The Journal of clinical endocrinology and metabolism最新文献

{"title":"Incomplete Evidence of Bone Density Normalization Following Long-Term Reproductive Hormone Treatment in Men With Hypogonadotropic Hypogonadism.","authors":"Nipun Lakshitha de Silva, Elizabeth Hyams, Bonnie Grant, Paras Dixit, Rajdeep Bassi, Paul Bassett, Alexander N Comninos, Channa N Jayasena","doi":"10.1210/clinem/dgaf488","DOIUrl":"https://doi.org/10.1210/clinem/dgaf488","url":null,"abstract":"<p><strong>Context: </strong>The prevalence and severity of low bone mineral density (BMD) in hypogonadotropic hypogonadism (HH), as well as the ability of reproductive hormone treatment to normalize BMD have not been investigated in large multicenter studies.</p><p><strong>Objective: </strong>We performed a systemic review and meta-analysis of several small, observational studies to investigate the effect of reproductive hormone treatment on BMD in men with HH compared with control groups where available.</p><p><strong>Methods: </strong>We searched OVID Medline, Embase, CINAHL, SCOPUS, Web of Science, and Cochrane Library for studies reporting BMD or fractures in men with HH (congenital [CHH] or acquired). Study selection and data extraction were performed using COVIDENCE and a prespecified tool. Results were summarized using descriptive statistics. Meta-analysis compared BMD in men with HH vs healthy controls. Meta-regression assessed relationships between treatment duration and BMD Z-scores against normative population data.</p><p><strong>Results: </strong>Of the 33 eligible studies, 24 included data specific to men with HH (n = 625). Men with HH had low lumbar spine (LS) and femoral neck BMD, improving with hormonal treatment. Meta-analysis of 5 studies found lower LS BMD in men with HH vs healthy controls (SMD -5.98; 95% CI; -11.5 to -0.47). Men with CHH may have persistently low BMD despite prolonged hormonal treatment. Higher BMD in HH was associated with younger age at treatment initiation, partial HH, and higher serum testosterone and estradiol concentrations. Fracture prevalence was high in the few studies systematically studying fractures as an outcome; in other studies, fractures were seldom reported.</p><p><strong>Conclusion: </strong>Men with HH have low BMD that improves with reproductive hormone treatment. However, current evidence suggests that incomplete BMD normalization may be common despite long-term reproductive hormone treatment in men with HH, particularly those with CHH.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208979","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":"GLP-1 receptor agonists and non-arteritic anterior ischaemic optic neuropathy: what an endocrinologist needs to know.","authors":"Livia Liu, Sharanya Mohan, Linda Wu","doi":"10.1210/clinem/dgaf541","DOIUrl":"https://doi.org/10.1210/clinem/dgaf541","url":null,"abstract":"<p><strong>Context: </strong>There is emerging evidence suggesting a possible association between glucagon-like peptide-1 receptor agonists (GLP-1 RA) and non-arteritic anterior ischaemic optic neuropathy (NAION) with retrospective cohort studies supporting this association reporting hazard ratios ranging from 2.19 to 7.74 when comparing exposed vs unexposed groups. This article explores the current research surrounding the risk of NAION with GLP-1 RA use in patients with type 2 diabetes and obesity, analyses patient factors that may increase susceptibility and highlights key areas warranting further research to guide endocrinologists in future prescribing.</p><p><strong>Conclusions: </strong>Whilst the emerging evidence suggests a possible association between commencement of GLP-1 RAs and NAION, absolute risk remains low and needs to be balanced with the known substantial benefits of GLP-1 RAs. Further research is needed to investigate whether specific patient characteristics such as optic disc parameters, blood pressure changes, degree of weight loss or improvement of glycaemic control can assist clinicians in identifying those at higher risk.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194392","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":"Modelling Follicular Growth During Ovarian Stimulation Using Agent-based Artificial Intelligence.","authors":"Artsiom Hramyka, Thomas W Kelsey, Simon Hanassab, Scott M Nelson, Arthur C Yeung, Sotirios Saravelos, Rehan Salim, Alexander N Comninos, Krasimira Tsaneva-Atanasova, Margaritis Voliotis, Geoffrey H Trew, Thomas Heinis, Waljit S Dhillo, Ali Abbara","doi":"10.1210/clinem/dgaf539","DOIUrl":"https://doi.org/10.1210/clinem/dgaf539","url":null,"abstract":"<p><strong>Context: </strong>Ovarian stimulation is a key step in medically assisted reproduction (MAR), whereby supraphysiological doses of FSH extend the 'FSH window' and induce multi-follicular growth. However, only limited data exist examining individual follicular growth rates during fertility treatment.