The latest medical research on Endocrinology
The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about endocrinology gathered by our medical AI research bot.
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Request AccessTestosterone therapy does not affect coagulation in male hypogonadism: a longitudinal study based on thrombin generation.
Clinical EndocrinologyTestosterone therapy has been variably associated with increased thrombotic risk but investigations of global coagulation in this setting are lacking.
To compare global coagulation of hypogonadal men before (T0) and 6 months after (T1) starting testosterone replacement therapy (TRT), and healthy controls.
The following TGA parameters were recorded: lag-time; thrombin-peak concentration; time-to-reach the peak, velocity index and endogenous thrombin potential (ETP), the latter representing the total amount of thrombin generated under the driving forces of procoagulants opposed by the anticoagulants. PC, antithrombin, factor (F)VIII, and fibrinogen were assessed.
No changes of TGA parameters were observed between T0 and T1. Hypogonadal men displayed significantly higher ETP, fibrinogen, and significantly lower antithrombin levels both at T0 and T1 compared to controls. Thrombin-peak of hypogonadal men was significantly higher than controls at T0 but not at T1. ETP and antithrombin were correlated with testosterone levels.
Hypogonadal men display a procoagulant imbalance detected by increased thrombin generation. Short-term TRT does not worsen global coagulation, suggesting that the treatment can be safely prescribed to men diagnosed with hypogonadism.
Moderate associations between the use of levonorgestrel-releasing intrauterine device and metabolomics profile.
Clinical EndocrinologyUse of levonorgestrel-releasing intrauterine device (LNG-IUD) has become common irrespective of age and parity. To date, only a few studies have examined its possible metabolic changes and large-scale biomarker profiles in detail and in a longitudinal design.
To apply the metabolomics technique to examine the metabolic profile associated with the use of LNG-IUD both in a cross-sectional and in a longitudinal design.
The study consists of cross-sectional and longitudinal analyses of a population-based survey (Health 2000) and its 11-year follow-up (Health 2011). All participants aged 18-49 years with available information on hormonal contraceptive use and metabolomics data (n=1767) were included. Altogether 212 metabolic measures in LNG-IUD users (n=341) were compared to those in non-users of hormonal contraception (n=1426) via multivariable linear regression models. Participants with complete longitudinal information (n=240) were divided into continuers, stoppers, starters, and never-user groups, and 11-year changes in levels of each metabolite were compared.
After adjustment for covariates, levels of 102 metabolites differed in LNG-IUD current users compared to non-users of hormonal contraception (median difference in biomarker concentration: -0.12 SD): lower levels of fatty acids concentrations and ratios, cholesterol, triglycerides and other lipids, as well as particle concentration, cholesterol, total lipids and phospholipids in lipoproteins. The 11-year metabolic changes did not differ in relation to changes in LNG-IUD use.
The use of LNG-IUD was associated with several moderate metabolic changes, mostly suggestive of a reduced arterial cardiometabolic risk. Changes in LNG-IUD use were not related to long-term metabolic changes.
Exome Sequencing has a high diagnostic rate in sporadic congenital hypopituitarism and reveals novel candidate genes.
Clinical EndocrinologyThe pituitary gland is key for childhood growth, puberty, and metabolism. Pituitary dysfunction is associated with a spectrum of phenotypes, from mild to severe. Congenital Hypopituitarism (CH) is the most commonly reported pediatric endocrine dysfunction with an incidence of 1:4000, yet low rates of genetic diagnosis have been reported.
We aimed to unveil the genetic etiology of CH in a large cohort of patients from Argentina.
We performed whole exome sequencing of 137 unrelated cases of CH, the largest cohort examined with this method to date.
Of the 137 cases, 19.1% and 16% carried pathogenic or likely pathogenic variants in known and new genes, respectively, while 28.2% carried variants of uncertain significance. This high yield was achieved through the integration of broad gene panels (genes described in animal models and/or other disorders), an unbiased candidate gene screen with a new bioinformatics pipeline (including genes high loss of function intolerance), and analysis of copy number variants. Three novel findings emerged. First, the most prevalent affected gene encodes the cell adhesion factor ROBO1. Affected children had a spectrum of phenotypes, consistent with a role beyond pituitary stalk interruption syndrome. Second, we found that CHD7 mutations also produce a phenotypic spectrum, not always associated with full CHARGE syndrome. Third, we add new evidence of pathogenicity in the genes PIBF1 and TBC1D32, and report 13 novel candidate genes associated with CH (e.g. PTPN6, ARID5B).
