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Sílvia Santos Monteiro Division of Endocrinology, Diabetes and Metabolism. Department of Medicine, Centro Hospitalar Universitário do Porto, Largo Professor Abel Salazar Porto, Portugal

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Tiago Silva Santos Division of Endocrinology, Diabetes and Metabolism. Department of Medicine, Centro Hospitalar Universitário do Porto, Largo Professor Abel Salazar Porto, Portugal

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Ana Martins Lopes Division of Endocrinology, Diabetes and Metabolism. Department of Medicine, Centro Hospitalar Universitário do Porto, Largo Professor Abel Salazar Porto, Portugal

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José Carlos Oliveira Department of Clinical Pathology, Centro Hospitalar Universitário do Porto, Largo Professor Abel Salazar Porto, Portugal

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Cláudia Freitas Division of Endocrinology, Diabetes and Metabolism. Department of Medicine, Centro Hospitalar Universitário do Porto, Largo Professor Abel Salazar Porto, Portugal

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André Couto Carvalho Division of Endocrinology, Diabetes and Metabolism. Department of Medicine, Centro Hospitalar Universitário do Porto, Largo Professor Abel Salazar Porto, Portugal

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has not been fully established, and may be defined as a thyroid-stimulating hormone (TSH) level above the upper limit of the reference range, under a daily LT4 dose of ≥1.9 µg/kg ( 4 ). Actually, some patients still exhibit refractory hypothyroidism

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Josi Vidart Thyroid Section, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
Intensive Care Unit, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil

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Paula Jaskulski Internal Medicine Division, Hospital de Clínicas de Porto Alegre, Internal Medicine Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil

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Ana Laura Kunzler Internal Medicine Division, Hospital de Clínicas de Porto Alegre, Internal Medicine Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil

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Rafael Aguiar Marschner Thyroid Section, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil

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André Ferreira de Azeredo da Silva Internal Medicine Division, Hospital de Clínicas de Porto Alegre, Internal Medicine Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil

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Simone Magagnin Wajner Thyroid Section, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
Internal Medicine Division, Hospital de Clínicas de Porto Alegre, Internal Medicine Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil

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(T4), and elevated plasma levels of the inactive hormone reverse T3 (rT3) in the presence of normal thyrotropin (TSH) levels ( 1 ). The pathophysiology of NTIS is multifactorial. In the early phase, the peripheral TH metabolism is impaired, with

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Ling Shan Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, People’s Republic of China
Department of Endocrinology and Metabolism, People's Hospital of Liaoning Province, Shenyang, People’s Republic of China

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Yingying Zhou Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, People’s Republic of China

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Shiqiao Peng Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, People’s Republic of China

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Xinyi Wang Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, People’s Republic of China
Department of Laboratory Medical, The First Hospital of China Medical University, Shenyang, People’s Republic of China

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Zhongyan Shan Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, People’s Republic of China

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Weiping Teng Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, People’s Republic of China

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Introduction Subclinical hypothyroidism (SCH), characterized by elevated levels of thyroid-stimulating hormone (TSH) with total thyroxine (TT4) within the normal reference range, is the most common type of thyroid disorder in pregnancy ( 1

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Xin He Laboratory of Functional Medicine, Division of Chronic Non-communicable Diseases and Injury, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China

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Qin Yan Laboratory of Functional Medicine, Division of Chronic Non-communicable Diseases and Injury, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China

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Chazhen Liu Laboratory of Functional Medicine, Division of Chronic Non-communicable Diseases and Injury, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China

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Zhengyuan Wang Department of Nutrition Hygiene, Division of Health Risk Factor Monitoring and Control, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China

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Ping Liao Laboratory of Functional Medicine, Division of Chronic Non-communicable Diseases and Injury, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China

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Tong Liu Laboratory of Functional Medicine, Division of Chronic Non-communicable Diseases and Injury, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China

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Zehuan Shi Department of Nutrition Hygiene, Division of Health Risk Factor Monitoring and Control, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China

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Qi Song Department of Nutrition Hygiene, Division of Health Risk Factor Monitoring and Control, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China

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Xueying Cui Department of Nutrition Hygiene, Division of Health Risk Factor Monitoring and Control, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China

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Wenjing Wang Laboratory of Functional Medicine, Division of Chronic Non-communicable Diseases and Injury, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China

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Jiajie Zang Department of Nutrition Hygiene, Division of Health Risk Factor Monitoring and Control, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China

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adulthood ( 2 , 5 , 6 ). Thyroid hormones can regulate metabolism associated with basal metabolic rate and body composition ( 7 , 8 ). In general, the thyroid-stimulating hormone (TSH) is positively correlated with BMI, whereas total thyroxine (TT4) and

