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Shaomin Shi Division of Nephrology, The First Affiliated Hospital of Yangtze University, Jingzhou, China

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Xinghua Chen Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China

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Wen Yu Department of Immunology, School of Medicine, Yangtze University, Jingzhou, China

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Xiaolan Ke Division of Nephrology, The First Affiliated Hospital of Yangtze University, Jingzhou, China

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Tean Ma Division of Nephrology, The First Affiliated Hospital of Yangtze University, Jingzhou, China

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Protection of podocytes is one of the important means to delay the progression of diabetic nephropathy (DN), and glucagon-like peptide-1 (GLP-1) has been shown to have a protective effect on the kidney in DN models, but whether it has a protective effect on podocytes and the potential mechanisms of action remain largely unknown. In the present study, we established a type 2 diabetes mellitus (T2DM) mouse model by high-fat diet feeding combined with streptozotocin (STZ) induction and administered the intervention for 14 weeks. We found that liraglutide significantly ameliorated podocyte injury in DN mice. Mechanistically, we detected glucagon-like peptide-1 receptor (GLP-1R) protein expression levels in kidney tissues by immunohistochemical staining, immunofluorescence staining, and western blotting and found that podocytes could express GLP-1R and liraglutide treatment could restore GLP-1R expression in the kidney tissues of DN mice. Furthermore, we found that NLRP3-induced inflammation and pyroptosis were positively correlated with podocyte injury in DN mice, and liraglutide inhibited the expression of NLRP3-induced inflammation and pyroptosis-related proteins. Our results suggest that liraglutide protects DN mouse podocytes by regulating GLP-1R in renal tissues and by regulating NLRP3-induced inflammation and pyroptosis.

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Zhengrong Jiang Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China

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Linghong Huang Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China

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Lijun Chen Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China

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Jingxiong Zhou Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China

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Bo Liang Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China

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Xuefeng Bai Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China

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Lizhen Wu Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China

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Huibin Huang Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China

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Background

Graves’ disease is a common autoimmune disease. Cytokines and their signalling pathways play a major part in the pathogenesis of Graves’ disease; however, the underlying mechanism needs to be clarified.

Aims

The aim of this study was to explore whether circular RNAs participate in the immunological pathology of Graves’ disease via cytokine-related signalling pathways.

Methods

Bioinformatics analysis was performed to identify differentially expressed circular RNAs and their targets and associated pathways. A total of three patients with Graves’ disease and three sex- and age-matched healthy controls were enrolled for validation with microarray analysis and real-time quantitative PCR (qPCR). An additional 24 patients with Graves’ disease and 24 gender- and age-matched controls were included for validation by real-time fluorescent qPCR. Flow cytometry and CCK8 assays were used to detect the apoptotic and proliferative levels of Jurkat cells (T lymphocytes) with the silenced expression of circRNA. ELISA was performed to detect the growth and apoptosis-related proteins. The competition mechanism of endogenous RNA was explored by real-time fluorescence qPCR.

Results

A total of 366 significantly differentially expressed circular RNAs were identified in the Graves’ disease group compared to healthy controls. The level of hsa_circ_0090364 was elevated in Graves’ disease patients and positively correlated with thyroid-stimulating hormone receptor antibodies. Further analyses suggested that hsa_circ_0090364 may regulate the JAK-STAT pathway via the hsa-miR-378a-3p/IL-6ST/IL21R axis to promote cell growth.

Conclusions

These results provide novel clues into the pathophysiological mechanisms of Graves’ disease and potential targets for drug treatment.

