoine Eskander, Zachary Bouck, Mina Tadrous, Sungho Bea, Eun-Young Choi, Ju-Young Shin, Karin Modig, Mats Talbäck, Rickard Ljung, Hanne Løvdal Gulseth, Øystein Karlstad, Blánaid Hicks, Anton Pottegård
{"title":"Glucagon-Like Peptide 1 Receptor Agonists and Risk of Thyroid Cancer: An International Multisite Cohort Study.","authors":"Sarah M Baxter, Lars Christian Lund, Jacob H Andersen, Thomas H Brix, Laszlo Hegedüs, Miyuki Hsing-Chun Hsieh, Chris Tzu-Ting Su, Michael Chun-Yuan Cheng, Zoe Chi-Jui Chang, Edward Chia-Cheng Lai, Swaleh Hussain, Cherry Chu, Tara Gomes, Tony Antoniou, Antoine Eskander, Zachary Bouck, Mina Tadrous, Sungho Bea, Eun-Young Choi, Ju-Young Shin, Karin Modig, Mats Talbäck, Rickard Ljung, Hanne Løvdal Gulseth, Øystein Karlstad, Blánaid Hicks, Anton Pottegård","doi":"10.1089/thy.2024.0387","DOIUrl":"10.1089/thy.2024.0387","url":null,"abstract":"<p><p><b><i>Introduction:</i></b> Concerns have been raised that glucagon-like peptide 1 receptor agonists (GLP1-RAs) may increase the risk of thyroid cancer, but evidence remains conflicting. We therefore investigated if GLP1-RA use, compared with use of dipeptidyl peptidase-4 inhibitors (DPP-4is), was associated with thyroid cancer risk in patients with type 2 diabetes. <b><i>Methods:</i></b> This multisite cohort study with subsequent meta-analysis included six population-based databases from Canada (Ontario), Denmark, Norway, South Korea, Sweden, and Taiwan. Study populations comprised patients with type 2 diabetes between 2007 and 2023. Cox regression models estimated hazard ratios (HR) and 95% confidence intervals (CIs) for thyroid cancer among GLP1-RA users compared with DPP-4is. Models were weighted using standardized mortality ratio weights generated from time-specific propensity scores. Site-specific HRs were pooled using a fixed-effects model. <b><i>Results:</i></b> We identified 98,147 users of GLP1-RA and 2,488,303 users of DPP-4i, with the median follow-up among users of GLP1-RA ranging from 1.8 to 3.0 years. Overall, use of GLP1-RA relative to use of DPP-4i was not associated with an increased risk of thyroid cancer (pooled weighted HR 0.81, CI 0.59-1.12). Similarly, we observed no increased risk in thyroid cancer with increasing cumulative dose of GLP1-RA among GLP1-RA ever-users. Subgroup analysis of types of thyroid cancer was not possible. Results remained consistent across a range of supplementary analyses. <b><i>Discussion:</i></b> In this large multisite study, utilizing data from six population-based databases, we found no evidence that GLP1-RA use is associated with an increased risk of thyroid cancer with follow-up ranging from 1.8 to 3.0 years, providing some reassurance to patients and clinicians about the short-term safety of these drugs. Nevertheless, evidence was insufficient to rule out excess risk with long-term use, due to the short follow-up.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"69-78"},"PeriodicalIF":5.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955407","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}
ThyroidPub Date : 2025-01-01Epub Date: 2024-12-18DOI: 10.1089/thy.2024.0405
Murat Faik Erdoğan, Adile Begüm Bahçecioğlu, Fatma Avcı Merdin, Atilla Halil Elhan, Rıfat Emral, Sevim Güllü
{"title":"Changes in the Volume and Diameter of Benign Thyroid Nodules: A 10-Year Follow-Up Study.","authors":"Murat Faik Erdoğan, Adile Begüm Bahçecioğlu, Fatma Avcı Merdin, Atilla Halil Elhan, Rıfat Emral, Sevim Güllü","doi":"10.1089/thy.2024.0405","DOIUrl":"10.1089/thy.2024.0405","url":null,"abstract":"<p><p><b><i>Background:</i></b> The incidence of asymptomatic thyroid nodules has risen enormously, with > 90% being benign. Despite limited long-term data, significant nodule growth (SNG) is common. Guidelines recommend cytology reevaluation if SNG occurs. Our study aimed to identify the rate and factors associated with SNG, compare diameter and volume-based assessments, and examine the association between SNG and