Thyroid最新文献

{"title":"<i>Letter to the Editor:</i> Molecular Testing: Adoption and Disparities in Utilization Across the United States.","authors":"Catherine B Jensen, Susan C Pitt","doi":"10.1089/thy.2024.0357","DOIUrl":"10.1089/thy.2024.0357","url":null,"abstract":"","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"1317-1318"},"PeriodicalIF":5.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141451617","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":"BRAF^V600E/p-ERK/p-DRP1(Ser616) Promotes Tumor Progression and Reprogramming of Glucose Metabolism in Papillary Thyroid Cancer.","authors":"Shi-Shuai Wen, Yi-Jun Wu, Jia-Yang Wang, Zhao-Xian Ni, Shuai Dong, Xiao-Jun Xie, Yu-Ting Wang, Yu Wang, Nai-Si Huang, Qing-Hai Ji, Ben Ma, Ning Qu","doi":"10.1089/thy.2023.0700","DOIUrl":"10.1089/thy.2023.0700","url":null,"abstract":"<p><p><b><i>Background:</i></b> Papillary thyroid cancer (PTC) with the BRAF^V600E mutation is associated with a poorer prognosis. BRAF inhibitors may demonstrate limited efficacy due to emerging drug resistance. The Warburg effect may have cancer therapeutic implications. It is not known if the BRAF^V600E mutation is associated with altered glucose metabolism in PTC. <b><i>Methods:</i></b> This study examined the effect of BRAF^V600E and dynamin-related protein 1 (DRP1) on various cellular processes in PTC cells, including cell proliferation, migration, invasion, mitochondrial fission, glucose metabolism, reactive oxygen species (ROS) generation, and apoptosis. We used RT-qPCR to assess the expression of key glycolytic enzymes in thyroid cancer tissues. Additionally, the regulatory interaction between BRAF^V600E and DRP1 was investigated through Western blot and immunohistochemical staining. We further evaluated the impact of DRP1 in PTC and the inhibitory effects of dabrafenib and 2-deoxy-d-glucose (2-DG) <i>in vitro</i> and <i>in vivo</i>. <b><i>Results:</i></b> We found that the BRAF^V600E mutation significantly augments aerobic glycolysis while suppressing oxidative phosphorylation in PTC. We identified the BRAF^V600E/p-ERK/p-DRP1(Ser616) signaling pathway as a critical mediator in PTC progression. First, the BRAF^V600E/p-ERK/p-DRP1(Ser616) signaling pathway enhances cell proliferation by upregulating hexokinase 2 expression and thereby increasing aerobic glycolysis. Second, it inhibits apoptosis by promoting mitochondrial fission and reducing ROS levels. Moreover, we demonstrated that the combination therapy of 2-DG and dabrafenib markedly impedes the progression of BRAF^V600E-positive PTC. <b><i>Conclusion:</i></b> The BRAF^V600E/p-ERK/p-DRP1(Ser616) signaling pathway plays a pivotal role in glucose metabolism reprogramming, contributing to the aggressiveness and progression of BRAF^V600E-positive PTC. Our findings suggest that a combined therapeutic approach using 2-DG and dabrafenib has the potential to improve the outcome of PTC patients with BRAF^V600E.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"1246-1259"},"PeriodicalIF":5.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Association Between Hypothyroidism and Cognitive Function Change in Women across the Menopause Transition: The Study of Women's Health Across the Nation.","authors":"Matthew D Ettleson, Kelly Karavolos, Sherri-Ann M Burnett-Bowie, Lynda H Powell, Imke Janssen","doi":"10.1089/thy.2024.0358","DOIUrl":"10.1089/thy.2024.0358","url":null,"abstract":"<p><p><b><i>Background:</i></b> Patients treated for hypothyroidism with levothyroxine (LT4) monotherapy may present with persistent hypothyroidism symptoms, including cognitive symptoms, despite having a normal thyroid stimulating hormone (TSH) level. It remains unclear whether LT4 monotherapy is sufficient to normalize cognitive function outcomes over time. <b><i>Methods:</i></b> This is a multisite longitudinal study of a diverse group of women during midlife representing 5 ethnic/racial groups from 7 enrollment sites across the United States in the Study of Women's Health Across the Nation. Women were screened for a history of thyroid disease and the use of LT4. The study consisted of two primary groups: women with LT4-treated hypothyroidism and control women without thyroid disease. Each participant completed up to 9 cognitive assessments over the study period testing processing speed, working memory, and episodic memory (immediate and delayed recall). Multivariable generalized linear mixed models of scores for each cognitive assessment were developed to determine the association between LT4-treated hypothyroidism and cognitive function trajectories. Covariates included sociodemographic, clinical characteristics, and menopausal status (pre/early peri, late peri, and surgical/post). Sensitivity analyses were conducted to