Thyroid

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Fernanda Bolfi Department of Internal Medicine, São Paulo State University (UNESP), Medical School, Botucatu, São Paulo, Brazil

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Maryan Borcsik Marum Department of Internal Medicine, São Paulo State University (UNESP), Medical School, Botucatu, São Paulo, Brazil

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Samantha Ellen da Silva Fonseca Department of Internal Medicine, São Paulo State University (UNESP), Medical School, Botucatu, São Paulo, Brazil

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Glaucia M F S Mazeto Department of Internal Medicine, São Paulo State University (UNESP), Medical School, Botucatu, São Paulo, Brazil

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Celia Regina Nogueira Department of Internal Medicine, São Paulo State University (UNESP), Medical School, Botucatu, São Paulo, Brazil

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Vania dos Santos Nunes-Nogueira Department of Internal Medicine, São Paulo State University (UNESP), Medical School, Botucatu, São Paulo, Brazil

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Objective

To assess whether individual diagnosis of low urinary iodine concentration (UIC) in pregnant women is associated with adverse maternal and neonatal outcomes.

Methods

Studies that compared pregnant women with UIC <150 μg/L and those with UIC 150–249 μg/L were systematically reviewed. MEDLINE, Embase, LILACS and CENTRAL were our source databases. Selection of studies, risk-of-bias assessment and data extraction were performed in pairs and independently. Relative risk (RR) with 95% confidence interval (CI) was calculated as an estimate of the effect of iodine <150 μg/L. Stata software was used to perform meta-analyses. The quality of evidence was determined according to the Grading of Recommendations Assessment, Development and Evaluation.

Results

In total, 7000 studies were identified, of which 63 were included. With low or very low certainty of the evidence, no difference in the incidence of miscarriage (RR: 0.87, 95% CI: 0.64–1.18, 6 studies, 4855 participants), maternal hypothyroidism (RR: 1.05, 95% CI: 0.68–1.60, 10 studies, 11,773 participants), preterm birth (RR: 1.20, 95% CI: 0.97–1.48, 13 studies, 15,644 participants), stillbirths (RR: 0.79, 95% CI: 0.34–1.82, 6 studies, 3406 participants), low birth weight (RR: 1.25, 95% CI: 0.88–1.78, 10 studies, 10,775 participants) and small for gestational age (RR: 1.11, 95% CI: 0.90–1.37, 5 studies, 4266 participants) was observed between the two groups.

Conclusion

In pregnant women, individual diagnosis of UIC <150 μg/L was not associated with adverse maternal and neonatal outcomes, emphasizing UIC as a limited method to assess individual iodine status during pregnancy.

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Litong Ran Department of Endocrinology, Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, Second Affiliated Hospital of Army Medical University, Chongqing, China

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Xiufei Liu Department of Endocrinology, Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, Second Affiliated Hospital of Army Medical University, Chongqing, China

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Yongfeng Tian Department of Endocrinology, Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, Second Affiliated Hospital of Army Medical University, Chongqing, China

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Jiaran Zhu Department of Endocrinology, Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, Second Affiliated Hospital of Army Medical University, Chongqing, China

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Zhengyuan Gong Department of Endocrinology, Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, Second Affiliated Hospital of Army Medical University, Chongqing, China

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Qiao Qiao Department of Endocrinology, Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, Second Affiliated Hospital of Army Medical University, Chongqing, China

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Xin Jiang Department of Endocrinology, Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, Second Affiliated Hospital of Army Medical University, Chongqing, China

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Yuren Wang Department of Endocrinology, Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, Second Affiliated Hospital of Army Medical University, Chongqing, China

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Guojun Yang Department of Clinical Laboratory, The Second Affiliated Hospital of the Army Medical University, Chongqing, China

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Hongting Zheng Department of Endocrinology, Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, Second Affiliated Hospital of Army Medical University, Chongqing, China

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Yi Zheng Department of Endocrinology, Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, Second Affiliated Hospital of Army Medical University, Chongqing, China
The 2nd Affiliated Hospital of Guizhou University of TCM, Guizhou, China

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Hua Qu Department of Endocrinology, Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, Second Affiliated Hospital of Army Medical University, Chongqing, China

