Thyroid最新文献

{"title":"Two Different Shades of Anaplastic Thyroid Cancer.","authors":"Iñigo Landa","doi":"10.1089/thy.2025.0097","DOIUrl":"https://doi.org/10.1089/thy.2025.0097","url":null,"abstract":"","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664359","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":"A Retrospective Case-Control Study Examining the Association of Thyroid-Stimulating Hormone Suppression and Vascular Wall Inflammation on [¹⁸F]FDG-PET/CT.","authors":"Holger Einspieler, Bengt Hennig, Bettina Reiterits, Hannah Klimpfinger, Marcus Hacker, Georgios Karanikas","doi":"10.1089/thy.2024.0476","DOIUrl":"https://doi.org/10.1089/thy.2024.0476","url":null,"abstract":"<p><p><b><i>Background:</i></b> This retrospective case-control study aimed to investigate the effects of thyroid-stimulating hormone (TSH) suppression on vascular wall inflammation, assessed by [¹⁸F]-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT). Vascular [¹⁸F]FDG-uptake is highly correlated with arterial inflammation, which represents a major risk factor for atherosclerotic plaques. <b><i>Methods:</i></b> Forty patients with differentiated thyroid cancer underwent [¹⁸F]FDG-PET/CTs under TSH suppression therapy following surgical removal of the thyroid and subsequent radioiodine ablation. The [¹⁸F]FDG-uptake was measured in the carotid arteries, aortic arch, and the ascending, descending, and abdominal aorta. All measurements in the PET scans were normalized to body weight and corrected for blood pool activity in the superior vena cava, creating target-to-background ratios (TBRs). Twenty-five patients with euthyroid hormone status were used as a control group. In addition, to evaluate long-term changes, the follow-up PET/CTs of 24 thyroid carcinoma patients under continued TSH suppression therapy were analyzed. <b><i>Results:</i></b> In patients with TSH suppression, significantly higher arterial [¹⁸F]FDG-uptake (<i>p</i> < 0.001) was observed in the ascending aorta, aortic arch, abdominal aorta, carotid artery, and for all arterial vessels combined (mean TBR_max ± standard deviation [SD]: 1.8 ± 0.4, 1.8 ± 0.3, 1.9 ± 0.4, 1.4 ± 0.3, 1.7 ± 0.2, respectively) compared with the euthyroid control group (TBR_max ± SD: 1.4 ± 0.2, 1.4 ± 0.2, 1.4 ± 0.2, 1.1 ± 0.2, 1.3 ± 0.1, respectively). In the subgroup of patients who received an additional follow-up scan after a mean duration of 1.9 ± 1.1 years of continued TSH suppression therapy, no significant changes in arterial [¹⁸F]FDG-uptake were found in the five arterial sites when both scans were compared over time (<i>p</i> > 0.05). <b><i>Conclusions:</i></b> Our study suggests that patients under TSH suppression may experience a significant increase in vascular [¹⁸F]FDG-uptake, a marker of arterial inflammation, and, therefore, might be at higher risk for cardiovascular disease. Interestingly, the duration of TSH suppression was not significantly associated with vascular [¹⁸F]FDG-uptake in our study, indicating that the observed increase in arterial inflammation may not be influenced by the duration of TSH suppression.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Maternal Thyroid Hormone Concentration with Normal Thyroid Function During Pregnancy and Preschoolers' Glycolipid Metabolism: A Birth Cohort Study.","authors":"Wenjin Cai, Lu Chen, Manyu Zhang, Jiajun Ouyang, Penggui Wu, Juan Tong, Guopeng Gao, Shuangqin Yan, Fangbiao Tao, Kun Huang","doi":"10.1089/thy.2024.0334","DOIUrl":"https://doi.org/10.1089/thy.2024.0334","url":null,"abstract":"<p><p><b><i>Background:</i></b> Thyroid hormones (THs) are essential endocrine hormones that play key roles in individual's growth and development. There is limited knowledge about the association between maternal TH concentrations variations with normal thyroid function during pregnancy and offspring's glycolipid metabolism. <b><i>Methods:</i></b> A total of 1130 mother-child pairs from the Ma'anshan birth cohort were included in this prospective study. Maternal TH levels and thyroid peroxidase antibodies were measured in the 1st, 2nd, and 3rd trimesters of pregnancy during the childhood follow-up period. Fasting venous blood was collected from children at 4-6 years of age and glycolipid metabolic indicators were assayed. Analyses were performed using Binary logistic regression models, linear regression models, and Generalized linear regression model. <b><i>Results:</i></b> Maternal TH trajectories were fitted via latent category growth models. During the 1st trimester of pregnancy, maternal T3 and free thyroxine (fT4) levels were positively associated with children's blood glucose levels (β = 0.007 [CI 0.028-0.181]; β = 0.022 [CI 0.004-0.040]), whereas high levels of fT4 may be associated with decreased risk of children's hypercholesterolemia (OR = 0.870 [CI 0.768-0.986]). Maternal T4 concentrations during the 3rd trimester of pregnancy were negatively associated with children's cholesterol levels (β = -0.002 [CI -0.003-0.00]). High maternal TH levels were associated with high fasting glucose level and low low-density lipoprotein concentrations in children. <b><i>Conclusions:</i></b> Maternal TH dynamic variations may be associated with glycolipid metabolism in preschoolers, even when women do not have clinically diagnosed thyroid disorders. The exact associations between maternal THs in specific trimesters of pregnancy under normal thyroid function conditions and glycolipid metabolism in offspring require further investigation.