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Sharmin Jahan Department of Medicine, Monash University, Melbourne, Victoria, Australia
Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Victoria, Australia
Department of Endocrinology and Metabolism, BSMMU, Dhaka, Bangladesh

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Jun Yang Department of Medicine, Monash University, Melbourne, Victoria, Australia
Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Victoria, Australia

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Jinbo Hu Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

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Qifu Li Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

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Peter J Fuller Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Victoria, Australia

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Primary aldosteronism (PA) is the most common cause of endocrine hypertension and is often underdiagnosed. This condition is associated with increased cardiovascular morbidity and mortality in comparison to age and blood pressure matched individuals with essential hypertension (EH). The diagnostic pathway for PA consists of three phases: screening, confirmatory testing, and subtyping. The lack of specificity in the screening step, which relies on the aldosterone to renin ratio, necessitates confirmatory testing. The Endocrine Society’s clinical practice guideline suggests four confirmatory tests, including the fludrocortisone suppression test (FST), saline suppression test (SST), captopril challenge test (CCT), and oral sodium loading test (SLT). There is no universally accepted choice of confirmatory test, with practices varying among centers. The SST and FST are commonly used, but they can be resource-intensive, carry risks such as volume overload or hypokalemia, and are contraindicated in severe/uncontrolled HTN as well as in cardiac and renal impairment. In contrast, CCT is a safe and inexpensive alternative that can be performed in an outpatient setting and can be applied when other tests are contraindicated. Despite its simplicity and convenience, the variability in captopril dose, testing posture, and diagnostic threshold limit its widespread use. This narrative review evaluates the diagnostic accuracy of the CCT across different populations, addresses controversies in its usage, and proposes recommendations for its use in the diagnosis of PA. Furthermore, suggestions for future research aimed at promoting the wider utilization of the CCT as a simpler, safer, and more cost-effective diagnostic test are discussed.

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Jiali Tian Ultrasound Department, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China

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Jinlei Liang Ultrasound Department, Zhuhai People's Hospital, Zhuhai, China

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Yuhong Lin Ultrasound Department, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China

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Liping Wang Ultrasound Department, Zhuhai Xiangzhou District People's Hospital, Zhuhai, China

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Xiaobo Chen Ultrasound Department, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China

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Objective

The aim was to investigate the ability of superb microvascular imaging (SMI) to improve the differential diagnosis of mummified thyroid nodules (MTNs) and papillary thyroid carcinomas (PTCs) using the 2017 American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS).

Materials and methods

We enrolled 110 cases of MTNs and 110 cases of PTCs confirmed by fine needle aspiration (FNA) or surgery. Conventional ultrasound (US) and the quantity of microvessels detected by SMI were analyzed for all nodules. Thyroid nodules were initially categorized by ACR-TIRADS based on US imaging features and then reclassified based on ACR-TIRADS combined with SMI blood-flow grade (SMI-TIRADS). We compared the diagnostic performances of ACR-TIRADS and SMI-TIRADS by receiver operating characteristic curve, sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV).

Results

US-detected margin, shape, and echogenic foci differed between MTNs and PTCs (P < 0.05). The SMI blood-flow grade was significantly greater in PTCs compared with MTNs (Χ 2 = 158.78, P < 0.05). There was no significant difference in ACR-TIRADS indicators between MTNs and PTCs (Χ 2 = 1.585, P = 0.453); however, reclassification by SMI-TIRADS showed significant differences between the groups (Χ 2 = 129.521, P < 0.001). The area under the curve was significantly lower for ACR-TIRADS compared with SMI-TIRADS (0.517 vs 0.887, P < 0.05). SMI-TIRADS had significantly higher diagnostic value for distinguishing MTNs and PTCs than ACR-TIRADS (sensitivity: 91.82% vs 74.55%, P < 0.05; specificity: 84.55% vs 21.82%, P < 0.05; accuracy: 88.18% vs 48.18%, P < 0.05; PPV: 85.59% vs 48.81%, P < 0.05; and NPV: 91.18% vs 46.15%, P < 0.05).

Conclusion

The detection of microvascular flow and large vessels in thyroid nodules by SMI resulted in high diagnostic specificity and sensitivity. ACR-TIRADS combined with SMI could effectively distinguish between MTNs and PTCs, to avoid unnecessary FNA or surgical excision.