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Abstract

Subacute thyroiditis (SAT) is an inflammatory thyroid disease characterized by neck pain, tenderness, general symptoms and thyroid dysfunction. Despite gaining new insights into the epidemiology, pathogenesis and treatment of SAT in recent years, the exact pathogenesis and determinants of its clinical progression remain unclear. Here, we profiled thyroid in situ protein alterations in fine-needle aspiration biopsy samples from SAT patients using proteomic analysis and uncovered 57 differentially abundant proteins. Gene ontology and KEGG enrichment analyses identified that these proteins were enriched in processes involving infection, inflammatory response and cell adhesion and junction, which likely contribute to the pathogenesis. Moreover, the top three high-abundance proteins (nicotinamide N-methyltransferase (NNMT), FTL and thymidine phosphorylase (TYMP)) were further validated in the plasma from a larger SAT cohort using an enzyme-linked immunosorbent assay. After adjusting for sex, Spearman correlation analysis showed that NNMT, FTL and TYMP levels were positively correlated with FT3, FT4, T3, T4, Tg and erythrocyte sedimentation rate and negatively correlated with thyroid-stimulating hormone. Furthermore, binary logistic regression analyses revealed that NNMT, FTL and TYMP were independent factors of SAT. We also conducted a receiver operating characteristic curve analysis to assess the diagnostic accuracy of NNMT, FTL and TYMP for SAT. The results revealed that each factor demonstrated an area under the curve score above 0.8. Thus, these high-abundance proteins can potentially serve as biomarkers for SAT diagnosis and outcome prediction. Our findings provide valuable insights into SAT biomarkers and shed light on the potential pathogenesis and therapeutic targets of SAT.

Highlights

  • Proteomic profiling identifies NNMT, FTL and TYMP as potential biomarkers for SAT.

  • This study reveals significant enrichment of infection, inflammatory response and cell adhesion pathways in SAT pathogenesis.

  • Elevated plasma NNMT, FTL and TYMP levels reflect SAT-related inflammatory and metabolic alterations.

Open access
Ying Wu Department of Endocrinology and Metabolism, Institute of Endocrine, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, Liaoning, PR China
Department of Endocrinology, The Affiliated Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China

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Qingling Guo Department of Endocrinology and Metabolism, Institute of Endocrine, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, Liaoning, PR China
Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, PR China

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Yongping Liu Department of Endocrinology and Metabolism, Institute of Endocrine, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, Liaoning, PR China

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Xun Gong Department of Endocrinology and Metabolism, Institute of Endocrine, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, Liaoning, PR China

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Wei Sun Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, PR China

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Yushu Li Department of Endocrinology and Metabolism, Institute of Endocrine, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, Liaoning, PR China

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Chenling Fan Department of Endocrinology and Metabolism, Institute of Endocrine, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, Liaoning, PR China

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Weiping Teng Department of Endocrinology and Metabolism, Institute of Endocrine, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, Liaoning, PR China

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Zhongyan Shan Department of Endocrinology and Metabolism, Institute of Endocrine, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, Liaoning, PR China

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Objectives

Inflammasomes are associated with various autoimmune diseases. Herein, we aimed to study the occurrence of inflammasomes in peripheral blood mononuclear cells (PBMCs) from patients with autoimmune thyroiditis (AIT), and the relationship between their abundance and the inflammatory response index of AIT. Furthermore, we examined the effect of iodine on inflammasomes containing NLR family pyrin domain-containing 3 (NLRP3) and inflammasome activation of helper T (Th) cell differentiation regulation in cultured PBMCs.

Methods

We collected PBMCs and serum samples from 50 patients with AIT with normal thyroid function and 50 controls matched for age and sex. In PBMCs, the mRNA and protein expressions of certain inflammasome constituents (e.g., NLRP1, NLRP3, absent in melanoma 2 (AIM2) and caspase-1), interleukin (IL)-1β and IL-18 were assessed using qRT-PCR and western blotting. Enzyme-linked immunosorbent assays (ELISAs) assessed the serum levels of IL-1β and IL-18. Flow cytometry was employed to examine NLRP3 expression on CD14+ monocytes and Th1 and Th17 cell percentages in the groups. AIT- or healthy control-derived PBMCs were stimulated using sodium iodide, with or without lipopolysaccharide (LPS) for 72 h.

