Endocrine Connections最新文献

{"title":"Interpreting salivary cortisol thresholds in ectopic ACTH syndrome.","authors":"Omer Denizhan Tatar","doi":"10.1530/EC-26-0399","DOIUrl":"10.1530/EC-26-0399","url":null,"abstract":"<p><p>This Perspective comments on a recent national cohort study of ectopic ACTH syndrome that identified late-night salivary cortisol (LNSC) ≥ 130 nmol/L as an independent predictor of mortality. The finding is clinically important because it supports the prognostic relevance of biochemical severity. However, its numerical interpretation should remain method-specific. LNSC is sensitive to sampling conditions and analytical platform, and absolute values are not necessarily interchangeable across immunoassays or between immunoassays and liquid chromatography-tandem mass spectrometry. In addition, dichotomizing a continuous biomarker can reduce information and overstate apparent separation at a data-derived cut point. Building on the original authors' own assay caveat, the threshold is best viewed as a Roche ECLIA-context signal of severe hypercortisolism, pending prospective multicenter validation using continuous biomarker modeling, assay harmonization, and subgroup analyses by tumor context and treatment era.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148344317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacovigilance evaluation of somatrogon-associated adverse events in real-world databases.","authors":"Mengyuan Cai, Qian Guo, Huqiang Dong, Yabo Wang, Zhongyu Han, Ping Xu","doi":"10.1530/EC-26-0292","DOIUrl":"10.1530/EC-26-0292","url":null,"abstract":"<p><strong>Background: </strong>Somatrogon, a long-acting recombinant human growth hormone, is used in children with growth hormone deficiency. While clinical trials have shown its safety, real-world post-marketing data are limited, and uncommon or delayed adverse events (AEs) may not be fully recognized.</p><p><strong>Methods: </strong>We analyzed somatrogon-related AEs from the US FDA Adverse Event Reporting System (FAERS) (Q1 2004-Q2 2025) and the WHO global safety database via VigiAccess (up to Dec 2024). Disproportionality analyses were performed using four signal detection methods: reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). AEs were assessed at both system organ class and preferred term (PT) levels. In FAERS, time to onset was examined to characterize the temporal pattern.</p><p><strong>Results: </strong>We identified 1,001 somatrogon-related reports in FAERS and 863 in VigiAccess. Most cases occurred in pediatric patients, with slightly more reports in males. At the SOC level, most AEs involved general disorders, administration site conditions, injuries, and product issues. At the PT level, recurring signals included injection-site reactions, device-related problems, and insulin-like growth factor abnormalities. Among 168 FAERS cases with valid onset data, 79.76% occurred within 30 days, with a median onset of 0 days.</p><p><strong>Conclusion: </strong>Somatrogon's real-world AE pattern shows early-onset injection-site reactions, device-related issues, and endocrine signals, highlighting the need for early treatment monitoring and ongoing post-marketing surveillance as its use grows globally.</p><p><strong>Key points: </strong>This dual-database pharmacovigilance study analyzed somatrogon-associated AE reports from FAERS and VigiAccess, providing a real-world overview of its post-marketing safety profile. Across both databases, the most consistent signal clusters were injection-site reactions, device- and product-related problems, and endocrine/laboratory abnormalities, particularly insulin-like growth factor disturbances. Among FAERS cases with valid onset data, 79.76% of reported events occurred within 30 days, with a median onset of 0 days, indicating that AEs tend to emerge early after treatment initiation. Serious outcomes were relatively uncommon, supporting the importance of early follow-up, injection-site assessment, device-use training, and IGF-1 monitoring in children receiving somatrogon.