European Thyroid Journal最新文献

{"title":"Response to letter: 'why so many doses, and why now?'","authors":"Michaela Kuhlen, Marina Kunstreich, Friederike Eilsberger, Markus Luster, Antje Redlich","doi":"10.1530/ETJ-25-0155","DOIUrl":"10.1530/ETJ-25-0155","url":null,"abstract":"","PeriodicalId":12159,"journal":{"name":"European Thyroid Journal","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential of bone marrow mesenchymal stem cells in iodine-induced autoimmune thyroiditis therapy.","authors":"Xun Liu, Likun Cui, Jianwei Dong, Jiancong Ren, Dongdong Xu, Yanshuo Han, Jian Zhang","doi":"10.1530/ETJ-24-0137","DOIUrl":"10.1530/ETJ-24-0137","url":null,"abstract":"<p><strong>Objective: </strong>Hashimoto's thyroiditis (HT) is a prevalent autoimmune disease without a cure. Mesenchymal stem cells (MSCs) may offer the opportunity to improve autoimmune thyroiditis.</p><p><strong>Methods: </strong>We replicated the pathogenic factors of HT and established a stable autoimmune thyroiditis model in NOD.H-2h4 mice by administering iodine for 12 weeks. We used orthotopic injection to transplant bone MSCs (BMSCs) into the thyroid. Immunohistochemistry, enzyme-linked immunosorbent assay, flow cytometry, and hematoxylin and eosin and immunofluorescence staining were used to evaluate the effects of cell transplantation.</p><p><strong>Results: </strong>Orthotopic BMSC transplantation decreased serum thyroglobulin antibody and caspase 3 levels; increased proliferating cell nuclear antigen levels; decreased CD4+/CD3+ T cells, Th1/Th2, and Th17/Treg ratios; decreased TNF-alpha (a proinflammatory cytokine) and interferon-gamma levels; and increased transforming growth factor-beta and interleukin-10 levels. In addition, it increased CD90/S100A4 and CD90/TTF-1 co-expression.</p><p><strong>Conclusion: </strong>Orthotopic BMSC transplantation improved the inflammatory environment by regulating the secretion of anti-inflammatory cytokines, promoting regeneration, and reducing apoptosis in the thyroid tissue. Bone marrow-derived stem cells inhibited T cell activation, maintained a balance between T cell subpopulation ratios, and halted thyroiditis progression. Finally, transplanted BMSCs could transform into fibroblasts and thyroid cells. This study elucidated the pathogenesis of HT and provided evidence supporting the potential of MSCs in HT treatments.</p>","PeriodicalId":12159,"journal":{"name":"European Thyroid Journal","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of autoimmune thyroid disease on cognitive and psychiatric disorders: focus on clinical, pre-clinical and molecular studies.","authors":"Agnieszka Piekiełko-Witkowska, Monika K Duda, Joanna Bogusławska, Urszula Mackiewicz","doi":"10.1530/ETJ-24-0406","DOIUrl":"10.1530/ETJ-24-0406","url":null,"abstract":"<p><p>Autoimmune thyroid disease (AITD) is the most prevalent organ-specific autoimmune condition, encompassing Graves' disease (typically linked with hyperthyroidism) and Hashimoto's thyroiditis (generally associated with hypothyroidism). The growing body of evidence suggests that AITD can interfere with brain function. Here, we review the impact of AITD on cognition, mood, and psychiatric disorders by analysing data from clinical, animal, ex vivo and in vitro studies to reveal the molecular mechanisms by which AITD affects brain function. Most reports indicate a stronger association between cognitive impairments and hyperthyroidism (including AITD-related) than hypothyroidism. Both hypothyroidism and hyperthyroidism are linked with a higher risk of depression. At least some of those effects can be mediated by altered concentrations of T3 (3,3',5-triiodo-L-thyronine), which regulates gene expression in the brain microenvironment, affecting neurogenesis, angiogenesis, neurotransmitter release, and synaptic transmission. Diminished TSH (thyrotropin) signalling may also impair learning and memory by inhibiting the Wnt5a-β-catenin pathway. Thyroid disorders may also contribute to neurodegeneration by T3-mediated attenuation of amyloid-β elimination or TRH-induced formation of neurofibrillary tangles. Surprisingly, most clinical studies do not specify the immune origin of hypothyroidism or hyperthyroidism, therefore further studies involving large, well-characterised patient cohorts are needed to clarify the relationships between AITD and cognitive impairments and psychiatric disorders. Furthermore, data on the effect of anti-thyroid antibodies on brain function are scarce and inconclusive. Given the association between hyperthyroidism and an increased risk of dementia, cognitive impairment and mood disorders, adequate treatment and careful monitoring of AITD patients are essential to prevent the induction of exogenous hyperthyroidism.