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Shams Ali Baig S Ali Baig, University of Birmingham College of Medical and Dental Sciences, Birmingham, B15 2TT, United Kingdom of Great Britain and Northern Ireland

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Kashish Malhotra K Malhotra, Department of Surgery, Dayanand Medical College and Hospital, Ludhiana, India

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Mukunth Kowsik M Kowsik, University of Birmingham, Birmingham, United Kingdom of Great Britain and Northern Ireland

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Josh Banerjee J Banerjee, University of Birmingham, Birmingham, United Kingdom of Great Britain and Northern Ireland

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Fazna Rahman F Rahman, University of Birmingham, Birmingham, United Kingdom of Great Britain and Northern Ireland

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Ashmethaa Ashokkumar A Ashokkumar, University of Birmingham, Birmingham, United Kingdom of Great Britain and Northern Ireland

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Caroline Gillett C Gillett, University of Birmingham, Birmingham, United Kingdom of Great Britain and Northern Ireland

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Punith Kempegowda P Kempegowda, University of Birmingham, Birmingham, B15 2TT, United Kingdom of Great Britain and Northern Ireland

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Objectives: To investigate the utility and effectiveness of a school outreach programme in areas of lower socioeconomic status to improve understanding of common endocrine topics and the medical profession.

Methods: Two secondary school outreach sessions were conducted in July 2022. Students were invited to attend lectures delivered by medical professionals and engage in poster-making sessions using the knowledge they had gained throughout the day. Participants completed anonymised pre- and post-session surveys. Outcomes were identified using Kirkpatrick’s training evaluation model. Self-reported perceptions and beliefs (Kirkpatrick’s Level 2a) were compared using chi-square tests. Thematic analysis of team-led poster presentations was performed.

Results: Of the 254 participants included, the response rates of pre- and post-session questionnaires were 75.6% and 56.2%, respectively. The outreach day increased students’ understanding of Obesity and Diabetes, PCOS, and Health Technology. The most well-received activities from the outreach day were voted to be the poster challenge (43.4%) and poster presentation (14.7%). Following the session, there was a trend towards an increased understanding of medical careers and interest in pursuing a medical career, although these did not reach statistical significance.

Conclusions: Outreach programmes could be a practical and effective approach to engaging prospective medical applicants from areas of lower socioeconomic status. Further studies are required to expand outreach programmes to investigate the efficacy of school engagement programmes.

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

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Junxin Chen J Chen, Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, Guang Zhou, China

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

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

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

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Yanbing Li Y Li, Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, Guanzhou, 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, Kaplan-Meier curve was used to analyze the prognosis. The cell migrative and invasive abilities were evaluated by wound healing assay and Transwell assay. CCK8 assays were used to evaluate 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 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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Mohamed Hssaini Department of Pediatric Endocrinology, University Hospital Center Hassan II, Fez, Morocco
Laboratory of Biotechnology, Environment, Food, and Health, Faculty of Sciences Dhar El Mahraz, Sidi Mohammed Ben Abdellah University, Fez, Morocco

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Sana Abourazzak Department of Pediatric Endocrinology, University Hospital Center Hassan II, Fez, Morocco

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Ihsane El Otmani Laboratory of Health Sciences and Technologies, Higher Institute of Health Sciences, Hassan First University of Settat, Morocco

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Mohamed Ahakoud Medical Genetics Laboratory, University Hospital Center Hassan II, Fez, Morocco

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Amina Ameli Department of Pediatric Endocrinology, University Hospital Center Hassan II, Fez, Morocco

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Laila Bouguenouch Medical Genetics Laboratory, University Hospital Center Hassan II, Fez, Morocco

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Hicham Bekkari Laboratory of Biotechnology, Environment, Food, and Health, Faculty of Sciences Dhar El Mahraz, Sidi Mohammed Ben Abdellah University, Fez, Morocco

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Background

Differences/disorders of sex development (DSD) encompass a wide range of conditions. Their clinical spectrum and etiological diagnosis have not been reported in Moroccan patients.

Aims

The study aims to highlight the clinical spectrum, etiological diagnosis, and management of patients with DSD.

Subjects and methods

This is a retrospective study of all patients diagnosed with DSD under the age of 18 years, who were referred to the Pediatric Endocrinology Department and the Medical Genetics Laboratory at HASSAN II University Hospital of Fez between June 2018 and June 2023.

