Journal of the Endocrine Society最新文献

{"title":"Angiotensin II and cAMP signaling pathways regulate mitochondrial biogenesis and activity in human adrenocortical cells.","authors":"Matías A Belluno, Fabrizio G Arona, Katia E Helfenberger, Martina A Rodrigo, María Mercedes Mori Sequeiros Garcia, Paula M Maloberti, Yanina Benzo, Cecilia Poderoso","doi":"10.1210/jendso/bvag218","DOIUrl":"https://doi.org/10.1210/jendso/bvag218","url":null,"abstract":"<p><p>Mitochondrial homeostasis, governed by the balance between biogenesis and mitophagy, is essential for steroidogenesis in adrenocortical cells. While the requirement of active mitochondria for steroid synthesis is well-established, the hormonal regulation of genes governing mitochondrial function remains poorly understood. This study investigated whether angiotensin II (Ang II) and the cAMP/PKA pathway modulate the expression of key regulatory factors involved in mitochondrial biogenesis and redox status in the human adrenocortical H295R cell line. Using real-time qPCR and Western blot, we show that Ang II and 8Br-cAMP-a permeant analog of cAMP-modulate NRF-1, Nrf2, UCP2, and ANT1 impacting on mitochondrial biogenesis, antioxidant defense, and respiratory activity. These molecular changes correlated with increased mitochondrial membrane polarization, as confirmed by MitoTracker red staining. Interestingly, Ang II stimulation promoted a time-dependent increase in TFAM levels, a key transcription factor in mitochondria, which correlates with the increase in mitochondrial DNA (mtDNA) content. The rate of oxygen consumption (OCR) and mitochondrial parameters were determined, with results showing that Ang II led to a significant increase in basal and maximum respiration, ATP production, and proton leak. These findings suggest that hormone stimulation favors mitochondrial activity, thereby enhancing the bioenergetic capacity of adrenocortical cells. Furthermore, treatment with the uncoupler CCCP triggered a retrograde signaling response, upregulating nuclear-encoded mitochondrial genes to counteract mitochondrial membrane depolarization. Our findings demonstrate for the first time that hormonal signals directly modulate the mitochondrial genetic program in H295R human adrenocortical cells, optimizing the bioenergetic platform required for efficient steroidogenic function.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 10","pages":"bvag218"},"PeriodicalIF":4.4,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111357","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":"Endocrine complications of COVID-19: diabetes, musculoskeletal, thyroid, pituitary, adrenal, and gonadal disorders.","authors":"Kamyar Asadipooya, Srividya Sriramula","doi":"10.1210/jendso/bvag219","DOIUrl":"https://doi.org/10.1210/jendso/bvag219","url":null,"abstract":"<p><p>COVID-19 is generally associated with both short- and long-term complications. It can affect multiple organ systems and lead to severe or prolonged organ dysfunction, including the endocrine system. It also places a substantial burden on individuals and the health-care system. Therefore, providing up-to-date information for health-care providers is valuable. In this review, we aim to consolidate the current literature regarding the endocrine complications of acute SARS-CoV-2 infection, with a particular focus on diabetes, calcium homeostasis, pituitary, thyroid, adrenal, and gonadal disorders. Although current therapeutic approaches for COVID-19 are mainly limited to antivirals, symptomatic therapies, and supportive care, advances in understanding the mechanisms of SARS-CoV-2 entry and immune responses may support a more effective and personalized approach to clinical care.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 10","pages":"bvag219"},"PeriodicalIF":4.4,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111502","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 effect of time-restricted eating accompanied by weight loss on thyroid function in adults with type 2 diabetes.","authors":"Yaanu Jeyakumar, Ravi Retnakaran, Denice S Feig, Bernard Zinman, Caroline K Kramer","doi":"10.1210/jendso/bvag216","DOIUrl":"https://doi.org/10.1210/jendso/bvag216","url":null,"abstract":"<p><strong>Context: </strong>Time-restricted eating (TRE) is a lifestyle intervention associated with beneficial cardiometabolic effects. The impact of TRE-induced weight reduction on thyroid hormonal responses is not well elucidated.</p><p><strong>Objective: </strong>To evaluate the effects of TRE accompanied by weight loss on thyroid function in adults with obesity and type 2 diabetes (T2DM).</p><p><strong>Methods: </strong>We performed an exploratory analysis of a randomized, crossover, open-label study in adults with obesity and T2DM who underwent 2 dietary interventions: TRE and standard lifestyle. Each intervention period lasted 6 weeks. Thyroid function was assessed by TSH, free T4 (fT4), free T3 (fT3), and reverse T3 (rT3).