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Hui Li Department of Thyroid Surgery, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan, P. R. China.

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Peng Wu Department of Thyroid Surgery, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan, P. R. China.

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Background

Epigenetics, which involves regulatory modifications that do not alter the DNA sequence itself, is crucial in the development and progression of thyroid cancer. This study aims to provide a comprehensive analysis of the epigenetic research landscape in thyroid cancer, highlighting current trends, major research areas, and potential future directions.

Methods

A bibliometric analysis was performed using data from the Web of Science Core Collection (WOSCC) up to 1 November 2023. Analytical tools such as VOSviewer, CiteSpace, and the R package ‘bibliometrix’ were employed for comprehensive data analysis and visualization. This process identified principal research themes, along with influential authors, institutions, and countries contributing to the field.

Results

The analysis reveals a marked increase in thyroid cancer epigenetics research over the past two decades. Emergent key themes include the exploration of molecular mechanisms and biomarkers, various subtypes of thyroid cancer, implications for therapeutic interventions, advancements in technologies and methodologies, and the scope of translational research. Research hotspots within these themes highlight intensive areas of study and the potential for significant breakthroughs.

Conclusion

This study presents an in-depth overview of the current state of epigenetics in thyroid cancer research. It underscores the potential of epigenetic strategies as viable therapeutic options and provides valuable insights for researchers and clinicians in advancing the understanding and treatment of this complex disease. Future research is vital to fully leverage the therapeutic possibilities offered by epigenetics in the management of thyroid cancer.

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Nishchil Patel N Patel, Endocrinology and Diabetes, University Hospitals Plymouth NHS Trust, Plymouth, PL6 8DH, United Kingdom of Great Britain and Northern Ireland

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Kagabo Hirwa K Hirwa, Department of Endocrinology, University Hospitals Plymouth NHS Trust, Plymouth, United Kingdom of Great Britain and Northern Ireland

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Gemma Gardner G Gardner, Endocrinology and Diabetes, University Hospitals Plymouth NHS Trust, Plymouth, United Kingdom of Great Britain and Northern Ireland

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Kirsten Pearce K Pearce, Department of Neuroradiology, University Hospitals Plymouth NHS Trust, Plymouth, United Kingdom of Great Britain and Northern Ireland

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Jinny Jeffery J Jeffery, Department of Biochemistry, University Hospitals Plymouth NHS Trust, Plymouth, United Kingdom of Great Britain and Northern Ireland

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Fizzah Iqbal F Iqbal, Morriston Hospital, Swansea, United Kingdom of Great Britain and Northern Ireland

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Daniel Flanagan D Flanagan, Department of Endocrinology, University Hospitals Plymouth NHS Trust, Plymouth, United Kingdom of Great Britain and Northern Ireland

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Aim: To define functional and anatomical pituitary disease following ICI therapy and describe any change in pituitary function with time.

Methods: Retrospective observational audit of patients on ICI therapy in our centre between 2013 and 2023. We reviewed all patients on ICI therapy under the oncology department at University Hospital Plymouth, and identified individuals referred to endocrinology with suspected adrenal insufficiency. Patients were established on adrenal steroid replacement and subsequently underwent formal pituitary testing. Pituitary disease was evidenced by low ACTH, other pituitary dysfunction and/or abnormalities on pituitary imaging.

Results: 954 patients received ICI therapy during the study period, and 37 developed HPA axis dysfunction. Median interval of onset of symptoms was 4 months. There was no recovery in cortisol or ACTH for any individual on repeated testing. Other permanent anterior pituitary hormone defects were unusual. Hypophysitis associated with immunotherapy appears to specifically target corticotrophs with no evidence of recovery. There was a specific abnormality seen in MRI scans of 7 of 27 patients who had scans, appearing to be a particular feature of immune mediated hypophysitis. These were confined to the anterior aspect of the pituitary as striations and were not visible on any scans performed more than three months after disease onset.

Conclusion: These data show that immune related (IR) hypophysitis is a common complication of immune checkpoint inhibitor therapy. This may result in an imaging abnormality within the areas of the pituitary richest in corticotrophs. The endocrine consequence of this is a permanent defect in ACTH and therefore cortisol production.

