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Izabelle Lövgren Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK

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Azadeh Abravan Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester, UK

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Abigail Bryce-Atkinson Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK

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Marcel van Herk Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester, UK

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Brain tumours make up nearly one-third of paediatric malignancies. Over time, advancements in oncological treatments like radiotherapy have helped reduce normal-tissue toxicity when treating cancers in the brain. However, clinicians are still facing a trade-off between treatment efficacy and potential side effects. The aim of this review is to address the late effects of cranial irradiation on the neuroendocrine system and to identify factors that make patients more vulnerable to radiation-induced endocrine sequelae. Radiation damage to the hypothalamic–pituitary axis, which orchestrates hormone release, can lead to endocrinopathy; up to 48.8% of children who have undergone cranial irradiation develop a hormone deficiency. This may lead to further health complications that can appear up to decades after the last treatment, lowering the patients’ quality of life and increasing long-term costs as lifelong hormone replacement therapy may be required. Growth hormone deficiency is the most common sequelae, followed by either thyroid or gonadotropic hormone deficiency. Adrenocorticotropic hormone deficiency tends to be the least common. Identified factors that increase the risk of late endocrine deficiency include total radiation dose, age at treatment, and time since last treatment. However, as there are various other factors that may potentiate the damage, a universal solution proven to be most effective in sparing the endocrine tissues is yet to be identified. Until then, accounting for the identified risk factors during treatment planning may in some cases help reduce the development of endocrine sequelae in childhood cancer survivors.

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J Gebauer Department of Internal Medicine I, University Hospital of Schleswig-Holstein, Campus Luebeck and Institute for Endocrinology and Diabetes, University of Luebeck, Luebeck, Germany

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R Skinner Department of Paediatric and Adolescent Haematology and Oncology and Children’s BMT Unit, Great North Children’s Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, and Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK

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R Haupt DOPO Clinic, Department of Hematology/Oncolgy, IRCCS Istituto Giannina Gaslini, Genova, Italy

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L Kremer Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Amsterdam UMC, Emma’s Children’s Hospital, Amsterdam, The Netherlands

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H van der Pal Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands

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G Michel Department of Health Sciences and Medicine, University of Lucerne, Luzern, Switzerland

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G T Armstrong Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA

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M M Hudson Department of Oncology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA

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L Hjorth Department of Clinical Sciences Lund, Paediatrics, Lund University, Skane University Hospital, Lund, Sweden

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H Lehnert Paris Lodron University of Salzburg, Salzburg, Austria

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T Langer Pediatric Hematology and Oncology, University Hospital of Schleswig-Holstein, Campus Luebeck, Luebeck, Germany

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Many long-term childhood cancer survivors suffer from treatment-related late effects, which may occur in any organ and include a wide spectrum of conditions. Long-term follow-up (LTFU) is recommended to facilitate early diagnosis and to ensure better health outcomes. Due to the heterogeneity of these sequelae, different specialists work together in the diagnosis and treatment of these conditions. Experts from both pediatric and internal medicine are involved in age-appropriate care by providing a transition process. Hence, LTFU of childhood cancer survivors is a prototypic example of multidisciplinary care for patients with complex needs treated in a specialized setting. International collaborations of healthcare professionals and scientists involved in LTFU of childhood cancer survivors, such as the International Guideline Harmonization Group, compile surveillance recommendations that can be clinically adopted all over the world. These global networks of clinicians and researchers make a joint effort to address gaps in knowledge, increase visibility and awareness of cancer survivorship and provide an excellent example of how progress in clinical care and scientific research may be achieved by international and multidisciplinary collaboration.

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Ru-Xuan Zhao Department of Endocrinology, Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Ting-Ting Shi Department of Endocrinology, Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Sha Luo Department of Nuclear Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Yun-Fu Liu Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Zhong Xin Department of Endocrinology, Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Jin-Kui Yang Department of Endocrinology, Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Background

Graves’ orbitopathy (GO) is an autoimmune disease with mechanical impairment of orbital muscles and lacrimal gland dysfunction. The frequently used methods of assessing GO activity include Clinical Activity Score (CAS), CT, and MRI. These approaches are mainly associated with orbital muscles; however, there are not many studies that focus on the lacrimal gland inflammation of GO patients.

Objective

The aim of this study is to assess the usefulness of 99mTc-DTPA single-photon emission (SPE) CT/CT in evaluating the lacrimal gland inflammation in GO, as compared with other methods.

Methods

A retrospective analysis of 48 patients with active GO compared with 33 controls was conducted. All subjects underwent clinical–endocrinological analyses, CAS evaluation, CT scans, and SPECT/CT examination. Lacrimal gland dimensions were determined and analyzed.