</p><p><strong>Objective: </strong>To model growth rates of individual ovarian follicles during ovarian stimulation in MAR cycles using an agent-based artificial intelligence (AI) model.</p><p><strong>Design: </strong>Observational cohort study.</p><p><strong>Setting: </strong>Eleven assisted conception clinics in Europe.</p><p><strong>Patients: </strong>11,572 patients (2005-2023) who underwent ovarian stimulation during MAR.</p><p><strong>Intervention: </strong>Predictive modelling was conducted using 39,698 scans including 434,082 follicles from 12,950 cycles during ovarian stimulation.</p><p><strong>Main outcome measures: </strong>Daily growth rates of individual ovarian follicles during stimulation were modelled to enable prediction of follicle sizes at the end of ovarian stimulation.</p><p><strong>Results: </strong>Mean follicle growth rate of ovarian follicles was 1.35mm per day (95% CI 1.346-1.353), and was significantly associated with antral follicle count and FSH dose changes (both p < 0.001). Using only the first scan, the model enabled prediction of follicles sizes within 2mm at the end of ovarian stimulation with 75.0% accuracy (95% CI 74.6-75.3%), increasing to 80.1% (95% CI 79.8-80.5%) when incorporating the first two scans. Predictive performance was stable across clinics, with a mean accuracy of 78.0% in a random training-test split, and 77.1% using cross-validation by clinic.</p><p><strong>Conclusion: </strong>We utilized advanced AI techniques to progress our understanding of follicle growth dynamics during ovarian stimulation. This model can reliably predict follicle size profiles at the end of stimulation enabling moderation of the number of scans required.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194403","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":"How to define success in prolactinoma treatment - a systematic review and theoretical framework.","authors":"Victoria R van Trigt, Kevin A Huynh, Leontine E H Bakker, Iris C M Pelsma, Ingrid M Zandbergen, Amir H Zamanipoor Najafabadi, Marco J T Verstegen, Wouter R van Furth, Nienke R Biermasz","doi":"10.1210/clinem/dgaf540","DOIUrl":"https://doi.org/10.1210/clinem/dgaf540","url":null,"abstract":"<p><strong>Purpose: </strong>As consensus regarding outcome sets for prolactinoma treatment evaluation is lacking, outcome parameters reported in literature were evaluated, and objective, clinically relevant outcome sets were proposed.</p><p><strong>Methods: </strong>A systematic review of studies up to February 2, 2024. Reported biochemical and radiological parameters, clinician-reported findings, patient-reported outcomes (PROs), and definitions of disease remission, control and recurrence were extracted and placed into clinical context. Subsequently, objective and clinically relevant definitions of clinical outcomes were proposed based on the findings, with comprehensive outcome sets to evaluate treatment success.</p><p><strong>Results: </strong>137 articles were included. Albeit ill-defined or subjective, 23 unique prolactin parameters, and 73 unique radiological parameters were reported. Seventy articles included clinician-reported findings, and none reported PROs. Ultimately, 27 unique definitions of remission, 3 unique definitions of disease control, and 20 unique definitions of recurrence were reported. We propose two separate definitions for biochemical and clinical remission/recurrence - either evaluating prolactin levels only, or including symptomology, gonadal function and radiology. Integrated outcome quadrants were illustrated to objectively categorize treatment success by combining achievement of treatment goals with occurrence of adverse effects. A three-tier outcome set based on the Value-Based Healthcare principles was provided.</p><p><strong>Conclusions: </strong>Heterogeneity in reported outcome parameters using varying definitions hamper comparison of prolactinoma treatment outcomes. This study proposes objective, easily applicable, and clinically relevant definitions of clinical outcomes, and offers a comprehensive outcome set. These parameters enable comparison of outcomes across treatment modalities and medical centers to gain insight into this rare disease and improve prolactinoma care.