</p><p><strong>Results: </strong>Thirty-nine participants without known thyroid disease (age 56.3 years, 35.9% male, body mass index 32.4 ± 5.7 kg/m²) were included. TRE induced significant weight loss (-2.93 kg) compared to the standard lifestyle period (0.59 kg) (mean differences between intervention periods of -3.50 kg ± 2.9; <i>P</i> < .001). Despite this robust weight-lowering effect, there were no significant differences in TSH (0.49 mUI/L ± 3.0; <i>P</i> = .32), fT3 (-0.57 pmol/L ± 2.7; <i>P</i> = .19), fT4 (fT4 -0.55 pmol/L ± 3.8; <i>P</i> = .38), and rT3 (-0.94 ng/dL ± 5.9; <i>P</i> = .350) between intervention periods. Reinforcing these findings, there was no treatment effect interaction on any thyroid function test evaluated. In addition, there was no significant change in the fT3: fT4 and fT3:rT3 ratios between treatment interventions.</p><p><strong>Conclusion: </strong>Despite inducing significant weight loss, TRE did not exert a significant effect on thyroid function in individuals with obesity and early T2DM.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 10","pages":"bvag216"},"PeriodicalIF":4.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111464","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":"Late recovery from chronic arginine vasopressin deficiency: a multicenter retrospective case-control study.","authors":"Clara O Sailer, Francesca Galbiati, Anna Aulinas, Maged Muhammed, Regine Boutin, Jenna Bourassa, Cihan Atila, Julia Crowley, Allie Dayno, Hannah Pearlstein, Lisa B Nachtigall, Karen K Miller, Nicholas A Tritos, Ursula B Kaiser, Shana E McCormack, Mirjam Christ-Crain, Laura E Dichtel, Elizabeth A Lawson","doi":"10.1210/jendso/bvag211","DOIUrl":"10.1210/jendso/bvag211","url":null,"abstract":"<p><strong>Context: </strong>Arginine vasopressin deficiency (AVP-D), caused by hypothalamic/pituitary damage from tumor or surgery, can be transient or chronic. Chronic AVP-D is thought to be permanent though emergent research indicates the possibility of late recovery. Little is known about clinical characteristics that predict late recovery from chronic AVP-D.</p><p><strong>Objective: </strong>Describe characteristics associated with late recovery from chronic AVP-D.</p><p><strong>Design: </strong>Multicenter, retrospective case-control study of AVP-D Recovered (n = 18) vs AVP-D Non-recovered (n = 36; matched for sex and disease duration).</p><p><strong>Main outcome measures: </strong>Clinical characteristics assessed at hypothalamic/pituitary disease diagnosis, AVP-D diagnosis, AVP-D recovery, and most recent clinical evaluation. We also present characteristics of three pediatric cases with AVP-D recovery.</p><p><strong>Results: </strong>At diagnosis of hypothalamic/pituitary disease, AVP-D Recovered, compared to AVP-D Non-recovered, were older (45 ± 19 vs 33 ± 13 years, <i>P</i> = .006) and more likely to have functioning pituitary tumors (33.3% vs 8.3%, <i>P</i> = .05). Following diagnosis of AVP-D, AVP-D Recovered received lower total daily doses of desmopressin (100 [IQR; 50, 100] vs 200 [100, 200] µg oral or equivalent, <i>P</i> = .01). Recovery occurred after a median of 6.3 years [1.7, 12.0] and occurred earlier in those without hypothyroidism (<i>P</i> = .049) or adrenal insufficiency at diagnosis of AVP-D (<i>P</i> = .008).</p><p><strong>Conclusion: </strong>Our study supports the notion that chronic AVP-D may not be permanent across the lifespan. Continued requirement for desmopressin, particularly in those with a history of functioning pituitary tumors, low doses of desmopressin, and without concurrent hypothyroidism or adrenal insufficiency at diagnosis, should be regularly reassessed.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 10","pages":"bvag211"},"PeriodicalIF":4.4,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111461","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":"Parental anxiety in differences of sex development and hypospadias: a psychosocial characterization.","authors":"Sarah F Schlegel, Jessica Kremen, Alayna Dutcher, Stacey Pereira, Ingrid A Holm, Yee-Ming Chan","doi":"10.1210/jendso/bvag212","DOIUrl":"10.1210/jendso/bvag212","url":null,"abstract":"<p><strong>Context: </strong>Parents of children with differences of sex development (DSD) and hypospadias experience significant psychological distress, but the factors contributing to parental anxiety remain poorly understood.</p><p><strong>Objective: </strong>Identify psychosocial factors associated with anxiety among parents of children with urogenital conditions and compare anxiety levels to parents in other pediatric settings.</p><p><strong>Design: </strong>Cross-sectional survey study.