Journal of Clinical Endocrinology & Metabolism最新文献

{"title":"The Microbial Regulation Spectrum of Metformin in Patients With Type 2 Diabetes: An Individual-Based Meta-Analysis of 1431 Participants.","authors":"Wenquan Su, Yanan Yang, Jiale Cheng, Naijia Dong, Yuan Li, Qinhua Fan, Hai Lin, Shengxian Wu, Chongming Wu","doi":"10.1210/clinem/dgaf238","DOIUrl":"10.1210/clinem/dgaf238","url":null,"abstract":"<p><strong>Context: </strong>The gut microbiota plays a significant role in metformin efficacy and therapeutic response. However, studies often have produced inconsistent outcomes.</p><p><strong>Objective: </strong>To gain a more comprehensive understanding of the transformation of gut microbiota in persons with diabetes and the subsequent modifications following metformin intervention.</p><p><strong>Data sources: </strong>Seven databases were searched, from the inception of each database up to October 30, 2024. The raw sequence reads of 9 available datasets were downloaded from the National Center for Biotechnology Information (NCBI).</p><p><strong>Study selection: </strong>The process of selecting and assessing papers for this study was meticulously managed by 2 authors, working independently to screen and evaluate each publication.</p><p><strong>Data extraction: </strong>For the data extraction phase, a standardized form was employed, capturing critical details.</p><p><strong>Data synthesis: </strong>Metformin significantly boosts the presence of Akkermansia and short-chain fatty acid (SCFA)-producing bacteria, such as Pseudobutyrivibrio, Oribacterium, and Anaerotruncus, and it simultaneously diminishes pathogenic bacteria, including Enterobacillus, Gemmobacter, Shinella, Klebsiella, and Enterocloster. In addition, Bifidobacterium and Blautia were increased in patients with type 2 diabetes (T2D) but restored to near normal levels by metformin, and this alteration is region-specific.</p><p><strong>Conclusion: </strong>Our analysis delivers more concrete evidence regarding the shifts in gut microbiota following metformin treatment, significantly enriching our understanding of the interplay between gut microbiome dynamics and the management of T2D.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"2383-2403"},"PeriodicalIF":5.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Weight Loss Induces Changes in Vitamin D Status in Women With Obesity But Not in Men: A Randomized Clinical Trial.","authors":"Rune Holt, Joachim Holt, Mads Joon Jorsal, Rasmus Michael Sandsdal, Simon B K Jensen, Sarah Byberg, Christian Rimer Juhl, Julie Rehné Lundgren, Charlotte Janus, Bente Merete Stallknecht, Jens Juul Holst, Anders Juul, Sten Madsbad, Martin Blomberg Jensen, Signe Sørensen Torekov","doi":"10.1210/clinem/dgae775","DOIUrl":"10.1210/clinem/dgae775","url":null,"abstract":"<p><strong>Context: </strong>Obesity is associated with low vitamin D status -, and recent studies have suggested a difference in vitamin D metabolism between females and males.</p><p><strong>Objective: </strong>The aim of this study was to investigate the effects of weight loss on vitamin D status in individuals with obesity, and secondarily, whether vitamin D metabolism differs between women and men.</p><p><strong>Methods: </strong>Secondary analysis from a randomized placebo-controlled trial, designed to investigate the efficacy of 52 weeks of treatment with either liraglutide, exercise, or both combined compared with placebo on weight loss maintenance after an 8-week low-calorie diet-induced weight loss in 195 individuals with obesity (body mass index 32-43 kg/m2).</p><p><strong>Results: </strong>The low-calorie diet-induced weight loss resulted in an increase in serum 25-hydroxyvitamin D (25(OH)D) in both women and men [12 nmol/L (95% confidence interval [CI] 9-15) and 13 nmol/L (95% CI 8-17); P < .001 for both]. Women who experienced a further weight loss during the 52 weeks of intervention had an increase in serum 25(OH)D compared with women regaining weight [14 nmol/L (95% CI 6-22); P = .001]. Interestingly, women experiencing further weight loss at week 52 had a lower serum 25(OH)D at baseline compared with women regaining weight [54 nmol/L (SD 19) vs 70 nmol/L (SD 25), P < .001.].</p><p><strong>Conclusion: </strong>Weight loss induced by a low-calorie diet resulted in an increase in serum 25(OH)D in both women and men. Only in women, further weight loss had an additional beneficial impact on vitamin D. Additionally, initial low serum 25(OH)D was associated with successful weight loss maintenance in women but not men.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov number: NCT04122716.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"2215-2224"},"PeriodicalIF":5.