Results

PBMCs from patients with AIT had significantly higher levels of pro-IL-18, pro-IL-1β and NLRP3 than did the PBMCs from the healthy controls (P < 0.05). Compared with those from the controls, AIT-derived PBMCs had enhanced levels of active IL-18 and active caspase-1 p20 (P < 0.05), whereas their abundance of active IL-1β was similar (P > 0.05). In serum, the AIT group had enhanced levels of IL-18 compared with the healthy controls (P < 0.05) but had similar levels of IL-1β (P > 0.05). NLRP3 expression on CD14+ monocytes from AIT patients was significantly augmented compared with the healthy controls (P< 0.01). Significantly increased percentages of Th1 and Th17 cells were detected in AIT patients compared with those in the healthy participants (P < 0.001). Sodium iodide treatment upregulated NLRP3 expression in PBMCs during 72 h of culture (P < 0.001). The percentage of Th1 and Th17 cells in AIT patients increased in an iodine-dependent manner (P < 0.01). Iodine had no significant effect on the number of these cells in the healthy control group (P > 0.05).

Conclusion

AIT-derived PBMC NLRP3 activity and expression increased. Iodine might regulate the immune and inflammatory response of patients with AIT by activating NLRP3 and promoting Th1 and Th17 cell differentiation.

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Shabnam Heydarzadeh Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

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Ali Asghar Moshtaghie Department of Biochemistry, Falavarjan Branch, Islamic Azad University, Isfahan, Iran

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Maryam Daneshpour Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

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Mehdi Hedayati Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

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Abstract

Aims and background

Curcumin’s function in affecting cancer metabolic reprogramming remains poorly understood. Herein, we aimed to elucidate a novel link between curcumin and the glucose uptake metabolism and the status of glucose transporters (GLUTs) in the SW1736 cell line derived from anaplastic thyroid cancer.

Materials and methods

The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test and flow cytometry were employed to test cell viability and cell death. For glucose uptake detection, the ‘glucose oxidase/peroxidase 4-aminoantipyrine’ enzymatic colorimetric assay was applied to measure the direct glucose levels inside the cells. Determination of GLUT1 and GLUT3 mRNA and protein expression in SW1736 cells was performed by qRT-PCR and western blotting. In addition, the scratch wound healing assay was conducted for cell migration.

Results

The data indicated that curcumin-induced cell death is independent of apoptosis in this type of thyroid cancer cell line. Furthermore, significantly reduced GLUT1 and GLUT3 expression was observed after treatment with curcumin, resulting in the inhibition of glucose uptake (P < 0.05). Scratch assay indicated the inhibition of cell migration in SW1736 cells treated with curcumin (P < 0.05).

Conclusion

It can be concluded that GLUTs, as metabolic targets, can be blocked specifically by curcumin for thyroid cancer prevention. Curcumin, as a promising anti-cancer agent, inhibits the growth of SW1736 anaplastic thyroid cancer cells by regulating the glucose uptake pathway and cell death. Altogether, these results suggest that the glucose pathway may be an essential target for therapeutic intervention to sensitize tumor cells to the cell death process by inhibition of glucose transporters.

Statement of translational relevance

As described in our previously published article, ‘Regulators of glucose uptake in thyroid cancer cell lines’, non-oncogene addiction is one of the recent principles of cancer therapy. Moreover, herein, for the first time, we decided to investigate the anti-thyroid cancer effects of a bioactive phytochemical and establish a signaling link between curcumin and the glucose uptake metabolism of anaplastic thyroid cancer cells. This title covers the entire range of the biological sciences, and we attempt to fill the gaps between cell biology, medicine, cancer and plant knowledge. The influence of cancer on human society is indescribable. Human studies are often contradictory around the effects of polyphenols against cancer. We believe that it is important to draw boundaries between the usages of polyphenols in cancer prevention versus cancer treatment. We anticipate that this study’s findings will contribute to a better understanding of the mechanism underlying curcumin’s anti-cancer properties, providing a theoretical foundation for the future clinical application of curcumin-related medications.

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Xiaodan Zhai Department of Endocrinology and Metabolism, Institute of Endocrinology, National Health Commission Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, Liaoning, P. R. China
Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, P. R. China

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Yongze Li Department of Endocrinology and Metabolism, Institute of Endocrinology, National Health Commission Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, Liaoning, P. R. China

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Xiaochun Teng Department of Endocrinology and Metabolism, Institute of Endocrinology, National Health Commission Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, Liaoning, P. R. China

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Weiping Teng Department of Endocrinology and Metabolism, Institute of Endocrinology, National Health Commission Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, Liaoning, P. R. China

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Xiaoguang Shi Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, P. R. China

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Zhongyan Shan Department of Endocrinology and Metabolism, Institute of Endocrinology, National Health Commission Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, Liaoning, P. R. China

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It is estimated that by the year 2050, 16% of the world’s population will be 65 years old and above. As the global aging population continues to grow, there is an increasing focus on thyroid disorders among older individuals. Thyrotropin is widely used in diagnosing subclinical thyroid diseases due to its high sensitivity as an indicator of changes in thyroid function. However, thyrotropin levels change with age, and different reference intervals have been proposed in various studies. The variation in thyrotropin ranges among older adults is probably caused by the heterogeneity of the studied population. This review aims to provide an overview of the existing literature on thyrotropin reference intervals in older adults and their distinction as adaptive or pathologic. Recent research indicates that older individuals may have slightly elevated levels of thyrotropin and higher upper limits of reference intervals. Therefore, a higher thyrotropin threshold for diagnosing and treating subclinical hypothyroidism in the elderly seems reasonable.