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13317830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone turnover marker rhythmicity: implications for osteoporosis treatment and fracture healing.","authors":"Megan M Tidd, Christine M Swanson","doi":"10.1530/EC-26-0114","DOIUrl":"10.1530/EC-26-0114","url":null,"abstract":"<p><strong>Abstract: </strong>Bone turnover is a dynamic process with markers of bone turnover displaying varying degrees of rhythmicity. The objective of this narrative review was to synthesize current evidence on the regulation of bone turnover marker (BTM) rhythmicity and to evaluate how these rhythms may influence clinically relevant outcomes in osteoporosis treatment and fracture healing. Structured literature searches were conducted in PubMed to identify studies that examined BTM rhythmicity, intrinsic versus extrinsic factors that influence this rhythmicity, and timing effects of osteoporosis medications and fracture-related healing to inform this narrative review. The reviewed evidence demonstrates that markers of bone resorption exhibit robust diurnal rhythms, whereas bone formation markers show lower-amplitude and more variable oscillations. These rhythms are primarily circadian driven and influenced by environmental factors (e.g. fasting) and have important implications for accurate use and interpretation when used clinically and in research. Clinical and preclinical studies further indicate that the administration time of some osteoporosis medications can influence efficacy and safety, with certain anabolic and antiresorptive agents showing differences in biochemical or structural responses depending on administration time, while others appear timing insensitive or remain unstudied. Emerging experimental data suggest that fracture healing may also display rhythmicity and be differentially impacted by the timing of interventions.</p><p><strong>Plain language summary: </strong>This review summarizes how bone turnover marker levels vary across the day and night and how this rhythmicity may influence the effects of some medications, with implications for optimal use of these markers in clinical practice and research to improve osteoporosis treatment and potentially fracture healing.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":"15 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13317851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148344363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"German law on protection of children with DSD: first data on care after enactment.","authors":"Uta Neumann, Gerhard Binder, Felicitas Eckoldt, Ulla Döhnert, Désirée Dunstheimer, Paul-Martin Holterhus, Barbara Ludwikowski, Martin Wabitsch, Joachim Woelfle, Annette Richter-Unruh, Clemens Kamrath","doi":"10.1530/EC-26-0194","DOIUrl":"10.1530/EC-26-0194","url":null,"abstract":"<p><strong>Introduction: </strong>In May 2021, a German law was implemented to protect children with differences of sex development (DSD) from non-consensual genital surgery. In children and persons incapable of giving consent, exceptions can occur in emergencies or with the approval of the family court. To this end, a favourable opinion from an interdisciplinary DSD committee can be submitted to initiate file-based court proceedings. This study analysed the frequency of referrals post-legislation, alongside diagnoses and demographic information.</p><p><strong>Methods: </strong>A survey by the German Society for Paediatric and Adolescent Endocrinology and Diabetology identified centres with interdisciplinary committees. Data from these centres were analysed descriptively.</p><p><strong>Results: </strong>Ten centres established interdisciplinary committees, evaluating 78 patients. The common karyotypes were 46,XX (36%) and 46,XY (55%), with other variations at 9%. The median age at initial presentation was 0.91 years, with most evaluations happening in surgical departments (80.8%). In 46,XX individuals, CAH due to 21-hydroxylase deficiency (21OHD) was predominant (93%), with a median Prader score of 4. In 46,XY individuals, phenotypic assessments mostly identified various levels of undervirilisation, mainly proximal hypospadias.</p><p><strong>Conclusion: </strong>This study highlights the significant impact of this legislation on clinical practice for DSD in Germany. Our results show that the majority of patients with DSD assessed by the interdisciplinary committee had a diagnosis of CAH or hypospadias. The composition of the interdisciplinary committee is prescribed by law, but the approach to counselling may vary depending on the discussions within the DSD committee. Open questions include reimbursement and evaluation criteria.</p><p><strong>Plain language summary: </strong>In 2021, Germany introduced a law to protect children with a difference of sex development who are not yet able to give their own consent. We investigated how often specialist teams were asked by families to provide an opinion to facilitate surgery, and the changes in care that have resulted from the law. Most of the children had CAH or hypospadias.