assess the impact of abnormal TSH levels and practice effects (i.e., improvements in scoring after repeated testing). <b><i>Results:</i></b> Of the 2033 women who were included in the study, 227 (11.2%) met criteria for LT4-treated hypothyroidism. At baseline, both processing speed and working memory scores were higher in LT4-treated women (mean processing speed scores: 56.5 vs 54.4; <i>p</i> value = 0.006; mean working memory scores: 6.8 vs 6.4; <i>p</i> value = 0.018). However, when considering the effect of LT4-treated hypothyroidism over time, there were no significant differences in the rate of cognitive decline (in any measure) between the hypothyroidism and control groups with or without covariate adjustment. The results were similar when considering LT4-treated women with abnormal TSH levels or after minimizing practice effects. <b><i>Conclusions:</i></b> We observed no difference in cognitive decline between women with LT4-treated hypothyroidism and women without thyroid disease. For similar aged patients with cognitive complaints, if thyroid function testing is normal, clinicians should consider causes other than inadequate thyroid hormone treatment to explain these symptoms.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"1205-1213"},"PeriodicalIF":5.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120673","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":"Comparison of Patient Reported Outcomes between Active surveillance and Immediate Lobectomy in Patients with Low-risk Papillary Thyroid Microcarcinoma: Initial Findings from the KoMPASS cohort.","authors":"Min Joo Kim,Hojeong Won,Won Bae Kim,Eun Kyung Lee,Chang Yoon Lee,Sun Wook Cho,Han-Sang Baek,Yong Sang Lee,Yae Eun Kang,Sun Wook Kim,Ho Cheol Kang,Jeongmin Lee,Mijin Kim,Min Ji Jeon,Jae Hoon Moon","doi":"10.1089/thy.2024.0264","DOIUrl":"https://doi.org/10.1089/thy.2024.0264","url":null,"abstract":"BACKGROUNDPatients diagnosed with low-risk papillary thyroid microcarcinoma (PTMC) face the decision between thyroid lobectomy and active surveillance (AS). This study aimed to investigate the factors influencing treatment decisions in low-risk PTMC and to compare the quality of life (QoL) according to the treatment plan.METHODSThe multicenter prospective cohort study comparing AS and thyroid lobectomy was conducted. Clinical characteristics were compared between the AS and Lobectomy groups. QoL questionnaires were administered every 6 months in the initial year and annually thereafter.RESULTSA total of 927 patients (453 in the AS group and 474 in the Lobectomy group) with low-risk PTMC were included in this study. The mean age was 47.4 ± 12.2 years, and 72.2% of the patients were women. Older age (odd ratio [OR] 1.04, 95% confidence interval [CI] 1.02 - 1.05, p <0.001), smaller tumor size (OR 0.78, 95% CI 0.69 - 0.87, p <0.001), family history of thyroid cancer (OR 1.48, 95% CI 1.03 - 2.12, p = 0.035), prior awareness of AS (OR 1.53, 95% CI 1.16 - 2.02, p = 0.003), and higher income (OR 1.79, 95% CI 1.13 - 2.83, p = 0.013) were significantly associated with a higher likelihood of choosing AS. The median follow-up was 27.3 months (23.9 - 43.9) in the AS group and 28.7 months (20.4 - 44.5) in the Lobectomy group. During the follow-up period, the AS group showed significantly better QoL scores compared to the Lobectomy group (β 0.17, 95% CI 0.02 - 0.33, p = 0.029). Although baseline QoL scores favored the AS group significantly (7.1 ± 1.2 vs. 6.7 ± 1.2, p < 0.001), no significant difference was observed after 12 months (7.2 ± 1.2 vs. 7.1 ± 1.2, p =0.592).CONCLUSIONSThis study demonstrated that age, tumor size, family history of thyroid cancer, awareness of AS, and income were associated with patients' treatment choices. Although the overall QoL scores were significantly higher in the AS group, the QoL became similar between the two groups after 12 months.","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":"16 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249483","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":"Consideration of Early Dynamic Risk Stratification to Guide Discharge from Oncologic Follow-up in Patients with Differentiated Thyroid Cancer.","authors":"Amina Attia,Eliane Touma,Charlotte Lussey-Lepoutre,Cécile Ghander,Anne Jouinot,Malanie Roy,Selma Housni,Nathalie Chereau,Fabrice Menegaux,Laurence Leenhardt,Camille Buffet","doi":"10.1089/thy.2024.0119","DOIUrl":"https://doi.org/10.1089/thy.2024.0119","url":null,"abstract":"BACKGROUNDThe current dogma is a life-long follow-up for patients treated for follicular-derived differentiated thyroid cancers (DTC). Our primary objective was to determine the time to recurrence in a series of DTC patients with an excellent response to therapy 6 months after