</p><p><strong>Setting: </strong>Pediatric subspecialty clinics at an academic medical center.</p><p><strong>Participants: </strong>One hundred and eight parents of children with urogenital conditions without established genetic diagnoses, compared with 346 parents from BabySeq, a newborn genomic sequencing trial (278 parents of healthy newborns, 68 parents of neonatal intensive care unit [NICU] infants).</p><p><strong>Main outcome measures: </strong>Anxiety symptoms (Generalized Anxiety Disorder 7-item scale [GAD-7]), stigma, and quality of life.</p><p><strong>Results: </strong>Clinically significant anxiety (GAD-7 ≥ 5) was present in 33% of parents of children with urogenital conditions, similar to the rate in parents of NICU infants (34%) and significantly higher than in parents of healthy newborns (21%, <i>P</i> = .03). Forty-one percent reported self-blame for their child's condition; 16% reported blaming their partners. Quality of life decreased with increasing stigma (<i>P</i> = .001), genital atypicality (<i>P</i> = .03), and anxiety scores (<i>P</i> = .04). Backward elimination and Least Absolute Shrinkage and Selection Operator regression with multiple imputation identified 4 key factors predicting increased anxiety: higher intolerance of uncertainty, increased parental health-related stress, lower educational level, and greater emotional stigma. Additional factors included greater genital atypicality, social isolation, and self-blame.</p><p><strong>Conclusion: </strong>Parents of children with urogenital conditions experience anxiety levels comparable to parents of infants in the NICU, despite their children being medically stable. Uncertainty intolerance and emotional stigma provide targets for clinical screening and early intervention.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 10","pages":"bvag212"},"PeriodicalIF":4.4,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081483","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":"Phenotyping and hierarchical clustering in genetically unresolved DSD identifies distinct multisystem clinical subgroups-a DSDgene study.","authors":"Chrysanthi Kouri, Malika Allimussina, S Faisal Ahmed, Christa E Flück","doi":"10.1210/jendso/bvag214","DOIUrl":"10.1210/jendso/bvag214","url":null,"abstract":"<p><strong>Context: </strong>A substantial proportion of individuals with differences of sex development (DSD) remain without an identifiable molecular diagnosis. Systematic phenotyping may reveal clinically relevant patterns and inform genomic investigation.</p><p><strong>Objective: </strong>To identify phenotypic patterns among individuals with genetically unresolved DSD and determine whether multisystem anomalies form distinct clinical clusters and exhibit overlap with established DSD-associated conditions.</p><p><strong>Design: </strong>Data from the I-DSD Registry were analyzed for individuals with 46,XY or 46,XX DSD lacking a molecular diagnosis. A 3-part approach was used: (1) unsupervised hierarchical clustering based on Gower distance; (2) supervised phenotype-guided classification using reference profiles for NR5A1/SF-1 deficiency and P450 oxidoreductase deficiency (PORD); and (3) exploratory comparison with Human Phenotype Ontology (HPO)-derived profiles of established DSD-associated genes.</p><p><strong>Results: </strong>Among 1391 screened individuals, 345 (24.8%) fulfilled inclusion criteria, including the presence of at least 1 additional organ anomaly, 83.8% had a 46,XY karyotype. The most frequent associated findings were small for gestational age (28.1%), cardiac anomalies (21.4%), central nervous system (CNS) (15.7%), and renal anomalies (14.5%). Unsupervised clustering identified 5 phenotypic groups, including craniofacial-dominant and CNS-dominant clusters. Phenotype-guided classification showed overlap with SF-1-deficiency-associated phenotypes in 11% of cases and with PORD-associated phenotypes in 22%. Comparison with HPO-derived profiles of 81 DSD-associated genes demonstrated phenotypic similarities between several clusters and known gene-associated anomaly spectra.</p><p><strong>Conclusion: </strong>Systematic phenotyping identifies recognizable patterns of multisystem involvement in genetically unresolved DSD. Several clusters overlap with established DSD-associated conditions and gene-specific anomaly profiles, supporting phenotype-driven surveillance, multidisciplinary care, and informing future genomic re-evaluation strategies.