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145188289","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":"Association of IGF-1 levels with height from childhood to adulthood: An observational and Mendelian randomization study.","authors":"Benjamin De La Barrera, Samuel De La Barrera, Isabel Gamache, Soren Harnois-Leblanc, Kaossarath Fagbemi, Ken K Ong, Despoina Manousaki","doi":"10.1210/clinem/dgaf532","DOIUrl":"https://doi.org/10.1210/clinem/dgaf532","url":null,"abstract":"<p><strong>Introduction: </strong>Growth hormone therapy, which increases circulating levels of insulin-like growth factor 1 (IGF-1), effectively enhances adult height in children with idiopathic short stature, although with varying responses. This raises the question whether normal IGF-1 variation within a population is causally associated with height across childhood and in adulthood.</p><p><strong>Methods: </strong>We used Two-Sample Mendelian Randomization (MR) to assess the causal effect of serum IGF-1 on adult height. Genetic instruments for IGF-1 were derived from a UK Biobank GWAS, and their effects on adult height were identified in the GIANT consortium GWAS, excluding UK Biobank (Non-Hispanic Whites: N=1,176,465; African Descent: N=168,191; South Asians: N= 49,032; East Asians: N=361,369; Hispanics: N=58,709). Using the Avon Longitudinal Study of Parents and Children (ALSPAC), we investigated cross-sectional and longitudinal associations between measured IGF-1 levels at ages 7-11 years or a genetic risk score (GRS) for IGF-1, with repeated height measurements at ages 7-17 years, adjusting for sex, BMI, and pubertal stage.</p><p><strong>Results: </strong>Inverse variance-weighted MR showed that a 1 SD increase in IGF-1 confers 0.09 SD taller adult height, which persisted after adjusting for childhood BMI. In ALSPAC, both measured IGF-1 levels at ages 7-8 years and IGF-1 GRS were positively associated with height at ages 7-17 years at both cross-sectional and longitudinal analyses.</p><p><strong>Conclusion: </strong>Our findings suggest that IGF-1 normal variation has small effects on height in childhood and on final adult height.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145188301","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":"Brighter bedroom light at night predicts risk for earlier pubertal onset: a two-year longitudinal study.","authors":"Yi Zhou, Wen-Qin Ding, Ying Li, Hao-Zheng Zhu, De-Yun Liu, Xue-Jiao Qie, Fang-Biao Tao, Ying Sun","doi":"10.1210/clinem/dgaf526","DOIUrl":"https://doi.org/10.1210/clinem/dgaf526","url":null,"abstract":"<p><strong>Context: </strong>Light at night (LAN), as an environmental endocrine disruptor, can accelerate gonadal development in animals, but evidence in humans remains limited.</p><p><strong>Objective: </strong>To investigate whether individual-level bedroom LAN exposure is associated with accelerated pubertal onset in boys and girls.</p><p><strong>Methods: </strong>This prospective study was performed from September 2022 in Tianchang, Anhui province, China, investigated 886 boys and girls aged 6 to 10 years. Bedroom LAN exposure was recorded at one-minute intervals for two nights using a portable illuminance meter at baseline. Breast development for girls and testicular volume for boys were assessed at baseline and every 6 months for 2 years. Accelerated failure time (AFT) models were utilized to examine the associations between timing, intensity and duration of LAN exposure with earlier onset of puberty.</p><p><strong>Results: </strong>Puberty started 3.84-month earlier among boys (TR, 0.96; 95%CI, 0.95-0.98) and 4.12-month earlier among girls (TR, 0.96; 95% CI, 0.94-0.98) in the highest LAN exposure group compared to the lowest exposure group. Each 30-minute increase in the duration of LAN exposure ≥ 3 lx was associated with an 9% higher risk of earlier testicular development in boys (HR, 1.09; 95% CI, 1.02-1.16), and a 12% higher risk of earlier thelarche in girls (HR, 1.12; 95% CI, 1.07-1.16). Notably, the increased risk was more pronounced with post-bedtime light (PBL) exposure compared to pre-awake light (PAL) exposure.</p><p><strong>Discussion: </strong>These findings suggest an accelerating effect of individual-level LAN exposure on pubertal onset in both boys and girls, particularly during the post-bedtime period.