Results

The lacrimal glands in patients with GO were significantly larger in all measured dimensions (P  < 0.001) on CT scans relative to those in controls. Increased lacrimal gland diethylene triamine pentaacetic acid (DTPA) uptake ratios (P  < 0.001) were displayed in active GO patients compared to controls and were also correlated with thyrotropin receptor antibody levels. The cut-off value for discriminating active and inactive disease was calculated to be 1.735, with specificity of 82.6% and sensitivity of 74.2%. SPECT/CT uptake ratios and CAS values were positively correlated in all GO patients. SPECT/CT uptake ratios were also positively correlated with CT measurements including lacrimal gland volume and coronal width in GO patients.

Conclusions

These data indicated that lacrimal gland SPECT/CT images can serve as a good tool for assessing the inflammation and disease activity of GO.

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Maria Stelmachowska-Banaś Department of Endocrinology, The Centre of Postgraduate Medical Education, Warsaw, Polska, Poland

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Izabella Czajka-Oraniec Department of Endocrinology, The Centre of Postgraduate Medical Education, Warsaw, Polska, Poland

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Immune checkpoint inhibitors (ICIs) belong to a new group of anticancer drugs targeting T-cell proteins involved in the activation of immune response toward malignancies. Their introduction into clinical practice was a milestone in modern cancer treatment. However, the significant advantage of ICIs over conventional chemotherapy in terms of therapeutic efficacy is accompanied by new challenges related to specific side effects. ICI-induced immune system activation could lead to the loss of self-tolerance, presenting as autoimmune inflammation and dysfunction of various tissues and organs. Thus, the typical side effects of ICIs include immune-related adverse events (irAEs), among which endocrine irAEs, affecting numerous endocrine glands, have been commonly recognized. This review aimed to outline the current knowledge regarding ICI-induced endocrine disorders from a clinical perspective. We present updated information on the incidence and clinical development of ICI-induced endocrinopathies, including the most frequent thyroiditis and hypophysitis, the rarely observed insulin-dependent diabetes mellitus and primary adrenal insufficiency, and the recently described cases of hypoparathyroidism and lipodystrophy. Practical guidelines for monitoring, diagnosis, and treatment of ICI-related endocrine toxicities are also offered. Rising awareness of endocrine irAEs among oncologists, endocrinologists, and other health professionals caring for patients receiving ICIs could contribute to better safety and efficacy. As immunotherapy becomes widespread and approved for new types of malignancies, increased incidences of endocrine irAEs are expected in the future.

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A Rouland Endocrinology Diabetics and Metabolic Disorders Department, Dijon University Hospital, Dijon, France

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J-C Chauvet-Gelinier Psychiatry Unit, Department of Neurosciences, Dijon University Hospital, Dijon, France
INSERM Unit, LNC-UMR 1231, University of Burgundy, Dijon, France

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A-L Sberna Endocrinology Diabetics and Metabolic Disorders Department, Dijon University Hospital, Dijon, France
INSERM Unit, LNC-UMR 1231, University of Burgundy, Dijon, France

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E Crevisy Endocrinology Diabetics and Metabolic Disorders Department, Dijon University Hospital, Dijon, France

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P Buffier Endocrinology Diabetics and Metabolic Disorders Department, Dijon University Hospital, Dijon, France

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T Mouillot Endocrinology Diabetics and Metabolic Disorders Department, Dijon University Hospital, Dijon, France

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J-M Petit Endocrinology Diabetics and Metabolic Disorders Department, Dijon University Hospital, Dijon, France
INSERM Unit, LNC-UMR 1231, University of Burgundy, Dijon, France

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B Vergès Endocrinology Diabetics and Metabolic Disorders Department, Dijon University Hospital, Dijon, France
INSERM Unit, LNC-UMR 1231, University of Burgundy, Dijon, France

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Objective

The Type A personality, characterized by impatience, strong career ambition and competitiveness, is associated with greater sensitivity to external stress. Type 1 diabetes (T1D) is an auto-immune disease, which is potentially influenced by stress, unlike type 2 diabetes (T2D). The aim of this study was to assess whether individuals with T1D and T2D exhibited significant differences on the Type A personality scale. We also assessed personality in patients with thyroid auto-immune diseases to validate potential links between auto-immune disease and Type A personality.

Design and methods

The Bortner questionnaire was used to assess Type A personality in 188 patients with T1D, 430 patients with T2D and 85 patients with auto-immune thyroid disease (Graves’ disease or Hashimoto’s thyroiditis).

Results

Type A Bortner scores were significantly higher in T1D patients than in T2D patients (188 ± 34 vs 177 ± 36, P < 0.0001). Patients with auto-immune thyroid diseases and T1D patients had similar Type A Bortner scores (189 ± 33 vs 188 ± 34, P = 0.860).

