Kamilla R Riis, Camilla B Larsen, Bjarke R Medici, Christian Z Jensen, Kristian H Winther, Emil L Larsen, Christina Ellervik, Jeppe L la Cour, Laszlo Hegedüs, Thomas H Brix, Henrik E Poulsen, Filip K Knop, Birte Nygaard, Steen J Bonnema
{"title":"Hypothyroid women have persistently higher oxidative stress compared to healthy controls.","authors":"Kamilla R Riis, Camilla B Larsen, Bjarke R Medici, Christian Z Jensen, Kristian H Winther, Emil L Larsen, Christina Ellervik, Jeppe L la Cour, Laszlo Hegedüs, Thomas H Brix, Henrik E Poulsen, Filip K Knop, Birte Nygaard, Steen J Bonnema","doi":"10.1530/ETJ-23-0167","DOIUrl":"10.1530/ETJ-23-0167","url":null,"abstract":"<p><strong>Objective: </strong>Some studies suggest that hypothyroidism is associated with increased oxidative stress. Urinary excretion of 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) represents whole-body RNA and DNA oxidation, respectively. These biomarkers have only been explored sparsely in patients with thyroid disorders.</p><p><strong>Methods: </strong>In 45 Danish women with newly diagnosed hypothyroidism, we compared 8-oxoGuo and 8-oxodG before or shortly after initiating levothyroxine with the excretion rates at euthyroidism. We also compared the excretion of 8-oxoGuo and 8-oxodG in the patients after restored euthyroidism with 18 healthy control subjects.</p><p><strong>Results: </strong>Compared with baseline, none of the biomarkers changed significantly in the patients after becoming euthyroid. The geometric mean of 8-oxoGuo was 1.63 (95% CI: 1.49-1.78) nmol/mmol creatinine at baseline and 1.67 nmol/mmol at euthyroidism (95% CI: 1.53-1.83) (P = 0.39), while that of 8-oxodG was 1.28 nmol/mmol creatinine at baseline (95% CI: 1.14-1.44) and 1.32 nmol/mmol at euthyroidism (95% CI: 1.18-1.48), respectively (P = 0.47). The relative mean differences were 0.97 (95% CI: 0.91-1.04) for 8-oxoGuo and 0.97 (95% CI: 0.88-1.06) for 8-oxodG. At baseline, multiple linear regression revealed a positive association between free thyroxine and both biomarkers (8-oxoGuo, P < 0.001; 8-oxodG, P = 0.04). Furthermore, 8-oxoGuo was positively associated with age (P = 0.04) and negatively associated with thyrotropin (P = 0.02). In the control group, the geometric mean of 8-oxoGuo was 1.23 nmol/mmol creatinine (95% CI: 1.07-1.42), while that of 8-oxodG was 1.04 nmol/mmol creatinine (95% CI: 0.88-1.23). Thus, compared with control subjects, euthyroid patients showed a significantly higher level of both 8-oxoGuo (P < 0.001) and 8-oxodG (P = 0.03).</p><p><strong>Conclusion: </strong>In hypothyroid women, no significant effect of levothyroxine treatment on the oxidative stress biomarkers 8-oxoGuo and 8-oxodG could be demonstrated. However, the excretion of these biomarkers was significantly higher than in healthy controls.</p>","PeriodicalId":12159,"journal":{"name":"European Thyroid Journal","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10692686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49675955","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 second 131I treatment in biochemical persistent differentiated thyroid cancer patients.","authors":"Carla Gambale, Alessandro Prete, Lea Contartese, Liborio Torregrossa, Francesca Bianchi, Eleonora Molinaro, Gabriele Materazzi, Rossella Elisei, Antonio Matrone","doi":"10.1530/ETJ-23-0052","DOIUrl":"10.1530/ETJ-23-0052","url":null,"abstract":"<p><strong>Background: </strong>Second 131I treatment is commonly performed in clinical practice in patients with differentiated thyroid cancer and biochemical incomplete or indeterminate response (BiR/InR) after initial treatment.</p><p><strong>Objective: </strong>The objective of the is study is to evaluate the clinical impact of the second 131I treatment in BiR/InR patients and analyze the predictive factors for structural incomplete response (SiR).</p><p><strong>Patients and methods: </strong>One hundred fifty-three BiR/InR patients after initial treatment who received a second 131I treatment were included in the study. The clinical response in a short- and medium- long-term follow-up was evaluated.