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13292827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148041652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perioperative management of patients with primary aldosteronism: a practical approach for the endocrinologist.","authors":"Patrícia da Cunha Brito, Adriana de Sousa Lages, Catarina Machado, Vera Fernandes","doi":"10.1530/EC-26-0178","DOIUrl":"10.1530/EC-26-0178","url":null,"abstract":"<p><p>Primary aldosteronism (PA) is the most common endocrine cause of secondary hypertension yet remains significantly underdiagnosed. Early recognition is essential, as excess aldosterone leads to substantial cardiovascular and renal morbidity. Approximately one-third of patients have unilateral disease, in whom adrenalectomy is associated with superior long-term clinical outcomes compared with medical therapy. Although current guidelines offer detailed recommendations for diagnosis and subtype classification, guidance on perioperative management remains limited. Preoperative goals should include optimizing blood pressure to <140/90 mmHg and correcting potassium levels, which can be achieved by initiating mineralocorticoid receptor antagonists (MRAs) in all patients. MRA titration ensures effective receptor blockade and supports recovery of contralateral adrenal function. A dedicated preoperative endocrinology consultation is essential to review expected surgical outcomes, address the anticipated postoperative decline in renal function, evaluate cortisol co-secretion, and assess the risk of postoperative adrenal insufficiency. Postoperatively, the primary concern is hyporeninemic hypoaldosteronism. Antihypertensive medications should be down-titrated, MRAs withheld, and a high-sodium diet encouraged. Early biochemical assessment does not establish cure but may still provide clinically relevant information. Follow-up includes weekly assessments during the first month and structured evaluation of clinical and biochemical outcomes at 6-12 months using the PASO criteria. Histological findings help predict recurrence risk and decide long-term follow-up. Patients achieving complete biochemical success, along with a complete or partial clinical response and having classic histopathological features, may transition to long-term follow-up in a primary care setting. This manuscript proposes a structured perioperative management approach for patients with PA undergoing adrenalectomy.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13280532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148137107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LAT1-mediated amino acid metabolism reprogramming: a novel metabolic vulnerability in recurrent pituitary neuroendocrine tumors.","authors":"Zhi-Jie Pei, Gao-Wei Li, Jiang-Hao Yu, Hong-Rui Yang, Yi Fang, Liang-Xue Zhou","doi":"10.1530/EC-25-0860","DOIUrl":"10.1530/EC-25-0860","url":null,"abstract":"<p><strong>Objective: </strong>Tumor recurrence remains a major challenge in the management of pituitary neuroendocrine tumors (PitNETs). This study aimed to investigate recurrence-associated metabolic alterations in PitNETs using an integrated metabolomic approach.</p><p><strong>Methods: </strong>Untargeted gas chromatography-mass spectrometry (GC-MS)-based metabolomic profiling was performed on tumor tissues from 44 patients with PitNETs as a discovery cohort. Differential metabolites were identified using non-parametric statistical analysis. An independent validation cohort of 40 patients (20 primary and 20 recurrent PitNETs) was used for protein-level validation by multiplex immunofluorescence staining of key amino acid transporters, including L-type amino acid transporter 1 (LAT1) and alanine-serine-cysteine transporter 2 (ASCT2).</p><p><strong>Results: </strong>Metabolomic analysis revealed distinct metabolic alterations between primary and recurrent PitNETs, characterized by selective enrichment of large neutral amino acids (LNAAs) in recurrent tumors. Pathway enrichment analysis indicated that the altered metabolites were predominantly involved in amino acid-related metabolic pathways. In the validation cohort, multiplex immunofluorescence demonstrated significantly increased LAT1 expression in recurrent PitNETs compared with primary tumors, whereas ASCT2 expression did not differ significantly between groups.</p><p><strong>Conclusion: </strong>These findings indicate that recurrence of PitNETs is associated with selective remodeling of amino acid metabolism, particularly involving LNAAs, accompanied by increased expression of the corresponding transporter LAT1. Together, our results suggest that altered amino acid transport represents an important component of metabolic adaptation in recurrent PitNETs and warrants further investigation.