total thyroidectomy and radioiodine therapy. The secondary objectives were to determine the time to suspicion of recurrence and to identify factors associated with recurrence.METHODSThis retrospective cohort study included patients treated for DTC between 2008 and 2012 and in remission 6 months after total thyroidectomy and radioiodine treatment. The criteria for remission were negative imaging and suppressed thyroglobulin (Tg) < 0.2 ng/mL or rh-TSH-(recombinant human TSH) stimulated Tg < 1 ng/mL according to the 2015 ATA (American Thyroid Association) guidelines. Recurrence was defined by cytologically and/or histologically proven cervical lymph node metastasis or the administration of a second radioiodine treatment.RESULTSAmong 721 patients treated for DTC, 158 were excluded because of persistent disease at 6 months and 71 because of missing follow-up data and 492 were included. The mean and median follow-up time were 7.0 and 7.9 years [IQR 2.1-11.3]. Recurrence occurred for 7 patients (1.4%), 1 initially classified as high recurrence risk, 3 as intermediate and 3 as low risk according to the 2015 ATA guidelines. All relapses occurred within 10 years after initial management (4 within the first 5 years). For patients with recurrence, rise in Tg and/or suspicious lymph node were detected in 6 out of 7 cases in the first 8 years, and for the last case 10 years after initial surgery.CONCLUSIONLow and intermediate recurrence risk DTC patients with excellent response 6 months after total thyroidectomy and radioiodine and in remission 10 years later have an extremely low recurrence risk. Follow-up might be undertaken by primary care providers from this time point. These discharge recommendations should be confirmed by further prospective studies.","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":"195 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249482","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 of Progression of Gestational Subclinical Hypothyroidism and Hypothyroxinemia to Overt Hypothyroidism After Pregnancy is Associated with Underlying Thyroid Autoimmunity.","authors":"Stacy Hander, Sun Y Lee","doi":"10.1089/thy.2024.0435","DOIUrl":"10.1089/thy.2024.0435","url":null,"abstract":"","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"1066-1067"},"PeriodicalIF":5.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894370","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":"Cardiac Electrical and Structural Changes after Iodinated Contrast Media Administration: A Longitudinal Cohort Analysis.","authors":"Kosuke Inoue, Muhammad T Bashir, Alberta L Warner, Ramin Ebrahimi, Natalia V Neverova, Jesse W Currier, Seo Young Sohn, Connie M Rhee, Martin L Lee, Angela M Leung","doi":"10.1089/thy.2024.0131","DOIUrl":"10.1089/thy.2024.0131","url":null,"abstract":"<p><p><b><i>Background:</i></b> Iodinated contrast is commonly used for radiological procedures, with one dose delivering several hundred-fold the daily requirements needed for normal thyroid hormone production. Risks of excess iodine include incident thyroid dysfunction, which is associated with adverse cardiac outcomes, yet there are no prospective studies investigating the changes in cardiac physiology following iodine contrast administration. This study was conducted to investigate the longitudinal relationships between the amount of iodinated contrast administration and changes in cardiac electrophysiology and structure. <b><i>Methods:</i></b> A longitudinal cohort study was conducted with prospectively enrolled participants who received iodine contrast for elective computed tomography or coronary angiography. Serum thyroid function tests, electrocardiograms (EKG), and transthoracic echocardiograms were obtained serially until 36 months. Trends of electrical and structural cardiac changes following iodine contrast administration were assessed using mixed effect models. <b><i>Results:</i></b> The cohort was composed of 129 patients (median age, 70 [interquartile range: 63, 75] years; 98% male). Larger amounts of iodine exposure were associated with increases in QRS and QTc durations and decreased ejection fraction (EF), and these associations were still observed for follow-up EF after additionally adjusting for baseline values (the high-iodine contrast group vs. the low-iodine contrast group, -4.23% [confidence interval, -7.66% to -0.79%]). Dose-response analyses also showed lower EF with larger amounts of iodine received; these trends were not significant for the EKG parameters studied. <b><i>Conclusions:</i></b> Over a period of up to 36 months, a larger amount of administered iodine contrast was associated with lower EF among participants. Further investigation is needed to elucidate the long-term trends of electrical and structural cardiac function after iodine contrast administration.