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Suvanjaa Sivalingam Department of Internal Medicine, Hospital of Southern Jutland, Sønderborg, Denmark

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Marianne Thvilum Department of Endocrinology and Metabolism, Odense University Hospital, Odense C, Denmark

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Thomas Heiberg Brix Department of Endocrinology and Metabolism, Odense University Hospital, Odense C, Denmark

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Laszlo Hegedüs Department of Endocrinology and Metabolism, Odense University Hospital, Odense C, Denmark
Department of Clinical Research, University of Southern Denmark, Odense M, Denmark

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Frans Brandt Department of Internal Medicine, Hospital of Southern Jutland, Sønderborg, Denmark
Department of Regional Health Research, University of Southern Denmark, Odense M, Denmark

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Background

Season of birth, an exogenous indicator of early life environment, has been linked with a higher risk of adverse health outcomes such as autoimmune thyroiditis, multiple sclerosis and schizophrenia later in life. Whether the development and cause of hyperthyroidism is influenced by season of birth is unclarified. We aimed, at a nationwide level, to investigate whether season of birth influences the risk of hyperthyroidism due to Graves’ disease (GD) and/or toxic nodular goitre (TNG).

Method

Register-based nationwide cohort study. By record-linkage between Danish health registers, 36,087 and 20,537 patients with GD and TNG, respectively, were identified. Each case was matched with four controls without thyroid disease, according to age and sex. Differences in month of birth across the year were evaluated by the Walter–Elwood test. Hazard ratios, for the risk of GD and TNG in individuals born in a certain month or season of the year, were calculated using Cox regression models.

Results

Neither for GD nor for TNG could we demonstrate a significant difference in birth rate across months or seasons of the year (Walter–Elwood’s test; X2 = 5.92 and X2 = 1.27, P = 0.052 and P = 0.53, respectively).

Conclusion

Irrespective of its cause, our findings do not support the hypothesis that season of birth is significantly related to the development of hyperthyroidism.

Open access
Milica Popovic Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland
Department of Clinical Research, University of Basel and University Hospital Basel, Basel, Switzerland

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Fahim Ebrahimi Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland
Department of Clinical Research, University of Basel and University Hospital Basel, Basel, Switzerland

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Sandrine Andrea Urwyler Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland
Department of Clinical Research, University of Basel and University Hospital Basel, Basel, Switzerland

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Marc Yves Donath Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland
Department of Biomedicine, University of Basel, Basel, Switzerland

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Mirjam Christ-Crain Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland
Department of Clinical Research, University of Basel and University Hospital Basel, Basel, Switzerland

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Arginine vasopressin (AVP) was suggested to contribute to cardiovascular risk and type 2 diabetes in patients with metabolic syndrome. The proinflammatory cytokine interleukin (IL)-1 is able to induce AVP secretion and plays a causal role in cardiovascular mortality and type 2 diabetes. We investigated in two studies whether copeptin levels – the surrogate marker for AVP – are regulated by IL-1-mediated chronic inflammation in patients with metabolic syndrome. Study A was a prospective, interventional, single-arm study (2014–2016). Study B was a randomized, placebo-controlled, double-blind study (2016–2017). n = 73 (Study A) and n = 66 (Study B) adult patients with metabolic syndrome were treated with 100 mg anakinra or placebo (only in study B) twice daily for 1 day (study A) and 28 days (study B). Fasting blood samples were drawn at day 1, 7, and 28 of treatment for measurement of serum copeptin. Patients with chronic low-grade inflammation (C-reactive protein levels ≥2 mg/L) and BMI >35 kg/m2 had higher baseline copeptin levels (7.7 (IQR 4.9–11.9) vs 5.8 (IQR 3.9–9.3) pmol/L, P inflamm = 0.009; 7.8 (IQR 5.4–11.7) vs 4.9 (IQR 3.7–9.8) pmol/L, P BMI = 0.008). Copeptin levels did not change either in the anakinra or in the placebo group and remained stable throughout the treatment (P = 0.44). Subgroup analyses did not reveal effect modifications. Therefore, we conclude that, although IL-1-mediated inflammation is associated with increased circulating copeptin levels, antagonizing IL-1 does not significantly alter copeptin levels in patients with metabolic syndrome.

