Journal of the Endocrine Society最新文献

{"title":"Personalization of incretin therapy: can GLP-1 and GIP receptor polymorphisms influence therapy response?","authors":"Sandro La Vignera, Rosita A Condorelli","doi":"10.1210/jendso/bvag149","DOIUrl":"10.1210/jendso/bvag149","url":null,"abstract":"<p><strong>Objective: </strong>Incretin-based therapies-glucagon-like peptide-1 receptor agonists (GLP-1RAs) such as semaglutide and the dual GLP-1/GIP receptor agonist tirzepatide-have transformed the management of type 2 diabetes (T2D) and obesity. However, substantial interindividual variability in therapeutic response remains incompletely explained by clinical factors alone.</p><p><strong>Methods: </strong>A systematic search of PubMed, SciSpace, and Google Scholar was conducted (through May 2026) using terms including GLP1R, GIPR, polymorphisms, pharmacogenomics, semaglutide, tirzepatide, and Italian population. Relevant original studies, genome-wide association studies, and reviews were included.</p><p><strong>Results: </strong>Common GLP1R variants-notably rs6923761 (Gly168Ser) and rs10305492 (Ala316Thr)-modulate receptor expression, G-protein coupling efficiency, and downstream cAMP signaling, translating to differential HbA1c reduction and weight loss with GLP-1RAs. GIPR rs1800437 (Glu354Gln), present at ∼20% frequency in Europeans, is associated with altered incretin effect and increased nausea/vomiting risk with tirzepatide (OR 1.83). Geographic analyses reveal significant allele frequency variation between European, East Asian, and African populations; Italian-specific data remain limited but suggest frequencies consistent with broader Southern European patterns.</p><p><strong>Conclusion: </strong>Pharmacogenomic profiling of GLP1R and GIPR variants holds promise for personalizing incretin therapy. Prospective studies in Italian and broader Mediterranean cohorts are needed to define clinically actionable genotype-phenotype relationships and inform precision endocrinology practice.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 8","pages":"bvag149"},"PeriodicalIF":4.4,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13389710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562239","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":"Clinical and pathological profile with prognostic insights in 9504 thyroid cancer cases: a single-center study (2008-2023).","authors":"Sijin Guo, Yang Wang, Changjiao Yan, Ting Wang","doi":"10.1210/jendso/bvag153","DOIUrl":"10.1210/jendso/bvag153","url":null,"abstract":"<p><strong>Background: </strong>Thyroid cancer incidence is rising worldwide, yet comprehensive longitudinal data linking contemporary demographic, pathological, and surgical trends to recurrence risk remain scarce.</p><p><strong>Methods: </strong>A retrospective analysis was performed on 9504 thyroid cancer patients from 2008 to 2023. Based on the year of treatment, patients were categorized into 3 groups for comparative assessment. Demographic features, clinical pathological characteristics, surgical approaches, and prognostic outcomes were evaluated.</p><p><strong>Results: </strong>Over the 16-year period, the annual number of new thyroid cancer cases demonstrated a consistent upward trend, with a growing proportion detected through routine health screenings. The male-to-female ratio was 1:2.76, with a gradual increase in male patients. The peak age at diagnosis remained between 30 and 60 years, while the proportion of juvenile patients declined steadily. Papillary thyroid carcinoma constituted the predominant histologic type. Surgical management shifted toward more conservative approaches. Although tumor size decreased over time, the incidence of multifocal lesions and the BRAF V600E mutation rate rose. Lymph node metastasis rates also increased, particularly in patients with central region metastases and metastases in ≤5 lymph nodes. Multivariate analysis identified age, tumor size, and number of metastatic lymph nodes as independent risk factors for recurrence in papillary thyroid carcinoma. Patients older than 55 years, those with larger lesions, or those with more lymph node metastases exhibited a significantly elevated recurrence risk.</p><p><strong>Conclusion: </strong>Although thyroid cancers are being detected at earlier stages and smaller sizes, the burdens of molecular, multifocal, and lymph node disease are increasing. Age, tumor size, and nodal metastatic load constitute robust independent predictors of recurrence in papillary thyroid carcinoma, informing risk-adapted surveillance and surgical strategies.