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 10","pages":"bvag214"},"PeriodicalIF":4.4,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081524","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":"Cardiometabolic and atherosclerotic cardiovascular disease outcomes associated with tirzepatide: insights from a 1-year multicenter observational study.","authors":"Rene de J Rivera Gutierrez, Regina Castaneda, Alfredo Verastegui, Wissam Ghusn, Dima Bechenati, Maria A Espinosa, Jose Villamarin, Elif Tama, Kirsten Frederiksen, Andres Acosta, Maria D Hurtado Andrade","doi":"10.1210/jendso/bvag210","DOIUrl":"10.1210/jendso/bvag210","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the association of long-term, continuous tirzepatide use with cardiometabolic risk parameters and estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk in real-world practice.</p><p><strong>Methods: </strong>This multicenter retrospective observational study included 1028 adults with overweight or obesity who received weekly subcutaneous tirzepatide for at least 12 months within the Mayo Clinic Health System from June 2022 through May 2024. Atherosclerotic cardiovascular disease risk analyses included 275 individuals with complete baseline and 12-month follow-up data. Outcomes were changes in cardiometabolic parameters, estimated 10-year ASCVD risk, and ASCVD risk category.</p><p><strong>Results: </strong>At 12 months, median total body weight loss (TBWL) was 12.6%. Fasting glucose, HbA1c, triglycerides, and alanine aminotransferase decreased by 19.5%, 16.0%, 8.5%, and 10.6%, respectively, whereas HDL-cholesterol increased by 11.3% (all <i>P</i>  <i><</i> .001). Mean 10-year ASCVD risk did not change significantly overall (mean relative change, -3.7%; <i>P</i> = .18), but changes differed by TBWL category (analysis of variance, <i>P</i>  <i><</i> .001). Atherosclerotic cardiovascular disease risk decreased among individuals achieving 10% to 20% TBWL (-9.6%; <i>P</i> = .009) and >20% TBWL (-14.2%; <i>P</i> = .005), but not among those achieving <10% TBWL (+7.7%; <i>P</i> = .22). Low-risk prevalence increased from 38.3% to 46.4% (<i>P</i>  <i><</i> .001), with 11.7% transitioning from higher-risk categories to low risk.</p><p><strong>Main findings: </strong>Continuous tirzepatide use for at least 12 months was associated with clinically meaningful improvements in cardiometabolic parameters. Reductions in estimated 10-year ASCVD risk were observed among individuals achieving at least 10% TBWL, supporting greater weight loss as an important marker of cardiovascular risk improvement.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 10","pages":"bvag210"},"PeriodicalIF":4.4,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081475","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":"Association of testosterone and testosterone replacement therapy with atrial fibrillation: an updated review.","authors":"Anand Reddy Maligireddy, Shumedha T Barua, Rajat S Barua","doi":"10.1210/jendso/bvag180","DOIUrl":"10.1210/jendso/bvag180","url":null,"abstract":"<p><p>Historically, low testosterone (T) has been linked to increased atrial fibrillation (AF) risk in men, yet recent evidence suggests that elevated T levels and testosterone replacement therapy (TRT) may also confer risk. This review synthesizes emerging literature to characterize the evolving T-AF relationship and inform clinical practice. A structured literature search of MEDLINE/PubMed and Embase, supplemented by hand-searching reference lists of relevant publications, was performed, using terms including \"testosterone,\" \"testosterone replacement therapy,\" and \"atrial fibrillation.\" Findings were heterogeneous. The 2023 TRAVERSE trial reported a higher AF incidence with TRT, contrasting with earlier VA data from Sharma et al. (2017) showing reduced AF risk when T normalized after treatment. A 2024 meta-analysis by Corona et al of 106 randomized placebo-controlled trials found no significant pooled AF signal. Real-world data remained mixed: a TriNetX-based replication did not confirm elevated AF risk, whereas a 5-year cohort study reported a hazard ratio of 1.27 in cisgender hypogonadal men receiving TRT. Population-level studies by Xu et al (2024) and post-hoc ASPREE analyses by Tran et al (2024) demonstrated a nonlinear association in which both low and high T levels increased AF risk. Updated mechanistic data support a U-shaped model: low T disrupts calcium handling, whereas high T alters potassium currents and promotes reentry. Converging evidence thus supports a U-shaped T-AF relationship. Until definitive data emerge, clinicians should prioritize risk-stratified TRT use, mid-physiologic T targets, stable formulations, and structured monitoring.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 9","pages":"bvag180"},"PeriodicalIF":4.