Journal of Clinical Endocrinology & Metabolism最新文献

{"title":"Circulating proteomic profiles are associated with type 2 diabetes in Asian populations - a longitudinal study.","authors":"Yujian Liang, Charlie G Y Lim, Scott C Ritchie, Nicolas Bertin, Jin-Fang Chai, Jiali Yao, Yun Li, E Shyong Tai, Rob M van Dam, Xueling Sim","doi":"10.1210/clinem/dgaf045","DOIUrl":"https://doi.org/10.1210/clinem/dgaf045","url":null,"abstract":"<p><strong>Context: </strong>Type 2 diabetes (T2D) is a major global concern, with Asia at its epicenter in recent years. Proteins, products of gene transcription, serve as dynamic biomarkers for pinpointing perturbed pathways in disease development. Previous T2D proteomic association studies primarily focused on European populations.</p><p><strong>Objective: </strong>The aim of this study was to investigate the relationship between plasma proteins and the incidence of T2D in Asian participants.</p><p><strong>Methods: </strong>We examined the association of 4,775 plasma proteins with incident T2D in a Singapore multi-ethnic cohort of 1,659 Asian participants (539 cases and 1,120 controls) using logistic regression. We used two-sample Mendelian randomization and colocalization analysis to evaluate the causal relationship between proteins and T2D.</p><p><strong>Results: </strong>Our analysis revealed 522 proteins that were associated with incident T2D after adjusting for age, sex, and ethnicity, and 17 proteins that remained significantly associated after adjusting for other T2D risk factors such as fasting glucose, waist circumference, and triglycerides. Among the 522 proteins associated with incident T2D, the change in 205 plasma proteins, observed in parallel with the development of T2D at baseline and six-years follow-up, were further associated with incident T2D. The associated proteins showed enrichment in neuron generation, glycosaminoglycan binding, and insulin-like growth factor binding. Two-sample Mendelian randomization analysis suggested three plasma proteins, GSTA1, INHBC, and FGL1, play causal roles in the development of T2D, with colocalization evidence supporting GSTA1 and INHBC.</p><p><strong>Conclusions: </strong>Our findings reveal plasma protein profiles linked to the onset of T2D in Asian populations, offering insights into the biological mechanisms of T2D development.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of the Parametric Thyroid Feedback Quantile Index in Cardiovascular Risk Evaluation Among Euthyroid Koreans.","authors":"Hun Jee Choe, Yun Mi Choi, Yeonjung Ha, Jinseob Kim, Minhyuk Kim, Ho Jin Cha, Jiwoo Lee, Mi Kyung Kwak, Eun-Gyoung Hong","doi":"10.1210/clinem/dgaf046","DOIUrl":"https://doi.org/10.1210/clinem/dgaf046","url":null,"abstract":"<p><strong>Context: </strong>Thyroid hormones play a crucial role in metabolic regulation and maintaining cardiovascular homeostasis. The Parametric Thyroid Feedback Quantile-based Index (PTFQI) assesses central thyroid hormone sensitivity by standardizing the inverse relationship between free thyroxine (T4) and thyroid-stimulating hormone (TSH).</p><p><strong>Objective: </strong>To investigate the relationship between PTFQI and cardiovascular risk in the euthyroid Korean population.</p><p><strong>Methods: </strong>Using data from the 2013-2015 Korea National Health and Nutrition Examination Survey, we included 5,160 euthyroid adults aged 18 to 80 who were not previously diagnosed with cardiovascular or thyroid disease. Cardiovascular risk was evaluated using the PREVENT (Predicting Risk of cardiovascular disease EVENTs) and PCE (Pooled Cohort Equations) scores.</p><p><strong>Results: </strong>Stratification by PTFQI quartiles revealed an inverse relationship between PTFQI and cardiovascular risk. Higher PTFQI quartiles were associated with lower risks of cardiovascular disease (adjusted odds ratio [aOR], -0.55; 95% confidence interval [CI], -0.92 to -0.18), atherosclerotic cardiovascular disease (aOR, -0.31; 95% CI -0.53 to -0.08), heart failure (aOR, -0.26; 95% CI -0.47 to -0.05), coronary heart disease (aOR, -0.15; 95% CI -0.28 to -0.02), and ischemic stroke (aOR, -0.18; 95% CI -0.30 to -0.06). These associations persisted after adjusting for thyroid peroxidase antibodies, iodine intake, alcohol consumption, physical activity, and income level. The PCE score demonstrated a strong correlation with the PREVENT score.</p><p><strong>Conclusion: </strong>The PTFQI inversely correlated with cardiovascular risk among euthyroid Koreans, indicating that reduced central sensitivity to thyroid hormone is associated with lower cardiovascular risk. These results underscore the importance of considering population-specific thyroid function parameters in cardiovascular risk assessment.