The Journal of clinical endocrinology and metabolism最新文献

{"title":"Approach to the patient after gestational diabetes mellitus: what's next?","authors":"Ellen W Seely, Sarah C Lassey, Nadine E Palermo","doi":"10.1210/clinem/dgag233","DOIUrl":"10.1210/clinem/dgag233","url":null,"abstract":"<p><p>The prevalence of gestational diabetes mellitus (GDM) continues to rise and is estimated to affect 14% of women worldwide. It is well established that early identification and treatment of GDM can improve maternal and fetal outcomes. While hyperglycemia typically resolves after delivery, metabolic risks to mother and offspring persist postpartum and continued surveillance is essential to prevent long-term complications. Women with prior GDM have increased risk of future type 2 diabetes (T2D), cardiovascular disease (CVD), and recurrence of GDM. There is evidence-based support for the prevention of diabetes following GDM, with both intensive lifestyle modification and metformin. Although specific data on how to decrease CVD risk in women with GDM are not currently available, it is prudent to apply general CVD recommendations to these women. Women with a history of GDM should have long-term monitoring and continued counseling, including family planning, with proactive approaches to reduce future risk of progression to diabetes and cardiovascular disease.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"e2429-e2438"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148475669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imminent fracture risk: contributing mechanisms, risk assessment, and implications for treatment.","authors":"Tatiane Vilaca, Richard Eastell","doi":"10.1210/clinem/dgag278","DOIUrl":"10.1210/clinem/dgag278","url":null,"abstract":"<p><p>Identifying imminent fracture risk is a critical opportunity to manage osteoporosis. This term refers to the sharply elevated probability of sustaining a subsequent fragility fracture within a determined period-typically 12 to 24 months-after an initial sentinel fracture. While a prior fracture is widely recognized as a primary predictor of future events, epidemiological data show that this risk is not uniform; rather, it peaks significantly within the first 3 to 6 months after injury. This review discusses a significant clinical gap: traditional assessment tools often focus on long-term, 10-year risk projections, which may delay treatment during this high-vulnerability period. Recognizing imminent risk highlights clinical urgency, indicating the need for early use of therapeutic interventions to rapidly reduce the risk of further fractures. Identifying patients at imminent risk offers an opportunity for secondary prevention, promoting immediate pharmacological action to interrupt the \"fracture cascade\" and enhance long-term skeletal health.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"e2347-e2355"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148440658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IGF-1 and recovery in anorexia nervosa: evidence from population-based and clinical cohorts.","authors":"Cristiano Dani, Livio Tarchi, Lorenzo Bonacchi, Sara Haydar, Emanuele Cassioli, Eleonora Rossi, Alessandra Fanelli, Francesco De Logu, Romina Nassini, Nadia Micali, Valdo Ricca, Giovanni Castellini","doi":"10.1210/clinem/dgag211","DOIUrl":"10.1210/clinem/dgag211","url":null,"abstract":"<p><strong>Context: </strong>Anorexia nervosa (AN) is associated with severe metabolic and endocrine alterations, including growth hormone (GH) resistance and reduced insulin-like growth factor 1 (IGF-1). The longitudinal behavior of IGF-1 during treatment remains incompletely characterized.</p><p><strong>Objective: </strong>To evaluate IGF-1 levels in current and weight-restored AN, determine metabolic correlates, and examine longitudinal changes during clinical treatment.</p><p><strong>Design: </strong>Cross-sectional analysis in a population-based cohort and longitudinal analysis in a clinical cohort.</p><p><strong>Setting: </strong>UK Biobank (UKB) and a specialist eating disorder clinic.</p><p><strong>Participants: </strong>(1) UKB: 129 adult women with current AN, 2380 weight-restored AN, and 2380 healthy controls (HC) matched for age, sex, and body mass index (BMI). (2) Clinical cohort: 189 adult women with AN assessed at baseline and 12-month follow-up.</p><p><strong>Main outcome measures: </strong>Plasma IGF-1 levels; secondary metabolic and reproductive hormones, including GH, insulin, glucose, free triiodothyronine (FT3), and gonadal hormones.