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Xiao-Shan Huang Department of Radiology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China

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Ning Dai Zhejiang Chinese Medical University, Hangzhou, China

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Jian-Xia Xu Department of Radiology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China

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Jun-Yi Xiang Department of Radiology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China

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Xiao-Zhong Zheng Department of Radiology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China

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Tian-Yu Ke Department of Radiology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China

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Lin-Ying Ma Department of Radiology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China

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Qi-Hao Shi Zhejiang Chinese Medical University, Hangzhou, China

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Shu-Feng Fan Department of Radiology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China

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Objective

Hashimoto’s thyroiditis is an inflammatory disease, and research suggests that a low-carbohydrate diet may have potential anti-inflammatory effects. This study aims to utilize Dixon-T2-weighted imaging (WI) sequence for a semi-quantitative assessment of the impact of a low-carbohydrate diet on the degree of thyroid inflammation in patients with Hashimoto’s thyroiditis.

Methods

Forty patients with Hashimoto’s thyroiditis were recruited for this study and randomly divided into two groups: one with a normal diet and the other with a low-carbohydrate diet. Antibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) were measured for all participants. Additionally, thyroid water content was semi-quantitatively measured using Dixon-T2WI. The same tests and measurements were repeated for all participants after 6 months.

Results

After 6 months of a low-carbohydrate diet, patients with Hashimoto’s thyroiditis showed a significant reduction in thyroid water content (94.84 ± 1.57% vs 93.07 ± 2.05%, P < 0.05). Concurrently, a decrease was observed in levels of TPOAb and TgAb (TPOAb: 211.30 (92.63–614.62) vs 89.45 (15.9–215.67); TgAb: 17.05 (1.47–81.64) vs 4.1 (0.51–19.42), P < 0.05). In contrast, there were no significant differences in thyroid water content or TPOAb and TgAb levels for patients with Hashimoto’s thyroiditis following a normal diet after 6 months (P < 0.05).

Conclusion

Dixon-T2WI can quantitatively assess the degree of thyroid inflammation in patients with Hashimoto’s thyroiditis. Following a low-carbohydrate diet intervention, there is a significant reduction in thyroid water content and a decrease in levels of TPOAb and TgAb. These results suggest that a low-carbohydrate diet may help alleviate inflammation in patients with Hashimoto’s thyroiditis.

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Chenghao Piao Department of Radiology, The Second Affiliated Hospital of Shenyang Medical College, Shenyang City, Liaoning Province, People’s Republic of China

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Xiaojie Wang Department of Human Anatomy, Shenyang Medical College, Shenyang City, Liaoning Province, 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 Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province, People’s Republic of China

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Xinyu Guo Department of Obstetrics, The Second Affiliated Hospital of Shenyang Medical College, Shenyang City, Liaoning Province, People’s Republic of China

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Hui Zhao Department of Laboratory Medicine, The Second Affiliated Hospital of Shenyang Medical College, Shenyang City, Liaoning Province, People’s Republic of China

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Li He Department of Gastroenterology, The Second Affiliated Hospital of Shenyang Medical College, Shenyang City, Liaoning Province, People’s Republic of China

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Yan Zeng Department of Obstetrics, The Second Affiliated Hospital of Shenyang Medical College, Shenyang City, Liaoning Province, People’s Republic of China

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Fan Zhang Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province, People’s Republic of China

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Kewen Zhu Department of Human Anatomy, Shenyang Medical College, Shenyang City, Liaoning Province, People’s Republic of China

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Yiwei Wang Department of Human Anatomy, Shenyang Medical College, Shenyang City, Liaoning Province, People’s Republic of China

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Objective

Gestational diabetes mellitus (GDM) is characterized by glucose intolerance during gestation. It is associated with a series of maternal and foetal complications. Interleukin (IL)-34 is a recently discovered pro-inflammatory cytokine that functions as a ligand for colony-stimulating factor-1 receptor (CSF-1R). The contribution of IL-34 in the development of multiple chronic inflammatory diseases and autoimmune diseases has been recently discovered. The aim of this study was to evaluate whether IL-34 participates in the pathogenesis of GDM.