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and Clinical Characteristics of 185 Japanese Children With 46,XY Differences of Sex Development.","authors":"Mie Hayashi, Satoshi Narumi, Takeshi Sato, Naoko Amano, Ayuko Suzuki Suwanai, Hidenori Haruna, Koji Muroya, Masanori Adachi, Hiroshi Asanuma, Hirofumi Ohashi, Tomohiro Ishii, Tomonobu Hasegawa","doi":"10.1210/clinem/dgae813","DOIUrl":"10.1210/clinem/dgae813","url":null,"abstract":"<p><strong>Context: </strong>46,XY differences of sex development (DSD) are heterogeneous in etiology. The detailed phenotypes of 46,XY DSD patients with monogenic disorders have not been fully elucidated.</p><p><strong>Objectives: </strong>To estimate the proportion of monogenic disorders in 46,XY DSD and to characterize the clinical phenotypes of patients with monogenic disorders.</p><p><strong>Methods: </strong>A total of 185 Japanese patients (178 families) were enrolled. We sequenced 25 genes related to 46,XY DSD and assessed the pathogenicity of the identified sequence variants according to the American College of Medical Genetics and Genomics guidelines, supplemented by in silico and/or in vitro analyses. We analyzed the clinical phenotypes of patients with monogenic disorders, with particular attention to the external or internal genitalia.</p><p><strong>Results: </strong>We identified 51 patients (47 families) with any monogenic disorders (26%), who possessed pathogenic variants in AR (11%), SRD5A2 (4.5%), NR5A1 (4.0%), SRY (2.8%), WT1 (1.1%), STAR (1.1%), CYP17A1 (0.56%), HSD3B2 (0.56%), or MAP3K1 (0.56%). The proportion of monogenic disorders was significantly higher in subjects with detected Müllerian derivatives (57%) than in those undetected (26%) (P = .029), and in subjects with female-typical genitalia (91%) than in those with ambiguous genitalia (19%) (P < .001).</p><p><strong>Conclusion: </strong>The proportion of monogenic disorders in Japanese 46,XY DSD patients was approximately 26%. Monogenic disorders were frequent among patients with severe undermasculinization of the external or internal genitalia.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e2682-e2690"},"PeriodicalIF":5.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Approach to the Pediatric Patient With Thyroid Nodules.","authors":"Sin-Ting Tiffany Lai, Andrew J Bauer","doi":"10.1210/clinem/dgaf090","DOIUrl":"10.1210/clinem/dgaf090","url":null,"abstract":"<p><p>Thyroid nodules in pediatrics carry a higher risk for thyroid carcinoma, and the risk of malignancy in indeterminate thyroid nodules is higher when compared to adults. Despite a substantial increase in the incidence of pediatric thyroid carcinoma since the 1990s, the 30-year disease survival remains >98% in pediatrics. The goal of thyroid nodule management focuses on reducing comorbidity of care while maintaining remission from disease and low disease-specific mortality. In 2014, the Cancer Genome Atlas introduced the concept that molecular subtypes better predict the invasive behavior of papillary thyroid carcinoma compared to pathological classification alone. Recent advancements in the understanding of the genetic landscape of pediatric thyroid carcinoma support the potential utility of incorporating somatic oncogene analysis to evaluate and manage thyroid nodules and thyroid carcinoma. In this Approach to the Pediatric Patient, we review the risk factors of differentiated thyroid carcinoma and present an integrative approach to evaluating and managing thyroid nodules in pediatric patients, incorporating sonographic and cytopathologic findings with somatic oncogene analysis. We illustrate the potential clinical application of knowledge on somatic oncogenic drivers to improve the preoperative accuracy in diagnosing differentiated thyroid carcinoma and present an integrative analysis paradigm designed to individualize the surgical approach of pediatric patients with thyroid nodules and differentiated thyroid carcinoma.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"2339-2352"},"PeriodicalIF":5.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feasibility, Acceptability, and Validity of Home Continuous Glucose Monitoring-Based Oral Glucose Tolerance Test in Youth.","authors":"Adriana Rodriguez Gonzalez, Caleb Harrison, Brianna Hewitt, Jennifer L Mejier, Mary Ellen Vajravelu","doi":"10.1210/clinem/dgae845","DOIUrl":"10.1210/clinem/dgae845","url":null,"abstract":"<p><strong>Context: </strong>Home-based approaches to type 2 diabetes (T2D) screening in youth may facilitate early diagnosis.</p><p><strong>Objective: </strong>This work aimed to evaluate feasibility, acceptability, and validity of a continuous glucose monitoring (CGM)-based oral glucose tolerance test (OGTT).