malignancy risk over the long term (10 years). <b><i>Methods:</i></b> The retrospective cohort study, conducted at Ankara University, School of Medicine, Department of Endocrinology and Metabolism, included 732 nodules from 376 euthyroid patients, all monitored over a 10-year period by the same experienced sonographer, with evaluations at baseline, 5th and 10th years. The nodules were cytologically benign and/or sonographically in the low-to-intermediate risk category. Size changes at the 5th and 10th years were considered significant if there was a 20% or 2 mm increment in two diameters according to diameter-based criterion (DBC) or 50% increment in volume-based criterion (VBC) designed by the ellipsoid formula. Generalized linear mixed-effects models were used to account for the clustered data structure and analyze factors affecting nodule growth. Nodule growth was the dependent variable, while sex, age at diagnosis, initial TSH level, total nodule count, nodule volume, echogenicity, and localization were independent variables. <b><i>Results:</i></b> At the 5th and 10th years, SNG frequencies were higher when calculated using VBC [27.7% (<i>n</i> = 203) and 44% (<i>n</i> = 321), respectively] compared with DBC [19.1% (<i>n</i> = 140) and 35% (<i>n</i> = 256), respectively], with the differences being statistically significant (McNemar test, <i>p</i> < 0.01). Factors associated with SNG included being younger than 45 years of age (VBC OR = 1.704, CI = 1.227-2.366, <i>p</i> = 0.002; DBC OR = 1.913, CI = 1.379-2.656, <i>p</i> < 0.001), having higher number of nodules (VBC: OR = 1.171, CI = 1.061-1.291, <i>p</i> = 0.002; DBC: OR = 1.147, CI = 1.040-1.265, <i>p</i> = 0.006), and having smaller nodule volume (VBC: OR = 0.870, CI = 0.806-0.940, <i>p</i> < 0.001; DBC: OR = 0.912, CI = 0.850-0.978, <i>p</i> = 0.010). Thyroid cancer was diagnosed in four original nodules (0.5%), whereas the malignancy rate in biopsies performed was 1.4% (<i>n</i> = 4). <b><i>Conclusions:</i></b> In long-term follow-ups of sonographically and/or cytologically benign thyroid nodules, SNG is not rare. Growth is more likely in younger patients, those with higher number of nodules and smaller nodules. In the follow-up of nodule size, VBCs yield augmented results compared with DBCs. However, malignancy is quite rare in growing nodules. Therefore, adopting flexible long-term follow-up protocols appears to be practical for benign nodular thyroid disease.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"31-40"},"PeriodicalIF":5.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847631","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}
ThyroidPub Date : 2025-01-01Epub Date: 2024-12-16DOI: 10.1089/thy.2024.0345
Guanghui Hu, Junyu Xue, Ju Yu, Qianyi Dou, Ye Sang, Anjia Han, Weiming Lv, Jie Li, Rengyun Liu
{"title":"High Prevalence of <i>TBC1D12</i> 5'UTR Mutations in Anaplastic Thyroid Cancer.","authors":"Guanghui Hu, Junyu Xue, Ju Yu, Qianyi Dou, Ye Sang, Anjia Han, Weiming Lv, Jie Li, Rengyun Liu","doi":"10.1089/thy.2024.0345","DOIUrl":"10.1089/thy.2024.0345","url":null,"abstract":"<p><p><b><i>Background:</i></b> Anaplastic thyroid cancer (ATC) is a rare but one of the most lethal types of human cancer. Although increasing evidence demonstrated that ATC tumors had a high mutation burden, little is known about the aberrancy of the noncoding genome of ATC except the well-investigated <i>telomerase reverse transcriptase</i> (<i>TERT</i>) promoter mutations. <b><i>Methods:</i></b> The mutational statuses of <i>TBC1D12</i> 5' untranslated region (5'UTR), <i>GPR126</i> intron 6, <i>SDHD</i> and <i>PLEKHS1</i> promoters, as well as the <i>TERT</i> promoter and <i>BRAF<sup>V600E</sup></i> mutations were determined using Sanger sequencing in 28 patients with ATC (19 women and 9 men) with a median (interquartile range) age of 64 (55-71) years, 14 thyroid cancer cell lines and a normal thyroid cell line. The prevalence of <i>TBC1D12</i> 5'UTR mutations