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 8","pages":"bvag153"},"PeriodicalIF":4.4,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549632","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":"Development of a sensitive plasma lenvatinib quantification method and validation in thyroid cancer patients.","authors":"Carla Colombo, Roberta Ottria, Matteo Trevisan, Erika Carbone, Claudia Moneta, Marina Lugaresi, Sara Casati, Sofia Vanerio, Daniele Ceruti, Massimiliano Succi, Valentina Cirello, Simone De Leo, Luca Persani, Pierangela Ciuffreda, Laura Fugazzola","doi":"10.1210/jendso/bvag154","DOIUrl":"10.1210/jendso/bvag154","url":null,"abstract":"<p><strong>Context: </strong>Lenvatinib (LEN) is effective in the treatment of radioactive iodine refractory differentiated thyroid cancer (DTC), though it is associated with frequent and potentially severe adverse events (AEs). The dose dependency of LEN-related toxicity remains unclear, since no data are available on this topic.</p><p><strong>Objective: </strong>This study aimed to investigate the relationship between LEN dose and plasma concentrations in real-life patients by a novel and validated method for quantifying LEN in plasma samples.</p><p><strong>Design and setting: </strong>A sensitive high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) assay for LEN quantification in plasma was set up, with a wide analytical range (0.7-500 ng/mL). Consecutive plasma samples from 19 patients with radioactive iodine-refractory, metastatic DTC were analyzed.</p><p><strong>Results: </strong>A positive correlation between the administered LEN dose and plasma concentrations was found, particularly in patients on low doses (<18 mg daily). Linear mixed-effects models (LMMs) demonstrated significant interindividual variability in plasma LEN concentrations, contributing to 17% to 28% of the total variance. This variability was more pronounced at higher doses (≥18 mg), being more likely the consequence of LEN-related AEs than of a dose-dependent effect.</p><p><strong>Conclusion: </strong>This is the first real-life evaluation of interindividual LEN pharmacokinetics variability in advanced DTC patients, obtained by means of the newly developed HPLC-MS/MS method. Our results suggest that the dose-response relationship of LEN in radioactive iodine-refractory DTC may be more complex than previously understood, with substantial interpatient variability and dose-dependent effects. Further studies are needed to determine the implications of our findings in the clinical management of these patients.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 8","pages":"bvag154"},"PeriodicalIF":4.4,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13370831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456151","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":"Size in small-for-gestational-age neonates correlates with insulin-like growth factor-binding protein proteolysis and insulin-like growth factor-I bioavailability.","authors":"Vicente Barrios, Álvaro Martín-Rivada, Gabriel Á Martos-Moreno, María Jiménez-Hernaiz, Ana Campillo-Calatayud, María Sánchez-Holgado, Adelina Pellicer, Julie A Chowen, Beatriz Corredor-Andrés, Leandro Soriano-Guillén, Jesús Argente","doi":"10.1210/jendso/bvag156","DOIUrl":"10.1210/jendso/bvag156","url":null,"abstract":"<p><strong>Context: </strong>Alterations in prenatal growth affect postnatal outcomes, but the factors involved in prenatal growth are not clearly defined. Cord blood levels of insulin-like growth factor (IGF)-I are associated with weight and length at birth; however, how pappalysins (pregnancy-associated plasma protein [PAPP]-A and PAPP-A2) and stanniocalcins (STC-1 and STC-2) regulate IGF-binding protein (IGFBP) cleavage and IGF bioavailability in relation to birth size and nutritional status in full-term neonates is unknown.</p><p><strong>Objective: </strong>We aimed to determine the relationship between serum levels of PAPP-A and STCs with other components of the IGF axis and ponderal index (PI) in full-term small-for-gestational-age (SGA), adequate-for-gestational-age (AGA), or large-for-gestational-age (LGA) neonates (according to gestational age or PI).</p><p><strong>Methods: </strong>Twenty-six SGA, 131 AGA, and 22 LGA neonates were studied, and circulating levels of IGF axis parameters were evaluated according to weight, length, weight-to-length ratio, and PI.