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Reproductive Factors, Sex Hormone Levels, and Differentiated Thyroid Cancer Risk: A Mendelian Randomization Study. 生殖因素、性激素水平和分化性甲状腺癌风险:一项孟德尔随机研究。
IF 5.8 1区 医学
Thyroid Pub Date : 2025-04-01 Epub Date: 2025-03-26 DOI: 10.1089/thy.2024.0548
See Hyun Park, Pierre-Emmanuel Sugier, Yazdan Asgari, Mojgan Karimi, Rudolf Kaaks, Renée Turzanski Fortner, Matthias Schulze, Claudia Agnoli, Fabrizio Pasanisi, Carlotta Sacerdote, Miguel Rodriguez-Barranco, Amaia Aizpurua, Natalia Cabrera Castro, Marcela Guevara, Sandar Tin Tin, Elisabete Weiderpass, Florent de Vathaire, Fabienne Lesueur, Pascal Guénel, Claire Mulot, Pierre Laurent-Puig, Evgenia Ostroumova, Anne Boland-Auge, Jean-François Deleuze, Hauke Thomsen, Asta Försti, Rosella Elisei, Federica Gemignani, Stefano Landi, Sabina Rinaldi, Alexis Elbaz, Cloé Domenighetti, Thérèse Truong
{"title":"Reproductive Factors, Sex Hormone Levels, and Differentiated Thyroid Cancer Risk: A Mendelian Randomization Study.","authors":"See Hyun Park, Pierre-Emmanuel Sugier, Yazdan Asgari, Mojgan Karimi, Rudolf Kaaks, Renée Turzanski Fortner, Matthias Schulze, Claudia Agnoli, Fabrizio Pasanisi, Carlotta Sacerdote, Miguel Rodriguez-Barranco, Amaia Aizpurua, Natalia Cabrera Castro, Marcela Guevara, Sandar Tin Tin, Elisabete Weiderpass, Florent de Vathaire, Fabienne Lesueur, Pascal Guénel, Claire Mulot, Pierre Laurent-Puig, Evgenia Ostroumova, Anne Boland-Auge, Jean-François Deleuze, Hauke Thomsen, Asta Försti, Rosella Elisei, Federica Gemignani, Stefano Landi, Sabina Rinaldi, Alexis Elbaz, Cloé Domenighetti, Thérèse Truong","doi":"10.1089/thy.2024.0548","DOIUrl":"10.1089/thy.2024.0548","url":null,"abstract":"<p><p><b><i>Background:</i></b> Differentiated thyroid carcinoma (DTC) is occurring three times more frequently in females than in males. However, the underlying biological mechanisms driving this discrepancy remain poorly understood. To investigate the causal role of sex hormones and reproductive factors in the risk of DTC, we implemented a two-sample Mendelian randomization (MR) analysis. <b><i>Methods:</i></b> We utilized genome-wide association studies (GWAS) summary statistics to explore these associations. GWAS data on DTC were derived from a meta-analysis of six studies including 7705 cases and 963,612 controls of European ancestry. GWAS summary statistics on sex hormones, reproductive factors, and gynecological conditions were retrieved from publicly available sources. We used the inverse-variance weighted (IVW) method to estimate odds ratio (OR), with additional sensitivity analyses and conducted multivariable MR (MVMR) to account for potential confounding by body mass index (BMI) and thyrotropin (TSH). <b><i>Results:</i></b> We identified a positive association between sex hormone binding globulin (SHBG) and DTC (OR<sub>ivw</sub> = 1.13, <i>p</i> = 0.046). After controlling for TSH and BMI in a MVMR analysis, the strength of this association remained similar but lost statistical significance. Bioavailable testosterone also showed a positive but marginally significant association with DTC after adjustment for BMI in the MVMR (OR<sub>ivw</sub> = 1.13, <i>p</i> = 0.07). Putative causal association was observed with uterine fibroids in females under 50 years old (OR<sub>ivw</sub> = 1.52, <i>p</i> = 0.017). Endometrial cancer was associated with DTC (OR<sub>ivw</sub> = 1.15, <i>p</i> = 9.0 × 10<sup>-3</sup>); however, a genetic correlation of r<sup>2</sup> = 13% suggested potential pleiotropy. No significant associations were observed for other investigated factors. <b><i>Conclusions:</i></b> Our study does not provide strong evidence for a causal role of reproductive and hormonal factors in DTC risk, despite the observed sex disparity in incidence rates. The associations observed with SHBG, bioavailable testosterone, uterine fibroids, and endometrial cancer indicate potential risk factors, but further investigation is required.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"433-443"},"PeriodicalIF":5.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Controversies Surrounding IGF-I Receptor Involvement in Thyroid-Associated Ophthalmopathy. 围绕igf - 1受体参与甲状腺相关性眼病的争议。