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Yujie Ren Department of Endocrinology and Metabolism, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China

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Yujiang Li Department of Endocrinology and Metabolism, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China

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Xiaoqiu Chu Department of Endocrinology and Metabolism, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China

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Guofang Chen Department of Endocrinology and Metabolism, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
Key Laboratory of TCM Syndrome and Treatment of Yingbing (Thyroid Disease) of State Administration of Traditional Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China

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Xue Han Department of Endocrinology and Metabolism, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China

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Yueting Zhao Department of Endocrinology and Metabolism, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China

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Chao Liu Department of Endocrinology and Metabolism, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
Key Laboratory of TCM Syndrome and Treatment of Yingbing (Thyroid Disease) of State Administration of Traditional Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China

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Jianhua Wang Key Laboratory of TCM Syndrome and Treatment of Yingbing (Thyroid Disease) of State Administration of Traditional Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
Department of General Surgery, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China

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Shuhang Xu Department of Endocrinology and Metabolism, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China

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Objective

To evaluate the therapeutic effects of microwave ablation (MWA) versus surgery in treating low-risk papillary thyroid microcarcinoma (PTMC) and to assess recurrence-free survival (RFS) in patients with and without the BRAFV600E mutation.

Methods

Between August 2016 and September 2022, 158 patients diagnosed with low-risk PTMC treated with MWA and 288 patients who underwent surgical treatment were retrospectively analyzed. All patients were followed-up for over a year. Local tumor progression (LTP), RFS and adverse events associated with both treatments were monitored. Following propensity score matching (PSM), comparisons were made regarding LTP, RFS, complications and treatment variables.

Results

Prior to matching, MWA patients were younger than those in the surgery group (38 (30.75, 47) vs 43 (34, 50.75), P = 0.000). Tumors treated with MWA had smaller maximum diameters (5.7 (4.6, 7.0) vs 6.9 (5.8, 8.6), P = 0.000) and volumes (70.7 (35.2, 120.9) vs 122.0 (63.9, 228.8), P = 0.000). After 1:1 PSM, each group contained 141 patients with comparable baseline characteristics. During the follow-up, LTP developed in nine patients: six in the MWA group and three in the surgery group. There were no cases of distant metastasis or cancer-related deaths. Adjusting for age, sex, tumor location and largest diameter, there was no significant association between treatment modality and recurrence (HR = 3.75, 95% CI: 0.94–14.98, P = 0.062). There were no significant differences in RFS between patients with and without the BRAFV600E mutation in both groups (P = 0.45 and 0.74, respectively). Furthermore, the incidence of complications was comparable between treatments.

Conclusion

Both MWA and surgical treatment offer similar efficacy and safety profiles for managing low-risk PTMC. MWA may represent a viable alternative to conventional surgical approaches, especially for patients harboring the BRAFV600E mutation.

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Julia Rohayem Centre of Reproductive Medicine and Andrology, University Hospital Münster, Münster, Germany
Children’s Hospital of Eastern Switzerland, St. Gallen, Switzerland

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Jan Idkowiak Department of Metabolism and Systems Science, College of Medicine and Health, University of Birmingham, Birmingham, United Kingdom
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, University of Birmingham, Birmingham, United Kingdom
Department of Endocrinology and Diabetes, Birmingham Children’s Hospital, Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham, United Kingdom

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Sebastian Huss Institute of Pathology, University Hospital Münster, Münster, Germany

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Thomas Balke Centre of Reproductive Medicine and Andrology, University Hospital Münster, Münster, Germany

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Hendrik Schürmann Institute of Pathology, University Hospital Münster, Münster, Germany
Department of Medical Oncology, University Hospital Essen, Essen, Germany

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Birthe Heitkötter Institute of Pathology, University Hospital Münster, Münster, Germany

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Joachim Wistuba Centre of Reproductive Medicine and Andrology, University Hospital Münster, Münster, Germany