</p><p><strong>Results: </strong>Small-for-gestational-age newborns had lower total and free IGF-I, total IGFBP-3, acid-labile subunit, and PAPP-A2 levels and higher total IGFBP-1 and IGFBP-2, intact IGFBP-4, and STC-1 levels than AGA newborns. Neonates in the first tertile of PI had lower total and free IGF-I and IGFBP-5 and higher IGFBP-1 and -2 levels than those in the third tertile. Pregnancy-associated plasma protein-A2 levels correlated positively with weight and length and inversely with IGFBP-4 and STC-1 levels. Insulin-like growth factor-I and PAPP-A2 levels are associated with length.</p><p><strong>Conclusion: </strong>Variations in IGF-I parameters, such as STCs and PAPPAs, according to length/weight or PI suggest that they play an important role in intrauterine growth and/or nutritional status.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 8","pages":"bvag156"},"PeriodicalIF":4.4,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13377456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579021","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":"Correction to: \"Diazoxide Choline Extended-Release (DCCR) Use in Prader-Willi Syndrome: Patient Selection, Dosing, and Management\".","authors":"","doi":"10.1210/jendso/bvag144","DOIUrl":"https://doi.org/10.1210/jendso/bvag144","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1210/jendso/bvag099.].</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 7","pages":"bvag144"},"PeriodicalIF":4.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13320698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368950","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":"Gemcitabine and oxaliplatin combination in patients with advanced adrenocortical carcinoma.","authors":"Lily Chen, Vania Balderrama-Brondani, Leonardo P Marcal, Camilo Jimenez, Jeena Varghese, Amishi Y Shah, Mouhammed Amir Habra, Matthew T Campbell","doi":"10.1210/jendso/bvag152","DOIUrl":"10.1210/jendso/bvag152","url":null,"abstract":"<p><strong>Context: </strong>Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy with limited treatment options beyond first-line therapy, underscoring the need for effective salvage regimens.</p><p><strong>Objective: </strong>To evaluate the clinical activity and safety of gemcitabine and oxaliplatin (GemOx) in advanced ACC.</p><p><strong>Design: </strong>Retrospective cohort study conducted from April 2023 to April 2024 with longitudinal follow-up.</p><p><strong>Setting: </strong>Single-center tertiary referral cancer center.</p><p><strong>Patients or other participants: </strong>Fourteen patients with histologically confirmed advanced ACC treated with GemOx were included. Patients were heavily pretreated, with a median of 3 prior systemic therapies (range, 2-9); 43% had hormonally functional tumors.</p><p><strong>Interventions: </strong>Gemcitabine (1000 mg/m² on days 1 and 8) and oxaliplatin (130 mg/m² on day 1) every 3 weeks until disease progression or unacceptable toxicity.</p><p><strong>Main outcome measures: </strong>Primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included objective response rate per Response Evaluation Criteria In Solid Tumors 1.1 and treatment-related toxic effects.</p><p><strong>Results: </strong>After a median follow-up of 10.7 months (95% CI, 8.5-15.7), median PFS was 3.2 months (95% CI, 0.4-6.0) and OS was 13.0 months (95% CI, 3.6-22.5). Among 13 evaluable patients, 2 (15.4%) achieved partial response, 8 (61.5%) had stable disease, and 3 (23.1%) had progressive disease, yielding a disease control rate of 76.9%. No treatment-related deaths occurred.</p><p><strong>Conclusion: </strong>GemOx demonstrated modest clinical activity with manageable safety in heavily pretreated patients with advanced ACC. These findings suggest a potential role for GemOx as a salvage option, though validation in larger prospective studies is needed.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 8","pages":"bvag152"},"PeriodicalIF":4.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13356958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148430552","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":"Identifying diabetic ketoacidosis encounters at diagnosis among children with type 1 diabetes in claims data.","authors":"R Brett McQueen, Nai-Chia Chen, Eric J Gutierrez, Kelly E Anderson, G Todd Alonso","doi":"10.1210/jendso/bvag146","DOIUrl":"10.1210/jendso/bvag146","url":null,"abstract":"<p><strong>Background: </strong>Quantify the performance of claims data in identifying diabetic ketoacidosis (DKA) cases and estimate healthcare resource utilization among newly diagnosed type 1 diabetes patients with and without DKA.