</p><p><strong>Methods: </strong>A prospective observational study was conducted at a pediatric clinical and translational research center. Participants were youth aged 8 to 18 years with overweight/obesity and prediabetes-range glycated hemoglobin A1c (HbA1c), fasting glucose, or 2-hour glucose on OGTT, and/or one or more guideline-based T2D risk factors. Participants completed two 75 g 2-hour OGTT 1) at the research center using serum samples (research-OGTT), and 2) at home using blinded CGM (home-OGTT). Feasibility: Percentage with valid home-OGTT data (date/time reported, transmitter returned). Acceptability: Survey and interview responses. Validity: Sensitivity, specificity, positive- and negative predictive value (PPV, NPV) of home- vs research-OGTT dysglycemia (fasting ≥100 mg/dL; 2-hour ≥140 mg/dL).</p><p><strong>Results: </strong>Thirty-nine youth (54% female; 33% Black, 8% Hispanic/Latinx, 13% multiracial, 46% non-Hispanic White; age 14.6 ± 2.0 years; mean body mass index 37.0 ± 6.7 kg/m2) participated. HbA1c was 5.7% ± 0.4%, fasting glucose 85.7 ± 8.0 mg/dL, and 2-hour glucose 115.9 ± 25.9 mg/dL. Thirty (77%) had valid home-OGTT data. Acceptability was high (92% excellent/great, 8% neutral). Due to higher average values on home-OGTT, sensitivity and NPV were high (≥80%), while specificity (fasting: 10%; 2-hour: 25%) and PPV (fasting: 3.6%, 2-hour: 18.2%) were low.</p><p><strong>Conclusion: </strong>Home-OGTT was acceptable, but strategies to precisely capture glucose ingestion timing could improve feasibility. Alternate dysglycemia thresholds may need to be defined prior to using CGM as a method for T2D screening in youth.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e2510-e2516"},"PeriodicalIF":5.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycemic Control and Adult Height: A Nationwide Swedish Cohort Study on Childhood Type 1 Diabetes.","authors":"Awad I Smew, Cecilia Lundholm, Tong Gong, Paul Lichtenstein, Lars Sävendahl, Catarina Almqvist","doi":"10.1210/clinem/dgae809","DOIUrl":"10.1210/clinem/dgae809","url":null,"abstract":"<p><strong>Context: </strong>Normal growth throughout childhood and adolescence is considered an indicator of adequate glycaemic control in patients with type 1 diabetes. While it has been suggested that growth in type 1 diabetes is reduced, the literature is conflicting and differences in final adult height and the risk of short stature depending on glycaemic control remain largely unexplored.</p><p><strong>Objective: </strong>This work aims to assess adult height outcomes across levels of glycemic control in children and adolescents with type 1 diabetes, as well as to investigate the effect of sex, age at disease onset, and timing of glycemic control in relation to puberty.</p><p><strong>Methods: </strong>In this population-based Swedish cohort study, we collected data on glycemic control and height from specialist health-care visits of all individuals with childhood-onset type 1 diabetes in the National Diabetes Register. Using linear and logistic regression, we compared suboptimal (glycated hemoglobin A1c [HbA1c] 53-75 mmol/mol [7.0-9.0%]) and poor (HbA1c > 75 mmol/mol [>9.0%]) to optimal (HbA1c < 53 mmol/mol [<7.0%]) glycemic control in relation to final adult height and the risk of short stature.</p><p><strong>Results: </strong>Poor glycemic control was associated with lower final adult height (-2.91 cm [95% CI, -3.48 to -2.33] for males, -1.83 cm [-2.42 to -1.23] for females) as well as a higher risk of short stature in males (odds ratio 1.90 [1.07-3.35]) but not in females (0.73 [0.36-1.51]). For females, adult height was lower only among those with type 1 diabetes since before puberty and if the poor glycemic control occurred before puberty. For males, adult height was lower irrespective of their age at diabetes onset, but only if they had poor glycemic control during or after puberty.</p><p><strong>Conclusion: </strong>Poor glycemic control after the onset of type 1 diabetes, compared to optimal control, is associated with lower adult height in males and females. The prepubertal period seems to be more critical for females than males.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e2765-e2777"},"PeriodicalIF":5.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142669507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced Outcomes in Type 2 Diabetes Patients With Acute Kidney Disease Through Thiazolidinedione.","authors":"Li-Yang Chang, Hung-Wei Liao, Jui-Yi Chen, Vin-Cent Wu","doi":"10.1210/clinem/dgae796","DOIUrl":"10.1210/clinem/dgae796","url":null,"abstract":"<p><strong>Context: </strong>Patients with diabetes are prone to acute kidney injury with the potential transition to chronic kidney disease. Few studies have investigated the role of thiazolidinedione (TZD) in these patients under acute kidney disease (AKD) phase.