</p><p><strong>Results: </strong>Across the UKB groups, IGF-1 levels showed a graded pattern: lowest in current AN, medium in weight-restored AN, and highest in HC. In the clinical cohort, IGF-1 correlated positively with insulin, glucose, and FT3, and negatively with GH, consistent with GH resistance. IGF-1 levels increased significantly over 12 months of treatment (P = .003), with higher BMI at baseline predicting greater increases. Higher IGF-1 levels were associated with a greater likelihood of menstrual function independent of BMI (P < .001).</p><p><strong>Conclusion: </strong>IGF-1 appears reduced in current AN and may only partly normalize with weight restoration. IGF-1 may reflect metabolic state and reproductive function, suggesting value as an indicator of severity and treatment response.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"3154-3162"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148008555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibrous dysplasia in hospitalized patients in France: prevalence and associated manifestations from a health database.","authors":"Lucie Levaillant, Régis Coutant, Patrice Rodien, Mathieu Levaillant, Claire Briet","doi":"10.1210/clinem/dgag209","DOIUrl":"10.1210/clinem/dgag209","url":null,"abstract":"<p><strong>Introduction: </strong>Fibrous dysplasia (FD)/McCune-Albright syndrome (MAS) is a rare mosaic disorder involving the skeleton and/or extraskeletal manifestations, particularly endocrine features. Population-based estimates of prevalence and incidence are scarce, including in France, and data on associated manifestations mainly derive from specialized centers. This study aimed to estimate the prevalence and incidence of FD/MAS in hospitalized patients in France and to evaluate the frequency of associated manifestations.</p><p><strong>Methods: </strong>This retrospective cohort study used the French National Health Insurance Database, to identify all patients hospitalized between 2012 and 2024 with a primary or associated diagnosis of monostotic FD (MFD; ICD-10 M85.0) or polyostotic FD/MAS (PFD/MAS; ICD-10 Q78.1). Prevalence and incidence were calculated for 2024. Associated manifestations were assessed using hospitalization diagnoses and outpatient drug dispensing data.</p><p><strong>Results: </strong>Over the 2012-2024 period, 2249 patients were hospitalized in France; 60% had PFD/MAS, 63% were female, and 26% were children. The 2024 prevalence was 5.36 per 1 000 000 inhabitants (95% CI: 4.83-5.94), and the 2024 incidence was 2.58 patients per 1 000 000 inhabitants (95% CI: 2.21-2.99). Regarding associated manifestations, 27% of patients per year received bisphosphonates, 7.4% received phosphate supplements, 3.3% aromatase inhibitors, 8% pituitary treatments, and 2.2% antithyroid agents.</p><p><strong>Conclusion: </strong>This nationwide study provides the first estimates of the prevalence and incidence of hospitalized FD/MAS in France, although estimates based on hospitalization data likely underestimate the true frequency of monostotic FD. Treatment-based proxies offer valuable insights into associated manifestations. Improved outpatient coding and integration of clinical data are needed to better capture the full spectrum of FD/MAS at the population level.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"3172-3180"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147985103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Approach to the patient with APS-1/APECED.","authors":"Taura Webb, Joseph Pechacek, Michail S Lionakis","doi":"10.1210/clinem/dgag282","DOIUrl":"10.1210/clinem/dgag282","url":null,"abstract":"<p><p>Autoimmune polyendocrine syndrome type 1 (APS-1), also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a monogenic disorder of impaired central immune tolerance classically inherited in an autosomal recessive manner and caused by biallelic deleterious variants in the autoimmune regulator (AIRE) gene, leading to chronic mucocutaneous candidiasis and multiorgan autoimmunity. Although hypoparathyroidism and adrenal insufficiency are among the most common and clinically consequential manifestations, it is increasingly recognized that several non-endocrine features-including autoimmune enteritis, urticarial eruption (termed APECED rash), enamel hypoplasia, autoimmune pneumonitis, and autoimmune hepatitis-often precede classical endocrinopathies, contributing to delayed diagnosis. Endocrinologists are often among the first specialists to encounter these patients and play a central role in early recognition and longitudinal care. Here, we present 5 cases that illustrate the expanding clinical spectrum of APS-1, novel genetic mechanisms, key diagnostic challenges, and emerging therapeutic approaches. These cases highlight the importance of applying expanded clinical criteria and recognizing the limitations of standard genetic testing, including the need to consider deep intronic and dominant-negative AIRE variants. Finally, evolving mechanistic insights have established APS-1 as an interferon-γ-driven disease, providing a rationale for emerging targeted immunomodulatory therapies such as Janus kinase inhibition with ruxolitinib. Early diagnosis enables proactive surveillance and may allow timely initiation of disease-modifying treatment.