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Shuqi Li S Li, Department of Endocrinology, Zhongshan Hospital Fudan University, Shanghai, China

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Chenye Shi C Shi, Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, China

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Haifu Wu H Wu, Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, China

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Hongmei Yan H Yan, Department of Endocrinology, Zhongshan Hospital Fudan University, Shanghai, China

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Mingfeng Xia M Xia, Department of Endocrinology, Zhongshan Hospital Fudan University, Shanghai, China

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Heng Jiao H Jiao, Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, China

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Yang He Y He, Department of Endocrinology, Zhongshan Hospital Fudan University, Shanghai, China

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Ming Zhong M Zhong, Department of Critical Care Medicine, Zhongshan Hospital Fudan University, Shanghai, China

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Wenhui Lou W Lou, Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, China

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Xin Gao X Gao, Department of Endocrinology, Zhongshan Hospital Fudan University, Shanghai, China

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Hua Bian H Bian, Department of Endocrinology, Zhongshan Hospital Fudan University, Shanghai, China

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Xinxia Chang X Chang, Department of Endocrinology, Zhongshan Hospital Fudan University, Shanghai, China

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Background: Bariatric surgery induces significant weight loss, increases insulin sensitivity and improves dyslipidemia. As one of the most widely performed bariatric surgeries, laparoscopic sleeve gastrectomy (LSG) is thought to improve metabolic profile along with weight loss. The objective of this study was to evaluate longitudinal changes in serum metabolite levels after LSG and elucidate the underlying mechanisms of metabolic improvement.

Methods: Clinical metabolic parameters and serum samples were collected preoperatively and at 1, 3, and 6 months postoperatively from nine patients with obesity undergoing LSG. Serum metabolites were measured using non-targeted metabolic liquid chromatography-mass spectrometry (LC-MS) method.

Results: During the 1, 3, and 6 months postoperative follow-up, the BMI, HOMA-IR, liver fat content showed a gradual descending trend. A total of 328 serum metabolites were detected and 38 were differentially expressed. The up-regulated metabolites were mainly enriched in ketone body metabolism, alpha linolenic acid and linoleic acid metabolism, pantothenate and CoA biosynthesis, glycerolipid metabolism, fructose and mannose degradation, while the down-regulated metabolites were closely related to caffeine metabolism, oxidation of branched chain fatty acids, glutamate metabolism, and homocysteine degradation. Notably, nine metabolites (oxoglutarate, 2-ketobutyric acid, succinic acid semialdehyde, phthalic acid, pantetheine, eicosapentaenoate, 3-hydroxybutanoate, oxamic acid, and dihydroxyfumarate) showed persistent differential expression at 1, 3, and 6 months follow-up. Some were found to be significantly associated with weight loss, insulin resistance improvement and liver fat content reduction.

Conclusions: This finding may provide a new perspective for revealing novel biomarkers and mechanisms of metabolic improvement in obesity and related comorbidities.

Open access
Junhui Zhang J Zhang, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China

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Hongyan Zhang H Zhang, Department of Histology and Embryology, Anhui Medical University, Hefei, China

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Bao Guo B Guo, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China

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Jun Yang J Yang, Anhui Medical University, Hefei, China

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Renxiang Yu R Yu, Anhui Medical University, Hefei, China

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Wenxiu Chen W Chen, Department of Histology and Embryology, Anhui Medical University, Hefei, China

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Muxin Zhai M Zhai, Anhui Medical University, Hefei, China

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Cao Yuhan C Yuhan, Anhui Medical University, Hefei, China

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Yajing Liu Y Liu, NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei, China

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Qiang Hong Q Hong, Department of Histology and Embryology, Anhui Medical University, Hefei, 230032, China

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Fenfen Xie F Xie, Department of Histology and Embryology, Anhui Medical University, Hefei, 230032, China

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The elevated level of hepatic oxidative stress (OS) in polycystic ovary syndrome (PCOS) is one of the important causes of liver abnormalities. Therefore, decreasing the level of hepatic OS in PCOS is beneficial to reduce the risk of PCOS-related liver diseases. Melatonin (MT), recognized as a potent antioxidant. Nevertheless, the efficacy of MT in alleviating hepatic OS associated with PCOS is yet to be established, and the precise mechanisms through which MT exerts its antioxidant effects remain to be fully elucidated. The aim of this study was to explore the potential mechanism by which MT reduces hepatic OS in PCOS. First, we detected elevated OS levels in the PCOS samples. Subsequently, with MT pretreatment, we discovered that MT could significantly diminish the levels of OS, liver triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT) and aspartate aminotransferase (AST),while concurrently ameliorating mitochondrial structural damage in PCOS liver. Furthermore, we identified elevated autophagy levels in the liver of PCOS rats and an inhibition of the Keap1-Nrf2 pathway. Through MT pretreatment, the expression of LC3 was significantly decreased, while the Keap1-Nrf2 pathway was activated. Our study showed that MT could affect the Nrf2 pathway dependent on the P62/LC3 autophagy pathway, thereby attenuating hepatic OS in PCOS. These findings offer novel insights and research avenues for the study of PCOS-related liver diseases.