Results

Out of 57 patients, 54.4% (n = 31) were diagnosed with 46,XX DSD, the most common type, while 45.6% (n = 26) had 46,XY DSD. Patients with 46,XX DSD presented earlier than those with 46,XY DSD, at a median age of 0.08 years and 0.96 years, respectively. The most commonly reported complaint was atypical genitalia. At the first presentation, the sex of rearing was already assigned to 26 males and 27 females. All patients with 46,XX DSD were diagnosed with congenital adrenal hyperplasia (CAH) at a median age of diagnosis of 0.92 years. Of these, 11 patients were raised as males. Disorders of androgen action or synthesis were more common in XY patients (69.2%). The consanguinity rate was 46.5%, and there were 19 cases with a positive family history, with 10 siblings having died.

Conclusion

DSD are not rare in Morocco. Overall, CAH remains the most frequent DSD etiology. Molecular genetic analyses are needed to determine the accurate etiological distribution of DSD, especially in XY patients.

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Hana Vítková Third Department of Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic

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Kateřina Anderlová Third Department of Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
Department of Gynaecology, Obstetrics and Neonatology, First Faculty of Medicine Charles University and General University Hospital in Prague, Prague, Czech Republic

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Jan Krátký Third Department of Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic

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Radovan Bílek Institute of Endocrinology, Prague, Czech Republic

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Drahomíra Springer Institute of Clinical Biochemistry and Laboratory Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic

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Felix Votava Department of Children and Adolescents, Third Faculty of Medicine, Charles University and University Hospital Kralovske Vinohrady, Prague, Czech Republic

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Tomáš Brutvan Third Department of Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic

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Adéla Krausová Third Department of Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic

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Kristýna Žabková Third Department of Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic

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Eliška Potluková University Center of Internal Medicine, Cantonal Hospital Baselland and University of Basel, Switzerland

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Jan Jiskra Third Department of Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic

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Introduction

Maternal urinary iodine concentration and blood neonatal thyroid-stimulating hormone (TSH) concentration reflect iodine status in pregnancy and serve as markers of iodine deficiency. As dietary measures in gestational diabetes mellitus (GDM) could affect iodine intake, our study aimed to investigate iodine supply in women with GDM compared to healthy pregnant women and to evaluate its relationship to maternal and neonatal thyroid function.

Methods

Urinary iodine concentration (UIC) and serum TSH, free thyroxine (FT4), and autoantibodies against thyroid peroxidase (TPOAb) were analyzed in 195 women with GDM and 88 healthy pregnant women in the second trimester. Subsequently, neonatal TSH concentrations measured 72 h after delivery in a subgroup of 154 newborns (115 of mothers with GDM and 39 controls) from the national register were analyzed.

Results

Median UIC was significantly lower in women with GDM compared to controls (89.50 µg/L vs. 150.05 µg/L; P < 0.001). Optimal iodine intake was found only in nine women with GDM (4.6%) and 33 healthy pregnant women (37.5%) (P < 0.001). Most pregnant women with GDM (88.7%) compared to one half of controls (50%) had iodine deficiency (P < 0.001). Although serum TSH and the prevalence of hypothyroidism (TSH > 4.0 mIU/L) were not different in both groups, hypothyroxinaemia was more prevalent in GDM compared to controls (12.3% vs 3.4%, P = 0.032). Consistently, neonatal TSH > 5.0 mIU/L indicating iodine deficiency, was found in 6 (5.2%) newborns of women with GDM as compared to none in controls. In women with GDM, the prevalence of perinatal complications was significantly lower in those who were taking dietary iodine supplements compared to those who were not (3/39 (7.69%) vs 46/156 (28.85%), P <0.001). In the multiple logistic and linear regression models in women with GDM, hypothyroxinaemia was associated with preterm births, and a negative association of serum FT4 and HbA1c was found.

Conclusion

Iodine deficiency in pregnancy was more prevalent among women with GDM compared to healthy pregnant controls. Serum FT4 negatively correlated with HbA1c, and hypothyroxinaemia was associated with preterm births in women with GDM. Conversely, women with GDM who used dietary iodine supplements had a lower risk of perinatal complications.