Method

A total of 120 women were enrolled in this study, which included 60 GDM patients and age- and sex-matched healthy pregnant women. The expression of IL-34 in serum, cord blood and placental tissues was analysed by ELISA and Western blot assays. The association between IL-34 levels and clinical features was also studied. We additionally evaluated the effect of recombinant mouse IL-34 (rmIL-34) on apoptosis and pancreatic β cell function.

Results

We found that IL-34 expression is highly increased in serum, cord blood and placental tissues in patients with GDM. In addition, there was a positive association between serum IL-34 and insulin resistance and glucose concentrations. Our data also revealed that IL-34 contributes to the apoptosis of pancreatic β cells in GDM caused by CSF-1R. Furthermore, functional studies found that IL-34 inhibited pancreatic β cell function and cell viability, while CSF-1R inhibitor blocked this effect.

Conclusion

IL-34 plays a crucial role in the development of GDM by targeting CSF-1R, insulin production and β cell function.

Open access
Natacha Driessens Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, Department of Endocrinology, Route de Lennik, Brussels, Belgium

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Madhu Prasai Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, Department of Endocrinology, Route de Lennik, Brussels, Belgium

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Orsalia Alexopoulou Department of Endocrinology, Cliniques Universitaires Saint Luc, Brussels, Belgium

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Christophe De Block Department of Endocrinology-Diabetology-Metabolism, Universitair Ziekenhuis Antwerpen & University of Antwerp, Drie Eikenstraat, Edegem, Belgium

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Eva Van Caenegem Department of Endocrinology, Academisch Ziekenhuis Sint-Jan Brugge – Oostende AV, Ruddershove, Brugge, Belgium

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Guy T’Sjoen Department of Endocrinology, Ghent Universitary Hospital, C. Heymanslaan, Gent, Belgium

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Frank Nobels Department of Endocrinology, Onze-Lieve Vrouw Ziekenhuis, Moorselbaan, Aalst, Belgium

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Christophe Ghys Department of Endocrinology, Universitair Ziekenhuis Brussel, Laarbeeklaan, Brussels, Belgium

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Laurent Vroonen Department of Endocrinology, Cliniques Universitaires de Liège, Avenue de l’hôpital, Liège, Belgium

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Corinne Jonas Department of Endocrinology, CHU UCL Namur - Godinne, Avenue Docteur Gaston Thérasse, Yvoir, Belgium

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Bernard Corvilain Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, Department of Endocrinology, Route de Lennik, Brussels, Belgium

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Dominique Maiter Department of Endocrinology, Cliniques Universitaires Saint Luc, Brussels, Belgium

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Objective

Primary adrenal insufficiency (PAI) is a rare disease with an increasing prevalence, which may be complicated by life-threatening adrenal crisis (AC). Good quality epidemiological data remain scarce. We performed a Belgian survey to describe the aetiology, clinical characteristics, treatment regimens, comorbidities and frequency of AC in PAI.

Methods

A nationwide multicentre study involving 10 major university hospitals in Belgium collected data from adult patients with known PAI.

Results

Two hundred patients were included in this survey. The median age at diagnosis was 38 years (IQR 25–48) with a higher female prevalence (F/M sex ratio = 1.53). The median disease duration was 13 years (IQR 7–25). Autoimmune disease was the most common aetiology (62.5%) followed by bilateral adrenalectomy (23.5%) and genetic variations (8.5%). The majority (96%) of patients were treated with hydrocortisone at a mean daily dose of 24.5 ± 7.0 mg, whereas 87.5% of patients also received fludrocortisone. About one-third of patients experienced one or more AC over the follow-up period, giving an incidence of 3.2 crises per 100 patient-years. There was no association between the incidence of AC and the maintenance dose of hydrocortisone. As high as 27.5% of patients were hypertensive, 17.5% had diabetes and 17.5% had a diagnosis of osteoporosis.

Conclusion

This study provides the first information on the management of PAI in large clinical centres in Belgium, showing an increased frequency of postsurgical PAI, a nearly normal prevalence of several comorbidities and an overall good quality of care with a low incidence of adrenal crises, compared with data from other registries.