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Angela Huebner Children’s Hospital, Universitätsklinikum Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany

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Human chorionic gonadotropin (hCG) has structural similarities with thyroid-stimulating hormone (TSH) and may stimulate TSH receptors at higher concentrations. During pregnancy, placental hCG causes TSH suppression, contributing to hyperemesis. However, in males, clinical manifestations caused by excess hCG are rare. Herein, we describe complications of life-threatening thyroid storm caused by paraneoplastic hCG secretion from testicular germ cell tumours (GCTs) and aim to identify high-risk groups through retrospective analysis in n = 20 males (aged 17–55 years) with testicular hCG-positive GCTs. Seven hCG-positive testicular GCTs were classified as seminoma, and 13 were classified as non-seminomatous GCTs (NSGCTs). In 3/7 males with seminomas (43%), serum β-hCG concentrations were mildly elevated (median: 0.3 U/L; range: 0.3–82.1 U/L). In contrast, β-hCG was increased in 12/13 (92%) males with a NSGCT (median: 71.1 U/L; range: 0.3–1,600,000 U/L). In 10/13 males with NSGCT (77%), we detected components of embryonal cell carcinoma (EC), and in 7/13 (54%), we detected components of a choriocarcinoma (ChC). TSH was suppressed with high free thyroxine levels in two cases with NSGCT and excessively elevated β-hCG concentrations, but there was no TSH suppression in a further case with high β-hCG. One patient with NSGCT and high β-hCG levels presented with thyroid storm and imminent decompensation refractory to anti-thyroid treatment, requiring a total thyroidectomy. In the second patient, anti-thyroid treatment was initiated shortly after the diagnosis, successfully normalizing hyperthyroxinaemia. In conclusion, paraneoplastic β-hCG production, occurring in NSGCTs with components of ECs or ChCs, is a rare cause of thyrotoxicosis. Early recognition and treatment are critical to prevent a life-threatening thyroid storm.

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Sannia Mia Svenningsen Sjöstedt Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Christoffer Holst Hahn Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Åse Krogh Rasmussen Department of Endocrinology and Metabolism, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Peter Sandor Oturai Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Per Karkov Cramon Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Introduction

Incidental uptake within or adjacent to the thyroid gland is occasionally observed on somatostatin receptor-targeted PET imaging in patients with neuroendocrine neoplasms (NENs). The reported prevalence and clinical relevance of such findings are not well established.

Materials and methods

We reviewed PET scan reports for all patients undergoing [68Ga]Ga-DOTA-TOC PET/CT or [64Cu]Cu-DOTA-TATE PET/CT in our department from 2018 to 2022. Scans reporting incidental uptake within or adjacent to the thyroid gland were reviewed post hoc to extract semi-quantitative scores of tracer uptake for the incidental lesions. We further extracted data from electronic patient charts, including cytology and histology.

Results

A total of 3692 PET scans were performed on 1808 unique patients. Incidental abnormal thyroid uptake was reported in 42 of the 1808 patients, with thyroid malignancy identified in five of these 42 patients. Two patients had medullary thyroid cancers, two had neuroendocrine tumor metastases, and one had a renal clear cell carcinoma metastasis. Focal uptake in close relation to the thyroid gland, suggestive of parathyroid adenoma, was reported in another 13 of the 1808 patients, with biochemical hyperparathyroidism found in six of these 13 patients.

Conclusion

In patients undergoing somatostatin receptor-targeted PET scans for evaluation of NENs, the prevalence of reported abnormal uptake within or adjacent to the thyroid gland was low. However, the rates of thyroid malignancy and parathyroid adenomas were substantial. Prospective studies are needed to determine the optimal diagnostic and therapeutic strategies for these incidental findings.

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Weiwei Liang Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

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Junxin Chen Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

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Hai Li Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

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Pengyuan Zhang Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

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Hongyu Guan Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

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Yanbing Li Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

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Background

Collagen type VIII α 1 chain (COL8A1), a collagen type VIII protein, has been suggested to exert various functions in progression of multiple cancers. However, the effect of COL8A1 in papillary thyroid cancer (PTC) has not been elucidated.

Methods

The Cancer Genome Atlas (TCGA) databases were applied to investigate the COL8A1 expression and its clinical significance in PTC. The COL8A1 expression level was further validated using Gene Expression Omnibus (GEO) data and clinical paired PTC tissues. Additionally, the Kaplan–Meier curve was used to analyze the prognosis. The cell’s migrative and invasive abilities were evaluated by wound healing assay and Transwell assay. CCK8 assays were used to evaluate the proliferation of PTC cells. Western blotting was conducted to explore the potential mechanisms involved in the pro-tumor role of COL8A1. The correlation between immune cell infiltration and COL8A1 was analyzed using the Tumor Immune Estimation Resource (TIMER) database and the single-sample GSEA (ssGSEA) method.