</p><p><strong>Results: </strong>After the second 131I treatment (median 8 months), 11.8% patients showed excellent response (ER), 17% SiR, while BiR/InR persisted in 71.2%. Less than half (38.5%) of SiR patients had radioiodine-avid metastases. Patients who, following the second 131I treatment, experienced SiR had larger tumor size and more frequently aggressive histology and vascular invasion than those experienced BiR/InR and ER. Also, the median values of thyroglobulin on levothyroxine therapy (LT4-Tg), Tg peak after recombinant human TSH stimulation (rhTSH-Tg) and thyroglobulin antibodies (TgAb) were significantly higher in patients who developed SiR. At last evaluation (median: 9.9 years), BiR/InR persisted in 57.5%, while 26.2% and 16.3% of the patients showed ER and SiR, respectively. About half of BiR/InR patients (71/153 (46.4%)) received further treatments after the second 131I treatment.</p><p><strong>Conclusions: </strong>Radioiodine-avid metastatic disease detected by the second 131I is an infrequent finding in patients with BiR/InR after initial treatment. However, specific pathologic and biochemical features allow to better identify those cases with higher probability of developing SiR, thus improving the clinical effectiveness of performing a second 131I treatment.</p>","PeriodicalId":12159,"journal":{"name":"European Thyroid Journal","volume":"12 6","pages":""},"PeriodicalIF":3.5,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49676006","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":"Radiofrequency ablation for thyroid Bethesda III nodules: preliminary results.","authors":"Pi-Ling Chiang, Sheng-Dean Luo, Yen-Hsiang Chang, Chen-Kai Chou, Shun-Yu Chi, Yi-Fan Chen, Wei-Che Lin","doi":"10.1530/ETJ-23-0105","DOIUrl":"10.1530/ETJ-23-0105","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to evaluate the feasibility of radiofrequency ablation (RFA) for thyroid nodules with cytological atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS, Bethesda III).</p><p><strong>Materials and methods: </strong>A total of 28 adults presenting with 30 initial Bethesda III nodules underwent thyroid RFA at a single medical center. Thyroid nodules with Bethesda IV or V according to the second aspiration were excluded. All RFA procedures were performed using the free-hand, 'moving-shot' technique under local anesthesia. Clinical features and demographics, RFA details, nodule volume reduction rate (VRR), and complications were analyzed.</p><p><strong>Results: </strong>The mean age of patients was 47.6 years, 82.1% of whom were females. Mean nodule volumes at pre-RFA, and at 6 months and 12 months post-RFA were 7.92, 2.42, and 1.25 mL, respectively, with a VRR of 77.9% at 6 months, and 87.4% at 12 months. Post-RFA complications were noted in two patients, one with transient vocal cord palsy and another with isthmus minor rupture.</p><p><strong>Conclusion: </strong>RFA may be another safe alternative except for active surveillance or surgical excision for AUS/FLUS nodules with low-suspicion Thyroid Imaging Reporting and Data System features for patients who are unsuitable or strongly refuse surgery. Long-term results remain uncertain, thus further follow-up study is necessary.</p>","PeriodicalId":12159,"journal":{"name":"European Thyroid Journal","volume":"12 6","pages":""},"PeriodicalIF":4.7,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138487028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 thyroid Bethesda III nodules: preliminary results.","authors":"Pi-Ling Chiang, Sheng-Dean Luo, Yen-Hsiang Chang, Chen-Kai Chou, Shun-Yu Chi, Yi-Fan Chen, Wei-Che Lin","doi":"10.1530/ETJ-23-0105","DOIUrl":"10.1530/ETJ-23-0105","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to evaluate the feasibility of radiofrequency ablation (RFA) for thyroid nodules with cytological atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS, Bethesda III).</p><p><strong>Materials and methods: </strong>A total of 28 adults presenting with 30 initial Bethesda III nodules underwent thyroid RFA at a single medical center. Thyroid nodules with Bethesda IV or V according to the second aspiration were excluded. All RFA procedures were performed using the free-hand, 'moving-shot' technique under local anesthesia. Clinical features and demographics, RFA details, nodule volume reduction rate (VRR), and complications were analyzed.