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Zhou Zheng Department of Medical Laboratory, The Affiliated Luohu Hospital of Shenzhen University, Shenzhen University, Shenzhen, Guangdong, China

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Xiuming Zhang Department of Medical Laboratory, The Affiliated Luohu Hospital of Shenzhen University, Shenzhen University, Shenzhen, Guangdong, China

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Fanggui Wu Department of Reproductive Medicine, The Affiliated Luohu Hospital of Shenzhen University, Shenzhen University, Shenzhen, Guangdong, China

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Haizhen Liao Department of Reproductive Medicine, The Affiliated Luohu Hospital of Shenzhen University, Shenzhen University, Shenzhen, Guangdong, China

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Huan Zhao Department of Reproductive Medicine, The Affiliated Luohu Hospital of Shenzhen University, Shenzhen University, Shenzhen, Guangdong, China

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Minqi Zhang Department of Reproductive Medicine, The Affiliated Luohu Hospital of Shenzhen University, Shenzhen University, Shenzhen, Guangdong, China

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Shangjie Liu Department of Reproductive Medicine, The Affiliated Luohu Hospital of Shenzhen University, Shenzhen University, Shenzhen, Guangdong, China

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Although several studies have reported that high maternal BMI could influence the cumulative live birth rate (CLBR) in fresh embryo transfer cycles, the association of BMI with CLBR remains unclear in patients that completed IVF treatment. In this study, we examined the association of maternal BMI with CLBR, including repetitive one oocyte pick-up (OPU) and all fresh and frozen embryo transfer until live birth or embryos were run out. A total of 16,126 patients’ data were included in the analysis and were divided into four groups based on BMI. We found that patients’ characteristics, embryo parameters, and pregnancy outcomes differed among different BMI groups. Multivariate logistic regression showed that being underweight was associated with a higher possibility of having live birth than the reference group (OR (95% CI) 1.40 (1.22–1.59), P < 0.001), whereas being overweight and obese were associated with a lower possibility of having live birth than the reference group ((OR (95% CI) 0.81 (0.74–0.90), P < 0.001) and (OR (95% CI) 0.68 (0.55–0.85), P < 0.001)). After adjustment for confounding factors, the reference group was associated with a higher possibility of having live birth, with a significant difference found between the obese and reference groups (OR (95% CI) 0.55 (0.43–0.70), P < 0.001). An association was found between CLBR and BMI, indicating that an increase in BMI results in a decline in CLBR. Moreover, the CLBR of patients with different characteristics differed in the various BMI groups. Taken together, our data show that maternal BMI has a significant impact on CLBR.

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Orwa Dandash Department of Psychiatry, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia

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James Allebone Department of Psychiatry, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia

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Adam Mirabelli Department of Psychiatry, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia

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Nicholas Russell Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia

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Mathis Grossmann Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia

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Andrea Gogos Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia
Department of Florey Institute, University of Melbourne, Parkville, Victoria, Australia

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Richard A Kanaan Department of Psychiatry, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia

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We investigated the effect of estradiol add-back therapy (EAT) on brain activation related to cognitive function and affect in addition to putative changes in gray and white matter volume in testosterone depleted participants with prostate cancer. We conducted a randomized controlled, double-blinded trial in which 40 patients received 0.9 mg of transdermal estradiol per day for 6 months or matched placebo. Anatomical MRI and three functional MRI (fMRI) scans were obtained for the emotion recognition task, verbal memory task, and visuospatial memory task. Activation in corresponding cognitive and affective brain networks was demonstrated for all tasks. Longitudinally, there was no difference in brain activation, reaction time, or accuracy in response to the fMRI tasks between the EAT group and placebo group at 6 months. In addition, there was no detectable change in whole-brain gray or white matter volume or in hippocampal volume between the two groups after 6 months. This study supports earlier findings that EAT does not improve verbal memory or affect and has no immediate effect on hippocampal volume in testosterone depleted patients with prostate cancer.