Overall, these results provide an unprecedented insight into the diverse genetic etiology of hypopituitarism.
Beyond Stages: Predicting Individual Time Dependent Risk for Type 1 Diabetes.
Clinical EndocrinologyEssentially all individuals with multiple autoantibodies will develop clinical type 1 diabetes. Multiple AABs and normal glucose tolerance define Stage 1 diabetes; abnormal glucose tolerance defines Stage 2. However, the rate of progression within these stages is heterogeneous, necessitating personalized risk calculators to improve clinical implementation.
We developed 3 models using TrialNet's Pathway to Prevention data to accommodate the reality that not all risk variables are clinically available. The Small model included AAB status, fasting glucose, HbA1c and age, while the Medium and Large models added predictors of disease progression measured via oral glucose tolerance testing.
All models markedly improved granularity regarding personalized risk missing from current categories of stages of T1D. Model derived risk calculations are consistent with the expected reduction of risk with increasing age and increase in risk with higher glucose and lower insulin secretion, illustrating the suitability of the models. Adding glucose and insulin secretion data altered model predicted probabilities within Stages. In those with high 2-hour glucose, a high C-peptide markedly decreased predicted risk; lower C-peptide obviated the age-dependent risk of 2-hour glucose alone, providing a more nuanced estimate of rate of disease progression within Stage 2.
While essentially all those with multiple AABs will develop type 1 diabetes, the rate of progression is heterogeneous and not explained by any individual single risk variable. The model-based probabilities developed here provide an adaptable personalized risk calculator to better inform decisions about how and when to monitor disease progression in clinical practice.
Association between visceral obesity index and diabetes: a systematic review and meta-analysis.
Clinical EndocrinologyThe correlation between visceral obesity index (VAI) and diabetes and accuracy of early prediction of diabetes are still controversial.
This study aims to review the relationship between high level of VAI and diabetes, and early predictive value of diabetes.
We extracted odds ratio (OR) between VAI and diabetes management after controlling for mixed factors, and the sensitivity, specificity and diagnostic four grid table for early prediction of diabetes.
53 studies, comprising 595,946 participants were included. The findings of the meta-analysis elucidated that in cohort studies, a high VAI significantly increased the risk of diabetes mellitus in males (OR = 2.83 (95% CI: 2.30-3.49)) and females (OR = 3.32 (95% CI: 2.48-4.45)). The ROC, sensitivity, and specificity of VAI for early prediction of diabetes in males were 0.64 (95% CI: 0.62-0.66), 0.57 (95% CI: 0.53-0.61), and 0.65 (95% CI: 0.61-0.69), respectively, and 0.67 (95% CI: 0.65-0.69), 0.66 (95% CI: 0.60-0.71), and 0.61 (95% CI: 0.57-0.66) in females, respectively.
VAI is an independent predictor of the risk of diabetes, yet its predictive accuracy remains limited. In future studies, determine whether VAI can be utilized in conjunction with other related indicators to early predict the risk of diabetes, to enhance the accuracy of prediction of the risk of diabetes.
CAHQL: A patient reported outcome instrument to assess health-related quality of life in congenital adrenal hyperplasia.
Clinical EndocrinologyMeasuring health-related quality of life (HRQoL) is a crucial aspect of evaluating health care outcomes. Patients with congenital adrenal hyperplasia (CAH) often self-report deficiencies in HRQoL.
The aim of our study was to develop a disease-specific patient reported outcome (PRO) instrument to evaluate the HRQoL of patients >16 years old with classic congenital adrenal hyperplasia (CAH).