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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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Purpose

The levothyroxine absorption test (LT4AT) is an important tool for distinguishing hypothyroidism due to malabsorption from ‘pseudomalabsorption’ conditions. Our aim was to review our institution’s LT4AT results and assess its role in the management of patients with refractory hypothyroidism.

Methods

We performed a retrospective study of all patients evaluated for refractory hypothyroidism who underwent LT4AT in our tertiary center between 2014 and 2020. Its results and the impact on thyroid function management during follow-up were assessed.

Results

Ten female patients were included with a mean age of 40 years (min-max: 26–62). Mean weight was 72 kg (min–max: 43–88) and baseline LT4 dosage ranged from 2.5 to 5.3 µg/kg/day. The most common causes of hypothyroidism were postsurgical in 50% (n  = 5) and autoimmune in 20% (n  = 2). During LT4AT, normal LT4 absorption was found in all but one individual (mean FT4 increase of 231%, min–max: 85–668). The only patient with objective LT4 absorption impairment (maximal increase of 48% by hour 5) presented also Helicobacter pylori gastritis and prior history of ‘intestinal surgery’ during childhood. No adverse events were reported during any of the LT4ATs. During follow-up (median 11.5 months (IQR 23)), three patients obtained euthyroidism and six had improved their hypothyroidism state.

Conclusions

The LT4AT is an effective and safe way to assess refractory hypothyroidism and provides valuable information to distinguish LT4 malabsorption from ‘pseudomalabsorption’. Our data suggest that most patients with suspicious LT4 malabsorption perform normally during LT4AT. This test provides relevant information for better management of patients with refractory hypothyroidism.

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Brijesh Krishnappa Department of Endocrinology, K E M Hospital and Seth G S Medical College, Mumbai, India

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Ravikumar Shah Department of Endocrinology, K E M Hospital and Seth G S Medical College, Mumbai, India

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Saba Samad Memon Department of Endocrinology, K E M Hospital and Seth G S Medical College, Mumbai, India

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Chakra Diwaker Department of Endocrinology, K E M Hospital and Seth G S Medical College, Mumbai, India

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Anurag R Lila Department of Endocrinology, K E M Hospital and Seth G S Medical College, Mumbai, India

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Virendra A Patil Department of Endocrinology, K E M Hospital and Seth G S Medical College, Mumbai, India

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Nalini S Shah Department of Endocrinology, K E M Hospital and Seth G S Medical College, Mumbai, India

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Tushar R Bandgar Department of Endocrinology, K E M Hospital and Seth G S Medical College, Mumbai, India

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Objectives

High-dose glucocorticoids are associated with improved recovery of deficits in primary autoimmune hypophysitis (PAH), but optimal dosing, route, and duration are unclear.

Design

We reviewed literature for first-line glucocorticoid treatment in PAH until December 2021 and performed an individual patient data meta-analysis to analyze clinical, hormonal, and radiological outcomes with respect to route, dose, and duration (<6.5 vs 6.5–12 vs >12 weeks) of glucocorticoid treatment according to disease severity.

Results

A total of 153 PAH patients from 83 publications were included. The median age at presentation was 41 (32.5–48) years with a female preponderance (70.3%). Visual field recovery was significantly better with i.v. (91.7%) as compared to oral (54.5%) route and high dose (100%) and very high dose (90.9%) as compared to medium dose (20%) of glucocorticoids. Corticotroph axis recovery was greater in i.v. (54.8% vs 28.1% oral, P = 0.033) route and increasing glucocorticoid dose group (0% vs 38.1% vs 57.1%), attaining statistical significance (P = 0.012) with very high-dose. A longer duration of treatment (>6.5 weeks) was associated with better corticotroph and thyrotroph recovery. The need for rescue therapy was lower with i.v. route (38% vs 17.5%, P = 0.012) and with increasing glucocorticoid doses (53.3% vs 34.3% vs 17.3%, P = 0.016). In severe disease, visual field and corticotroph axis recovery were significantly higher with i.v. route and very high-dose steroids. The adverse effects of glucocorticoids were independent of dose and duration of treatment.