in papillary thyroid cancer (PTC) and their association with clinicopathologic characteristics were explored by analyzing The Cancer Genome Atlas thyroid cancer dataset. <b><i>Results:</i></b> The noncoding mutations in <i>TERT</i>, <i>SDHD</i> and <i>PLEKHS1</i> promoters, <i>TBC1D12</i> 5'UTR, and <i>GPR126</i> intron 6 were collectively found in 82.1% (23/28) of ATC samples. Specifically, <i>TERT</i> promoter mutations were detected in 22 (78.6%) samples; <i>GPR126</i> intron mutations were detected in 2 (7.1%) samples; and both <i>SDHD</i> and <i>PLEKHS1</i> promoter mutations were detected in 1 (3.6%) ATC sample. Two hotspot mutations in <i>TBC1D12</i> 5'UTR were observed in 14 of 28 (50%) ATCs, 7 of 492 (1.4%) PTCs, and 1 cell line derived from ATC. <i>TBC1D12</i> 5'UTR mutations were significantly associated with older age at diagnosis (60 vs. 46 for wild type, <i>p</i> = 0.003), pathological T3/T4 stage (85.7% vs. 37.7%, <i>p</i> = 0.010), and advanced tumor stages (85.7% vs. 32.5%, <i>p</i> = 0.006) in PTC. <b><i>Conclusions:</i></b> This preliminary study for the first time showed a high prevalence of <i>TBC1D12</i> 5'UTR mutations in ATC and indicated an association between <i>TBC1D12</i> mutation and aggressive characteristics of PTC, which needs to be confirmed in large cohort studies.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"115-119"},"PeriodicalIF":5.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839729","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}
ThyroidPub Date : 2025-01-01Epub Date: 2024-12-18DOI: 10.1089/thy.2024.0522
Sang Yi Moon, Minkook Son, Jung-Hwan Cho, Hye In Kim, Ji Min Han, Ji Cheol Bae, Sunghwan Suh
{"title":"Association Between Metabolic Dysfunction-Associated Steatotic Liver Disease and Thyroid Cancer.","authors":"Sang Yi Moon, Minkook Son, Jung-Hwan Cho, Hye In Kim, Ji Min Han, Ji Cheol Bae, Sunghwan Suh","doi":"10.1089/thy.2024.0522","DOIUrl":"10.1089/thy.2024.0522","url":null,"abstract":"<p><p><b><i>Background:</i></b> Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a hepatic manifestation of metabolic syndrome. This study investigated the association between newly developed nomenclature MASLD and the risk of thyroid cancer in the Korean population. <b><i>Methods:</i></b> After excluding individuals with a history of liver disease or malignancy, we analyzed a cohort of 214,502 Korean adults aged 40 years and above who participated in the National Health Screening Program from 2009 to 2010. Participants were categorized into four groups: no steatotic liver disease (SLD) without a cardiometabolic risk factor (CMRF), no SLD with at least one CMRF, MASLD, and metabolic and alcohol-related/associated liver disease (MetALD). SLD was diagnosed using a fatty liver index threshold of ≥30. The primary outcome was the diagnosis of new thyroid cancer during the follow-up period. We examined the relationship between CMRF/SLD and thyroid cancer incidence using the multivariable-adjusted Cox proportional hazards model. <b><i>Results:</i></b> A total of 2761 participants (1.3%) were newly diagnosed with thyroid cancer over an average follow-up of 9.61 years. Compared with participants without CMRF and SLD, those with CMRF (hazard ratio [HR] 1.33, confidence interval [CI] 1.16-1.52), those with MASLD (HR 1.36, CI 1.17-1.58), and the MetALD group (HR 1.40, CI 1.04-1.88) exhibited a significantly higher risk of thyroid cancer. In addition, MetALD is significantly associated with thyroid cancer incidence solely in men. <b><i>Conclusions:</i></b> In addition to CMRF, MASLD and MetALD were associated with a higher incidence of thyroid cancer in the Korean population. This study is the first to demonstrate the association between thyroid cancer and the CMRF-MASLD-MetALD continuum.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"79-86"},"PeriodicalIF":5.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847627","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}