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Reference Values for Thyroid Volume by Ultrasound in German Children and Adolescents From a Population-Based Study.","authors":"Raphael Hirtz, Roma Thamm, Ronny Kuhnert, Klaus-Peter Liesenkötter, Michael Thamm, Corinna Grasemann","doi":"10.1210/clinem/dgae194","DOIUrl":"10.1210/clinem/dgae194","url":null,"abstract":"<p><strong>Context: </strong>Reliable reference values for thyroid ultrasound measurements are essential to effectively guide individual diagnostics and direct population-level health care measures, such as iodine fortification programs. However, the latest reference values for total thyroid volume (Tvol) provided by the World Health Organization (WHO) in 2004 only apply to the 6- to 12-year-old age group and are limited to countries with a long history of iodine sufficiency, which does not reflect the situation in most European countries, including Germany.</p><p><strong>Objective: </strong>This study aims to derive up-to-date thyroid volume ultrasound reference values in German children and adolescents.</p><p><strong>Methods: </strong>Data from the baseline assessment of a nationwide study in German children and adolescents (KiGGS) conducted between 2003 and 2006 were used to determine sex-specific reference values for Tvol in thyroid-healthy participants aged 6 to 17 years by age and body surface area according to the lambda-mu-sigma method.</p><p><strong>Results: </strong>Data from 5559 participants were available for reference chart construction (2509 girls [45.1%]). On average, the 97th percentile is 33.4% and 28.5% higher than the corresponding WHO reference values for boys and girls, respectively. These findings are consistent with most other studies in German and European children and adolescents at a similar time of investigation. Notably, the sample used for this study was iodine-sufficient according to WHO criteria.</p><p><strong>Conclusion: </strong>The reference values provided by the WHO are overly conservative for this population and could potentially apply to other European countries with a similar history of iodine supply.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e382-e390"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140289483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potassium Iodide Use and Patient Outcomes for Thyroid Storm: An Observational Study.","authors":"Yuichiro Matsuo, Atsushi Miyawaki, Hideaki Watanabe, Hiroki Matsui, Kiyohide Fushimi, Hideo Yasunaga","doi":"10.1210/clinem/dgae187","DOIUrl":"10.1210/clinem/dgae187","url":null,"abstract":"<p><strong>Context: </strong>Iodine, combined with antithyroid drugs, is recommended as an initial pharmacologic treatment for thyroid storm according to some clinical guidelines. However, the clinical efficacy of iodine in managing thyroid storm remains unexplored.</p><p><strong>Objective: </strong>This study aimed to determine whether early potassium iodide (KI) use is associated with mortality in patients hospitalized for thyroid storm.</p><p><strong>Methods: </strong>Using the Japanese Diagnosis Procedure Combination database, we identified patients hospitalized with thyroid storm between July 2010 and March 2022. We compared in-hospital mortality, length of stay, and total hospitalization costs between patients who received KI within 2 days of admission (KI group) vs those who did not (non-KI group). Prespecified subgroup analyses were performed based on the presence of the diagnosis of Graves' disease.</p><p><strong>Results: </strong>Among 3188 eligible patients, 2350 received KI within 2 days of admission. The crude in-hospital mortality was 6.1% (143/2350) in the KI group and 7.8% (65/838) in the non-KI group. After adjusting for potential confounders, KI use was not significantly associated with in-hospital mortality (odds ratio [OR] for KI use, 0.91; 95% CI, 0.62-1.34). In patients with the diagnosis of Graves' disease, in-hospital mortality was lower in the KI group than in the non-KI group (OR, 0.46; 95% CI, 0.25-0.88). No significant difference in in-hospital mortality was observed in patients without the diagnosis of Graves' disease (OR, 1.11; 95% CI, 0.67-1.85). Length of stay was shorter (subdistribution hazard ratio, 1.15; 95% CI, 1.05-1.27), and total hospitalization costs were lower (OR, 0.92; 95% CI, 0.85-1.00) in the KI group compared with the non-KI group.</p><p><strong>Conclusion: </strong>Our findings suggest that KI may reduce in-hospital mortality among patients hospitalized for thyroid storm with Graves' disease.