IF 5.8 1区 医学
Thyroid Pub Date : 2025-03-01 Epub Date: 2025-02-05 DOI: 10.1089/thy.2024.0606
Terry J Smith
{"title":"Controversies Surrounding IGF-I Receptor Involvement in Thyroid-Associated Ophthalmopathy.","authors":"Terry J Smith","doi":"10.1089/thy.2024.0606","DOIUrl":"10.1089/thy.2024.0606","url":null,"abstract":"<p><p><b><i>Background:</i></b> Thyroid-associated ophthalmopathy (TAO, aka thyroid eye disease [TED], Graves' orbitopathy) remains poorly understood and inadequately treated since its initial description. It is disfiguring, can threaten vision, and represents an autoimmune process closely associated with thyroid disease. Unambiguous connections linking TAO to the glandular maladies of Graves' disease (GD) remain incompletely clarified. Detecting the thyrotropin receptor (TSHR) in periocular tissues suggests that this cell-surface protein represents a shared autoantigen with the thyroid gland, but we now know that its expression is ubiquitous. Most patients with TAO have relatively high circulating levels of activating anti-TSHR autoantibodies. Emerging more recently is the importance of insulin-like growth factor I receptor (IGF-IR) in the pathogenesis of TAO. The TSHR/IGF-IR signaling complex apparently drives circulating fibrocytes and the unique phenotypes of fibroblasts inhabiting the TAO orbit (GD-OF). <b><i>Methods:</i></b> The PubMed database was scanned for articles dating back to the earliest time periods covered. Keywords used for primary searches included thyroid-associated ophthalmopathy, Graves' orbitopathy, TED, orbit, TSH receptor, IGF-I receptor, and autoimmune thyroid disease. Secondary searches used numerous other search terms. <b><i>Results:</i></b> GD-OF have been characterized extensively as being particularly responsive to the immunological factors and key effectors in TAO pathogenesis. Both TSHR and IGF-IR are overexpressed by GD-OF and CD34<sup>+</sup> fibrocytes and form a signaling complex. They are activated through this TSHR/IGF-IR complex to produce large amounts of hyaluronan and express multiple cytokines. This complex mediates cellular responses to pathogenic IgGs in TAO. CD34<sup>+</sup> fibrocytes and CD34<sup>+</sup> OF also express relatively high levels of multiple thyroid autoantigens. Identifying IGF-IR as a key component of a receptor complex and its intertwining signaling activities with those of TSHR has led to a targeted medical therapy for TAO. This therapy involves the selective systemic inhibition of IGF-IR. <b><i>Conclusions:</i></b> Much has been learned over the preceding decades about the pathogenesis of TAO. Among these is the identification of IGF-IR as a pivotal component underpinning the disease. This has led directly to development of an effective targeted therapy. Important gaps in our understanding persist, and current therapies have limitations. Thus, despite these advancements, considerably more remains to be achieved.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"232-244"},"PeriodicalIF":5.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Letter to the Editor: Does Thermal Ablation of Thyroid Nodules Increase the Complexity of Subsequent Thyroidectomy? 致编辑的信:甲状腺结节热消融是否会增加后续甲状腺切除术的复杂性?