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Agata Hanna Bryk-Wiązania Chair and Department of Endocrinology, Jagiellonian University Medical College, Krakow, Poland
Department of Endocrinology, Oncological Endocrinology and Nuclear Medicine, University Hospital, Krakow, Poland

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Mari Minasyan Department of Endocrinology, Oncological Endocrinology and Nuclear Medicine, University Hospital, Krakow, Poland

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Alicja Hubalewska-Dydejczyk Chair and Department of Endocrinology, Jagiellonian University Medical College, Krakow, Poland
Department of Endocrinology, Oncological Endocrinology and Nuclear Medicine, University Hospital, Krakow, Poland

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Aleksandra Gilis-Januszewska Chair and Department of Endocrinology, Jagiellonian University Medical College, Krakow, Poland
Department of Endocrinology, Oncological Endocrinology and Nuclear Medicine, University Hospital, Krakow, Poland

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Objective

Cushing’s syndrome (CS) is associated with an 18-fold greater risk of venous thromboembolism (VTE). We aimed to identify factors which provoke VTE among patients with CS and VTE and to describe the anticoagulant regimen used in these cases.

Methods

In this retrospective observational study, patients included in the European Registry on CS (ERCUSYN) in Krakow center, Poland, were followed for the occurrence of VTE and anticoagulant treatment. We identified factors provoking VTE according to the International Society of Thrombosis and Hemostasis (ISTH), along with factors included in the Padua score and CS-VTE score.

Results

Of the 128 patients followed for a median of 4.3 years, there were nine patients who experienced ten VTE episodes (prevalence of 7.8% and incidence of 13.4 per 1000 patient-years). All VTEs were classified as provoked according to the ISTH guidance, predominantly due to the transient major and minor (50% and 20%, respectively) factors, while they were less commonly due to persistent (30%) factors. In 2/9 patients, we could not identify any risk factor for VTE according to the Padua score, while in 2/6 patients according to the CS-VTE score. Patients were mostly anticoagulated with vitamin K antagonists (4/8 patients), followed by direct oral anticoagulants (3/8) and low-molecular-weight heparin (1/8). The median duration of anticoagulation was 2.75 years and exceeded beyond the primary treatment in 28% of episodes provoked by transient factors.

Conclusion

Further, multicenter studies are required to create a validated thrombotic risk score and guidelines regarding VTE treatment in CS patients.

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Waleed K W Al-Badri Orbital center Amsterdam, Department of Ophthalmology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands

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Hinke Marijke Jellema Orbital center Amsterdam, Department of Ophthalmology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands

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Arnaud R G G Potvin Orbital center Amsterdam, Department of Ophthalmology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands

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Ruth M A van Nispen Amsterdam University Medical Center, Vrije Universiteit, Department of Ophthalmology, Amsterdam Public Health research institute, Amsterdam, the Netherlands

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Peter H Bisschop Department of Endocrinology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands

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Peerooz Saeed Orbital center Amsterdam, Department of Ophthalmology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands

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Purpose

This review aims to discuss the psychological aspects of Graves’ ophthalmopathy (GO), estimate the prevalence of depression and anxiety disorders in GO, examine whether these psychiatric disorders are more prevalent in GO than in Graves’ disease (GD) without eye disease, and evaluate the main contributors for depression and anxiety in GO.

Methods

A review of the literature.

Results

Both depression and anxiety are associated with GO. The prevalence of depression and anxiety disorders specifically in GO patients was estimated at 18–33% and 26–41%, respectively. The reported prevalence in GD patients ranged from 9% to 70% for depression and from 18% to 88% for anxiety disorders. Significantly higher levels of depression and anxiety were found in GD patients compared with patients with non-autoimmune hyperthyroidism. Conflicting results have been reported regarding the association of antithyroid autoantibodies with depression and anxiety disorders. Serum thyroid hormone levels do not correlate with the severity of depression and anxiety. An improvement of psychiatric symptoms is observed in hyperthyroid patients after treatment of thyrotoxicosis. Moreover, depression and anxiety are significantly related to impaired quality of life (QoL) in GO. Exophthalmos and diplopia were not associated with depression nor anxiety, but orbital decompression and strabismus surgery do seem to improve QoL in GO patients.