</p><p><strong>Methods: </strong>We matched individuals <18 years of age from the Barbara Davis Center for Diabetes Registry to the Colorado all-payer claims database to estimate variation in the performance of claims (ie, type 1 diabetes and DKA codes in emergency department [ER] and inpatient [IP] settings) in identifying DKA cases from 2014 to 2019. We estimated the unadjusted and adjusted associations of laboratory-confirmed DKA with resource utilization using encounters and incidence rate ratios with 95% confidence intervals.</p><p><strong>Results: </strong>After applying algorithms for identifying type 1 diabetes with continuous enrollment criteria, n = 728 (62% match of the sample) represented an insured population residing in Colorado. Mean age at onset was approximately 9.48 years, with a proportion of DKA events at diagnosis of 56%. Strict coding definitions of DKA (DKA and type 1 diabetes) had lower sensitivity (63%) and higher specificity (76%) than looser definitions (type 1 diabetes or DKA), which had higher sensitivity (89%) and lower specificity (60%). Laboratory-confirmed DKA was associated with over 5 times the rate of IP encounters compared with no confirmed DKA (incidence rate ratio [IRR], 5.49; 95% confidence interval, 4.03-7.47) but fewer ER-only encounters (IRR, 0.36; 95% confidence interval, 0.24-0.54).</p><p><strong>Conclusion: </strong>Claims data may not capture all DKA encounters at type 1 diabetes diagnosis. Future research should provide sensitivity analyses across coding and settings to estimate the burden of DKA.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 8","pages":"bvag146"},"PeriodicalIF":4.4,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13366538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148447769","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":"US race/ethnic disparities in diabetes technologies: a systematic review and meta-analysis of 950 000 individuals.","authors":"Maria L M Rego, Maxim Barnett, Maria Helena Siqueira Tavares de Melo, Ana Rivadeneira","doi":"10.1210/jendso/bvag150","DOIUrl":"10.1210/jendso/bvag150","url":null,"abstract":"<p><strong>Purpose: </strong>To provide a descriptive summary and to quantitatively examine racial and ethnic disparities in the use of continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion (CSII) among people living with diabetes in the United States.</p><p><strong>Research design and methods: </strong>We followed the Cochrane and PRISMA guidelines (PROSPERO: CRD420251124678). Search was conducted on PubMed, Embase, and Cochrane up to August 2025. Observational studies were included if they (1) were conducted in the United States, (2) evaluated the use of CGM/CSII across different races/ethnic groups, and (3) reported odds ratios (ORs) for between-group comparisons. Three-level random-effect meta-analyses examined OR in the use of CGM/CSII across different groups: Non-Hispanic White (NHW; reference group) vs Black/African American, Hispanic, Asian, and Other. Subgroup analyses were conducted for children vs adults, and type 1 vs type 2 diabetes.</p><p><strong>Results: </strong>Totally, 1737 studies were screened, and 18 studies were included (N = 955 556 individuals). Most participants were NHW (70.9%). Approximately 40% of individuals had type 2 diabetes, and 98.9% were adults. Black/African Americans (OR = 0.47, 95% CI = 0.38-0.60), Hispanics (OR = 0.59, 95% CI = 0.50-0.69), and \"Other\" (OR = 0.69, 95% CI = 0.58-0.83) were less likely to use CGM, relative to NHW individuals, while Asians were equally likely. Black/African Americans (OR = 0.31, 95% CI = 0.23-0.42) and Hispanics (OR = 0.48, 95% CI = 0.42-0.55) were less likely to use a CSII when compared to NHW. No analysis was conducted for \"Asian\" or \"Other.\" Limitations include moderate/substantial heterogeneity and reliance on electronic medical record data.</p><p><strong>Conclusion: </strong>Racial and ethnic disparities exist in the use of diabetes technologies. Its recognition is essential to advance solutions that promote equitable care in diabetes.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 8","pages":"bvag150"},"PeriodicalIF":4.4,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13356960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148430573","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":"Clinical outcomes of thyroid function in patients with thyrotropin receptor blocking antibody-positive hypothyroidism.","authors":"Rei Hirose, Jaeduk Yoshimura Noh, Natsuko Watanabe, Tatsuya Iida, Toshino Suzuki, Masahiro Ichikawa, Masakazu Koshibu, Nami Suzuki, Masako Matsumoto, Miho Fukushita, Ai Yoshihara, Kiminori Sugino, Koichi Ito","doi":"10.1210/jendso/bvag147","DOIUrl":"10.1210/jendso/bvag147","url":null,"abstract":"<p><strong>Context: </strong>Thyrotropin receptor blocking antibodies (TBAbs) are uncommon but not a rare cause of hypothyroidism. However, clinical outcomes of thyroid function in patients with TBAb-positive hypothyroidism remain unclear.