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e310-e320"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140307679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Manifestations and Treatment Challenges in Infants and Children With Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency.","authors":"Natalie J Nokoff, Cindy Buchanan, Jennifer M Barker","doi":"10.1210/clinem/dgae563","DOIUrl":"10.1210/clinem/dgae563","url":null,"abstract":"<p><p>The most common form of congenital adrenal hyperplasia (CAH) is secondary to 21-hydroxylase deficiency (21OHD). This review will summarize the clinical manifestations, recommended treatments, monitoring, clinical challenges and management strategy, and treatment challenges in special situations for infants and children with classic CAH due to 21OHD. Specifically, we review newborn screening and the initial diagnosis, glucocorticoid and mineralocorticoid treatment, and recommended monitoring, including anthropometric and laboratory measures. Children with CAH may have premature adrenarche, precocious puberty, and early growth plate closure and have an increased risk of hypertension and overweight/obesity. Many 46,XX individuals will also have genital differences, which may include clitoromegaly and/or a urogenital sinus. We review psychosocial and surgical considerations, including suggestions on how to talk with children, family, and caregivers about bodily difference. These suggestions may be used by families and/or providers caring for individuals with CAH.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":"110 Supplement_1","pages":"S13-S24"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Proteomics of Diabetic Kidney Disease Among Asians With Younger-Onset Type 2 Diabetes.","authors":"Resham Lal Gurung, Huili Zheng, Hiromi Wai Ling Koh, Yiamunaa M, Jian-Jun Liu, Sylvia Liu, Clara Chan, Keven Ang, Clara Si Hua Tan, Radoslaw Mikolaj Sobota, Tavintharan Subramaniam, Chee Fang Sum, Su Chi Lim","doi":"10.1210/clinem/dgae266","DOIUrl":"10.1210/clinem/dgae266","url":null,"abstract":"<p><strong>Context: </strong>Patients with younger onset of type 2 diabetes (YT2D) have increased risk for kidney failure compared to those with late onset. However, the mechanism of diabetic kidney disease (DKD) progression in this high-risk group is poorly understood.</p><p><strong>Objective: </strong>This work aimed to identify novel biomarkers and potential causal proteins associated with DKD progression in patients with YT2D.</p><p><strong>Methods: </strong>Among YT2D (T2D onset age <40 years), 144 DKD progressors (cases) were matched for T2D onset age, sex, and ethnicity with 292 nonprogressors (controls) and divided into discovery and validation sets. DKD progression was defined as decline of estimated glomerular filtration rate (eGFR) of 3 mL/min/1.73 m2 or greater or 40% decline in eGFR from baseline. A total of 1472 plasma proteins were measured through a multiplex immunoassay that uses a proximity extension assay technology. Multivariable logistic regression was used to identify proteins associated with DKD progression. Mendelian randomization (MR) was used to evaluate causal relationship between plasma proteins and DKD progression.</p><p><strong>Results: </strong>Forty-two plasma proteins were associated with DKD progression, independent of traditional cardiorenal risk factors, baseline eGFR, and urine albumin-to-creatinine ratio. The proteins identified were related to inflammatory and remodeling biological processes. Our findings suggest angiogenin as one of the top signals (odds ratio = 5.29; 95% CI, 2.39-11.73; P = 4.03 × 10-5). Furthermore, genetically determined plasma angiogenin level was associated with increased odds of DKD progression.</p><p><strong>Conclusion: </strong>Large-scale proteomic analysis identified novel proteomic biomarkers for DKD progression in YT2D. Genetic evidence suggest a causal role of plasma angiogenin in DKD progression.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e239-e248"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140860025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Overweight on Risk of Thyroid Nodules in Children and Adolescents: The Fukushima Health Management Survey.","authors":"Tetsuya Ohira, Masanori Nagao, Fumikazu Hayashi, Hiroki Shimura, Satoru Suzuki, Seiji Yasumura, Hideto Takahashi, Satoshi Suzuki, Manabu Iwadate, Mitsuaki Hosoya, Akira Sakai, Tetsuo Ishikawa, Fumihiko Furuya, Shinichi Suzuki, Susumu Yokoya, Hitoshi Ohto, Kenji Kamiya","doi":"10.1210/clinem/dgae161","DOIUrl":"10.1210/clinem/dgae161","url":null,"abstract":"<p><strong>Context: </strong>Examining how overweight/obesity impacts thyroid nodule development in children and adolescents by sex and age allows speculation on the mechanism.