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Antonella Giampietro Pituitary Unit, Department of Endocrinology, Fondazione A Gemelli, IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy

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Sabrina Chiloiro Pituitary Unit, Department of Endocrinology, Fondazione A Gemelli, IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy

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Claudio Urbani Endocrinology II Unit, Department of Medicine, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy

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Rosario Pivonello Dipartimento Di Medicina Clinica E Chirurgia, Sezione Di Endocrinologia, Università Federico II di Napoli, Naples, Italy

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Martin Ove Carlsson Global Medical Affairs, Pfizer Rare Disease, Brussels, Belgium

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Francesca Dassie Department of Medicine - DIMED, University of Padua, Padua, Italy

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Nunzia Prencipe Division of Endocrinology, Diabetology and Metabolism, Department of Medical Science, University of Turin, Turin, Italy

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Marta Ragonese Unit of Endocrinology, Department of Human Pathology, University of Messina, Messina, Italy

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Roy Gomez Global Medical Affairs, Pfizer Rare Disease, Brussels, Belgium

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Simona Granato Medical Department, Pfizer Italia, Rome, Italy

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Salvatore Cannavò Unit of Endocrinology, Department of Human Pathology, University of Messina, Messina, Italy

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Silvia Grottoli Division of Endocrinology, Diabetology and Metabolism, Department of Medical Science, University of Turin, Turin, Italy

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Pietro Maffei Department of Medicine - DIMED, University of Padua, Padua, Italy

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Annamaria Colao Dipartimento Di Medicina Clinica E Chirurgia, Sezione Di Endocrinologia, Università Federico II di Napoli, Naples, Italy

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Fausto Bogazzi Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

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Antonio Bianchi Pituitary Unit, Department of Endocrinology, Fondazione A Gemelli, IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy

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Purpose

The aim of this study was to examine the probability of achieving acromegaly disease control according to several patient-, disease- and treatment-related factors longitudinally.

Methods

We analyzed data from ACROSTUDY, an open-label, noninterventional, post-marketing safety surveillance study conducted in 15 countries. A total of 1546 patients with acromegaly and treated with pegvisomant, with available information on baseline IGF-1 level, were included. Factors influencing IGF-1 control were assessed up to 10 years of follow-up by mixed-effects logistic regression models, taking into account changing values of covariates at baseline and at yearly visits. Twenty-eight anthropometric, clinical and treatment-related covariates were examined through univariate and multivariate analyses. We tested whether the probability of non-control was different than 0.50 (50%) by computing effect sizes (ES) and the corresponding 95% CI.

Results

Univariate analysis showed that age <40 years, normal or overweight, baseline IGF-1 <300 µg/L or ranged between 300 and 500 µg/L, and all pegvisomant dose <20 mg/day were associated with a lower probability of acromegaly uncontrol. Consistently, in multivariate analyses, the probability of uncontrolled acromegaly was influenced by baseline IGF-1 value: patients with IGF-1 <300 µg/L had the lowest risk of un-controlled acromegaly (ES = 0.29, 95% CI: 0.23–0.36). The probability of acromegaly uncontrol was also lower for values 300–500 µg/L (ES = 0.37, 95% CI: 0.32–0.43), while it was higher for baseline IGF-1 values ≥700 µg/L (ES = 0.58, 95% CI: 0.53–0.64).

Conclusion

Baseline IGF-l levels were a good predictor factor for long-term acromegaly control. On the contrary, our data did not support a role of age, sex, BMI and pegvisomant dose as predictors of long-term control of acromegaly.

Significance statement

Among factors that could influence and predict the efficacy of pegvisomant therapy in controlling acromegaly, a central role of baseline IGF-1 values on the probability of achieving a biochemical control of acromegaly during the treatment with pegvisomant was identified, in a real-life setting.

Open access
Marie Oertel Division of Endocrinology and Diabetes, Department of Internal Medicine, University Hospital, University of Würzburg, Würzburg, Germany

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Christian G Ziegler Division of Endocrinology and Diabetes, Department of Internal Medicine, University Hospital, University of Würzburg, Würzburg, Germany
Department of Internal Medicine III, University Hospital Carl Gustav Carus Dresden, Dresden, Germany

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Michael Kohlhaas Comprehensive Heart Failure Center, Würzburg, Germany

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Alexander Nickel Comprehensive Heart Failure Center, Würzburg, Germany

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Simon Kloock Division of Endocrinology and Diabetes, Department of Internal Medicine, University Hospital, University of Würzburg, Würzburg, Germany