</p><p><strong>Results: </strong>The mean age of patients was 47.6 years, 82.1% of whom were females. Mean nodule volumes at pre-RFA, and at 6 months and 12 months post-RFA were 7.92, 2.42, and 1.25 mL, respectively, with a VRR of 77.9% at 6 months, and 87.4% at 12 months. Post-RFA complications were noted in two patients, one with transient vocal cord palsy and another with isthmus minor rupture.</p><p><strong>Conclusion: </strong>RFA may be another safe alternative except for active surveillance or surgical excision for AUS/FLUS nodules with low-suspicion Thyroid Imaging Reporting and Data System features for patients who are unsuitable or strongly refuse surgery. Long-term results remain uncertain, thus further follow-up study is necessary.</p>","PeriodicalId":12159,"journal":{"name":"European Thyroid Journal","volume":"12 6","pages":""},"PeriodicalIF":4.7,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10563608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49675960","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}
Markus Eszlinger, Alexandra Stephenson, Shideh Mirhadi, Konrad Patyra, Michael F Moran, Moosa Khalil, Jukka Kero, Ralf Paschke
{"title":"Activation of mitogen-activated protein kinase signaling and development of papillary thyroid carcinoma in thyroid-stimulating hormone receptor D633H knockin mice.","authors":"Markus Eszlinger, Alexandra Stephenson, Shideh Mirhadi, Konrad Patyra, Michael F Moran, Moosa Khalil, Jukka Kero, Ralf Paschke","doi":"10.1530/ETJ-23-0049","DOIUrl":"10.1530/ETJ-23-0049","url":null,"abstract":"<p><strong>Objective: </strong>Nonautoimmune hyperthyroidism (NAH) is rare and occurs due to a constitutively activating thyroid stimulating hormone receptor (TSHR) mutation. In contrast to other thyroid nodules, no further evaluation for malignancy is recommended for hot thyroid nodules. In the first model for NAH in mice nearly all homozygous mice had developed papillary thyroid cancer by 12 months of age.</p><p><strong>Methods: </strong>To further evaluate these mice, whole exome sequencing and phosphoproteome analysis were employed in a further generation of mice to identify any other mutations potentially responsible and to identify the pathways involved in thyroid carcinoma development.</p><p><strong>Results: </strong>Only three genes (Nrg1, Rrs1, Rasal2) were mutated in all mice examined, none of which were known primary drivers of papillary thyroid cancer development. Wild-type and homozygous TSHR D633H knockin mice showed distinct phosphoproteome profiles with an enrichment of altered phosphosites found in ERK/mitogen-activated protein kinase (MAPK) signaling. Most importantly, phosphosites with known downstream effects included BRAF p.S766, which forms an inhibitory site: a decrease of phosphorylation at this site suggests an increase in MEK/ERK pathway activation. The decreased phosphorylation at BRAF p.S766 would suggest decreased AMP-activated protein kinase (AMPK) signaling, which is supported by the decreased phosphorylation of STIM1 p.S257, a downstream AMPK target.</p><p><strong>Conclusion: </strong>The modified phosphoproteome profile of the homozygous mice in combination with human literature suggests a potential signaling pathway from constitutive TSHR signaling and cAMP activation to the activation of ERK/MAPK signaling. This is the first time that a specific mechanism has been identified for a possible involvement of TSH signaling in thyroid carcinoma development.</p>","PeriodicalId":12159,"journal":{"name":"European Thyroid Journal","volume":"12 6","pages":""},"PeriodicalIF":4.7,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138487116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Markus Eszlinger, Alexandra Stephenson, Shideh Mirhadi, Konrad Patyra, Michael F Moran, Moosa Khalil, Jukka Kero, Ralf Paschke