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"3277-3285"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148475698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct genetic alterations drive Cushing disease vs silent corticotroph adenomas.","authors":"Ticiana Paes, Qilin Zhang, Clarice O Borges, Dipika R Mohan, Victor Vaz, Beatriz S Soares, Rona S Carroll, Ursula B Kaiser, Timothy R Smith, Wenya Linda Bi, David Meredith, Antonio M Lerario, Ana Paula Abreu","doi":"10.1210/clinem/dgag229","DOIUrl":"10.1210/clinem/dgag229","url":null,"abstract":"<p><strong>Background: </strong>Corticotroph adenomas (CA) include functioning tumors causing Cushing disease (CD) and silent corticotroph adenomas (SCA), which differ markedly in size, clinical presentation, and aggressiveness. The molecular basis for these differences remains incompletely understood.</p><p><strong>Objective: </strong>To characterize genomic and transcriptomic alterations underlying the divergent clinical behavior of CD and SCA.</p><p><strong>Methods: </strong>Thirty-eight tumors from 34 patients underwent whole-exome sequencing, copy-number variation (CNV) analysis, and mRNA sequencing. Molecular findings were integrated with clinical, radiological, and pathological data.</p><p><strong>Results: </strong>USP8/USP48 mutations were present in 10 of 21 CD tumors (48%) and were associated with low CNV levels, minimal invasion, and favorable post-operative remission. In contrast, five of 13 SCAs harbored TP53/ATRX/DAXX mutations, all had markedly elevated CNV, and aggressive clinical features. Transcriptomic analysis identified an ATRX-FAM138A mRNA fusion, resulting in loss of ATRX expression in an aggressive tumor. Unsupervised transcriptome analyses defined four clusters. All USP8/USP48-mutant CD clustered together had low CNV and low recurrence rates. Cluster 2 consisted of a mixture of CD and SCA, with intermediate CNV and nonaggressive behavior. Cluster 3 included USP8-wildtype CD with heterogeneous yet generally nonaggressive courses. Cluster 4 represented high-CNV tumors enriched for TP53/ATRX/DAXX alterations, with the highest rates of radiological invasion, persistent disease, and recurrence or progression. Across the cohort, higher CNV was significantly associated with parameters of aggressiveness.</p><p><strong>Conclusion: </strong>CA comprise distinct molecular subtypes. USP8/USP48-mutant CD represents a low-CNV, low-risk group, whereas tumors harboring TP53/ATRX/DAXX mutations exhibit high CNV and aggressive clinical behavior. CNV and mutation profiling may assist in postoperative risk stratification.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"3062-3074"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148221680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social determinants of health and cardiovascular disease in women with polyendocrine metabolic ovarian syndrome (PCOS/PMOS).","authors":"Snigdha Alur-Gupta, Julia D DiTosto, Kyle R Busse, Jennifer Lewey, Daniel E Soffer, Qing Liu, Colleen Brensinger, Sunni L Mumford, Anuja Dokras","doi":"10.1210/clinem/dgag308","DOIUrl":"10.1210/clinem/dgag308","url":null,"abstract":"<p><strong>Context: </strong>No studies have explored racial differences in atherosclerotic cardiovascular disease (ASCVD) in women with polycystic ovary syndrome (PCOS), which is now known as polyendocrine metabolic ovarian syndrome (PMOS).</p><p><strong>Objective: </strong>Compare ASCVD risk by race/ethnicity among women with PMOS and determine whether social determinants of health (SDoH) drive associations.</p><p><strong>Design: </strong>Cohort study.</p><p><strong>Setting: </strong>Optum's de-identified Clinformatics® Data Mart Database (2000-2022).</p><p><strong>Participants: </strong>Women aged 18 to 50 with PMOS using PCOS International Classification of Diseases 9/10 codes. Race/ethnicity was categorized as White, Black, Asian, or Hispanic.</p><p><strong>Interventions: </strong>None.