</p><p><strong>Objective: </strong>We examined whether overweight/obesity in children and adolescents is associated with thyroid nodule development by sex and age.</p><p><strong>Methods: </strong>Approximately 300 000 participants who underwent thyroid ultrasonography in the Fukushima Health Management Survey after a nuclear accident were enrolled. Those without nodules in the initial 2 examinations (1-3 and 4-5 years postaccident) were prospectively assessed for nodule development in the third examination (6-7 years postaccident) relative to baseline overweight status, with an average follow-up of 4.2 years. This was a population-based prospective cohort study. The first and second thyroid examinations involved 299 939 and 237 691 participants, respectively, excluding those with thyroid nodules. After the third examination, 184 519 participants were finalized for analysis. Multivariable adjusted odds ratios of new detected thyroid nodules for overweight participants were compared with normal-weight participants.</p><p><strong>Results: </strong>New thyroid nodules were detected in 660 participants. Being overweight was positively associated with thyroid nodules. The adjusted odds ratio (95% CI) of thyroid nodules for overweight participants compared with other participants was 1.27 (1.04-1.57). Additionally, the multivariable adjusted odds ratios for overweight males and females were 1.21 and 1.32, respectively, and those for different age groups (0-9, 10-14, and 15-19 years) ranged from 1.17 to 1.75.</p><p><strong>Conclusion: </strong>Being overweight was associated with thyroid nodules in children and adolescents, mostly adolescent females, regardless of their proximity to the nuclear power plant.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e478-e486"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140112132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced Chronic Inflammation and Increased Branched-Chain Amino Acids in Adrenal Disorders: A Cross-Sectional Study.","authors":"Annop A Kittithaworn, Prerna Dogra, Jasmine Saini, Eke G Gruppen, Elizabeth Atkinson, Sara Achenbach, Kai Yu, Karthik Thangamuthu, Margery A Connelly, Robin P F Dullaart, Irina Bancos","doi":"10.1210/clinem/dgae204","DOIUrl":"10.1210/clinem/dgae204","url":null,"abstract":"<p><strong>Context: </strong>Patients with adrenal hormone excess demonstrate increased cardiovascular (CV) risk and mortality.</p><p><strong>Objective: </strong>We aimed to determine the effect of adrenal disorders on the inflammation marker glycoprotein acetylation (GlycA), total branched-chain amino acids (BCAAs), ketone bodies, and the gut microbiome-derived metabolites trimethylamine N-oxide (TMAO) and betaine.</p><p><strong>Methods: </strong>We conducted a single-center cross-sectional study of patients with nonfunctioning adenomas (NFAs), mild autonomous cortisol secretion (MACS), primary aldosteronism (PA), Cushing syndrome (CS), pheochromocytoma/paragangliomas (PPGLs), other benign or malignant adrenal masses, and adrenocortical carcinoma (ACC) between January 2015 and July 2022 (n = 802). Referent individuals included participants in the PREVEND (Prevention of Renal and Vascular End-Stage Disease) study (n = 5241). GlycA, BCAAs, ketone bodies, TMAO, and betaine were measured using nuclear magnetic resonance spectroscopy. Multivariable logistic analyses were adjusted for age, sex, body mass index, smoking, hypertension, diabetes mellitus, and statin therapy.</p><p><strong>Results: </strong>In age- and sex-adjusted comparison to referent individuals, increased GlycA was noted in all patient categories, increased BCAAs in NFA, MACS, CS, PA, and ACC, increased TMAO in patients with other malignant adrenal masses, increased betaine in NFA and MACS, and increased ketone bodies in NFA, CS, and ACC. Essentially similar findings were observed in fully adjusted analysis and after exclusion of participants with diabetes and CV disease.</p><p><strong>Conclusion: </strong>Patients with functioning and nonfunctioning adrenal masses demonstrated increased GlycA and BCAAs, biomarkers associated with adverse cardiometabolic disorders and mortality. Patients with NFA demonstrated an adverse metabolic profile similar to patients with MACS and CS.