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Christoph Maack Comprehensive Heart Failure Center, Würzburg, Germany

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Vasco Sequeira Comprehensive Heart Failure Center, Würzburg, Germany

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Martin Fassnacht Division of Endocrinology and Diabetes, Department of Internal Medicine, University Hospital, University of Würzburg, Würzburg, Germany

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Ulrich Dischinger Division of Endocrinology and Diabetes, Department of Internal Medicine, University Hospital, University of Würzburg, Würzburg, Germany
Comprehensive Heart Failure Center, Würzburg, Germany

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Objective

Combination therapies with gut hormone analogs represent promising treatment strategies for obesity. This pilot study investigates the therapeutic potential of modulators of the glucagon-like peptide 1 (GLP-1) and neuropeptide Y (NPY) system using GLP-1 receptor agonists (semaglutide) and antagonists (exendin 9-39), as well as non-selective and NPY-Y2-receptor selective peptide tyrosine tyrosine (PYY) analogs (PYY3-36/NNC0165-0020 and NNC0165-1273) and an NPY-Y2 receptor antagonist (JNJ31020028).

Methods

High-fat diet (HFD)-induced obese rats were randomized into following treatment groups: group 1, nonselective PYY analog + semaglutide (n = 4); group 2, non-selective and NPY-Y2 receptor selective PYY analog + semaglutide (n = 2); group 3, GLP-1 receptor antagonist + NPY-Y2 receptor antagonist (n = 3); group 4, semaglutide (n = 5); and group 5, control (n = 5). Animals had free access to HFD and low-fat diet. Food intake, HFD preference and body weight were measured daily.

Results

A combinatory treatment with a non-selective PYY analog and semaglutide led to a maximum body weight loss of 14.0 ± 4.9% vs 9.9 ± 1.5% with semaglutide alone. Group 2 showed a maximum weight loss of 20.5 ± 2.4%. While HFD preference was decreased in group 2, a strong increase in HFD preference was detected in group 3.

Conclusions

PYY analogs (especially NPY-Y2 selective receptor agonists) could represent a promising therapeutic approach for obesity in combination with GLP-1 receptor agonists. Additionally, combined GLP-1 and PYY3-36 receptor agonists might have beneficial effects on food preference.

Open access
Xinyuan Zhang Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan, China

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Suiyan Li School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan, China

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Hongwei Liu Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China

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Huai Bai Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China

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Qingqing Liu Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China

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Chunyi Yang Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China

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Ping Fan Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China

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Oxidative stress and metabolic disorders are involved in the pathogenesis of polycystic ovary syndrome (PCOS). Heme oxygenase 2 (HMOX2) plays a critical role in preserving heme metabolism as well as in modulating glycolipid metabolism, oxidative stress, and inflammation. This study examined the correlation between HMOX2 G554A (rs1051308) and A-42G (rs2270363) genetic variants with the risk of PCOS and assessed the effects of these genotypes on clinical, hormonal, metabolic, and oxidative stress indices using a case–control design that included 1014 patients with PCOS and 806 control participants. We found that the allelic and genotypic frequencies of the HMOX2 G554A and A-42G polymorphisms were comparable between the PCOS and control groups in Chinese women (P > 0.05). Nevertheless, it was discovered that patients with the AA or AG genotype of A-42G polymorphism had notably elevated levels of estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH ratio, high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (apo)B, and/or apoB/apoA1 ratio than those with the GG genotypes (P < 0.05). Patients with the GG or AG genotype of G554A polymorphism had elevated serum levels of LH, FSH, E2, LH/FSH ratio, TC, HDL-C, LDL-C, apoB, and/or apoB/apoA1 ratio and lower 2-h glucose concentration compared with those with the AA genotype (P < 0.05). Our findings indicate a potential association between the genetic variants and endocrine abnormalities in the reproductive system and metabolic irregularities in glycolipid levels in patients, thus suggesting their potential role in the pathogenesis of PCOS.