IF 5.8 1区 医学
Thyroid Pub Date : 2025-03-01 Epub Date: 2025-02-05 DOI: 10.1089/thy.2025.0002
Xinxin Zhao, Ye Yang
{"title":"<i>Letter to the Editor:</i> Does Thermal Ablation of Thyroid Nodules Increase the Complexity of Subsequent Thyroidectomy?","authors":"Xinxin Zhao, Ye Yang","doi":"10.1089/thy.2025.0002","DOIUrl":"10.1089/thy.2025.0002","url":null,"abstract":"","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"338-339"},"PeriodicalIF":5.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Radiofrequency Ablation for Solitary Autonomously Functioning Thyroid Nodules: Multicenter Study from Latin America. 射频消融治疗独立自主功能甲状腺结节:来自拉丁美洲的多中心研究。
IF 5.8 1区 医学
Thyroid Pub Date : 2025-03-01 Epub Date: 2024-12-19 DOI: 10.1089/thy.2024.0338
Juan Pablo Dueñas, Nathalia Buitrago-Gómez, Antonio Rahal, Jose Higinio Steck, Cristhian García, Rafael De Cicco, Leonardo G Rangel, Ana Voogd, Lorena Savluk, Erivelto Martinho Volpi
{"title":"Radiofrequency Ablation for Solitary Autonomously Functioning Thyroid Nodules: Multicenter Study from Latin America.","authors":"Juan Pablo Dueñas, Nathalia Buitrago-Gómez, Antonio Rahal, Jose Higinio Steck, Cristhian García, Rafael De Cicco, Leonardo G Rangel, Ana Voogd, Lorena Savluk, Erivelto Martinho Volpi","doi":"10.1089/thy.2024.0338","DOIUrl":"10.1089/thy.2024.0338","url":null,"abstract":"<p><p><b><i>Background:</i></b> Autonomously functioning thyroid nodules (AFTNs) represent ∼5% of all thyroid nodules and often necessitate definitive treatments such as surgery or radioiodine (<sup>131</sup>I), both of which have inherent risks. Radiofrequency ablation (RFA) has emerged as an effective and safe therapeutic option for managing AFTNs. This study aims to assess the effectiveness and safety of RFA for solitary AFTNs in various countries across Latin America. <b><i>Methods:</i></b> This retrospective, observational, multicenter cohort study included patients with a solitary AFTN that was histologically confirmed as benign and treated with a single session of RFA. The study included an analysis of patient demographics, sonographic characteristics of the nodules, thyroid profile assessment at each follow-up visit, evaluation of clinical symptoms to determine the achievement of a euthyroid state, and the measurement of nodule volume reduction. In addition, a bivariate analysis was conducted to identify associations between these variables and the resolution of hyperthyroidism. <b><i>Results:</i></b> Our study enrolled 81 patients with a solitary, benign AFTN. The volume reduction ratio (VRR) consistently increased over the follow-up period, with medians of -50%, -74.9%, -78.4%, and -90.2% at 1, 3, 6, and 12 months, respectively. The rate of resolution of hyperthyroidism was 93.8% (76/81). Following the RFA procedure, 58.02% of patients (47/81) normalized their thyrotropin levels within 1 month of follow-up, and by 3 months, an additional 33.3% had achieved normalization (27/81). Notably, a baseline volume ≥10, 20, or 30 mL did not affect the achievement of clinical success. In bivariate analyses, a VRR ≥50% at the 6-month follow-up was associated with the resolution of hyperthyroidism. Overall complications occurred in 6.2% of patients (5/81), including 1.2% (1/81) of a major complication (transient Horner syndrome), 3.7% cases of transient dysphonia (3/81), and 1.2% (1/81) of hypothyroidism requiring low-dose levothyroxine replacement. <b><i>Conclusions:</i></b> The results of this multicenter study suggest that RFA is a promising treatment option for patients with solitary AFTN, regardless of their baseline characteristics, including volume, age, or composition. The clinical success of the intervention may be related to the VRR at 6 months.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"283-290"},"PeriodicalIF":5.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Epidemiological Landscape of Thyroid Cancer and Estimates of Overdiagnosis in China: A Population-Based Study. 中国甲状腺癌的流行病学概况和过度诊断估计:一项基于人群的研究。
IF 5.8 1区 医学
Thyroid Pub Date : 2025-03-01 Epub Date: 2025-02-19 DOI: 10.1089/thy.2024.0583
Qixun Zhu, Junli Liu, Junrong Hu, Yanting Zhang
{"title":"The Epidemiological Landscape of Thyroid Cancer and Estimates of Overdiagnosis in China: A Population-Based Study.","authors":"Qixun Zhu, Junli Liu, Junrong Hu, Yanting Zhang","doi":"10.1089/thy.2024.0583","DOIUrl":"10.1089/thy.2024.0583","url":null,"abstract":"<p><p><b><i>Background:</i></b> In China, thyroid cancer (TC) is the most common cancer in females and the fifth most common cancer in males. TC overdiagnosis leads to overtreatment, lifelong medical care, and side effects. This study systematically quantifies the epidemiological profile of TC incidence in China, as well as estimating TC incidence attributable to overdiagnosis. <b><i>Methods:</i></b> Data were derived from the Cancer Incidence in Five Continents databases. Age-standardized incidence rates (ASIRs) per 100,000 person-years were calculated using the world standard population. Joinpoint regression and age-period-cohort models were conducted to examine temporal ASIR trends and period effects, respectively. We estimated TC incidence attributable to overdiagnosis among patients aged 15-84 years by comparing shapes of age-specific curves