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Rohit Barnabas Department of Endocrinology, Seth GS Medical College and KEM Hospital, Parel, Mumbai, India

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Swati Jadhav Department of Endocrinology, Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, India

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Anurag Ranjan Lila Department of Endocrinology, Seth GS Medical College and KEM Hospital, Parel, Mumbai, India

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Sirisha Kusuma Boddu Consultant Pediatric Endocrinology & Diabetes, Rainbow Children’s Hospital, Hyderabad, India

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Saba Samad Memon Department of Endocrinology, Seth GS Medical College and KEM Hospital, Parel, Mumbai, India

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Sneha Arya Department of Endocrinology, Seth GS Medical College and KEM Hospital, Parel, Mumbai, India

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Samiksha Chandrashekhar Hegishte Department of Endocrinology, Seth GS Medical College and KEM Hospital, Parel, Mumbai, India

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Manjiri Karlekar Department of Endocrinology, Seth GS Medical College and KEM Hospital, Parel, Mumbai, India

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Virendra A Patil Department of Endocrinology, Seth GS Medical College and KEM Hospital, Parel, Mumbai, India

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Vijaya Sarathi Department of Endocrinology, Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, India

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Nalini S Shah Department of Endocrinology, Seth GS Medical College and KEM Hospital, Parel, Mumbai, India

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Tushar Bandgar Department of Endocrinology, Seth GS Medical College and KEM Hospital, Parel, Mumbai, India

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Background

The data on Leydig cell hypoplasia (LCH) resulting from biallelic Luteinizing hormone/chorionic gonadotropin receptor (LHCGR) inactivating variants is limited to case series.

Methods

We aim to describe our patients and perform systematic review of the patients with LHCGR inactivating variants in the literature. Detailed phenotype and genotype data of three patients from our centre and 85 (46,XY: 67; 46,XX: 18) patients from 59 families with LHCGR-inactivating variants from literature were described.

Results

Three 46,XY patients (age 6–18 years) from our center, with two reared as females, had two novel variants in LHCGR. Systematic review (including our patients) revealed 72 variants in 88 patients. 46,XY patients (n = 70, 56 raised as females) presented with pubertal delay (n = 41) or atypical genitalia (n = 17). Sinnecker score ≥3 (suggesting antenatal human chorionic gonadotropin (hCG) inaction) was seen in 80% (56/70), and hCG-stimulated testosterone was low (<1.1 ng/mL) in 77.4% (24/31), whereas puberty/postpubertal age, high luteinizing hormone (LH) (97.6%, 41/42) and low (<1.0 ng/mL) basal testosterone (94.9%, 37/39) was observed in most. Follicle stimulating hormone was elevated in 21/51 of these patients. Variants with <10% receptor function were exclusively seen in cohorts with Sinnecker 4/5 (10/15 vs 0/5, P = 0.033). 46,XX patients (n = 18) presented with oligo/amenorrhea and/or anovulatory infertility and had polycystic ovaries (7/9) with median LH of 10 IU/L (1.2–38).

Conclusion

In summary, this study comprehensively characterizes LHCGR variants, revealing genotype-phenotype correlations and informing clinical management of LCH. In 46,XY LCH patients, pubertal LH inaction is uniform with variable severity of antenatal hCG inaction. Few mutant LHCGR have differential actions for LH and hCG.

Open access
G Amiyangoda Department of Pharmacology, Faculty of Medicine, University of Peradeniya, Sri Lanka
Diabetes and Endocrine Unit, National Hospital, Kandy, Sri Lanka

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C N Antonypillai Diabetes and Endocrine Unit, National Hospital, Kandy, Sri Lanka

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S S C Gunatilake Diabetes and Endocrine Unit, National Hospital, Kandy, Sri Lanka

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T T Weerathunge Department of Community Medicine, Faculty of Medicine, University of Colombo, Sri Lanka

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D Ediriweera Health Data Science Unit, Faculty of Medicine, University of Kelaniya, Sri Lanka

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S G P D Kosgallana Diabetes and Endocrine Unit, National Hospital, Kandy, Sri Lanka

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R D P Jayawardana Department of Biochemistry, National Hospital, Kandy, Sri Lanka

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H A N D Thissera Department of Biochemistry, National Hospital, Kandy, Sri Lanka

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W J Emalka Faculty of medicine, University of Peradeniya, Sri Lanka

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H U Daraniyagala Faculty of medicine, University of Peradeniya, Sri Lanka