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"1163-1170"},"PeriodicalIF":5.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005339","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":"Thyroid Hormone Replacement Dosing after Bariatric Surgery in Patients with Primary Hypothyroidism And Severe Obesity: Tehran Obesity Treatment Study.","authors":"Maryam Barzin, Danial Molavizadeh, Maryam Mahdavi, Alireza Khalaj, Sara Sadeghi, Majid Valizadeh, Fereidoun Azizi, Farhad Hosseinpanah","doi":"10.1089/thy.2024.0073","DOIUrl":"10.1089/thy.2024.0073","url":null,"abstract":"<p><p><b><i>Background:</i></b> Obesity and hypothyroidism are common medical conditions that are associated with each other. Bariatric surgery (BS) is a common approach used to achieve substantial weight loss in obese patients. However, there is limited evidence regarding the need for postsurgery levothyroxine (LT4) dose adjustment in patients with hypothyroidism undergoing BS. <b><i>Methods:</i></b> This was a three-year prospective cohort study assessing postsurgery LT4 requirements with attention to body composition changes. The current study included 1030 patients with hypothyroidism, who underwent sleeve gastrectomy (SG) (<i>n</i> = 707, 88.3% women) or one anastomosis gastric bypass (OAGB) (<i>n</i> = 323, 92% women). Patients were followed for 36 months after surgery. A bioelectrical impedance analyzer was used for body composition assessment. LT4 requirements were assessed by generalized estimating equation (GEE) methods adjusted for weight as a time-varying covariate. <b><i>Results:</i></b> During the follow-up, TSH (mIU/L) and T4 (ng/dL) measurements did not significantly change in the OAGB group over time. However, in the SG group, TSH measurement decreased over time (<i>p_trend</i> = <0.001). In the third year of the follow-up, 56.1% and 33.3% of patients in the SG and OAGB groups experienced LT4 (μg/day) dose reduction, while 24.4% and 9.1% of the participants experienced LT4 dose increments, respectively. GEE analysis showed a significant increase in the LT4/fat mass (FM) (μg/kg) ratio after 36 months of follow-up compared with the baseline in both the SG [1.8 (1.5-2.2) to 2.7 (2.0-3.5), <i>p_trend</i> = 0.039)] and OAGB [1.7 (1.4-2.2) to 3.2 (2.7-4.8), <i>p_trend</i> = <0.001)] groups. Moreover, patients who underwent OAGB experienced greater LT4/FM (μg/kg) dose adjustments compared to those undergoing SG (<i>p_between</i> = 0.060). In both groups, after the first year, the increase in LT4/FM (μg/kg) plateaued (<i>p_interaction</i> = 0.009). <b><i>Conclusion:</i></b> Most hypothyroid patients experienced either a reduction or no change in LT4 (μg/day) dosage after 36 months in both surgical groups. The LT4/FM (μg/kg) was significantly increased in patients undergoing either SG or OAGB with greater alterations in the latter. Further studies on larger populations and with longer duration of follow-up are needed to confirm our results.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"1105-1116"},"PeriodicalIF":5.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000719","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":"Prevalence and Management of Complications of Percutaneous Ethanol Injection for Cystic Thyroid Nodules: A Systematic Review of Literature and Meta-analysis.","authors":"Lorenzo Scappaticcio, Pamela Ferrazzano, Nicole Di Martino, Roberto Negro, Maurilio Deandrea, Maria Ida Maiorino, Paola Caruso, Michela Di Nuzzo, Miriam Longo, Giovanni Docimo, Giampaolo Papi, Pierpaolo Trimboli, Katherine Esposito, Giuseppe Bellastella","doi":"10.1089/thy.2024.0241","DOIUrl":"10.1089/thy.2024.0241","url":null,"abstract":"<p><p><b><i>Background:</i></b> We assessed the prevalence of complications from percutaneous ethanol injection (PEI) for benign and cystic thyroid nodules (CTNs) and their management. <b><i>Methods:</i></b> We conducted a systematic review with meta-analysis of data from published observational studies on PEI of CTNs. We also included unpublished retrospectively collected data on complications after PEI from all consecutive patients with cytologically benign CTNs who underwent PEI at the Unit of Endocrinology and Metabolic Diseases, AOU University of Campania Luigi Vanvitelli (Naples, Italy) between June 1, 2021, and March 31, 2024. A random effects meta-analysis was performed on the prevalence rate data. Pooled prevalence data were presented with confidence intervals (CIs). The <i>I</i>² statistic index was used to quantify the heterogeneity. The details of the complications and the management were qualitatively described. <b><i>Results:</i></b> The literature search yielded 1189 studies, of which 48 