{"title":"Activation of mitogen-activated protein kinase signaling and development of papillary thyroid carcinoma in thyroid-stimulating hormone receptor D633H knockin mice.","authors":"Markus Eszlinger, Alexandra Stephenson, Shideh Mirhadi, Konrad Patyra, Michael F Moran, Moosa Khalil, Jukka Kero, Ralf Paschke","doi":"10.1530/ETJ-23-0049","DOIUrl":"10.1530/ETJ-23-0049","url":null,"abstract":"<p><strong>Objective: </strong>Nonautoimmune hyperthyroidism (NAH) is rare and occurs due to a constitutively activating thyroid stimulating hormone receptor (TSHR) mutation. In contrast to other thyroid nodules, no further evaluation for malignancy is recommended for hot thyroid nodules. In the first model for NAH in mice nearly all homozygous mice had developed papillary thyroid cancer by 12 months of age.</p><p><strong>Methods: </strong>To further evaluate these mice, whole exome sequencing and phosphoproteome analysis were employed in a further generation of mice to identify any other mutations potentially responsible and to identify the pathways involved in thyroid carcinoma development.</p><p><strong>Results: </strong>Only three genes (Nrg1, Rrs1, Rasal2) were mutated in all mice examined, none of which were known primary drivers of papillary thyroid cancer development. Wild-type and homozygous TSHR D633H knockin mice showed distinct phosphoproteome profiles with an enrichment of altered phosphosites found in ERK/mitogen-activated protein kinase (MAPK) signaling. Most importantly, phosphosites with known downstream effects included BRAF p.S766, which forms an inhibitory site: a decrease of phosphorylation at this site suggests an increase in MEK/ERK pathway activation. The decreased phosphorylation at BRAF p.S766 would suggest decreased AMP-activated protein kinase (AMPK) signaling, which is supported by the decreased phosphorylation of STIM1 p.S257, a downstream AMPK target.</p><p><strong>Conclusion: </strong>The modified phosphoproteome profile of the homozygous mice in combination with human literature suggests a potential signaling pathway from constitutive TSHR signaling and cAMP activation to the activation of ERK/MAPK signaling. This is the first time that a specific mechanism has been identified for a possible involvement of TSH signaling in thyroid carcinoma development.</p>","PeriodicalId":12159,"journal":{"name":"European Thyroid Journal","volume":"12 6","pages":""},"PeriodicalIF":4.7,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10563634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49675958","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}
Jacopo Manso, Simona Censi, Cristina Clausi, Ilaria Piva, Yi Hang Zhu, Alberto Mondin, Maria Chiara Pedron, Susi Barollo, Loris Bertazza, Giulia Midena, Raffaele Parrozzani, Caterina Mian
{"title":"Circulating miR-146a predicts glucocorticoid response in thyroid eye disease.","authors":"Jacopo Manso, Simona Censi, Cristina Clausi, Ilaria Piva, Yi Hang Zhu, Alberto Mondin, Maria Chiara Pedron, Susi Barollo, Loris Bertazza, Giulia Midena, Raffaele Parrozzani, Caterina Mian","doi":"10.1530/ETJ-23-0083","DOIUrl":"10.1530/ETJ-23-0083","url":null,"abstract":"<p><strong>Objective: </strong>Thyroid eye disease (TED) is an immune-mediated disorder of the eye. Intravenous glucocorticoid (GC) is the first-line treatment for patients with active moderate-to-severe TED. However, the response rate is between 50% and 80%. There are still no simple and reliable markers of responsiveness to GC therapy. We aimed to explore the possible role of miR-146a and miR-21 as predictors of responsiveness to GC treatment in TED.</p><p><strong>Methods: </strong>We carried out a prospective longitudinal study on 30 consecutive adult patients with active moderate-to-severe TED and eligible for GC therapy. All patients received the standard GC treatment with methylprednisolone i.v. In cases of progressive worsening of Gorman Score for diplopia or with duction restriction <30° in at least two consecutive controls, patients also underwent orbital radiotherapy. Response to GC treatment was defined as a decrease of two or more points in the clinical activity score (CAS) or CAS <4/10 at 24 weeks. Circulating miRNAs were extracted from patients' serum and quantified by real-time PCR.</p><p><strong>Results: </strong>Twenty-three (77%) patients responded to GC. Thyroid surgery, higher CAS, greater proptosis and higher pre-treatment circulating levels of miR-146a emerged as predictive factors of responsiveness to GC. A ROC analysis revealed that miR-146a could predict responsiveness to GC with a positive predictive value of 100%.