</p><p><strong>Objective: </strong>The aim of this study was to explore the clinical outcomes of thyroid function in patients with TBAb-positive hypothyroidism and investigate factors associated with hypothyroidism outcomes.</p><p><strong>Methods: </strong>A single-center retrospective observational study was conducted from 2024 to 2025. Overall, 137 patients with TBAb-positive hypothyroidism without Graves' disease (Non-GD group) and 181 with TBAb-positive hypothyroidism during or after antithyroid drug therapy for Graves' disease (Prior GD group), almost all Japanese, were included. Thyroid functional outcomes were assessed in all patients; serial TBAb measurements were available for 31% and 36% of the patients, respectively. The main outcome was thyroid function at the final visit after a median follow-up period of 6.8 years. Clinical factors associated with hypothyroidism outcomes were analyzed using logistic regression analysis.</p><p><strong>Results: </strong>Hypothyroidism persisted in 84% and 43% of the patients in the Non-GD and Prior GD groups, respectively. In both groups, persistent TBAb positivity was associated with hypothyroid outcomes (Non-GD: univariate analysis, odds ratio [OR], 3.51; 95% CI, 1.14-40.6; <i>P</i> = .013; Prior GD: univariate analysis, OR, 6.75; 95% CI, 1.87-24.4; <i>P</i> = .0016; multivariate analysis, OR, 6.88; 95% CI, 1.89-25.1; <i>P</i> = .0015).</p><p><strong>Conclusion: </strong>Most patients with TBAb-positive hypothyroidism remain hypothyroid over the long term, whereas outcomes are more heterogeneous in patients with prior Graves' disease who develop TBAb-positive hypothyroidism. Persistent TBAb positivity is associated with the hypothyroidism outcomes.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 8","pages":"bvag147"},"PeriodicalIF":4.4,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13343486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412150","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":"The impact of statins on aldosterone production in healthy adults: a randomized controlled study.","authors":"Yan Emily Yuan, Lindsey M Porter, Andrea V Haas, Ezra S Hornik, Andrew W Koefoed, Rebecca Easly-Merski, Gillian Murray, Subrina Farah, Gail K Adler, Jonathan S Williams","doi":"10.1210/jendso/bvag141","DOIUrl":"10.1210/jendso/bvag141","url":null,"abstract":"<p><strong>Background: </strong>Statins lower atherosclerotic cholesterol, but the cardiovascular benefit from treatment may extend beyond lipid management. Our group previously described in an observational study that individuals on statin therapy had 33% lower aldosterone (ALDO) than individuals not on statins, and this effect was greater in individuals taking a lipophilic statin (eg, simvastatin) than a hydrophilic statin (eg, pravastatin). Further, studies in isolated rodent adrenal zona glomerulosa cells demonstrated that statins lowered ALDO, and again lipophilic statins had a greater effect. We, therefore, tested the hypothesis that treatment with simvastatin would result in lower than treatment with pravastatin or placebo in a randomized controlled trial.</p><p><strong>Methods: </strong>We conducted a 12-week, double-blind, randomized, placebo-controlled clinical trial among healthy adults with low-density lipoprotein cholesterol (LDL-C) > 70 mg/dL. Participants were randomized 1:1:1 to placebo, simvastatin 20 mg, or pravastatin 40 mg, stratified by sex. The study medication dose was doubled at Week 6 if the LDL-C decreased by less than 35% from screening values. We performed ALDO assessments at pretreatment, Week 6, and Week 12 posttreatment after 5 days on a controlled low-sodium diet.</p><p><strong>Results: </strong>Multivariate regression analysis controlling for sex, age, race, BMI, and pretreatment angiotensin II (AngII)-stimulated ALDO showed no significant differences in 12-week posttreatment AngII-stimulated ALDO between placebo and simvastatin (<i>P</i>, .56; primary endpoint) nor between simvastatin and pravastatin (<i>P</i>, .90; secondary endpoint).</p><p><strong>Conclusion: </strong>Among healthy individuals on a low-sodium diet, 12-week treatment with simvastatin or pravastatin did not alter ALDO responsiveness to AngII.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 7","pages":"bvag141"},"PeriodicalIF":4.4,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13329661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148391107","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}