</p><p><strong>Objective: </strong>We sought to examine whether using TZD during AKD could reduce the risk of future major adverse outcomes.</p><p><strong>Design and methods: </strong>We employed the TriNetX platform before September 30, 2022, for TZD administration to patients with type 2 diabetes mellitus (T2DM) within 90 days of an AKD diagnosis. Clinical endpoints include the risk of all-cause mortality, major adverse cardiovascular events (MACE), and major adverse kidney events (MAKE). Hazard ratios (HRs) and 95% confidence intervals were calculated with 1:1 ratio propensity score matching (PSM).</p><p><strong>Results: </strong>Among the cohort of 263,101 patients with AKD and T2DM, we identified 2723 individuals (1.03%) who were TZD users during the AKD period. After PSM, the final cohort of TZD users included 2555 individuals, with 53.82% being male and a mean age of 64.0 ± 13.5 years. Over a median follow-up period of 1.5 years, the TZD group exhibited a lower risk across various outcomes, with HRs of 0.68 [95% confidence interval (CI), 0.57-0.81] for all-cause mortality, 0.68 (95% CI, 0.58-0.80) for MACE, and 0.75 (95% CI, 0.66-0.86) for MAKE.</p><p><strong>Conclusion: </strong>TZD demonstrated a notable reduction in mortality, cardiovascular events, and kidney-related adverse events among T2DM patients with AKD. These findings suggest a potential benefit of TZD usage for managing cardiovascular events in T2DM patients with AKD.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"2205-2214"},"PeriodicalIF":5.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased Ambient Temperature and Hyponatremia Presentations: A 10-Year Retrospective Study at an Australian Hospital.","authors":"Thomas Nicholls, Rudolf Hoermann, Elizabeth Wootton, Negar Mansouri, Meg Stevens, Hung Vo, Mathis Grossmann, Annabelle M Warren","doi":"10.1210/clinem/dgae820","DOIUrl":"10.1210/clinem/dgae820","url":null,"abstract":"<p><strong>Objective: </strong>To determine the relationship between ambient air temperature and the incidence of hyponatremia in a heat-prone region.</p><p><strong>Methods: </strong>We conducted a retrospective study that correlated serum sodium concentrations documented at the Austin Hospital in Melbourne over 10 years from January 2014 to December 2023 with publicly available temperature data from the Australian Bureau of Meteorology. The main outcome measures were serum sodium concentrations and incidence of hyponatremia admissions when correlated to temperature, and, following heatwave events, defined as temperature above 30 °C over 5 consecutive days.</p><p><strong>Results: </strong>Over this period, 45 718 low serum sodium results were identified from 26 557 unique patients. Serum sodium concentrations in January (Australian summer) were 0.55 mmol/L lower (95% CI 0.36 to 0.77, P < .001) than in September (Australian early spring). Women had lower sodium concentrations than men (-0.21 mmol/L, 95% CI -0.29 to -0.12, P < .001), as did patients older than 80 years when compared with those younger than 65 years (-0.39 mmol, 95% CI -0.50 to -0.29, P < .001). Hospital admissions with hyponatremia were more frequent during summer months. Profound hyponatremia admissions (sodium ≤125 mmol/L) were more frequent following a heatwave than without (7.6% vs 6.5%, P = .04).</p><p><strong>Conclusion: </strong>Our study demonstrates that serum sodium concentrations are lower and profound hyponatremia-related hospital admissions higher when ambient temperatures are warmer. This suggests that hyponatremia is a climate-associated health issue. Local public health advice for water consumption during heatwaves should consider this risk, and prompt action to limit climate change is required to mitigate this risk.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e2666-e2673"},"PeriodicalIF":5.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers Improving Genetic and Metastatic Disease Prediction in Paraganglioma: Insights From a Prospective Study.","authors":"Tom Drossart, Alexandre Buffet, Ali Janbain, Chris Ottolenghi, Laurence Amar, Rossella Libé, Delphine Drui, Charlotte Lussey-Lepoutre, Maxence Mancini, Timgad Lounis, Armelle Guénégou-Arnoux, Tchao Méatchi, Jérôme Bertherat, Nelly Burnichon, Judith Favier, Anne-Paule Gimenez-Roqueplo","doi":"10.1210/clinem/dgae797","DOIUrl":"10.1210/clinem/dgae797","url":null,"abstract":"<p><strong>Context and objective: </strong>Identifying the risk of malignancy and genetic status in primary paraganglioma or pheochromocytoma (PPGL) is a key challenge. The aim was to assess the diagnostic accuracy of genomic, metabolomic and histopathological biomarkers for predicting metastatic and genetic status.