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors Associated with Response to Intravenous Glucocorticoids in Active Moderate-to-Severe Thyroid Eye Disease.","authors":"Natalia Baczewska, Orsalia Alexopoulou, Stefan M Constantinescu, Chantal Daumerie, Maëlle Coutel, Antonella Boschi, Maria-Cristina Burlacu","doi":"10.1089/thy.2024.0629","DOIUrl":"https://doi.org/10.1089/thy.2024.0629","url":null,"abstract":"<p><p><b><i>Background:</i></b> Intravenous glucocorticoids (IVGCs) are the first-line treatment for active moderate-to-severe thyroid eye disease (TED) in many countries worldwide, mainly because of their anti-inflammatory efficacy. <b><i>Methods:</i></b> Retrospective cohort study of 64 patients with active moderate-to-severe TED, without dysthyroid optic neuropathy, treated between 2003 and 2023 at a single tertiary centre with the 12 weeks IVGC EUGOGO (European Group on Graves Orbitopathy) protocol. All patients were evaluated for response to IVGC according to the clinical judgment (CL) and 44/64 (69%) patients were also evaluated with the EUGOGO 2021 revised composite index (CI). <b><i>Results:</i></b> The mean patients' age at IVGC initiation was 51.7 ± 11 years, 47/64 (73.5%) were women, 56/64 (87.5%) were Caucasians, and 33/64 (51.5%) were active smokers. At 6 months after IVGC, 48 out of 64 (75%) patients evaluated with CL and 32 out of 44 (73%) patients evaluated with EUGOGO CI responded to the treatment. Nonresponders tended to be older than responders (56.6 ± 10.2 vs. 50.1 ± 10.8 years, <i>p</i> = 0.040 for CL and 56.5 ± 11.9 vs. 50.3 ± 11.6 years, <i>p</i> = 0.131 for EUGOGO CI) and had higher clinical activity score (CAS) before IVGC (5.0 ± 1.1 vs.4.2 ± 1.1, <i>p</i> = 0.022 for CL and 4.7 ± 0.6 vs. 3.1 ± 0.8, <i>p</i> < 0.001 for EUGOGO CI). In patients evaluated with CL or EUGOGO CI, respectively, multivariable logistic regression identified age at IVGC initiation (odds ratio [OR] = 0.92 [95% confidence interval (CI) 0.86-0.99], <i>p</i> = 0.024 and OR = 0.88 [CI 0.77-0.99], <i>p</i> = 0.046) and CAS before IVGC (OR = 0.53 [CI 0.31-0.90], <i>p</i> = 0.021 and OR= 0.08 [CI 0.01-0.38], <i>p</i> = 0.001) but not active smoking as independent factors associated with response to IVGC. The optimal cut-off associated with poorer response to IVGC was CAS ≥4.5/7 (66.7% specificity, 56.3% sensitivity; Area Under the Curve [AUC] = 0.689 [CI 0.54-0.83], <i>p</i> = 0.010) in patients evaluated with CL and CAS ≥3.5/5 (65.6% specificity, 91.7% sensitivity; AUC = 0.910 [CI 0.80-1.01], <i>p</i> < 0.001) in patients evaluated with EUGOGO CI. <b><i>Conclusion:</i></b> Older age and higher CAS before treatment were associated with poorer response to IVGC. Patients with these characteristics could be offered other immunotherapies as a first-line treatment for active moderate-to-severe TED.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA Methylation Dynamics and Prognostic Implications in Metastatic Differentiated Thyroid Cancer.","authors":"Helena Rodríguez-Lloveras, Carles Zafon, Carmela Iglesias, Jennifer Marcos-Ruiz, Joan Gil, Anna Rueda-Pujol, Lorena González, Regina Mayor, Esther N Klein Hesselink, Bettien M van Hemel, Cristina Carrato, Cecília Perelló-Fabregat, Javier Hernández-Losa, Rosa Somoza, Raquel Pluvinet, Jose F Sánchez-Herrero, Lauro Sumoy, Joan Seoane, Garcilaso Riesco-Eizaguirre, Cristina Montero-Conde, Mercedes Robledo, Jorge Hernando, Jaume Capdevila, Jordi L Reverter, Manel Puig-Domingo, Thera P Links, Mireia Jordà","doi":"10.1089/thy.2024.0303","DOIUrl":"https://doi.org/10.1089/thy.2024.0303","url":null,"abstract":"<p><p><b><i>Background:</i></b> Distant metastases (DM) are the leading cause of thyroid cancer-related death in patients with differentiated thyroid cancer (DTC). Despite significant progress in understanding DNA methylation in DTC, the methylation landscape of metastatic primary tumors and DM remains unclear. Our primary objective was to investigate DNA methylation dynamics during DTC progression, with a secondary goal of assessing potential clinical implications. <b><i>Materials and Methods:</i></b> We conducted a multicenter retrospective study in patients with DTC who underwent surgery at five university hospitals. We profiled DNA methylation in a discovery series of 97 samples (15 normal tissues, 30 non-metastatic [non-mDTC], and 35 metastatic [mDTC] primary DTC, and 17 paired metastases [lymph nodes and DM]). Results were validated in an independent series of 17 non-mDTC and 13 mDTC. We used receiver operating characteristic curve analysis