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874355","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":"Genetic screening and functional characterization of <i>DUOX2</i> mutations in patients with congenital hypothyroidism.","authors":"Su-Hong Huang, Feng Sun, Fei Luo, Hui-Lan Li, Hai-Lin Huang, Jing-Min Guo, Chong Guo, Xue-Hua Zhang, Shuang-Xia Zhao, Bo-Kun Wei, Huai-Dong Song, Rui Li, Feng Cheng","doi":"10.1210/jendso/bvag188","DOIUrl":"10.1210/jendso/bvag188","url":null,"abstract":"<p><strong>Context: </strong>Congenital hypothyroidism (CH) is the most prevalent endocrine disorders detected via newborn screening. Variants in dual oxidase 2 (<i>DUOX2</i>) have been established as a major genetic contributor to CH in Chinese populations.</p><p><strong>Objective: </strong>To characterize the genetic spectrum of <i>DUOX2</i> variants and explore their clinical correlations in a cohort of CH patients from Fujian Province, China, and to assess variant impact on enzymatic activity.</p><p><strong>Methods: </strong>We enrolled 184 Han Chinese CH patients. <i>DUOX2</i> variants were screened via exome sequencing. Clinical data (thyroid function, ultrasonography) were integrated with in vitro measurement of H₂O₂ generation for selected variants.</p><p><strong>Results: </strong>Of the 184 patients, 114 (61.96%) carried genetic variants. <i>DUOX2</i> was the most prevalent, accounting for 43.48% (80/184) of cases. Notably, statistically significant differences in TSH, FT4, and FT3 levels were observed between <i>DUOX2</i> variant carriers and noncarriers. Ultrasonography revealed that normal thyroid morphology was the predominant finding in children with <i>DUOX2</i> variants. In vitro functional assays revealed that 5 out of 11 <i>DUOX2</i> variants exhibited significantly impaired H₂O₂ production capacity. Notably, variants in both functional and unstructured domains impaired residual enzymatic activity.</p><p><strong>Conclusion: </strong><i>DUOX2</i> is the most common causative gene for CH in the Fujian cohort, and its variants are associated with a more severe biochemical phenotype at onset diagnosis. Functional heterogeneity suggests that impaired enzymatic activity is a key, but not exclusive, pathogenetic mechanism. Ultimately our findings highlight the critical need for integrating genetic and functional analyses into the clinical management and genetic counseling of CH.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 9","pages":"bvag188"},"PeriodicalIF":4.4,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13519044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840574","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":"A single dose trial of mizagliflozin for the treatment of postbariatric hypoglycemia.","authors":"Helen M Lawler, Tracey L McLaughlin, Soroush Shakeri, Ethan F Stortz, Aanchal Gupta, Vatsala Singh, Nicole Turk, Susan Walker, William Wilkison, Bentley Cheatham","doi":"10.1210/jendso/bvag181","DOIUrl":"10.1210/jendso/bvag181","url":null,"abstract":"<p><strong>Context: </strong>Postbariatric hypoglycemia (PBH) is a complication of bariatric surgery characterized by severe postprandial hypoglycemia for which there is no approved therapy.</p><p><strong>Objective: </strong>To evaluate efficacy and safety of mizagliflozin, a sodium glucose cotransporter 1 inhibitor, for treatment of PBH.</p><p><strong>Methods: </strong>This was a phase 2, open-label, randomized, single-dose, crossover study. Nine participants with PBH were randomized to receive a baseline mixed meal tolerance test (MMTT), and single doses of mizagliflozin before each of 2 additional MMTTs. Doses included a 2.5-mg liquid formulation, and 2.5-, 5-, and 10-mg capsules. The primary outcome was change from baseline in glucose nadir, and the main secondary outcomes were change from baseline peak glucose and peak insulin.</p><p><strong>Results: </strong>Compared to baseline, all individual doses of mizagliflozin raised the glucose nadir: 6.2 mg/dL (2.5-mg capsule), 17.5 md/dL (2.5-mg liquid), 4.0 mg/dL (5-mg capsule) and 31.5 mg/dL (10-mg capsule). In a post hoc analysis of participants that exhibited hypoglycemia (<70 mg/dL) during the baseline MMTT, mizagliflozin (all capsule doses combined) raised the glucose nadir by 38% (<i>P</i> = .03). Treatment with mizagliflozin also lowered both peak glucose by 21% (<i>P</i> = .03) and peak insulin by 53% (<i>P</i> = .016). Glucose-dependent insulinotropic peptide area under the curve_0-3h was reduced by 45% from baseline (<i>P</i> = .048).</p><p><strong>Conclusion: </strong>Mizagliflozin resulted in improved glucose nadir, reduction in both postprandial peak glucose and peak insulin, and reduction in postprandial glucose-dependent insulinotropic polypeptide. The results from this proof-of-concept study suggest mizagliflozin represents a promising novel oral treatment for PBH that warrants further clinical development.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 9","pages":"bvag181"},"PeriodicalIF":4.4,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865163","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}