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Run-Qing Xiong Department of Ultrasonic Imaging, Xiamen Medical College Affiliated Second Hospital, Fujian, China

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Yan-Ping Li Key Laboratory of Functional and Clinical Translational Medicine, Fujian Province University, Xiamen Medical College, Fujian, China

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Lu-Ping Lin Department of Endocrinology, Xiamen Medical College Affiliated Second Hospital, Fujian, China

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Jeng-Yuan Yao Key Laboratory of Functional and Clinical Translational Medicine, Fujian Province University, Xiamen Medical College, Fujian, China

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Diabetic cardiomyopathy (DCM) is a serious complication of type 2 diabetes mellitus (T2DM) that contributes to cardiovascular morbidity and mortality. However, the metabolic alterations and specific biomarkers associated with DCM in T2DM remain unclear. In this study, we conducted a comprehensive metabolomic analysis using liquid chromatography–mass spectrometry (LC-MS) to investigate the plasma metabolite profiles of T2DM patients with and without DCM. We identified significant differences in metabolite levels between the groups, highlighting the dysregulation of various metabolic pathways, including starch and sucrose metabolism, steroid hormone biosynthesis, tryptophan metabolism, purine metabolism, and pyrimidine metabolism. Although several metabolites showed altered abundance in DCM, they also shared characteristics of DCM and T2DM rather than specific to DCM. Additionally, through biomarker analyses, we identified potential biomarkers for DCM, such as cytidine triphosphate, 11-ketoetiocholanolone, saccharopine, nervonic acid, and erucic acid. These biomarkers demonstrated distinct patterns and associations with metabolic pathways related to DCM. Our findings provide insights into the metabolic changes associated with DCM in T2DM patients and highlight potential biomarkers for further validation and clinical application. Further research is needed to elucidate the underlying mechanisms and validate the diagnostic and prognostic value of these biomarkers in larger cohorts.

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Magdalena Lech Faculty of Life Sciences and Medicine, School of Life Course Sciences, King’s College London, London, UK

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Ruvini Ranasinghe Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK

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Royce P Vincent Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK
Faculty of Life Sciences and Medicine, School of Life Course Sciences, King’s College London, London, UK

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David R Taylor Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK

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Lea Ghataore Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK

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James Luxton Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK

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Fannie Lajeunesse-Trempe Department of Endocrinology ASO/EASO COM, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK
Quebec Heart and Lung Institute, Laval University, Quebec, Canada

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Pia Roser Department of Endocrinology and Diabetes, University Medical Centre Hamburg Eppendorf, Hamburg, Germany

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Eftychia E Drakou Department of Clinical Oncology, Guy's Cancer Centre - Guy's and St Thomas' NHS Foundation Trust, Great Maze Pond, London, UK

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Ling Ling Chuah Department of Endocrinology ASO/EASO COM, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK

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Ashley B Grossman Green Templeton College, University of Oxford, Oxford, UK
Barts and the London School of Medicine, Centre for Endocrinology, William Harvey Institute, London, UK
Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK

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Simon J B Aylwin Department of Endocrinology ASO/EASO COM, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK

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Georgios K Dimitriadis Department of Endocrinology ASO/EASO COM, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK
Obesity, Type 2 Diabetes and Immunometabolism Research Group, School of Cardiovascular and Metabolic Medicine & Sciences, Faculty of Life Course Sciences, King’s College London, London, UK
Division of Reproductive Health, Warwick Medical School, University of Warwick, Coventry, UK

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Introduction

Adrenocortical carcinoma (ACC) is a rare malignancy of the adrenal cortex. Whilst surgery is the preferred treatment, adjunctive therapy with mitotane may be offered post-surgically to minimise the risk of recurrence or, in the absence of surgery, to attenuate progression.

Aim

The objective was to evaluate the effects of mitotane treatment on serum protein concentrations in patients treated for ACC with mitotane therapy and compare this to patients with other adrenal neoplasms and a normal pregnant cohort.

Methods

Serum cortisol, thyroid function tests, adrenocorticotrophic hormone (ACTH), cortisol-binding globulin (CBG), thyroxine-binding globulin (TBG), gonadotrophins and androgens were measured on plasma and serum samples. Thirty-five patients with ACC were included, and mitotane levels were noted to be sub-/supra-therapeutic. Data were tested for normality, reported as mean ± s.d., and compared to other two cohorts using paired-sample t-test with a 5% P-value for significance and a 95% CI.