</p><p><strong>Design, setting, and patients: </strong>COMETE-TACTIC is a prospective study (NCT02672020) conducted from November 2015 to March 2019 across 16 referral centers. Tumor samples and liquid biopsies from 231 consecutive patients with PPGL were collected.</p><p><strong>Main outcome measures: </strong>Germline and somatic genetic status were determined by next-generation sequencing, SDHB, SDHA and CA9 immunohistochemistries were performed on tumor tissues. TERT promoter methylation was assessed by pyrosequencing. Metabolomic profile and circulating miRNAs were measured in liquid biopsies by gas chromatography MS/MS and TaqMan assay quantified by droplet digital PCR, respectively.</p><p><strong>Results: </strong>Tumor analysis outperformed germline analysis for determining genetic status. Positive SDHA and SDHB staining combined with negative CA9 labeling indicated the absence of SDHx and VHL variants. Plasma succinate levels above 4.94 µM identified SDHx mutation carriers with 65% sensitivity and 92% specificity [area under the receiver operating characteristic curve (AUC-ROC) 0.82, 95% confidence interval (CI) 0.70-0.93]. Among circulating miRNAs, miR-483-5p was the best classifier of metastatic status (AUC-ROC 0.64, 95%CI 0.52-0.77). A sum of dinucleotide methylation rate of TERT promoter CpGs above 42% predicted metastatic status (AUC-ROC 0.75, 95% CI 0.65-0.85). Multivariate analyses showed that biomarker combinations significantly predicted SDHx status (AUC-ROC 0.99, 95% CI 0.98-1.00) and metastatic potential (AUC-ROC 0.93, 95% CI 0.84-1).</p><p><strong>Conclusion: </strong>Circulating miR-483-5p, plasma succinate, TERT promoter methylation, and SDHB immunostaining are valuable for PPGL risk stratification. Combining biomarkers with clinical data provides excellent diagnostic accuracy for metastatic patients (AUC-ROC 0.97, 95%CI 0.93-1).</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"2193-2204"},"PeriodicalIF":5.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex Differences in Insulin-Induced Hippocampus Functional Connectivity During Visual Food-Cue Presentation.","authors":"Sixiu Zhao, Ralf Veit, Lorenzo Semeia, Julia Hummel, Leontine Sandforth, Andreas Fritsche, Andreas L Birkenfeld, Martin Heni, Hubert Preissl, Stephanie Kullmann","doi":"10.1210/clinem/dgae833","DOIUrl":"10.1210/clinem/dgae833","url":null,"abstract":"<p><strong>Context: </strong>Central insulin has been shown to regulate eating behavior and cognitive processes in a sex-specific manner. Besides memory, the hippocampus is pivotal in the control of appetite.</p><p><strong>Objective: </strong>This work aimed to investigate how insulin interacts with the hippocampal food-cue response and evaluate the potential role of sex hormones.</p><p><strong>Methods: </strong>Using functional magnetic resonance imaging, we evaluated task-based functional connectivity (FC) of the hippocampus during food-cue presentation in 60 participants (age: 21-69 years; 30 women) after intranasal insulin or placebo administration, in a randomized within-subject design. In an exploratory analysis, we investigated whether hippocampal FC after intranasal insulin administration is related to estradiol and progesterone levels during the follicular and luteal phase of the menstrual cycle in 13 premenopausal women (age: 20-28 years).</p><p><strong>Results: </strong>Intranasal insulin increased hippocampal FC with the prefrontal cortex compared to placebo, regardless of sex. This correlated with stronger reduction in subjective feeling of hunger and food craving. Moreover, we observed an interaction between sex and nasal spray condition with higher hippocampal FC to the calcarine gyrus after insulin compared to placebo in men, while women showed a lower response. In premenopausal women, the centrally mediated effect of insulin on hippocampus to calcarine gyrus FC negatively correlated with the estradiol/progesterone ratio in the luteal phase.</p><p><strong>Conclusion: </strong>Central insulin influences hippocampal FC to regions vital for inhibitory control during high-caloric food-cue presentation, implying a potential role of the hippocampal network in modulating insulin's anorexic effects. The observed sex differences between the hippocampus and visual cortex might be influenced by sex hormone action.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e2631-e2639"},"PeriodicalIF":5.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}