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13266307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148053440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thyroid function tests and resting heart rate in Graves' disease: a prospective longitudinal study.","authors":"Beatrice Egger, Uwe Riedmann, Lisa Schmitt, Daniel Arian Kraus, Hannah Pichler, Christian Trummer, Verena Theiler-Schwetz, Stefanie Lindschinger, Winfried März, Oleksiy Tsybrovskyy, Markus Reichhartinger, Stefan Pilz","doi":"10.1530/EC-26-0129","DOIUrl":"10.1530/EC-26-0129","url":null,"abstract":"<p><strong>Objective: </strong>Increased resting heart rate (RHR) is a typical sign of thyrotoxicosis. RHR may therefore serve as a monitoring tool, but longitudinal data on continuous measures of RHR and thyroid hormones are sparse. We evaluated the association between continuously monitored RHR and thyroid function tests in Graves' disease (GD).</p><p><strong>Design: </strong>This is a double-center, prospective, longitudinal cohort study in 30 patients with GD on antithyroid drug treatment. Participants were followed up with monthly study visits over six months at two hospitals in Graz, Austria.</p><p><strong>Methods: </strong>Free thyroxine (fT4) and free triiodothyronine (fT3) were measured at each study visit. Participants were encouraged to continuously wear a wristband activity tracker (Fitbit Charge 6) to assess RHR. Associations of RHR (mean value over ten days) with thyroid hormones were determined by generalized estimating equation analyses.</p><p><strong>Results: </strong>From September 2024 to November 2025, we enrolled 30 participants (24 women, mean (SD) age of 40.7 (14.6) years) and performed 176 study visits. Thyrotoxicosis was present in 24 participants (80%) at baseline. One SD increase in RHR of 8.8 beats per minute was associated with fT4 (beta = 0.856, 95% CI: 0.641-1.071, P < 0.001), fT3 (beta = 0.836, 95% CI: 0.620-1.051, P < 0.001), and thyrotoxicosis (odds ratio: 5.134, 95% CI: 2.192-12.025, P < 0.001), respectively.</p><p><strong>Conclusion: </strong>RHR assessed by a wearable device is strongly associated with thyroid hormones in GD. Further trials are required to evaluate whether RHR is useful to guide timing of thyroid function tests during antithyroid drug treatment and for GD diagnostics.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13266306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148137035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fertility preservation in prepubertal boys: management and follow-up challenges.","authors":"Vittorio Ferrari, Federico Baronio, Marcello Lanari, Rod T Mitchell","doi":"10.1530/EC-26-0146","DOIUrl":"10.1530/EC-26-0146","url":null,"abstract":"<p><p>Survival after childhood cancer and severe haematological disorders has improved substantially, shifting clinical attention towards long-term quality-of-life outcomes. Preservation of male reproductive potential represents a major challenge, particularly in boys exposed to gonadotoxic therapies before the onset of spermatogenesis. While sperm cryopreservation is an established fertility preservation strategy for postpubertal males, no clinically validated option currently exists for prepubertal boys. Male fertility depends on the establishment and lifelong maintenance of a finite spermatogonial stem cell (SSC) pool within a specialized somatic microenvironment. Although the prepubertal testis lacks active spermatogenesis, it already contains the SSC populations required for future fertility and these are vulnerable to cytotoxic injury. Clinical and histological evidence shows that chemotherapy and radiotherapy, including conditioning regimens for haematopoietic stem cell transplantation, can deplete SSCs even when exposure occurs in early childhood, with consequences that may become apparent only at puberty or later in adulthood. Testicular tissue cryopreservation (TTC) has emerged as the only potential fertility preservation strategy for prepubertal boys at high risk of treatment-induced infertility. TTC aims to preserve immature testicular tissue containing SSCs for possible future use through experimental approaches. However, no human pregnancies have yet been achieved using tissue cryopreserved before puberty, and all current applications remain experimental. This review summarizes current practice for TTC in prepubertal boys, with a particular focus on the issues most relevant to paediatric endocrinologists involved in the long-term follow-up and management of these patients.