</p><p><strong>Conclusion: </strong>This is the first study investigating the role of pre-treatment circulating miR-21 and miR-146a to predict responsiveness to GC in TED. miR-146a emerged as a simple, objective, new marker of GC sensitivity that could be used to avoid ineffective administration of GC therapy to TED patients.</p>","PeriodicalId":12159,"journal":{"name":"European Thyroid Journal","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10563606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10414476","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}
Stan R Ursem, Anita Boelen, Jacquelien J Hillebrand, Wendy P J den Elzen, Annemieke C Heijboer
{"title":"How low can we (reliably) go? A method comparison of thyroid-stimulating hormone assays with a focus on low concentrations.","authors":"Stan R Ursem, Anita Boelen, Jacquelien J Hillebrand, Wendy P J den Elzen, Annemieke C Heijboer","doi":"10.1530/ETJ-23-0123","DOIUrl":"10.1530/ETJ-23-0123","url":null,"abstract":"<p><strong>Objective: </strong>International guidelines concerning subclinical hyperthyroidism and thyroid cancer advice absolute cut-off values for aiding clinical decisions in the low range of thyroid-stimulating hormone (TSH) concentrations. As TSH assays are known to be poorly standardized in the normal to high range, we performed a TSH assay method comparison focusing on the low range.</p><p><strong>Methods: </strong>Sixty samples, selected to cover a wide range of TSH concentrations (<0.01 to 120 mIU/L) with oversampling in the lower range (<0.4 mIU/L), were used for the method comparison between three TSH immunoassays (Cobas, Alinity and Atellica). In addition, 20 samples were used to assess the coefficient of variation from duplicate measurements in these three methods.</p><p><strong>Results: </strong>The TSH immunoassays showed standardization differences with a bias of 7-16% for the total range and 1-14% for the low range. This could lead to a different classification of 1.5% of all measured TSH concentrations <0.40 mIU/L measured in our laboratory over the last 6 months, regarding the clinically important cut-off value of TSH = 0.1 mIU/L. As the imprecision of the immunoassays varied from 1.6-5.5%, this could lead to a similar reclassification as the bias between immunoassays.</p><p><strong>Conclusions: </strong>We established the standardization differences of frequently used TSH assays for the total and low concentration ranges. Based on the proportional bias and the imprecision, this effect seems to have limited clinical consequences for the low TSH concentration range. Nevertheless, as guidelines mention absolute TSH values to guide clinical decision-making, caution must be applied when interpreting values close to these cut-offs.</p>","PeriodicalId":12159,"journal":{"name":"European Thyroid Journal","volume":"12 5","pages":""},"PeriodicalIF":4.7,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/40/a7/ETJ-23-0123.PMC10503215.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10259539","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":"Circadian clock disruption in autoimmune thyroiditis.","authors":"Jinrong Fu, Zihao Fan, Liang He, Qian Liu, He Liu, Yushu Li, Haixia Guan","doi":"10.1530/ETJ-23-0035","DOIUrl":"10.1530/ETJ-23-0035","url":null,"abstract":"<p><strong>Objective: </strong>A vicious cycle between circadian disruption and escalating immune responses has been described in diverse inflammatory disease. The current study aimed to explore the role of circadian clock disruption in autoimmune thyroiditis (AIT).</p><p><strong>Methods: </strong>Thirty AIT patients and 30 controls were enrolled and biopsied for thyroid tissues. Alterations of core clock genes expression in AIT thyroid tissues, and its association with serum and tissue inflammatory biomarkers were assessed. For animal studies, C57BL/6J mice administered with porcine thyroglobulin or PBS (as control) combined with adjuvants were sacrificed at four time points to investigate the circadian characteristic of experimental autoimmune thyroiditis (EAT). Light shift (LS) conditions were used to explore the influence of external circadian disturbance on EAT.