Conclusion

Patients with auto-immune T1D have higher Type A scores than T2D patients. Furthermore, patients with auto-immune thyroid disease also have elevated Type A scores similar to those observed in type 1 diabetes, suggesting that an elevated Type A score in T1D is potentially related to its auto-immune origin. This suggests a possible link between Type A personality and auto-immune diseases via stress-triggering psychobiological pathways. The different personality score between T1D and T2D is an important factor, which could influence self-care coping strategies in diabetes and long-term prognosis.

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Justyna Modrzynska Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Christine F Klein Department of Cardiology, Herlev Gentofte Hospital, Herlev, Denmark

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Kasper Iversen Department of Clinical Medicine, Herlev Gentofte Hospital, Herlev, Denmark

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Henning Bundgaard Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Bolette Hartmann Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Maike Mose Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

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Nikolaj Rittig Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark

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Niels Møller Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark

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Jens J Holst Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Nicolai J Wewer Albrechtsen Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Objective

Glucagon and glucagon-like peptide-1 (GLP-1) originate from the common precursor, proglucagon, and their plasma concentrations have been reported to be increased during inflammatory conditions. Increased blood glucose levels are frequently observed in septic patients, and therefore we hypothesized that glucagon, but not GLP-1, is increased in individuals with inflammation.

Design

Prospective longitudinal cohort study.

Materials and methods

We measured glucagon and GLP-1 in plasma sampled consecutively in three cohorts consisting of patients with infective endocarditis (n = 16), urosepsis (n = 28) and post-operative inflammation following percutaneous aortic valve implantation or thoracic endovascular aortic repair (n = 5). Correlations between C-reactive protein (CRP), a marker of systemic inflammation, and glucagon and GLP-1 concentrations were investigated. Additionally, glucagon and GLP-1 concentrations were measured after a bolus infusion of lipopolysaccharide (LPS, 1 ng/kg) in nine healthy young males.

Results

Glucagon and CRP were positively and significantly correlated (r = 0.27; P = 0.0003), whereas no significant association between GLP-1 and CRP was found (r = 0.08, P = 0.30). LPS infusion resulted in acute systemic inflammation reflected by increased temperature, pulse, tumor necrosis factor-α (TNFα), interleukin-6 (IL-6) and concomitantly increased concentrations of glucagon (P < 0.05) but not GLP-1.

Conclusions

Systemic inflammation caused by bacterial infections or developed as a non-infected condition is associated with increased plasma concentration of glucagon, but not GLP-1. Hyperglucagonemia may contribute to the impaired glucose control in patients with systemic inflammatory diseases.

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Huiyuan Zhai Department of Pharmacy, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Affiliated with Nanjing University of Chinese Medicine, Nanjing, China

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Dongxu Wang Department of Geriatrics, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Affiliated with Nanjing University of Chinese Medicine, Nanjing, China

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Yong Wang Department of Pharmacy, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Affiliated with Nanjing University of Chinese Medicine, Nanjing, China

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Hongwei Gu Central Laboratory, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Affiliated with Nanjing University of Chinese Medicine, Nanjing, China

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Juan Jv Department of Cardiology, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Affiliated with Nanjing University of Chinese Medicine, Nanjing, China

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Liangliang Yuan Department of Pharmacy, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Affiliated with Nanjing University of Chinese Medicine, Nanjing, China

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Chao Wang Department of Pharmacy, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Affiliated with Nanjing University of Chinese Medicine, Nanjing, China

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Leiyao Chen Department of Pharmacy, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Affiliated with Nanjing University of Chinese Medicine, Nanjing, China

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Chronic inflammation induced by obesity plays a crucial role in the pathogenesis of insulin resistance. The infiltration of macrophages into adipose tissues contributes to adipose tissue inflammation and insulin resistance. Kaempferol, a flavonoid present in various vegetables and fruits, has been shown to possess remarkable anti-inflammatory properties. In this study, we used leptin receptor-deficient obese mice (db/db) as an insulin-resistant model and investigated the effects of kaempferol treatment on obesity-induced insulin resistance. Our findings revealed that the administration of kaempferol (50 mg/kg/day, for 6 weeks) significantly reduced body weight, fat mass, and adipocyte size. Moreover, it effectively ameliorated abnormal glucose tolerance and insulin resistance in db/db mice. In the adipose tissue of obese mice treated with kaempferol, we observed a reduction in macrophage infiltration and a downregulation of mRNA expression of M1 marker genes TNF-α and IL-1β, accompanied by an upregulation of Arg1 and IL-10 mRNA expression. Additionally, kaempferol treatment significantly inhibited the STING/NLRP3 signaling pathway in adipose tissue. In vitro experiments, we further discovered that kaempferol treatment suppressed LPS-induced inflammation through the activation of NLRP3/caspase 1 signaling in RAW 264.7 macrophages. Our results suggest that kaempferol may effectively alleviate inflammation and insulin resistance in the adipose tissue of db/db mice by modulating the STING/NLRP3 signaling pathway.