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e330-e338"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140307678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adrenal Suppression From Vamorolone and Prednisone in Duchenne Muscular Dystrophy: Results From the Phase 2b Clinical Trial.","authors":"Alexandra Ahmet, Rebecca Tobin, Utkarsh J Dang, Raoul Rooman, Michela Guglieri, Paula R Clemens, Eric P Hoffman, Leanne M Ward","doi":"10.1210/clinem/dgae521","DOIUrl":"10.1210/clinem/dgae521","url":null,"abstract":"<p><strong>Context: </strong>Vamorolone, a novel \"dissociative\" steroid, demonstrated similar efficacy in muscle function relative to prednisone 0.75 mg/kg/day but improved linear growth and bone turnover markers in a randomized trial of pediatric Duchenne muscular dystrophy (DMD).</p><p><strong>Objectives: </strong>To determine the frequency of adrenal suppression (AS) induced by vamorolone and prednisone in pediatric DMD and to assess cortisol thresholds using a monoclonal antibody immunoassay.</p><p><strong>Methods: </strong>Post hoc analysis of cortisol levels was performed on data from a randomized, double-blind, placebo- and prednisone-controlled 24-week trial of vamorolone with a 24-week crossover extension. Morning and ACTH-stimulated cortisol levels were measured using the Elecsys II immunoassay, with AS defined as a stimulated cortisol of <500 nmol/L (\"historical threshold\") and <400 nmol/L (\"revised threshold\").</p><p><strong>Results: </strong>Mean age at enrolment was 5.41 ± 0.86 years (n = 118). At week 24, the proportion of participants with AS using the historical and revised cortisol thresholds, respectively, were as follows: prednisone 0.75 mg/kg/day = 100% (25/25) and 92.0% (23/25); vamorolone 6 mg/kg/day = 95.2% (20/21) and 90.5% (19/21); vamorolone 2 mg/kg/day = 84.2% (16/19) and 47.5% (9/19); and placebo = 20.0% (4/20) and 0% (0/20). Morning and peak ACTH-stimulated cortisol were strongly correlated in steroid-treated boys (Spearman correlation week 48 = 0.83).</p><p><strong>Conclusion: </strong>AS after vamorolone and prednisone was frequent and vamorolone-associated AS appeared dose-dependent. A lower stimulated cortisol threshold may be appropriate when using a monoclonal assay. We recommend hydrocortisone for glucocorticoid stress dosing in patients receiving vamorolone.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"334-344"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141890698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CASRdb: A Publicly Accessible Comprehensive Database for Disease-Associated Calcium-Sensing Receptor Variants.","authors":"Nipith Charoenngam, Phuuwadith Wattanachayakul, Michael Mannstadt","doi":"10.1210/clinem/dgae769","DOIUrl":"10.1210/clinem/dgae769","url":null,"abstract":"<p><strong>Context: </strong>Genetic testing of the calcium-sensing receptor (CASR) gene is crucial for confirming diagnoses of familial hypocalciuric hypercalcemia type I (FHH1) and autosomal dominant hypocalcemia type I (ADH1). Therefore, we created a publicly accessible comprehensive database of the disease-causing variants of the CASR gene.</p><p><strong>Evidence acquisition: </strong>We used 2 sources for variant reports: (1) we conducted a systematic review in the Embase and PubMed databases from inception to March 2023, using search strategies associated with CASR. We identified all articles reporting CASR variants associated with disorders of calcium metabolism. (2) Additionally, data associated with pathogenic (P) or likely pathogenic (LP) variants in the ClinVar and LOVD databases were retrieved. Benign or likely benign variants were excluded. Variants of uncertain significance (VUS) were included only if they were reported in the literature. We generated a library of CASR variants associated with phenotypes, which has been made available on a website.</p><p><strong>Evidence synthesis: </strong>We identified a total of 498 variants, of which 121 (24.3%) were associated with ADH1 and 377 (75.7%) with FHH1. Most included variants were identified from the literature (117 activating and 352 inactivating variants), and the majority of these were not documented in ClinVar/LOVD (73/117, 62.4% activating variants; 207/352, 58.8% inactivating variants).</p><p><strong>Conclusion: </strong>We developed CASRdb, a database that compiles information on all CASR variants associated with disorders of calcium metabolism from existing literature and genomic databases. Our database stands out due to the substantially higher number of disease-associated variants it contains, highlighting its comprehensive nature. The website is available at http://casrdb.mgh.harvard.edu.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"297-302"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}