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Refractory hypothyroidism is associated with high morbidity and increased healthcare expenditure. In general, the use of the levothyroxine absorption test looks promising in evaluating refractory hypothyroidism but has shown significant variability in protocols in multiple settings. We intended to assess the usefulness of the levothyroxine absorption test in a low-resource setting and to assess the factors associated with refractory hypothyroidism. A cross-sectional study among age-matched 25 cases of refractory hypothyroidism and 24 treatment-responsive hypothyroid controls was conducted. A supervised levothyroxine absorption test was performed with levothyroxine 1000 μg tablets after a 10-h fast, and serum free tetraiodothyronine (FT4) levels were measured at 0, 1, 2, 3, 4, and 5 h. Descriptive statistics, chi-square test, Student’s t-test, and logistic regression were used in the analysis. Results showed no significant difference in age, body weight, etiology of hypothyroidism, interfering medications, thyroxine storage, and ingestion technique in cases and controls. Cases had a longer duration of hypothyroidism and males had a higher peak FT4 concentration. During pooled analysis, serum FT4 peaked at 3 h with an increment of 149.4% (128.4–170.5%) from baseline and plateaued thereafter. The absolute value of FT4 at 3 h was 41.59 (s.d. 14.14) pmol/L (3.23 ng/dL). We concluded that there was no significant difference in the pattern of levothyroxine absorption in both groups. The most common cause of refractory disease was pseudo-malabsorption. Rapid supervised levothyroxine absorption test with two blood samples for FT4 at baseline and at the peak of absorption (3 h) is simple, convenient, and cost-effective, particularly in low-resource settings.

Open access
Xu-Feng Chen Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China

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Cong He Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China

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Peng-Cheng Yu Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China

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Wei-Dong Ye Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China

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Pei-Zheng Han Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China

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Jia-Qian Hu Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China

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Yu-Long Wang Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of 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 tumors in the 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 from July 2021 to August 2022. Among the cohort, 2337 (82%) cases 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 older age, smaller tumor size, less vascular invasion, more frequent tumor multifocality, and a significantly higher cervical lymph node metastatic rate. Mutation at RET gene codons 918 and 634 is strongly correlated with medullary thyroid cancer. However, it did not display more invasive clinical characteristics. TERT-positive patients are more likely to have older age, and have larger tumor size, more tumor invasiveness, and more advanced TNM stage, indicating a poor prognosis. Patients with TERT, RET/PTC1, and CHEK2 mutations are more susceptible to lateral lymph node metastasis. In conclusion, NGS can be a useful tool that provides practical gene evidence in the process of diagnosis and treatment in thyroid tumors.

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Ayanthi Wijewardene Department of Endocrinology, Royal North Shore Hospital, Sydney, Australia
Faculty of Medicine, The University of Sydney, Sydney, Australia

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Matti Gild Department of Endocrinology, Royal North Shore Hospital, Sydney, Australia
Faculty of Medicine, The University of Sydney, Sydney, Australia

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Lyndal Tacon Department of Endocrinology, Royal North Shore Hospital, Sydney, Australia
Faculty of Medicine, The University of Sydney, Sydney, Australia

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Venessa Tsang Department of Endocrinology, Royal North Shore Hospital, Sydney, Australia
Faculty of Medicine, The University of Sydney, Sydney, Australia

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Anthony J Gill Faculty of Medicine, The University of Sydney, Sydney, Australia
Department of Anatomical Pathology, NSW Health Pathology, Royal North Shore Hospital, Sydney, Australia
Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney Australia

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Anthony Robert Glover Faculty of Medicine, The University of Sydney, Sydney, Australia
Department of Endocrine Surgery, Royal North Shore Hospital, Sydney, Australia

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Mark Sywak Faculty of Medicine, The University of Sydney, Sydney, Australia
Department of Endocrine Surgery, Royal North Shore Hospital, Sydney, Australia

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Stan Sidhu Faculty of Medicine, The University of Sydney, Sydney, Australia
Department of Endocrine Surgery, Royal North Shore Hospital, Sydney, Australia

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Bruce Robinson Department of Endocrinology, Royal North Shore Hospital, Sydney, Australia
Faculty of Medicine, The University of Sydney, Sydney, Australia

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Paul Roach Faculty of Medicine, The University of Sydney, Sydney, Australia
Department of Nuclear Medicine, Royal North Shore Hospital, Sydney, Australia

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Geoffrey Schembri Faculty of Medicine, The University of Sydney, Sydney, Australia
Department of Nuclear Medicine, Royal North Shore Hospital, Sydney, Australia

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Jeremy Hoang Faculty of Medicine, The University of Sydney, Sydney, Australia
Department of Nuclear Medicine, Royal North Shore Hospital, Sydney, Australia

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Roderick Clifton-Bligh Department of Endocrinology, Royal North Shore Hospital, Sydney, Australia
Faculty of Medicine, The University of Sydney, Sydney, Australia

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Summary

Background

Noise, an unwanted variability in judgment, 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 differentiated thyroid cancer (DTC).