</p><p><strong>Main outcome measures: </strong>Primary outcome was risk of composite ASCVD (coronary artery disease, cerebrovascular disease, peripheral artery disease). Secondary outcomes included each component. Adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models that were unadjusted (Model 1), adjusted for medical comorbidities (Model 2), and adjusted for comorbidities plus SDoH: homeownership, net worth, and education (Model 3).</p><p><strong>Results: </strong>The sample included 413 450 women with PMOS. Accounting for medical comorbidities (Model 2), Asian women with PMOS were at a lower risk for ASCVD compared with White women (aHR, .65; 95% CI, .56-.74), and Black (aHR, 1.10; 95% CI, 1.02-1.19) and Hispanic women (aHR, 1.21; 95% CI, 1.12-1.29) were at a higher risk. After adjusting for SDoH (Model 3), the findings for Asian and Hispanic women remained significant, whereas those for Black women did not. When looking at individual components of ASCVD, the higher risk for multiple components among Black women was no longer significant after controlling for SDoH.</p><p><strong>Conclusion: </strong>Racial differences exist in risk of ASCVD among women with PMOS.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"e2403-e2416"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148623812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of alert systems on glucocorticoid administration for adrenal insufficiency in the emergency department.","authors":"Primploy Greeviroj, Ramita Anakepeerasak, Subhanudh Thavaraputta, Stephen J Kerr, Jutamas Saoraya, Patinut Buranasupkajorn, Wasita W Parksook, Thiti Snabboon, Sarat Sunthornyothin","doi":"10.1210/clinem/dgag225","DOIUrl":"10.1210/clinem/dgag225","url":null,"abstract":"<p><strong>Context: </strong>Inappropriate glucocorticoid management in adrenal insufficiency (AI) can lead to adrenal crises, particularly in an emergency setting. Clinical decision support (CDS) can be helpful, but its impact on AI management in emergency departments (EDs) remains limited.</p><p><strong>Objective: </strong>To evaluate the efficacy of CDS on glucocorticoid administration time in known AI patients presenting to the ED.</p><p><strong>Design: </strong>Quasi-experimental (pre and post intervention) design.</p><p><strong>Setting: </strong>Tertiary academic hospital.</p><p><strong>Patients: </strong>A total of 211 patients with AI; 145 had no ED visits, 66 patients had 187 ED encounters.</p><p><strong>Main outcome measures: </strong>Time from ED arrival to intravenous hydrocortisone administration pre vs post-CDS implementation.</p><p><strong>Results: </strong>The incidence of ED visits was 42 events per 100 patient-years, and the incidence of ED visits presenting with hypotension was 7 events per 100 patient-years. Among patients with ED visits, the number of visits was 73 before and 114 after CDS implementation. Events requiring intravenous hydrocortisone were 19 before and 24 after implementation, with treatment given in 89% vs 92%, respectively (P = .81). The median time from ED arrival to hydrocortisone administration decreased from 202 (IQR: 99-306) minutes to 77 (IQR: 45-153) minutes (P = .01). The proportion of patients receiving hydrocortisone within 1 hour increased from 0% to 42% (P = .002). New-onset hypotension occurred in 4 cases (21%) before implementation and in 1 case (4%) after implementation.</p><p><strong>Conclusion: </strong>Following CDS implementation, the time to hydrocortisone administration was significantly shorter among patients with known AI. These findings highlight the value of CDS in improving AI recognition and management in high-risk settings.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"3094-3101"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148177503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First large-scale screening of Notch biallelic variants implicates novel candidate genes in congenital hypothyroidism.","authors":"Feng-Yao Wu, Chen-Yang Wu, Zheng Wang, Zhi-Gang Tian, Ye-Ke Song, Ren-Jie Cui, Rui-Feng Yang, Hai-Yang Zhang, Ming-Yuan Li, Xiao-Yu Liu, Ming Zhan, Liu Yang, Jing Wu, Mei Dong, Jia-Yida Nulali, Feng-Xue Zhang, Yu Bao, Shi-Yang Song, Shi-Han Song, Rui Li, Mei-Fang Peng, Rui-Meng Yang, Shuang-Xia Zhao, Huai-Dong Song","doi":"10.1210/clinem/dgag208","DOIUrl":"10.1210/clinem/dgag208","url":null,"abstract":"<p><strong>Context: </strong>Congenital hypothyroidism (CH) is a major preventable cause of developmental and cognitive impairment. Current genetic testing identifies causative variants for only half of cases, leaving the majority without a molecular diagnosis. Although animal studies implicate Notch signaling in thyroid development, its role in human CH remains unexplored.</p><p><strong>Objective: </strong>To investigate whether Notch pathway variants contribute to genetically unexplained CH.