with those observed before diagnostic practices. <b><i>Results:</i></b> In 2013-2017, there were 37,862 and 117,979 new TC cases in males and females in China, respectively, with ASIRs of 6.9/100,000 and 21.1/100,000. Significant upward trends were observed from 1993 to 2017, with average annual percent changes being 14.7% for males and 16.2% for females. Incidence rate ratios of period effects markedly increased from 1.0 to 61.8 for males and from 1.0 to 42.9 for females from 1993 to 2017. Overdiagnosis accounted for 83.5% (31,455/37,685) and 88.7% (104,222/117,509) of cases in males and females in 2013-2017, respectively, yielding ASIRs of 5.9/100,000 and 19.1/100,000. ASIRs attributable to overdiagnosis in urban populations (6.9/100,000 for males and 21.7/100,000 for females) were significantly higher than in rural populations (1.3/100,000 and 6.4/100,000). Among the 25 included provinces, ASIRs attributable to overdiagnosis ranged from 0.3/100,000 in Sichuan to 18.5/100,000 in Shanghai in males and from 0.1/100,000 in Shanxi to 49.4/100,000 in Shanghai in females. The national ASIRs attributable to overdiagnosis increased from 2.6/100,000 in 2008-2012 to 5.9/100,000 in 2013-2017 for males and from 9.2/100,000 to 19.1/100,000 for females. <b><i>Conclusions:</i></b> The incidence rates of TC have considerably increased over the past 25 years in China. Rapidly increasing trends and considerable geographic variations in TC incidence attributable to overdiagnosis highlight the need to adjust TC screening strategies and clinical practices, optimize healthcare resource allocation, and monitor the impacts of TC overdiagnosis on population-level health.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"307-320"},"PeriodicalIF":5.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Thyroid Nodules with Indeterminate Cytology and Negative Molecular Profile: Prevalence of Malignancy and Practice Paradigms for Surveillance. 不确定细胞学和阴性分子特征的甲状腺结节:恶性肿瘤的患病率和监测的实践范例。
IF 5.8 1区 医学
Thyroid Pub Date : 2025-03-01 Epub Date: 2025-01-28 DOI: 10.1089/thy.2024.0455
Sapir Nachum, Isabella Tondi Resta, Zubair Baloch, Susan J Mandel
{"title":"Thyroid Nodules with Indeterminate Cytology and Negative Molecular Profile: Prevalence of Malignancy and Practice Paradigms for Surveillance.","authors":"Sapir Nachum, Isabella Tondi Resta, Zubair Baloch, Susan J Mandel","doi":"10.1089/thy.2024.0455","DOIUrl":"10.1089/thy.2024.0455","url":null,"abstract":"<p><p><b><i>Background:</i></b> In the era of molecular testing, thyroid nodules with indeterminate cytology are increasingly being managed nonoperatively. The false-negative rates of these molecular tests, and therefore missed malignancies, are not well defined in real-world clinical practice. <b><i>Methods:</i></b> This retrospective study of patients undergoing fine needle aspiration (FNA) biopsy at our health system between November 2017 and March 2022 included nodules with The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) III and IV cytology and negative, currently negative, or negative but limited ThyroSeq version 3 (TSv3) results. Surgical pathology of resected nodules, as well as details of ultrasound (US) surveillance practices, was recorded. A range of prevalence of malignancy (PoM) estimates were calculated based on all nodules (PoM low) and surgically resected nodules (PoM high). <b><i>Results:</i></b> The study cohort consisted of 556 nodules. TSv3 results were distributed as 443 (80%) negative, 85 (15%) currently negative, and 28 (5%) negative but limited. Overall, 75 nodules were resected: 54 nodules (9.7%) had immediate surgery, and 21 nodules (3.8%) had delayed surgery after surveillance imaging. Currently negative and negative but limited nodules were more likely to undergo immediate surgical resection compared with negative nodules (20%, 18%, and 7%, respectively, <i>p</i> < 0.001). The PoM in molecularly benign TBSRTC III and IV thyroid nodules ranged between 3% and 23% depending on the inclusion of all versus resected nodules. TBSRTC IV molecularly benign nodules had a higher PoM than TBSRTC III (PoM low 7.3% vs. 1.6%, <i>p</i> < 0.001; PoM high 48% vs. 13%, <i>p</i> = 0.0013). In the 90% of nodules that were managed nonoperatively, 63% had at least one surveillance US. Timing of initial surveillance US ranged from 3 to 60 months (median 13 months, interquartile [IQR] 11-19 months). Median follow-up duration was 25 months (IQR 17-34 months). Nodule growth occurred in 24% of nodules; only a minority (7%) underwent repeat FNA. <b><i>Conclusions:</i></b> Negative subtype of TSv3 should be considered in clinical management recommendations. For negative but limited samples, repeat FNA should be performed. Optimal surveillance strategy for nonresected negative and currently negative nodules remains unknown. Until further real-world data are available, surveillance ultrasonography is recommended for TSN and TSCN nodules, similar to the ATA guidelines for TBSRTC II nodules.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"265-273"},"PeriodicalIF":5.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Is Radioactive Iodine Contraindicated in Patients with Moderate-to-Severe and Active Graves' Orbitopathy? 中重度活动性Graves眼病患者是否禁忌使用放射性碘?