Methods

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

Results

A significant difference was observed in administered activity between the 2021–2022 and 2017–2021 cohorts in patients stratified as intermediate risk (median activity 3.95 GBq, interquartile range 2.03–4.04 vs 4 GBq, 4–4) and high risk (4.07 GBq, 3.95–5.7 vs 6 GBq, 6–6) with P-values of 0.01 and <0.01, respectively. No difference was seen in low-risk patients (2.01 GBq, 1.03–3.98 vs 1 GBq, 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 continue to be established. Our data suggest that 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.

Open access
Zeting Li Department of Endocrinology, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China

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Ling Pei Department of Endocrinology, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China

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Huangmeng Xiao Department of Endocrinology, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China

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Nan Chen Department of Endocrinology, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China

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Fenghua Lai Department of Endocrinology, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China

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Shufang Yue Department of Endocrinology, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China

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Changliu Xu Department of Endocrinology, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China

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Yanbing Li Department of Endocrinology, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China

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Haipeng Xiao Department of Endocrinology, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China

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Xiaopei Cao Department of Endocrinology, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China

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Glucose-like peptide-1 (GLP-1) is a vital hormone in the intestines that regulates glucose metabolism. Although pancreatic-derived factor (PANDER) overexpression is known to suppress GLP-1, the underlying mechanisms are unclear. Our study aims to uncover how PANDER influences GLP-1 synthesis and secretion. We established a PANDER overexpression model in STC-1 intestinal cells, confirming its inhibitory effect on GLP-1 secretion. This effect was reversed in PANDER-knockout cells. Additionally, a negative correlation between PANDER and GLP-1 was observed in patients with a history of gestational diabetes. Subsequently, through whole transcriptome gene sequencing in PANDER-overexpressed STC-1 cells, we discovered that the activation of IL-6 and its related STAT3 signaling pathway was significantly inhibited, and this finding was validated by Western blotting and quantitative reverse transcription PCR. Finally, rescue experiments confirmed that the IL-6-related STAT3/Akt/GSK3β/β-catenin signaling pathway mediates the negative regulatory effect of PANDER on GLP-1. Taken together, our data identify IL-6 as a bridge connecting PANDER and GLP-1 in the STC-1 cells, demonstrating potential therapeutic targets for diabetes treatment by targeting the PANDER–IL-6–GLP-1 axis.

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Qian Yang Q Yang, Department of Endocrinology, Fifth People's Hospital of Shanghai Fudan University, Shanghai, China

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Qiannan Zhang Q Zhang, shanghai, China

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Fanfan Pan F Pan, Department of Endocrinology, Fifth People's Hospital of Shanghai Fudan University, Shanghai, 200240, China

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Bingbing Zha B Zha, shanghai, 200240, China

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Background: Signal transducer and activator of transcription 6 (STAT6) is an important nuclear transcription factor. Previous study demonstrated that blockading STAT6 can ameliorate thyroid function by reducing serum T3 and T4. Sodium/iodide symporter (NIS) is a key protein that mediates active iodine uptake and plays an important role in regulating thyroid function. This study explored the interaction between STAT6 and NIS.

Methods: Immunohistochemical staining was performed for detecting the expression of NIS in different tissues. Reverse transcription-polymerase chain reaction (RT-PCR) was performed for evaluating the mRNA level of NIS when Nthy-ori 3-1cells were incubated with IL4, TSH (Thyroid stimulating hormone) or monoclonal TSAb (thyroid-specific stimulatory autoantibody) for 24h. Quantitative RT-PCR,Western blot and immunofluorescence analysis were performed for detecting NIS expression after inhibiting STAT6 phosphorylation by AS1517499. Finally, we used Luciferase reporter assays to explore the ability of STAT6 to regulate the promoter activity of the NIS-coding gene.

Results: NIS was highly expressed in thyroid epithelial cells of EAGD mice or Graves' disease (GD) patients and TSAb increased the expression of NIS. We show that STAT6 phosphorylation inhibitor can attenuate the effect of TSAb on increasing NIS protein and mRNA levels. Finally, we confirm that transcription factor STAT6 can mediate NIS transcription and co-activator P100 protein can enhance STAT6-dependent transcriptional activation.

Conclusion: In Graves' disease, TSAb induces STAT6 signaling to upregulate NIS expression and STAT6 blockade ameliorates thyroid function via downregulation of the sodium/iodide symporter. Our study furthers understanding of the effects of STAT6 on thyroid function and reveals new avenues for GD treatment.

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