</p><p><strong>Results: </strong>The expression of clock genes BMAL1 and PER2 was significantly reduced in thyroid tissues from AIT patients and was negatively correlated to levels of thyroid peroxidase antibodies. In mouse models, diurnal fluctuations of proinflammatory cytokines were demonstrated, and further exposing mice to LS led to overproduction of TNF-α, IFN-γ, and anti-thyroglobulin antibodies. Circadian analysis revealed significant oscillations of Bmal1, Clock, Per2, Cry1, Ror, and Rev-erb, which was broadly disturbed in EAT, LS, and EAT + LS groups.</p><p><strong>Conclusions: </strong>This study demonstrates that expression pattern of clock genes was disrupted in AIT thyroid, and chronic circadian disruption may aggravate the inflammatory responses in AIT. Whether maintaining a regular circadian rhythm can alleviate autoimmune thyroid diseases warrants further research.</p>","PeriodicalId":12159,"journal":{"name":"European Thyroid Journal","volume":"12 5","pages":""},"PeriodicalIF":4.7,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/69/07/ETJ-23-0035.PMC10503217.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10271407","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}
Ana Piñar-Gutiérrez, Ana R Romero-Lluch, Suset Dueñas-Disotuar, Irene de Lara-Rodríguez, Mª Ángeles Gálvez-Moreno, Tomás Martín-Hernández, Jorge García-Alemán, Guillermo Martínez-de Pinillos, Elena Navarro-González
{"title":"Bone metastases from differentiated thyroid cancer: characteristics and prognostic factors in a multicenter series.","authors":"Ana Piñar-Gutiérrez, Ana R Romero-Lluch, Suset Dueñas-Disotuar, Irene de Lara-Rodríguez, Mª Ángeles Gálvez-Moreno, Tomás Martín-Hernández, Jorge García-Alemán, Guillermo Martínez-de Pinillos, Elena Navarro-González","doi":"10.1530/ETJ-23-0086","DOIUrl":"10.1530/ETJ-23-0086","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study is to describe the characteristics, survival and prognostic factors of a cohort of patients with bone metastases (BMs) from differentiated thyroid carcinoma (DTC).</p><p><strong>Methods: </strong>This was a multicenter retrospective observational study including patients diagnosed with BMs from DTC between 1980 and 2021. A Cox regression was performed to study prognostic factors for 5- and 10-year survival. Kaplan-Meier and log-rank tests were performed for the survival analysis and comparison between groups.</p><p><strong>Results: </strong>Sixty-three patients were evaluated. Median follow-up from BM diagnosis was 35 (15-68) months. About 30 (48.4%) patients presented with synchronous BMs. Regarding histology, 38 (60.3%) had the papillary variant. BMs were multiple in 32 (50.8%) patients. The most frequent location was the spine (60.3%). Other metastases were present in 77.8%, mainly pulmonary (69.8%). Concerning treatment, 54 (85.9%) patients received I131, with BM uptake in 31 (49.2%) and 25 (39.7%) received treatment with multikinase inhibitors. Regarding complications, 34 (54%) patients had skeletal-related events, 34 (54%) died and 5- and 10-year overall survival was 42.4% and 20.4%, respectively. Significant prognostic factors in the multivariate analysis were the presence of lymph node involvement (hazard ratio (HR): 2.916; 95% confidence interval (CI): 1.013-8.391; P = 0.047) and treatment with I131 (HR 0.214 (95% CI 0.069-0.665); P = 0.008) at 5 years, the presence of other metastases (HR 6.844. 95% CI 1.017-46.05; P = 0.048) and treatment with I131 (HR 0.23 (95% CI 0.058-0.913); P = 0.037) at 10 years.</p><p><strong>Conclusions: </strong>Our study reflects the management of patients with bone metastases from differentiated thyroid carcinoma in real clinical practice in several centers in southern Spain. Overall survival at 5 and 10 years was lower in patients who were not treated with I131, had nodal involvement and/or had other metastases.</p>","PeriodicalId":12159,"journal":{"name":"European Thyroid Journal","volume":"12 5","pages":""},"PeriodicalIF":4.7,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10448562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10081947","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}