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181060","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":"Children with Pancreatic Hypoplasia Experience Poor Weight Gain and Labile Diabetes but Low Incidence of DKA.","authors":"Anna M Denson, Karen E Rodriguez, Lisa R Letourneau-Freiberg, Balamurugan Kandasamy, Rochelle N Naylor, Hussein D Abdullatif, Robert W Benjamin, Erin Cobry, Michael S Freemark, Inas H Thomas, Siri Atma W Greeley","doi":"10.1210/clinem/dgaf473","DOIUrl":"https://doi.org/10.1210/clinem/dgaf473","url":null,"abstract":"<p><strong>Context: </strong>Pathogenic variants in GATA6, GATA4 and PDX1 cause pancreatic hypoplasia (PH) or agenesis and early onset diabetes mellitus. There is a lack of information about long-term outcomes and clinical management of these complicated patients, including how best to approach their exocrine pancreatic insufficiency (EPI), weight gain, and glycemic management.</p><p><strong>Participants: </strong>We investigated clinical features and treatment of patients with pathogenic variants in GATA6, GATA4, and PDX1 identified through the US Monogenic Diabetes Registry. Data were self-reported or extracted from medical records.</p><p><strong>Results: </strong>Eleven children were studied. Pancreatic hypoplasia/agenesis, EPI, gallbladder agenesis, and congenital heart defects were common in this cohort. Novel features were present, such as recurrent infections and epilepsy. All participants were born small for gestational age (SGA) and many had difficulties with weight gain. Insulin treatment was discontinued and later reinstated for three infants. Glycemic control in nearly all patients was sub-optimal with the mean HbA1c being 8.7, but only one episode of diabetic ketoacidosis (DKA) was reported. Fasting and postprandial hypoglycemia were common. Eight of eleven children required pancreatic enzymes. Two children required enteral feedings to maintain nutritional balance.</p><p><strong>Conclusion: </strong>Children with pathogenic variants in GATA6, GATA4, and PDX1 have labile, insulin-dependent diabetes mellitus and varying degrees of EPI caused by pancreatic hypoplasia/agenesis. Intrauterine growth restriction and postnatal difficulties with weight gain are common but rates of DKA are low, which may in part be due to a lack of glucagon, an important driver of ketosis.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181068","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":"An oral glucose tolerance test in pregnancy can serve as a valuable predictor for future diabetes.","authors":"Tal Schiller, Linoy Gabay, Oren Barak, Alena Kirzhner, Haitham Abu Khadija, Gabriel Chodick, Edi Vaisbuch, Yael Barer","doi":"10.1210/clinem/dgaf534","DOIUrl":"https://doi.org/10.1210/clinem/dgaf534","url":null,"abstract":"<p><strong>Background: </strong>Adherence to screening following a pregnancy with gestational diabetes mellitus (GDM) remains low.</p><p><strong>Objective: </strong>To assess the risk of future type 2 diabetes (T2D) based on the number and type of abnormal results of a 100-gram oral glucose tolerance test (OGTT) performed during pregnancy.</p><p><strong>Study design: </strong>This retrospective study used data from a major Israeli healthcare provider. Women aged 20 to 50 years without a prior diagnosis of T2D who had a complete 100-gram OGTT during their last pregnancy between January 2000 and December 2022 were included. The primary outcome was the development of T2D by September 2024. Risk was assessed using Cox proportional hazards models based on the number and type of abnormal OGTT values.</p><p><strong>Results: </strong>The study included 107,889 women (age 34.1±5.2 years; BMI 27.6±5.3 kg/m²). Median follow-up was 6.7 years (IQR 3.3-12.4), totaling 900,000 person-years. T2D developed in 4,500 women (0.5%). When compared to women with all OGTT values normal, the risk of T2D rose with each additional abnormal value: hazard ratio (HR) 3.45 (95% CI: 3.15-3.77) for one abnormal value, 4.03 (3.69-4.41) for two, 7.15 (6.49-7.88) for three, and 10.60 (9.28-12.20) for four. Abnormal fasting glucose was associated with a higher risk (HR 5.28; 95% CI: 4.83-5.76) than abnormal non-fasting values (HR 3.03; 95% CI: 2.78-3.29). A previous diagnosis of GDM was significantly associated with future T2D risk, even in patients with no current abnormal OGTT values.</p><p><strong>Conclusions: </strong>The number and type of abnormal OGTT results strongly predict future T2D. These findings can inform targeted postpartum interventions and predictive tools for early prevention in high-risk women.