IF 5.8 1区 医学
Thyroid Pub Date : 2025-03-01 Epub Date: 2025-02-12 DOI: 10.1089/thy.2025.0059
Luigi Bartalena, Maria Laura Tanda
{"title":"Is Radioactive Iodine Contraindicated in Patients with Moderate-to-Severe and Active Graves' Orbitopathy?","authors":"Luigi Bartalena, Maria Laura Tanda","doi":"10.1089/thy.2025.0059","DOIUrl":"10.1089/thy.2025.0059","url":null,"abstract":"","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"230-231"},"PeriodicalIF":5.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Biphasic Effect of Thyroid Hormone on Megakaryopoiesis and Platelet Production. 甲状腺激素对巨核生成和血小板生成的双相影响。
IF 5.8 1区 医学
Thyroid Pub Date : 2025-03-01 Epub Date: 2024-12-18 DOI: 10.1089/thy.2024.0361
Baichuan Xu, Xianpeng Ye, Zhaoyang Wen, Jun Chen, Mo Chen, Mingqiang Shen, Yang Xu, Junping Wang, Shilei Chen
{"title":"Biphasic Effect of Thyroid Hormone on Megakaryopoiesis and Platelet Production.","authors":"Baichuan Xu, Xianpeng Ye, Zhaoyang Wen, Jun Chen, Mo Chen, Mingqiang Shen, Yang Xu, Junping Wang, Shilei Chen","doi":"10.1089/thy.2024.0361","DOIUrl":"10.1089/thy.2024.0361","url":null,"abstract":"<p><p><b><i>Background:</i></b> Abnormal platelet counts are frequently observed in patients with thyroid dysfunction; however, the direct impact of thyroid hormones on thrombopoiesis remains largely undefined. <b><i>Methods:</i></b> This study elucidates the dose-response effect of the thyroid hormone triiodothyronine (T<sub>3</sub>) on megakaryocyte (MK) development and thrombopoiesis using both a murine model of hyperthyroidism/hypothyroidism and <i>in vitro</i> cultures of human cord blood CD34<sup>+</sup> cell-derived MKs. After the application of inhibitors to MKs, the examination of total and phosphorylated protein levels of the phosphoinositide 3-kinase (PI3K)/AKT pathway was utilized to assess the specific mechanisms of T<sub>3</sub> action. The use of autophagy dual-staining lentivirus and transmission electron microscopy was employed to evaluate the impact of T<sub>3</sub> on the autophagy flux in MKs. Mouse whole-body irradiation and bone marrow transplantation models are applied to assess the influence of T<sub>3</sub> on the recovery of MKs/platelets <i>in vivo</i>. <b><i>Results:</i></b> We found that physiological or slightly elevated thyroid hormone levels are essential for sustaining MK development and thrombopoiesis, primarily through the TRα-PI3K/AKT signaling pathway. In contrast, supraphysiological thyroid hormone concentrations induce MK apoptosis via excessive autophagy, thereby reducing platelet production. <b><i>Conclusions:</i></b> Here, we present evidence that the thyroid hormone influences MK development and platelet production in a concentration-dependent manner, exhibiting a dualistic role. Our discoveries shed new light on the intricate relationship between thyroid hormones and platelet formation, offering novel perspectives on the pathophysiological consequences of thyroid disorders.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"321-334"},"PeriodicalIF":5.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ablative Versus Conservative Approach for Hyperthyroidism Treatment in Patients with Graves' Orbitopathy: A Retrospective Cohort Study. 消融与保守治疗甲状腺机能亢进Graves眼病:一项回顾性队列研究。
IF 5.8 1区 医学
Thyroid Pub Date : 2025-03-01 Epub Date: 2025-02-05 DOI: 10.1089/thy.2024.0633
Giada Cosentino, Giulia Lanzolla, Simone Comi, Maria Novella Maglionico, Chiara Posarelli, Dalì Antonia Ciampa, Francesca Menconi, Roberto Rocchi, Francesco Latrofa, Michele Figus, Ferruccio Santini, Michele Marinò