studies were included in the systematic review and meta-analysis, in addition to our institutional experience (3670 CTNs in total). The overall quality of each included study was judged as fair. The prevalence of \"Overall\" complications of PEI was 32% ([CI 25-40%], <i>I</i>² 92.7%, 967 of 3195 thyroid nodules [TNs]). The prevalence of \"Minor\" complications of PEI was 32% ([CI 25-40%], <i>I</i>² 92.7%, 952 of 3195 TNs). The prevalence of \"Major\" complications of PEI was 2% ([CI 1-2%], <i>I</i>² 0%, 22 of 3670 TNs). Sensitivity analyses did not modify the results. The pooled prevalence rate of local pain was 21% (CI [16-27] <i>I</i>² 90.3). Local pain was typically transient and mild, sometimes moderate, and requiring analgesics for few days. The pooled prevalence rate of dysphonia was 1% (CI [1-2], <i>I</i>² 0). Dysphonia was transient and could last from several hours to 12 months after PEI. <b><i>Conclusions:</i></b> Complications of PEI for benign and CTNs are relatively common, but most are minor and usually transient, not requiring treatment. Dysphonia was a major complication, but it was uncommon and transient. PEI for CTNs could be considered a generally safe technique.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"1068-1081"},"PeriodicalIF":5.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731422","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>FGFR</i> Alterations in Thyroid Carcinoma: A Novel Class of Primary Drivers with Significant Therapeutic Implications and Secondary Molecular Events Potentially Mediating Resistance in Thyroid Malignancy.","authors":"Mark F Sabbagh, Tyler Janovitz, Dora Dias-Santagata, Stephanie Siegmund, Valentina Nardi, Lori J Wirth, Gregory W Randolph, Jochen K Lennerz, Brennan Decker, Vania Nose, Bayan A Alzumaili, William C Faquin, Justine A Barletta, Long P Le, A John Iafrate, Peter M Sadow, Adam S Fisch","doi":"10.1089/thy.2024.0216","DOIUrl":"10.1089/thy.2024.0216","url":null,"abstract":"<p><p><b><i>Background:</i></b> Diagnostic classification of thyroid malignancy is primarily accomplished through examination of histomorphological features and may be substantiated and clarified by molecular data. Individual molecular drivers show relatively robust and specific associations with histological subtypes of thyroid malignancy, including <i>BRAF</i> sequence variants and kinase gene fusions in papillary thyroid carcinoma, predominantly <i>RAS</i> variants in follicular-patterned neoplasia, and additional \"late\" mutations affecting <i>TERT</i> promoter, <i>TP53</i>, and the PI3K/AKT/PTEN pathway in high-grade malignancies. Given the oncogenic role of <i>FGFR</i>, particularly <i>FGFR1-3</i>, the goal of this study was to explore the role of <i>FGFR</i> in thyroid carcinoma biology. <b><i>Methods:</i></b> We completed a multicenter retrospective observational study for thyroid carcinomas with pathogenic alterations in the <i>FGFR</i> gene family. We performed this study by querying the molecular data accumulated for thyroid carcinomas from each center. <b><i>Results:</i></b> Overall, 5030 sequenced thyroid malignancies were reviewed, yielding 17 tumors with <i>FGFR</i> alterations, including 11 where <i>FGFR</i> was the primary molecular driver and 6 where <i>FGFR</i> was a secondary pathogenic alteration, with a subset for which there was available clinical follow-up data. Of the 11 carcinomas with an <i>FGFR</i> driver, 9 were gene fusions involving <i>FGFR2:VCL</i> (4 tumors), <i>TG::FGFR1</i> (3 tumors), <i>FGFR2::CIT</i>, and <i>FGFR2::SHTN1</i>, and the remaining 2 were driven by <i>FGFR1</i> amplification. In the 6 tumors where a canonical driver of thyroid neoplasia was present (5 cases) or no clear primary driver was detected (1 case), sequencing detected secondary <i>FGFR2</i> p.W290C, p.Y375C, and p.N549K, as well as <i>FGFR1</i> p.N546K in the respective tyrosine kinase domains, some at subclonal variant allele frequencies. <b><i>Conclusions:</i></b> This study presents the first description of a collection of thyroid carcinomas grouped by primary driver alterations in <i>FGFR</i>, as well as a cohort of thyroid tumors with secondary alterations that potentially lead to tumor progression or resistance to targeted therapy. Given the availability of small molecular inhibitors targeting oncogenic <i>FGFR</i>, this study emphasizes the significant implications for patients from identification of <i>FGFR</i> alterations as they are currently under-recognized in the literature and, most importantly, have potential novel treatment options.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"1137-1149"},"PeriodicalIF":5.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604140","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}