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181089","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":"Functional Domain Mapping of TPO: Insights from Six Variants in Sudanese Kindreds with Congenital Hypothyroidism.","authors":"Mohammad S Islam, Ruy Andrade Louzada Neto, Jessica Bouviere, Amna E Ahmed, Ernesto Bernal-Mizrachi, Alexandra M Dumitrescu, Samuel Refetoff, Roy E Weiss","doi":"10.1210/clinem/dgaf536","DOIUrl":"https://doi.org/10.1210/clinem/dgaf536","url":null,"abstract":"<p><strong>Context: </strong>Congenital hypothyroidism (CH) is a leading cause of preventable intellectual disability worldwide if left untreated. Thyroid peroxidase (TPO) is a key enzyme that uses hydrogen peroxide from the DUOX/DUOXA system to oxidize iodide for thyroid hormone synthesis.</p><p><strong>Objective: </strong>Identification of the pathogenic TPO variants responsible for CH.</p><p><strong>Methods: </strong>Variants identified by whole-exome sequencing were analyzed using in silico tools and structural modeling for pathogenicity. TPO function was assessed through in vitro studies on intracellular trafficking, enzymatic activity, and interaction with DUOX/DUOXA proteins.</p><p><strong>Results: </strong>Six TPO variants were identified: p.G395D, p.V618M, p.M706V, and p.T725P in Family 1, and p.R648G and p.G771R in Families 2 and 3, respectively. Affected individuals in Family 1 exhibited compound heterozygous or homozygous variants for the four variants. In silico analyses showed incomplete concordance in predicting pathogenicity. In vitro studies confirmed p.G395D as the primary pathogenic variant in Family 1, and p.R648G and p.G771R in Families 2 and 3. Notably, p.V618M, p.M706V, and p.T725P did not impair TPO function, either individually or in combination, suggesting that these regions are not critical for enzymatic activity. Further functional analyses revealed that p.G771R is essential for proper membrane insertion, whereas p.R648G is necessary for enzymatic activity.</p><p><strong>Conclusion: </strong>When multiple TPO variants occur within the same family, a combination of in silico and in vitro analyses can help identify the variant responsible for the phenotype. In silico methods, however, cannot predict the different mechanisms of impairment, such as enzyme activity versus cellular localization, where the protein's topology is essential for normal function.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181063","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":"Genomic Insights into Short Stature in Children Born Small for Gestational Age: A Korean Multicenter Exome Study.","authors":"Yena Lee, Hwal Rim Jeong, Eun Young Kim, Eu-Seon Noh, Hye Young Jin, Eun Byul Kwon, Hye Jin Lee, Sang Hee Park, Young-Jun Seo, Go Hun Seo, Su Jin Kim, Ji-Eun Lee, Nan Young Kim, Sangkyoon Hong, Min Jae Kang, Il Tae Hwang","doi":"10.1210/clinem/dgaf533","DOIUrl":"https://doi.org/10.1210/clinem/dgaf533","url":null,"abstract":"<p><strong>Context: </strong>Most infants born small for gestational age (SGA) experience catch-up growth within two years, while 10‒15% remain short. The cause of this persistent growth failure remains unknown.</p><p><strong>Objective: </strong>To investigate the genetic causes of SGA with short stature (SGA-SS) due to failure of catch-up growth.</p><p><strong>Methods: </strong>A total of 191 children from multicenter SGA-SS cohorts across seven hospitals in South Korea underwent whole-exome sequencing. Identified copy number variants (CNVs) were confirmed via chromosomal microarray analysis.</p><p><strong>Results: </strong>Genetic variants were identified in 34 children (17.8% diagnostic rate). CNVs accounted for 50% (17/34), including six children with 22q11.2 microdeletion syndrome, predominantly exhibiting mild dysmorphic features without severe intellectual disability (ID), developmental delay (DD) or severe anomalies. Single-nucleotide variants (SNVs) were identified in 17 children (17/34, 50%). One had compound heterozygous mutations in SLC26A2, one likely pathogenic mutation, and another of uncertain significance. The remaining children had heterozygous variants, including 5 pathogenic variants in COL2A1, ACAN, SALL1, TAOK1, ANKRD11 and 11 likely pathogenic variants in PIK3R1, PLAG1, SCUBE3, COL9A2 [in two patients], SMAD4, PTPN11 [in two patients], CDKN1C, ACAN, NF1. A novel familial Silver-Russell syndrome case was linked to a CDKN1C mutation. Genetic causes were identified in 14 (58.3%) of 24 patients with ID/DD: 9 with CNVs and 5 with SNVs.</p><p><strong>Conclusion: </strong>SGA-SS has a heterogeneous genetic basis, with CNVs significantly contributing. The variable presentation of 22q11.2 microdeletion syndrome highlights its relevance. A genetic diagnosis is more likely in familial cases or those with ID/DD, supporting the utility of genetic testing.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145153249","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}