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13261344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148028410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shared diagnostic biomarkers in metabolic syndrome and coronary artery disease identified by integrated bioinformatics and machine learning.","authors":"Nuojin Wang, Keyan Hu, Shuting Zhang, Hongxing Zhao, Tianrong Pan, Tong Wang, Yi Zhang, Xueying Liu","doi":"10.1530/EC-26-0240","DOIUrl":"10.1530/EC-26-0240","url":null,"abstract":"<p><strong>Background: </strong>Metabolic syndrome (MetS) comprises various complicated metabolic disorders. Coronary artery disease (CAD) is a major cardiovascular disease worldwide. These two diseases are the principal causes of morbidity and mortality in older adults. Previous studies have suggested a potential link between these two diseases. To date, finding sensitive and effective diagnostic biomarkers of MetS and CAD remains challenging. This research examined the potential shared biomarkers of MetS and CAD using a comprehensive bioinformatics approach.</p><p><strong>Methods: </strong>Five microarray datasets about MetS and CAD were used in our analysis. Integrated bioinformatics methods, such as differentially expressed gene (DEG) analysis, weighted gene co-expression network analysis (WGCNA), and machine learning (ML) algorithms, were utilized to discern hub genes of MetS and CAD. Meanwhile, single-sample gene enrichment analysis and single-cell analysis were leveraged to analyze immune cell infiltration and the abundance of gene expression in immune cells. Finally, the expression levels of key biomarkers were primarily verified by RT-qPCR.</p><p><strong>Results: </strong>We identified 666 DEGs associated with MetS and 762 DEGs related to CAD, with 22 overlapping genes. Meanwhile, 3 hub genes related to MetS and CAD were screened by WGCNA, which were APOBEC3B, SGSM2, and LRRC32. Two hub genes, ADRB2 and KDM6A, were downregulated in the two diseases. ROC curves confirmed their diagnostic value. Furthermore, single-cell sequencing analysis and RT-qPCR obtained consistent findings.</p><p><strong>Conclusion: </strong>ADRB2 and KDM6A are identified as hub candidate diagnostic biomarkers for MetS and CAD. These genes may offer new targets for MetS and CAD and assist in exploring the molecular mechanisms underlying both diseases.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13250652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147981150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of postpartum metabolic dysfunction-associated steatotic liver disease in women with a history of gestational diabetes mellitus.","authors":"Weiqin Li, Shuang Zhang, Yubei Huang, Rui Shi, Lingyan Feng","doi":"10.1530/EC-25-0864","DOIUrl":"10.1530/EC-25-0864","url":null,"abstract":"<p><strong>Abstract: </strong>Gestational diabetes mellitus (GDM) is a rapidly increasing global health challenge that is closely linked to the rising rates of obesity and type 2 diabetes mellitus. Similarly, metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a leading cause of chronic liver disease. Emerging evidence indicates that a history of GDM is associated with a significantly elevated risk of postpartum MASLD that may persist for decades. This review synthesizes the shared and distinct pathophysiological mechanisms linking GDM to postpartum MASLD, with a particular focus on the enduring metabolic memory effect induced by GDM. While sharing common features with MASLD, the synergistic effects of amplified insulin resistance, chronic low-grade inflammation, and oxidative stress during GDM profoundly impact hepatic lipid metabolism. Critically, this programmed vulnerability persists postpartum, causing persistent mitochondrial dysfunction, endoplasmic reticulum stress, and reprogramming of the adipose-liver and gut-liver axes. These enduring alterations, extending beyond transient hyperglycemia, impair hepatic lipid metabolism and trigger MASLD. Further exploration into emerging mechanisms, including metabolomic profiles, genetic susceptibility, and gut microbiota dysbiosis, reveals a complex association network and highlights potential avenues for early detection and targeted intervention. Understanding these intricate mechanisms is crucial for developing effective intervention strategies. Future research focusing on gut microbiota modulation, precision epigenetic profiling, and multi-omics integration holds promise for dual prevention and management of both GDM and postpartum MASLD.</p><p><strong>Highlights: </strong>This review synthesizes shared and distinct pathophysiological mechanisms linking GDM to postpartum MASLD. It highlights the critical and unique role of the metabolic memory effect of GDM, where persistent organelle dysfunction, inflammation, and epigenetic reprogramming predispose women with prior GDM to postpartum MASLD. This review provides a comprehensive framework for understanding the GDM-MASLD transition, identifying key targets for dual prevention and management, with potential future strategies including gut microbiota modulation, precision epigenetic interventions, and multi-omics integration.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13250653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}