Results

Patients on mitotane therapy had a higher mean serum CBG concentration compared to the adrenal neoplasm group (sub-therapeutic: 79.5 (95% CI: 33.6, 125.4 nmol/L), therapeutic: 85.3 (95% CI: 37.1–133.6 nmol/L), supra-therapeutic: 75.7 (95% CI: −19.3, 170.6 nmol/L) and adrenal neoplasm: 25.5 (95% CI: 17.5, 33.5 nmol/L). Negative correlations between serum cortisol and CBG concentration were demonstrated within the supra-therapeutic plasma mitotane and adrenal neoplasm groups.

Conclusion

Patients with ACC and therapeutic plasma mitotane concentrations had higher serum CBG concentrations compared to those with adrenal neoplasms or pregnant women, and higher serum cortisol. Whilst there was no direct correlation with cortisol and mitotane level, the negative correlation of cortisol with CBG may suggest that the direct effect of mitotane in increasing cortisol may also reflect that mitotane has a direct adrenolytic effect.

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Jorge Gabriel Ruiz-Sánchez Servicio de Endocrinología y Nutrición. Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD, UAM), Hospital Universitario Fundación Jiménez Díaz, Madrid, España
Facultad de Medicina, Universidad Complutense de Madrid, Madrid, España

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Alfonso Luis Calle-Pascual Facultad de Medicina, Universidad Complutense de Madrid, Madrid, España
Servicio de Endocrinología y Nutrición. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico San Carlos, Madrid, España
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, España

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Miguel Ángel Rubio-Herrera Facultad de Medicina, Universidad Complutense de Madrid, Madrid, España
Servicio de Endocrinología y Nutrición. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico San Carlos, Madrid, España

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María Paz De Miguel Novoa Facultad de Medicina, Universidad Complutense de Madrid, Madrid, España
Servicio de Endocrinología y Nutrición. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico San Carlos, Madrid, España

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Emilia Gómez-Hoyos Servicio de Endocrinología y Nutrición, Hospital Clínico Universitario de Valladolid, Valladolid, España

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Isabelle Runkle Facultad de Medicina, Universidad Complutense de Madrid, Madrid, España
Servicio de Endocrinología y Nutrición. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico San Carlos, Madrid, España

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Introduction

Hypoaldosteronism is characterized by hyperkalemia, and/or hypovolemic hyponatremia (HH), often accompanied by metabolic acidosis. HH is typical of hypoaldosteronism, whereas euvolemic hyponatremia (EH) is not. The purpose of the current study is to describe the characteristics of hyponatremia in hypoaldosteronism and elucidate whether EH can be considered part of the disease’s spectrum.

Methods

In a hypoaldosteronism cohort, we analyzed the factors associated with hyponatremia, comparing the characteristics of EH and HH and their associated factors. Correlation analyses of mineralocorticoid biomarkers, such as the transtubular potassium gradient (TTKG), the urinary Na+/K+ ratio (UNa+/UK+) with serum, and urinary electrolytes were performed in both types of hyponatremia.

Results

Of 112 hypoaldosteronism episodes, 77.7% were ≥65 years old, 44.6% were women, and 80 (71.4%) had hyponatremia. Hyponatremia was negatively associated with the presence of chronic kidney disease, and positively with a hypovolemic state, malnutrition, a prior history of hyponatremia, and glucocorticoid therapy. HH: 61/80 and EH: 19/80 episodes. HH was associated with an age ≥65 years and the use of diuretics, as well as factors related to an aldosterone deficit and/or mineralocorticoid resistance. In HH but not in EH, urinary potassium was correlated with the TTKG, and urinary sodium with both the TTKG and the UNa+/UK+.

Conclusion

Both HH and EH can be observed in hypoaldosteronism. However, only the former would be related to insufficient mineralocorticoid activity.

Significance statement

Isolated hypoaldosteronism is a poorly understood and underdiagnosed endocrinological disorder, classically recognized only when hyperkalemia is present. The development of hypovolemic hyponatremia, however, is also easily explained by the physiopathology of the disorder. The current study addresses the features of hyponatremia when found in the context of mineralocorticoid insufficiency, and confirms an association between hypovolemic hyponatremia and isolated hypoaldosteronism. Thus, the clinical spectrum of hypoaldosteronism is extended to include hypovolemic hyponatremia as a frequent manifestation of the disorder.

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