Conclusions

Very high-dose glucocorticoids by i.v. route and cumulative longer duration (>6.5 weeks) lead to better outcomes and could be considered as first-line treatment of severe PAH cases.

Open access
Liangming Li Center for Scientific Research and Institute of Exercise and Health, Guangzhou Sport University, Guangzhou, China
Key Laboratory of Sports Technique, Tactics and Physical Function of General Administration of Sport of China, Scientific Research Center, Guangzhou Sport University, Guangzhou, China

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Yuan Wei Center for Scientific Research and Institute of Exercise and Health, Guangzhou Sport University, Guangzhou, China
Key Laboratory of Sports Technique, Tactics and Physical Function of General Administration of Sport of China, Scientific Research Center, Guangzhou Sport University, Guangzhou, China

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Chunlu Fang Center for Scientific Research and Institute of Exercise and Health, Guangzhou Sport University, Guangzhou, China
Key Laboratory of Sports Technique, Tactics and Physical Function of General Administration of Sport of China, Scientific Research Center, Guangzhou Sport University, Guangzhou, China

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Shujing Liu Center for Scientific Research and Institute of Exercise and Health, Guangzhou Sport University, Guangzhou, China
Key Laboratory of Sports Technique, Tactics and Physical Function of General Administration of Sport of China, Scientific Research Center, Guangzhou Sport University, Guangzhou, China

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Fu Zhou Key Laboratory of Sports Technique, Tactics and Physical Function of General Administration of Sport of China, Scientific Research Center, Guangzhou Sport University, Guangzhou, China

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Ge Zhao Key Laboratory of Sports Technique, Tactics and Physical Function of General Administration of Sport of China, Scientific Research Center, Guangzhou Sport University, Guangzhou, China

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Yaping Li Key Laboratory of Sports Technique, Tactics and Physical Function of General Administration of Sport of China, Scientific Research Center, Guangzhou Sport University, Guangzhou, China

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Yuan Luo Key Laboratory of Sports Technique, Tactics and Physical Function of General Administration of Sport of China, Scientific Research Center, Guangzhou Sport University, Guangzhou, China

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Ziyi Guo Key Laboratory of Sports Technique, Tactics and Physical Function of General Administration of Sport of China, Scientific Research Center, Guangzhou Sport University, Guangzhou, China

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Weiqun Lin Department of Clinical Nutrition, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China

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Wenqi Yang Center for Scientific Research and Institute of Exercise and Health, Guangzhou Sport University, Guangzhou, China
Key Laboratory of Sports Technique, Tactics and Physical Function of General Administration of Sport of China, Scientific Research Center, Guangzhou Sport University, Guangzhou, China

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Exercise has been recommended as an important strategy to improve glucose metabolism in obesity. Adipose tissue fibrosis is associated with inflammation and is implicated in glucose metabolism disturbance and insulin resistance in obesity. However, the effect of exercise on the progression of adipose tissue fibrosis is still unknown. The aim of the present study was to investigate whether exercise retarded the progression of adipose tissue fibrosis and ameliorated glucose homeostasis in diet-induced obese mice. To do so, obesity and adipose tissue fibrosis in mice were induced by high-fat diet feeding for 12 weeks and the mice subsequently received high-fat diet and exercise intervention for another 12 weeks. Exercise alleviated high-fat diet-induced glucose intolerance and insulin resistance. Continued high-fat diet feeding exacerbated collagen deposition and further increased fibrosis-related gene expression in adipose tissue. Exercise attenuated or reversed these changes. Additionally, PPARγ, which has been shown to inhibit adipose tissue fibrosis, was observed to be increased following exercise. Moreover, exercise decreased the expression of HIF-1α in adipose fibrosis, and adipose tissue inflammation was inhibited. In conclusion, our data indicate that exercise attenuates and even reverses the progression of adipose tissue fibrosis, providing a plausible mechanism for its beneficial effects on glucose metabolism in obesity.

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