Following the FDA guidelines for developing PRO instruments, we developed a conceptual framework for the instrument. A preliminary instrument was created after interviewing a representative sample of 12 patients with CAH between 16 to 68 years old and 3 parents, and obtaining expert feedback from 4 endocrinologists. The instrument was edited after cognitive interviews with 6 patients. Internal consistency of the instrument was evaluated using Cronbach's alpha. Validity was assessed by comparing the scores of our instrument with scores from widely used validated instruments for HRQoL and PRO not specific to CAH.
Sixty-nine patients 16 to 75 years old participated in validating our preliminary instrument. The final questionnaire consists of 44 questions within 7 domains: General Health, Adrenal Insufficiency, Glucocorticoid Excess, Physical Functioning, Mental Health and Cognition, Social Functioning, and Sexual Functioning, with acceptable internal consistency (Chronbach's alpha≥0.6) and validity (r = -0.350 to 0.866).
CAHQL is the first validated PRO instrument to capture disease specific HRQoL outcomes in CAH. In addition to its anticipated use in the clinical setting, the instrument could be used to assess the efficacy of novel treatments in development.
Pancreatic neuroendocrine tumors in French VHL mutation carriers: a multicentric retrospective study.
Clinical EndocrinologyVon Hippel-Lindau disease (VHL) is a rare autosomal dominant hereditary cancer-predisposition syndrome caused by germline pathogenic variants (PV) in VHL gene. It is associated with a high penetrance of benign and malignant vascular tumors in multiples organs, including pancreatic neuroendocrine tumors (PanNETs), whose long-term natural history is ill-known.
Patients with both documented germline PV in VHL gene and PanNETs included in the French PREDIR database between 1995 and 2022 were included. Primary endpoint was the proportion of patients with PanNET-related metastases and secondary endpoint was overall survival (OS). Genotype/phenotype correlations were studied.
We included 121 patients with 259 PanNETs. Median age at diagnosis was 38 years. Median follow-up was 89.5 months. PanNET surgical resection was performed in 51 patients. Overall, 29 patients (24%) had metastases (5 synchronous, 10 metachronous), with a higher risk in case of larger PanNET size (p=0.0089; best threshold 28 mm) and grade 2 PanNET (p=0.048), and a pejorative prognostic impact (p=0.043). Patients with PV in VHL exon 1 had larger PanNETs (p=0.018), more often metastatic disease (48% vs 11.5%; p < 0.001) and a trend toward shorter OS (p=0.16).
The risk of metastases associated to VHL-related PanNETs remains low (24%) but increases with tumor size >28 mm, higher grade and in case of PV located VHL exon 1. These data might help improving the management of these patients, who should be referred to an expert center.
Risk of gestational diabetes in women with PCOS based on body mass index: The Japan Environment and Children's Study.
Clinical EndocrinologyWomen with polycystic ovary syndrome (PCOS), which is the most common endocrine disorder in women of reproductive age, have a potentially increased risk of gestational diabetes mellitus (GDM).
To examine the impact of PCOS on GDM based on maternal body mass index (BMI) using data from a large birth cohort study in Japan.
Participants were categorized according to their pre-pregnancy BMIs: G1 (<18.5 kg/m2), G2 (18.5-19.99 kg/m2), G3 (20.0-22.99 kg/m2), G4 (23.0-24.99 kg/m2), and G5 (≥25.0 kg/m2). The impact of PCOS on early (Ed) and late-onset (Ld) GDM for each group was estimated using a multiple logistic regression model.
We included 92774 participants, comprising 2012 PCOS(+) cases. GDM occurrence was higher in women with PCOS (p<0.001). PCOS had no effect on GDM in G1, G2, and G3. In G4, PCOS increased the risk of Ed GDM (adjusted odds ratio [aOR]: 3.27, 95% confidence interval [CI]: 1.29-8.29). In G5, PCOS increased the risk of both Ed (aOR: 2.48, 95% CI: 1.53-4.02) and Ld GDM (aOR: 1.94, 95% CI: 1.23-3.07).
The impact of PCOS on GDM occurrence depended on the pre-pregnancy BMIs, which may facilitate personalized preconception counseling among women with PCOS.
Associations of Plasma and Fecal Metabolites with Body Mass Index and Body Fat Distribution in Children.