</p>","PeriodicalId":12159,"journal":{"name":"European Thyroid Journal","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insight into the metabolic shifts in Graves' hyperthyroidism: a study of acylcarnitine and lipid profiles.","authors":"Mikael Thomassen Neset, Arve Ulvik, Kristian Løvås, Johnny Laupsa-Borge, Lars Ertesvåg Breivik, Ann-Elin Meling Stokland, Bjørn Gunnar Nedrebø, Eyvind Rødahl, Eystein Husebye, Grethe Åstrøm Ueland, Hans Olav Ueland","doi":"10.1530/ETJ-25-0004","DOIUrl":"10.1530/ETJ-25-0004","url":null,"abstract":"<p><strong>Objective: </strong>Graves' disease increases metabolism and leads to net lipid degradation. Circulating acylcarnitines reflect lipid metabolism and the state of fatty acid oxidation in individuals. The aim of this study was to explore the lipid and acylcarnitine profiles in patients with Graves' disease.</p><p><strong>Methods: </strong>Seven lipids/apolipoproteins and 23 acylcarnitines were analysed in 100 newly diagnosed Graves' disease patients and validated in another 51 patients. Both groups were age- and sex-matched with healthy subjects.</p><p><strong>Results: </strong>The hyperthyroid Graves' disease patients (n = 88) from the main cohort (78 females, median age 42 (17-67) years) had significantly (P < 0.05) higher levels of medium- and long-chain acylcarnitines, and lower levels of short-chain acylcarnitines, compared with healthy subjects. Factor analysis showed that medium- and long-chain acylcarnitines explained most of the differences between the two groups. Serum levels of the five lipids/apolipoproteins were significantly lower in the hyperthyroid Graves' disease patients compared with healthy subjects. Patients (n = 21) treated with antithyroid drugs for 6 weeks had acylcarnitine levels closer to healthy subjects, compared with 79 treatment-naïve hyperthyroid patients. The main findings were confirmed in the validation group.</p><p><strong>Conclusion: </strong>Increased levels of medium- and long-chain acylcarnitines in patients with newly diagnosed Graves' disease may reflect accelerated catabolism. Lower levels of short-chain acylcarnitines point to Graves' disease being a catabolic condition, with a shift in energy source from carbohydrates to fat.</p>","PeriodicalId":12159,"journal":{"name":"European Thyroid Journal","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Usefulness of local therapy for distant metastases of differentiated thyroid cancer.","authors":"Sueyoshi Moritani, Masao Takenobu, Masakazu Yasunaga, Taihei Fujii, Hiroya Kitano","doi":"10.1530/ETJ-24-0237","DOIUrl":"10.1530/ETJ-24-0237","url":null,"abstract":"<p><strong>Objective: </strong>Treatment for distant metastases (DM) of differentiated thyroid cancer (DTC) aims to improve the prognosis and quality of life (QOL). Radioactive iodine and molecular targeted therapies are the primary systemic treatments for DM. Combining these with local treatments, such as surgery and radiotherapy targeting metastatic sites, may provide additional benefits to systemic therapy.</p><p><strong>Methods: </strong>This study reviewed the additional effects of local therapies on common metastatic sites of DTC, such as pulmonary or bone metastases (BM), the efficacy of bone-modifying agents (BMAs) for BM, and the therapeutic effects of local treatments for less common brain metastases.</p><p><strong>Results: </strong>Although based on retrospective studies with no definitive conclusions on the effectiveness of each treatment, local therapy for DM in DTC patients has been shown to enhance prognosis and QOL in several studies. Considering the results of clinical trials for metastatic tumors, local therapy for one or a few pulmonary or BM in DTC should be considered, if expected to improve prognosis and QOL. Surgical intervention is recommended for spinal metastases presenting with spinal compression symptoms or for long BM in extremities at risk of pathological or impending fractures. BMAs are also recommended to reduce the risk of skeletal-related events. Surgery, stereotactic radiotherapy, and whole-brain radiotherapy are suggested for brain metastases to improve the prognosis and QOL.