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Kusum Lata Departments of Obstetrics and Gynecology, Endocrinology, Pharmacology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

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Pinaki Dutta Departments of Obstetrics and Gynecology, Endocrinology, Pharmacology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

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Subbiah Sridhar Departments of Obstetrics and Gynecology, Endocrinology, Pharmacology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

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Minakshi Rohilla Departments of Obstetrics and Gynecology, Endocrinology, Pharmacology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

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Anand Srinivasan Departments of Obstetrics and Gynecology, Endocrinology, Pharmacology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

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G R V Prashad Departments of Obstetrics and Gynecology, Endocrinology, Pharmacology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

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Viral N Shah Departments of Obstetrics and Gynecology, Endocrinology, Pharmacology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

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Anil Bhansali Departments of Obstetrics and Gynecology, Endocrinology, Pharmacology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

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vacutainers at the initial visit. Each blood sample was analysed for TSH, free tri-iodothyronine (FT 3 ), free T 4 (FT 4 ) and anti-TPO by electro-chemiluminescence immunoassay (ELECSYS-2010, Roche–Hitachi Diagnostics). The reference range for the above

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Nella Augusta Greggio Endocrinology and Adolescence Unit, Department of Woman and Child Health, University of Padova, Padova, Italy

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Elisa Rossi CINECA – Interuniversity Consortium (Health Service), Bologna, Italy

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Silvia Calabria CORE srl – Collaborative Outcome Research, Bologna, Italy

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Alice Meneghin Endocrinology and Adolescence Unit, Department of Woman and Child Health, University of Padova, Padova, Italy

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Joaquin Gutierrez de Rubalcava Endocrinology and Adolescence Unit, Department of Woman and Child Health, University of Padova, Padova, Italy

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Carlo Piccinni CORE srl – Collaborative Outcome Research, Bologna, Italy

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Antonella Pedrini CORE srl – Collaborative Outcome Research, Bologna, Italy

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Introduction Subclinical hypothyroidism (SH) is a biochemical condition defined as serum thyroid-stimulating hormone (TSH) exceeding the limit of its reference range by age, while the concentration of serum free thyroxin (FT4) remains within

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Marcus Heldmann Department of Neurology, University of Lübeck, Lübeck, Germany
Department of Psychology II, University of Lübeck, Lübeck, Germany

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Krishna Chatterjee Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK

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Carla Moran Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK

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Berenike Rogge Department of Neurology, University of Lübeck, Lübeck, Germany

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Julia Steinhardt Department of Neurology, University of Lübeck, Lübeck, Germany

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Tobias Wagner-Altendorf Department of Neurology, University of Lübeck, Lübeck, Germany

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Martin Göttlich Department of Neurology, University of Lübeck, Lübeck, Germany

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Hannes Schacht Department of Neuroradiology, University of Lübeck, Lübeck, Germany

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Peter Schramm Department of Neuroradiology, University of Lübeck, Lübeck, Germany

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Georg Brabant Department of Internal Medicine I, University of Lübeck, Lübeck, Germany
Department of Endocrinology, The Christie, University of Manchester, Manchester, UK

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Thomas F Münte Department of Neurology, University of Lübeck, Lübeck, Germany
Department of Psychology II, University of Lübeck, Lübeck, Germany

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Anna Cirkel Department of Neurology, University of Lübeck, Lübeck, Germany

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determination of TSH, which is generally normal, or slightly elevated in some cases. However, free thyroxine (fT4) is universally elevated ( 4 ). In RTHβ, the sensitivity of the hypothalamic–pituitary axis to thyroid hormone is reduced, due to altered signalling

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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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Isabel M Abreu Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, Porto, Portugal

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Eva Lau Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, Porto, Portugal
Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar S. João, Alameda Professor Hernâni Monteiro, Porto, Portugal
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal

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Bernardo de Sousa Pinto Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, Porto, Portugal

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Davide Carvalho Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, Porto, Portugal
Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar S. João, Alameda Professor Hernâni Monteiro, Porto, Portugal
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal

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Introduction Subclinical hypothyroidism (SCH) is diagnosed biochemically when both serum-free thyroxine (FT4) and free triiodothyronine (FT3) are within the normal range, whereas the serum thyroid-stimulating hormone (TSH) is elevated ( 1

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Signe Kirkegaard Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark

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Nanna Maria Uldall Torp Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark

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Stig Andersen Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
Department of Geriatrics, Aalborg University Hospital, Aalborg, Denmark

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Stine Linding Andersen Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark

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hypothyroidism seen as part of Hashimoto’s thyroiditis (HT) ( 2 ). In GD, antibodies against the thyroid-stimulating hormone (TSH) receptor (TRAb) stimulate the thyroid gland to an increased production of thyroid hormone that causes the biochemical

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