Conclusions

The results of this review suggest that altered thyroid hormone levels and autoimmunity are prognostic factors for depression and anxiety in GO. With regard to the visual and disfiguring aspects of GO as contributing factors for depression and anxiety, no decisive conclusions can be made.

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Xu-Feng Chen X Chen, Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, China

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Cong He C He, Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, China

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Peng-Cheng Yu P Yu, Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, China

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Wei-Dong Ye W Ye, Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, China

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Peizhen Han P Han, Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, China

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Jia-Qian Hu J Hu, Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, China

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Yulong Wang Y Wang, Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, China

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Next-generation sequencing (NGS) is of great benefit to clinical practice in terms of identifying genetic alterations. This study aims to clarify the gene background and its influence on thyroid tumor in Chinese population. NGS data and corresponding clinicopathological features (sex, age, tumor size, extrathyroidal invasion, metastasis, multifocality and TNM stage) were collected and analyzed retrospectively from 2844 individual thyroid tumor samples during July 2021 to August 2022. 2337 (82%) of the cohort possess genetic alterations including BRAF (71%), RAS (4%), RET/PTC (4%), TERT (3%), RET (2.2%) and TP53 (1.4%). Diagnostic sensitivity before surgery can be significantly increased from 0.76 to 0.91 when cytology is supplemented by NGS. Our results show that BRAF positive papillary thyroid cancer (PTC) patients tend to have elder age, smaller tumor size, less vascular invasion, more frequent tumor multifocality and significantly higher cervical lymph node metastatic rate. Mutation at RET gene codon 918 and 634 is strongly correlated with medullary thyroid cancer (MTC), However it did not display more invasive clinical characteristics. TERT positive patients are more likely to have elder age, larger tumor size, more tumor invasiveness, and more advanced TNM stage, indicating poor prognosis. Patients with TERT, RET/PTC1 and CHEK2 mutation are more susceptible to lateral lymph node metastasis. In conclusion. NGS can be a useful tool which provides practical gene evidence in the process of diagnosis and treatment in thyroid tumors.

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Pamela Stratton Office of the Clinical Director, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA

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Neelam Giri Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

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Sonia Bhala Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

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Martha M Sklavos Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA

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Blanche P Alter Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

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Sharon A Savage Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

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Ligia A Pinto Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA

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Fanconi anemia (FA), dyskeratosis congenita-related telomere biology disorders (DC/TBD), and Diamond–Blackfan anemia (DBA) are inherited bone marrow failure syndromes (IBMFS) with high risks of bone marrow failure, leukemia, and solid tumors. Individuals with FA have reduced fertility. Previously, we showed low levels of anti-Müllerian hormone (AMH), a circulating marker of ovarian reserve, in females with IBMFS. In males, AMH may be a direct marker of Sertoli cell function and an indirect marker of spermatogenesis. In this study, we assessed serum AMH levels in pubertal and postpubertal males with FA, DC/TBD, or DBA and compared this with their unaffected male relatives and unrelated healthy male volunteers. Males with FA had significantly lower levels of AMH (median: 5 ng/mL, range: 1.18–6.75) compared with unaffected male relatives (median: 7.31 ng/mL, range: 3.46–18.82, P = 0.03) or healthy male volunteers (median: 7.66 ng/mL, range: 3.3–14.67, P = 0.008). Males with DC/TBD had lower levels of AMH (median: 3.76 ng/mL, range: 0–8.9) compared with unaffected relatives (median: 5.31 ng/mL, range: 1.2–17.77, P = 0.01) or healthy volunteers (median: 5.995 ng/mL, range: 1.57–14.67, P < 0.001). Males with DBA had similar levels of AMH (median: 3.46 ng/mL, range: 2.32–11.85) as unaffected relatives (median: 4.66 ng/mL, range: 0.09–13.51, P = 0.56) and healthy volunteers (median: 5.81 ng/mL, range: 1.57–14.67, P = 0.10). Our findings suggest a defect in the production of AMH in postpubertal males with FA and DC/TBD, similar to that observed in females. These findings warrant confirmation in larger prospective studies.