</p><p><strong>Conclusion: </strong>Incorporating local therapy alongside systemic treatment can enhance the prognosis and QOL and should be considered a viable treatment option.</p>","PeriodicalId":12159,"journal":{"name":"European Thyroid Journal","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical management of alemtuzumab-induced autoimmune thyroid diseases: a narrative review.","authors":"Jacopo Manso, Ilaria Muller, Caterina Mian","doi":"10.1530/ETJ-25-0007","DOIUrl":"10.1530/ETJ-25-0007","url":null,"abstract":"<p><p>Alemtuzumab is a powerful anti-CD52 drug that is an established treatment option in patients with multiple sclerosis due to its proven efficacy. However, in about 50% of patients, the use of alemtuzumab is burdened by the development of secondary autoimmune thyroid diseases, constituting a range of alemtuzumab-induced autoimmune thyroid diseases (AIATDs). Graves' disease (GD) is the most common AIATD, with an incidence of approximately 60%, and presents different characteristics from the conventional form. Indeed, GD with a fluctuating course is significantly more prevalent (15-50%), which poses a major challenge for physicians in its management. Other AIATDs also exhibit distinct features compared to their conventional counterparts; notably, hypothyroidism is frequently associated with TSH-receptor blocking antibodies, and alemtuzumab-induced GD demonstrates a higher rate of fluctuating course and potential for spontaneous remission. Alemtuzumab-induced thyroid eye disease (TED) is less common than conventional TED, with similar clinical and management characteristics. In this review, we summarize the latest evidence, also from real-world studies, with a focus on clinical management and possible predictors of AIATDs.</p>","PeriodicalId":12159,"journal":{"name":"European Thyroid Journal","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12152848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations in gene expression associated with invasion of RAS-mutant thyroid tumors and their potential diagnostic and therapeutic utility.","authors":"Vincenzo Condello, William R Doerfler, Alyaksandr V Nikitski, Daniel M Spagnolo, Ian J Fornal, Gavin M Schmidt, Abigail I Wald, Marina N Nikiforova, Yuri E Nikiforov","doi":"10.1530/ETJ-25-0022","DOIUrl":"10.1530/ETJ-25-0022","url":null,"abstract":"<p><strong>Introduction: </strong>Mutations of RAS genes are detected in a spectrum of follicular-patterned thyroid tumors. Preoperative prediction of invasive cancers based on the presence of RAS mutation alone is challenging because non-invasive and invasive tumors tend to have similar sonographic and cytologic features. The aim of this study was to perform clinicopathologic and molecular analyses of RAS-mutant tumors, identify molecular and clinical markers associated with invasiveness, and determine their diagnostic and therapeutic potentials.</p><p><strong>Methods: </strong>We collected clinicopathologic characteristics and performed RNA-seq on 48 surgically resected RAS-mutant thyroid tumors (23 non-invasive and 25 invasive). A classifier using expression data of selected invasiveness markers and clinical parameters was applied to an independent set of 54 RAS-mutant fine-needle aspiration (FNA) samples to predict invasion. Selected markers were investigated in vitro and in vivo.</p><p><strong>Results: </strong>On RNA-seq analysis, invasive RAS-mutant tumors showed different gene expression profiles compared to non-invasive tumors. Expression levels of six selected genes (CA12, CD44, LRP4, ECM1, FN1, and CRABP1) were associated with invasiveness on qRT-PCR. Expression levels of these genes plus nodule size predicted invasion in RAS-mutant FNA samples with 95% sensitivity and 89% specificity. siRNA silencing and chemical inhibition of CA12 reduced invasion of RAS-mutant human thyroid cells. Treatment of RAS-mutant xenografts with CA12 inhibitors arrested tumor growth.</p><p><strong>Conclusions: </strong>Development of invasion in RAS-mutant tumors is associated with significant alteration in gene expression. Expression levels of six genes and nodule size may predict invasion in RAS-mutant thyroid nodules, whereas chemical inhibition of CA12 may have a potential therapeutic effect in RAS-mutant tumors.