to evaluate the identified prognostic CpG-signature. <b><i>Results:</i></b> DNA methylation alterations, mostly hypomethylation, increased progressively from primary tumors to DM, both in papillary (PTC) and follicular (FTC) thyroid carcinomas. Compared with normal tissue, non-metastatic primary PTC (non-mPTC) exhibited more hypomethylated than hypermethylated CpGs in contrast to non-metastatic primary FTC (non-mFTC). However, metastatic tumors, both mPTC and mFTC, predominantly exhibited hypomethylated CpGs. The overlap of differentially methylated CpGs (DMe-CpGs) was low between non-mPTC and non-mFTC (14% non-mPTC DMe-CpGs present in non-mFTC) but significantly higher between mPTC and mFTC (60% mPTC DMe-CpGs present in mFTC), underscoring the convergence of epigenetic changes during metastatic progression. The presence of many <i>de novo</i> DMe-CpGs from metastatic primary tumors (83% from mPTC and 40% from mFTC) in DM, including metachronous DM, supports the hypothesis that DM originates from a major subclone of the primary tumor. We identified and validated a 156-CpG signature in primary tumors capable of distinguishing between non-mDTC and mDTC, offering potential prognostic value for DM development regardless of histology. <b><i>Conclusions:</i></b> These results show a progressive increase in DNA methylation alterations, mainly hypomethylation, during PTC and FTC metastatic progression, suggesting a linear model, though the DNA methylation dynamics differs between the two histological types. The analysis of the 156-CpG signature in primary tumors may help identify patients with DTC at high risk for DM, enhancing a more personalized treatment.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Nomogram to Integrate Molecular Testing and Clinical Variables to Improve Malignancy Risk Assessment Among Cytologically Indeterminate Thyroid Nodules.","authors":"Jiahui Wu, Paul Stewardson, Markus Eszlinger, Moosa Khalil, Sana Ghaznavi, Erik Nohr, Adrian Box, Ralf Paschke","doi":"10.1089/thy.2024.0481","DOIUrl":"https://doi.org/10.1089/thy.2024.0481","url":null,"abstract":"<p><p><b><i>Background:</i></b> The introduction of molecular testing (MT) of cytologically indeterminate thyroid nodules (ITNs) alone has not impacted thyroidectomy rates. Due to this, we evaluated the incremental diagnostic value of various clinical variables in addition to MT results, in predicting the risk of malignancy (ROM) among ITNs. <b><i>Methods:</i></b> This prospective observational study included 1024 consecutive ITNs that underwent reflexive ThyroSPEC MT between Jul 30, 2020, and Oct 30, 2023. A multivariable logistic regression model was built to assess the relationship between histology outcomes and clinical variables, including nodule discovery by palpation, ultrasound risk categories, maximum nodule size, Bethesda category, Bethesda atypia, and ThyroSPEC categories. A total of 332 out of 1024 patients who underwent surgery and had complete data for all variables were included in the model. A nomogram was subsequently developed based on the model. <b><i>Results:</i></b> The model achieved a cross-validated AUC of 0.831 (95% confidence intervals: 0.787-0.874). Patients with high-risk mutations or malignant molecular markers exhibited significantly higher odds (152.79 times) of malignancy compared to those with mutation-negative or benign molecular marker results. Patients with maximum nodule size >5 cm have 4.34 times higher odds of malignancy than those 0-2 cm. The presence of nuclear atypia increased the odds of malignancy by 4.26 times, while ultrasound malignancy risk category 5 increased the odds of malignancy by 2.89 times compared to categories 1-3. Positive palpation discovery increased the odds by 1.83 times. The integrated ROM estimated from the regression model is significantly associated with the surgery type (<i>p</i> < 0.001). In the low (0-30%) and intermediate ROM (31-70%) categories, lobectomy alone is the most common surgery (61% and 70%, respectively), while in the high ROM (>70%) category, total thyroidectomy dominates (62%). <b><i>Conclusions:</i></b> Although MT alone played an important role in decision-making regarding surveillance versus surgery in our study population, integrating MT results with additional clinical variables improved the malignancy risk prediction for ITNs. Our results highlight the importance of contextualizing MT results within an integrated interdisciplinary thyroid nodule diagnostic pathway.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557359","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":"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 (¹³¹I), 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}

{"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}

{"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⁺ 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⁺ fibrocytes and CD34⁺ 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}

{"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}