</p><p><strong>Design: </strong>Genetic screening using whole-exome sequencing with zebrafish functional validation.</p><p><strong>Setting: </strong>Endocrinology outpatient clinic at Shanghai Ninth People's Hospital.</p><p><strong>Patients or other participants: </strong>A total of 781 unrelated Chinese patients with CH. After identifying variants in 21 known causative genes in 364 patients, the remaining 417 unsolved cases were screened for variants in 77 Notch signaling pathway genes.</p><p><strong>Main outcome measure(s): </strong>Identification of biallelic Notch pathway variants; functional validation through zebrafish morpholino knockdown experiments assessing thyroid morphology and hormone production; clinical phenotype including thyroid function parameters, thyroid morphology, and levothyroxine dosage requirements; comparison with 267 DUOX2 patients.</p><p><strong>Results: </strong>We identified biallelic variants in 11 Notch pathway genes (NEURL1, CNTN6, NOTCH3, DTX1, DVL1, DTX2, ATXN1, SPEN, CTBP2, NCOR2, MAMLD1) in 21 patients. Zebrafish knockdown provided functional support for the potential pathogenic role of these genes, showing reduced thyroglobulin expression, abnormal morphology, elevated tsh levels, and decreased T4. Notch-variant patients showed higher initial FT4 but required significantly higher levothyroxine doses than DUOX2 patients.</p><p><strong>Conclusion: </strong>Notch pathway variants may contribute to approximately 5% of genetically unexplained CH. Variants across multiple pathway components collectively impair thyroid function. These findings suggest a potential expansion of CH genetic architecture and suggest that Notch-variant patients may require enhanced hormone replacement despite milder initial presentation, warranting pathway-specific screening.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"3111-3127"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148039239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"68Ga-DOTA-exendin-4 PET/CT for insulinoma localization in patients with negative or inconclusive conventional imaging.","authors":"Julia G Fricke, Katharina Laubner, Manuela Schildmeijer, Lea Menz, Camilla Wojsa, Philipp T Meyer, Jochen Seufert, Damian Wild, Emanuel Christ, Martin T Freitag","doi":"10.1210/clinem/dgag214","DOIUrl":"10.1210/clinem/dgag214","url":null,"abstract":"<p><strong>Context: </strong>Insulinomas are the main cause of endogenous hyperinsulinemic hypoglycemia (EHH) in adults, with surgery as the only cure. Pancreas-preserving surgery is preferred, making precise preoperative localization crucial. GLP-1R-targeted imaging, such as [68Ga]Ga-DOTA-exendin-4 PET/CT, outperforms other imaging procedures for insulinoma localization.</p><p><strong>Objective: </strong>To investigate the performance and clinical impact of [68Ga]Ga-DOTA-exendin-4 PET/CT for the detection of insulinomas in patients with EHH and prior negative or inconclusive conventional imaging.</p><p><strong>Methods: </strong>In this retrospective, real-world, dual-center imaging study, 101 patients with biochemically proven EHH and/or a positive Whipple's triad underwent [68Ga]Ga-DOTA-exendin-4 PET/CT at two tertiary centers between April 2017 and March 2024. Among these, 58 patients with prior negative or inconclusive conventional imaging constituted the primary analysis cohort. Endpoints: Insulinoma detection rate and sensitivity by [68Ga]Ga-DOTA-exendin-4 PET/CT after negative or inconclusive conventional imaging and impact on clinical management.</p><p><strong>Results: </strong>Among the 58 patients with prior negative or inconclusive conventional imaging, [68Ga]Ga-DOTA-exendin-4 PET/CT was positive in 42 patients, corresponding to a detection rate of 72% (95% CI, 59-83%). Thirty patients subsequently underwent PET/CT-guided surgery. Overall, 32 patients had histological verification (including two PET/CT-negative cases), corresponding to a sensitivity of 93.8% (95% CI, 79-99%).</p><p><strong>Conclusion: </strong>In real-world clinical practice, [68Ga]Ga-DOTA-exendin-4 PET/CT provides a high detection rate of 72% for localizing insulinomas, including one case of diffuse nesidioblastosis in patients with EHH and prior negative or inconclusive conventional imaging, thereby enabling PET/CT-guided surgical approaches. These findings underscore the substantial clinical impact of GLP-1R-targeted PET/CT on patient management and prognosis.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"3163-3171"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147990804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}