Results

We found that COL8A1 was upregulated in PTC (P < 0.05). High COL8A1 expression level was significantly associated with advanced T stage (P < 0.01), N stage (P < 0.001) and poor prognosis (P = 0.0142) in PTC. Furthermore, cell migration and invasion were significantly reduced following COL8A1 knockdown (P < 0.001). Mechanistic studies demonstrated that the epithelial-to-mesenchymal transition (EMT) related proteins (FN1, MMP9, MMP7, ZEB2 and Twist1) and phosphorylation of AKT and ERK were obviously down-regulated after COL8A1 knockdown (P < 0.01). Moreover, COL8A1 expression was correlated with immune cell infiltration.

Conclusion

Our study demonstrates that COL8A1 may function as an oncogene and a potential prognostic biomarker for PTC patients.

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Tal Almagor Pediatric Endocrine Institute, Ha’Emek Medical Center, Afula, Israel

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Shlomo Almashanu The National Newborn Screening Program, Ministry of Health, Tel Hashomer, Ramat Gan, Israel

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Ghadir Elias-Assad Pediatric Endocrine Center, Clalit Health Services, Northern Region, Israel

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Osnat Admoni Pediatric Endocrine Center, Clalit Health Services, Northern Region, Israel

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Hanna Ludar Pediatric Health Center, Clalit Health Services, Haifa, Israel

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Shira London Pediatric Health Center, Clalit Health Services, Haifa, Israel

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Shoshana Rath Pediatric Endocrine Center, Clalit Health Services, Northern Region, Israel
Pediatric Endocrinology Service, Northern Health Center, Poria, Israel

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Alina German Pediatric Endocrine Institute, Ha’Emek Medical Center, Afula, Israel

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Naama Shwartz Department of Epidemiology, Carmel Medical Center, Haifa, Israel

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Yardena Tenenbaum-Rakover The Ruth & Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel
Children's Endocrinology Consulting Center, Clalit Health Services, Afula, Israel

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Objectives

The incidence of congenital hypothyroidism (CH) has increased worldwide over the last decades, mainly due to the lowering of screening thresholds, resulting in the increased identification of newborns with transient CH. Several studies have reported the prevalence and the predictive parameters of transient CH, but reports on the long-term outcome are rare. This study aimed to assess the long-term course of neonates with transient CH.

Design

Neonates diagnosed with transient and permanent CH between the years 1998 and 2018 at the Pediatric Endocrine Institute of Ha’Emek Medical Center were enrolled in the study. Data were retrieved retrospectively from medical files.

Results

A total of 76 newborns (45M, 59%) with transient CH and 53 (25M, 47%) with permanent CH were included in the study. The major causes of transient CH were prematurity (29%) and subclinical hypothyroidism (30%). During retrospective follow-ups of up to 23 years, reinitiation of levothyroxine therapy was not required, apart from four patients with underlying syndromic etiologies. Neurodevelopmental impairment occurred in 16% of children with transient CH compared with 29.4% in the permanent CH group.

Conclusions

Transient CH is frequent among preterm infants but is generally limited to infancy. Subclinical hypothyroidism frequently presents as overt hypothyroidism at birth, but in most cases, the requirement for levothyroxine supplemental therapy is limited to the first years of life, suggesting that long-term follow-up of thyroid function tests may be unnecessary for non-syndromic children. The high rate of neurodevelopmental impairment in newborns with transient CH emphasizes the need for neurodevelopmental monitoring in these patients.

Significance statement

A high rate of transient CH has been identified over the past decades following the lowering of TSH screening thresholds. The long-term outcome of transient CH has been evaluated in a few studies with inconclusive results. In the current study, we assessed the long-term outcomes of transient CH for up to 23 years. We found that 29% of cases were attributed to prematurity and 30% to subclinical hypothyroidism. No morphological anomalies were identified. Only syndromic patients (three with Down syndrome and one with Coffin-Lowry syndrome) required levothyroxine supplemental therapy at the time of the study, indicating that long-term thyroid function monitoring may be unnecessary. The high prevalence of neurodevelopmental impairment suggests the need for close neurodevelopmental monitoring in this population.

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