{"title":"Ablative Versus Conservative Approach for Hyperthyroidism Treatment in Patients with Graves' Orbitopathy: A Retrospective Cohort Study.","authors":"Giada Cosentino, Giulia Lanzolla, Simone Comi, Maria Novella Maglionico, Chiara Posarelli, Dalì Antonia Ciampa, Francesca Menconi, Roberto Rocchi, Francesco Latrofa, Michele Figus, Ferruccio Santini, Michele Marinò","doi":"10.1089/thy.2024.0633","DOIUrl":"10.1089/thy.2024.0633","url":null,"abstract":"<p><p><b><i>Background:</i></b> Treatment for Graves' hyperthyroidism (GH) in patients with Graves' orbitopathy (GO) remains a topic of debate. This study aimed to investigate the outcome of GO following glucocorticoids, depending on the chosen thyroid treatment. <b><i>Methods:</i></b> This retrospective cohort study included 49 consecutive patients with GH and moderate-to-severe, active GO, as defined by the European Group on Graves' Orbitopathy guidelines. Twenty-four patients were treated with radioactive iodine (RAI) and 25 with methimazole (MMI). All patients were administered intravenous methylprednisolone. Follow-up visits occurred at weeks 24, 48, and 72. The primary endpoint was the overall outcome of GO at week 24. Response was defined as a change in at least two of the following eye features: reduction ≥1 point in clinical activity score; proptosis reduction ≥2 mm; eyelid aperture reduction ≥2 mm; increase in eye ductions ≥8 degrees. <b><i>Results:</i></b> Follow-up duration was 72 weeks for both groups (interquartile range 66-72 for RAI and 48-72 for MMI). The proportion of responders for week 24 overall GO outcome was greater in RAI (54.1% vs. 16%; odds ratio [OR] 6.2 [confidence interval (CI): 1.6-23.6], <i>p</i> = 0.0075), but it increased in MMI at weeks 48 and 72, with no differences between groups. There was a trend indicating a better response in RAI regarding individual eye features. Improvement in GO-specific quality of life questionnaire at week 24 was trendily more pronounced in RAI (responders 50% vs. 28% in MMI; OR = 2.5 [CI: 0.7-8.4], <i>p</i> = 0.11), although results were similar in both groups at later time points. At week 24, only one patient (4%) in RAI and three (12%) in MMI experienced worsening of GO. Fifty-nine adverse events were recorded among 36 patients, with no differences between groups, except for infections, which were more frequent in RAI (53.8% vs. 15.3% in MMI; OR = 6.41 [CI: 1.7-23.9], <i>p</i> = 0.0056). <b><i>Conclusions:</i></b> RAI appears to be associated with an earlier response of GO to intravenous glucocorticoids. In the long term, a conservative approach also seems to be effective. RAI appears to be relatively safe when patients are concurrently treated with glucocorticoids. However, randomized clinical trials are necessary to confirm these findings.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"298-306"},"PeriodicalIF":5.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
International Women's Day: An Occasion for a Tribute to Women Leaders in the American Thyroid Association. 国际妇女节:向美国甲状腺协会妇女领袖致敬的场合。
IF 5.8 1区 医学
Thyroid Pub Date : 2025-03-01 Epub Date: 2025-02-20 DOI: 10.1089/thy.2025.0073
Jacqueline Jonklaas
{"title":"International Women's Day: An Occasion for a Tribute to Women Leaders in the American Thyroid Association.","authors":"Jacqueline Jonklaas","doi":"10.1089/thy.2025.0073","DOIUrl":"10.1089/thy.2025.0073","url":null,"abstract":"","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"227-229"},"PeriodicalIF":5.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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