</p>","PeriodicalId":12159,"journal":{"name":"European Thyroid Journal","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12152851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Why so many doses, and why now?","authors":"S Bilgic, B Akovalı","doi":"10.1530/ETJ-25-0115","DOIUrl":"10.1530/ETJ-25-0115","url":null,"abstract":"","PeriodicalId":12159,"journal":{"name":"European Thyroid Journal","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Follow-up and transition of care for low recurrence risk thyroid cancer patients in Canada.","authors":"Ralf Paschke, Sana Ghaznavi, Syed Ali Imran, Jennifer Jacquier, Heather Lochnan, Marie-Hélène Massicotte, Elliot Mitmaker, Deric Morrison, Vicki Munro, Michelle Sveistrup, Sam M Wiseman, Afshan Zahedi","doi":"10.1530/ETJ-25-0072","DOIUrl":"10.1530/ETJ-25-0072","url":null,"abstract":"<p><p>The incidence of differentiated thyroid cancer (DTC) has increased significantly in recent decades. Following initial diagnosis, DTC patients are classified according to the American Thyroid Association (ATA) as low, intermediate, and high risk for recurrence. Patients in the ATA low recurrence-risk category have a recurrence risk of ≤5%, with 20-year disease-specific mortality of <1%. Accordingly, there has been a shift to de-escalating initial treatment, including the relaxation of thyroid-stimulating hormone suppression. In addition, fewer low-risk patients undergo total thyroidectomy or radioactive iodine therapy. However, the optimal long-term surveillance strategy remains unclear, with many patients continuing follow-up in speciality clinics for many years. In addition, emerging evidence suggests that long-term surveillance can be effectively managed in primary care settings. To enhance understanding among Canadian thyroid practitioners and to improve care for Canadian patients diagnosed with low-risk DTC, we developed this consensus statement by collecting feedback from a multidisciplinary team led by one chairperson (endocrinologist), an additional eight endocrinologists, two surgeons, and one patient partner. This consensus statement reflects current evidence and expert opinion regarding initial management and long-term surveillance of low-risk DTC patients. This work is valuable to Canadian thyroid practitioners as it provides standardized guidelines to ensure optimal care and improved outcomes for low-risk DTC patients.</p>","PeriodicalId":12159,"journal":{"name":"European Thyroid Journal","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenic MCT8V235L creates a steric clash that is alleviated by a compensating mutation of MCT8F285A.","authors":"Niklas Sonntag, Felix Schreiner, Ulrich Schweizer, Doreen Braun","doi":"10.1530/ETJ-25-0009","DOIUrl":"10.1530/ETJ-25-0009","url":null,"abstract":"<p><strong>Objective: </strong>The monocarboxylate transporter (MCT) 8 is a specific transporter for thyroid hormones. Pathogenic variants in MCT8 lead to a severe psychomotor disorder called MCT8 deficiency. A recently published patient carries a MCT8V235 to leucine substitution that was incapable of T3 transport. Analyses of our MCT8 homology model predicted steric clashes between Leu235 and Phe285 as well as Gln288, possibly affecting another transport-sensitive phenylalanine at position 287.</p><p><strong>Methods: </strong>We analyzed the occurrence of potential van der Waals (VDW) interactions between Leu235 and Phe285 as well as Gln288 in the homology model. We overexpressed MCT8V235 and MCT8F287 mutants with altered side-chain properties in cells to assess their role in T3 transport function. In addition, we created an MCT8V235L,F285A double mutant.</p><p><strong>Results: </strong>Mutations of MCT8V235 to alanine, threonine or isoleucine, as well as the analysis of potential VDW interactions, helped us to identify Phe285, but not Gln288, as the amino acid responsible for the inactivity of MCT8V235L. The hypothesis was supported by activity measurements of an MCT8V235L,F285A double mutant that showed rescued T3 transport with KM values similar to wild-type MCT8. The analyses of MCT8F287 mutated to tyrosine, tryptophan and valine revealed that the size and/or the aromatic properties of the amino acid side chain are crucial for proper membrane expression and T3 transport.</p><p><strong>Conclusion: </strong>We were able to restore transport activity of MCT8V235L by introducing a second mutation (MCT8V235L,F285A). We speculate that the additional mutation prevents a shift of Phe287 into the potential transport cavity, eventually restoring T3 transport.</p>","PeriodicalId":12159,"journal":{"name":"European Thyroid Journal","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}