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Ayanthi Wijewardene A Wijewardene, Endocrinology, St Leonards, 2066, Australia

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Matti Gild M Gild, Department of Endocrinology, Royal North Shore Hospital, St Leonards, Australia

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Lyndal J Tacon L Tacon, St Leonards, Australia

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Venessa Tsang V Tsang, Cancer Genetics, Kolling Institute of Medical Research, St Leonards, Australia

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Anthony J Gill A Gill, Dept of Anatomical Pathology, Royal North Shore Hospital, St Leonards, Australia

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Anthony R. Glover A Glover, St Leonards, Australia

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Mark Sywak M Sywak, Department of Endocrine Surgery, Royal North Shore Hospital, St Leonards, Australia

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Stan Sidhu S Sidhu, Department of Endocrine Surgery, Royal North Shore Hospital, St Leonards, Australia

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Bruce G Robinson B Robinson, St Leonards, Australia

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Paul Roach P Roach, Department of Nuclear Medicine, Royal North Shore Hospital, St Leonards, Australia

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Geoffrey Schembri G Schembri, Department of Nuclear Medicine, Royal North Shore Hospital, St Leonards, Australia

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Jeremy Hoang J Hoang, Department of Nuclear Medicine, Royal North Shore Hospital, St Leonards, Australia

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Roderick Clifton-Bligh R Clifton-Bligh, Endocrinology, Royal North Shore Hospital, Sydney, Australia

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Background: Noise, an unwanted variability in judgement, is ubiquitous in medicine, including in the prescription of radioactive iodine (RAI). Building upon our recently developed predictive risk model, we created an online clinical support tool to facilitate the translation of our model into clinical practice. The aim of this study is to assess the utility of an online clinical support tool to reduce noise in the treatment for patients with DTC.

Methods: The tool was accessible via weblink or a QR code. Activity recommendations were applied to the calculators four risk catgeories: 0GBq for very low risk, 1GBq for low risk; 4GBq for intermediate risk, and 6GBq for high risk. The tool was applied prospectively to 103 patients who received RAI at Royal North Shore Hospital between 2021-2022, and retrospectively to 393 patients treated with RAI between 2017-2021.

Results: A significant difference was observed in administered activity between the 2021-2022 vs 2017-2021cohorts in patients stratified as intermediate (median activity 3.95GBq, IQR 2.03-4.04 vs 4GBq, 4-4), and high risk (4.07GBq, 3.95-5.7 vs 6GBq, 6-6) with p-values of 0.01 and <0.01 respectively. No difference was seen in low risk patients (2.01GBq, 1.03-3.98 vs 1GBq, 1-4,p = 0.30). Additionally, no clinically significant recurrence was observed between the two cohorts (6.6% vs 4.5%,p = 0.628).

Conclusion: Optimal risk classification and activity recommendation continues to be established; our data suggests providing risk stratification and activity recommendation in an easy to access online tool can reduce noise and variability in activity prescription for patients with DTC.

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Yunting Lin Department of Surgical Medicine, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China

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Endi Song Department of Internal Medicine, Ningbo Yinzhou No.2 Hospital, Ningbo, Zhejiang, China

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Han Jin Department of Medicine, Ningbo University, Ningbo, Zhejiang, China

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Yong Jin Department of Internal Medicine, Ningbo Yinzhou No.2 Hospital, Ningbo, Zhejiang, China

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Background

Reproductive hormones may be a risk factor for cardiovascular disease (CVD), but their influence is often underestimated. Obesity can exacerbate the progression of CVD. Arterial stiffness (AS) is correlated with the risk of CVD. Brachial-ankle pulse wave velocity (baPWV) has served as a practical tool for assessing AS with broad clinical applications. This study aimed to investigate the association between reproductive hormones and baPWV in obese male and female subjects.

Methods

A retrospective case–control design was designed. AS was assessed using baPWV, with a baPWV ≥ 1400 cm/s indicating increased AS. Between September 2018 and October 2022, 241 obese subjects with increased AS were recruited from Ningbo Yinzhou No. 2 Hospital. The control group consisted of 241 obese subjects without increased AS. A 1:1 propensity score matching was performed to correct potential confounders by age and sex. We additionally performed a sex-based sub-analysis.

Results

Correlation analysis demonstrated that luteinizing hormone (LH) (r = 0.214, P = 0.001) and follicle-stimulating hormone (FSH) (r = 0.328, P < 0.001) were positively correlated with baPWV in obese male subjects. In the multivariate conditional logistic regression analysis, FSH (OR = 1.407, 95% CI = 1.040–1.902, P = 0.027) rather than LH (OR = 1.210, 95% CI = 0.908–1.612, P = 0.194) was independently and positively associated with increased AS in obese male subjects. However, there was no significant correlation between reproductive hormones and baPWV in women.

Conclusions

Our study identified FSH as a potential risk factor for arteriosclerosis in obese male subjects. This provides a novel and intriguing perspective on the pathogenesis of CVD in obese subjects.

Open access