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Stavroula A Paschou Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, ‘Aghia Sophia’ Children’s Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece

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Nektaria Papadopoulou-Marketou Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, ‘Aghia Sophia’ Children’s Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece

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George P Chrousos Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, ‘Aghia Sophia’ Children’s Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece

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Christina Kanaka-Gantenbein Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, ‘Aghia Sophia’ Children’s Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece

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Type 1 diabetes mellitus (T1DM) results from the autoimmune destruction of β cells of the endocrine pancreas. Pathogenesis of T1DM is different from that of type 2 diabetes mellitus, where both insulin resistance and reduced secretion of insulin by the β cells play a synergistic role. We will present genetic, environmental and immunologic factors that destroy β cells of the endocrine pancreas and lead to insulin deficiency. The process of autoimmune destruction takes place in genetically susceptible individuals under the triggering effect of one or more environmental factors and usually progresses over a period of many months to years, during which period patients are asymptomatic and euglycemic, but positive for relevant autoantibodies. Symptomatic hyperglycemia and frank diabetes occur after a long latency period, which reflects the large percentage of β cells that need to be destroyed before overt diabetes become evident.

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Nancy J Olsen Division of Rheumatology, Division of Endocrinology, Diabetes, and Metabolism, College of Medicine, Milton S Hershey Medical Center, The Pennsylvania State University, Mail Code H044, 500 University Drive, Hershey, Pennsylvania 17033-0850, USA

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Ann L Benko Division of Rheumatology, Division of Endocrinology, Diabetes, and Metabolism, College of Medicine, Milton S Hershey Medical Center, The Pennsylvania State University, Mail Code H044, 500 University Drive, Hershey, Pennsylvania 17033-0850, USA

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William J Kovacs Division of Rheumatology, Division of Endocrinology, Diabetes, and Metabolism, College of Medicine, Milton S Hershey Medical Center, The Pennsylvania State University, Mail Code H044, 500 University Drive, Hershey, Pennsylvania 17033-0850, USA

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Clinical and experimental evidence support a role for gonadal steroids in modulating the expression and course of autoimmune diseases such as lupus. Whether or not inherited variation in sensitivity to circulating androgenic hormones could influence the manifestations of such disease is, however, unknown. We sought to determine whether differences in androgen sensitivity conferred by variation in the exon 1 CAG repeat region of the androgen receptor (AR) gene were associated with differences in the clinical or humoral immune manifestations of lupus in a cohort of female subjects. We found that shorter AR CAG repeat lengths in lupus subjects correlated with a higher Systemic Lupus Erythematosus Disease Activity Index score, higher ANA levels, and expression of a broader array of IgG autoantibodies. Our findings of more severe clinical manifestations and more exuberant humoral autoimmunity in women with a shorter AR exon 1 CAG repeat length suggest a role for genetically determined sensitivity to androgens as a modulator of autoimmune processes.

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Weiwei He Department of Endocrinology, Affiliated Hospital of Yanan Medical University, Shaanxi, China

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Bin Wang Department of Endocrinology, Jinshan Hospital of Fudan University, Shanghai, China

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Kaida Mu Department of Endocrinology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, China

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Jing Zhang Department of Endocrinology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, China

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Yanping Yang Department of Endocrinology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, China

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Wei Yao Department of Endocrinology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, China

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Sheli Li Department of Endocrinology, Affiliated Hospital of Yanan Medical University, Shaanxi, China

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Jin-an Zhang Department of Endocrinology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, China

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Background

Accumulating data have shown that interleukin-27 (IL27) polymorphisms are linked to the susceptibility of some autoimmune diseases. We assessed whether there was an association between three single-nucleotide polymorphisms (SNPs) of IL27 gene and autoimmune thyroid diseases (AITDs).

Methods

Three SNPs (rs153109, rs17855750 and rs181206) of IL27 gene were genotyped by Hi-SNP high-throughput genotyping in 843 patients with AITDs (516 Graves’ disease (GD) and 327 Hashimoto’s thyroiditis (HT)) and 677 healthy controls in Chinese Han population.

Results

Compared with controls, rs153109 displayed significant associations with GD in allele and genotype frequencies (P = 0.002 and P = 0.008, respectively) and rs17855750 displayed significant associations with HT in allele frequencies (P = 0.02), whereas no differences in genotype or allele frequencies were found between AITD patients and controls at rs181206.

Conclusion

Our study, for the first time, showed the significant association of the IL27 gene SNPs with AITD.

Open access