Clinical EndocrinologyChildhood obesity continues to be a critical public health concern with far-reaching implications for the well-being.
This study aimed to investigate the association between metabolites in plasma and feces and indicators including body mass index (BMI), BMI for age Z score (BMIZ), and body fat distribution among children aged 6-9 years in China.
This cross-sectional study enrolled 424 healthy children, including 186 girls and 238 boys. Dual-energy X-ray absorptiometry (DXA) was used to determine the body fat content and regional fat distribution. Plasma and fecal metabolites were analyzed using targeted metabolomic technologies.
A total of 200 plasma metabolites and 212 fecal metabolites were accurately quantified via ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). By using Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) and random forest model, we discovered that 9 plasma metabolites and 11 fecal metabolites were associated with different weight statuses. After adjusting for potential covariates and false discovery rate (FDR) correction, multiple linear regression analyses revealed that plasma metabolites (fumaric acid, glycine, l-glutamine, methylmalonic acid, and succinic acid) and fecal metabolites (protocatechuic acid) were negatively associated (β: -1.373--0.016, pFDR: <0.001-0.031; β: -1.008--0.071, pFDR: 0.005-0.033), while plasma metabolites (isovaleric acid, isovalerylcarnitine, l-glutamic acid, and pyroglutamic acid) and fecal metabolites (3-aminoisobutanoic acid, butyric acid, N-acetylneuraminic acid, octanoylcarnitine, oleoylcarnitine, palmitoylcarnitine, stearoylcarnitine, taurochenodesoxycholic acid, and taurodeoxycholic acid) exhibited positive associations with BMI, BMIZ, and body fat distribution (β: 0.023-2.396, pFDR: <0.001; β: 0.014-1.736, pFDR: <0.001-0.049).
Plasma and fecal metabolites such as glutamine may serve as a potential therapeutic target for the development of obesity.
N-Terminal Pro-B-Type Natriuretic Peptide and Risk for Diabetes Mellitus and Metabolic Syndrome.
Clinical EndocrinologyNatriuretic peptide concentrations are inversely associated with risk of diabetes mellitus and may be protective from metabolic dysfunction.
We studied associations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) with incident diabetes, metabolic syndrome (MetS), and MetS components.
Incident diabetes, defined as fasting glucose ≥126 mg/dL, random glucose ≥200 mg/dL, or use of insulin or hypoglycemic drugs at follow-up but not baseline. Incident MetS, in participants with ≥3 harmonized criteria at follow-up and <3 at baseline.
310 participants (2,364 at risk) developed diabetes and 361 (2,059 at risk) developed MetS over mean 9.4 years follow-up. NT-proBNP was inversely associated with odds of incident diabetes (fully-adjusted OR per-SD higher log NT-proBNP 0.80, 95% CI 0.69-0.93) and MetS in the highest vs. lowest quartile only (fully-adjusted OR 0.59, 95% CI 0.37-0.92); the linear association with incident MetS was not statistically significant. NT-proBNP was inversely associated with incident dysglycemia in all models (fully-adjusted OR per-SD log NT-proBNP 0.65, 95% CI 0.53-0.79), but not with other MetS components. Effect modification by sex, race, age, or BMI was not observed.
NT-proBNP was inversely associated with odds of diabetes, MetS, and the MetS dysglycemia component. The metabolic implications of B-type natriuretic peptides appear important for glycemic homeostasis.
Can incorporating molecular testing improve the accuracy of newborn screening for congenital adrenal hyperplasia?
Clinical EndocrinologySingle-tier newborn screening (NBS) for CAH using 17-hydroxyprogesterone (17OHP) measured by fluoroimmunoassay (FIA) in samples collected at 24-48 hours produces a high false-positive rate (FPR). 2nd tier steroid testing can reduce the FPR and has been widely implemented. We investigated the accuracy of an alternative multi-tier CAH NBS protocol that incorporates molecular testing of the CYP21A2 gene and reduces the 1st tier 17OHP cutoff to minimize missed cases.
Created a Minnesota-specific CYP21A2 pathogenic variants panel; develop a rapid, high-throughput multiplex, allele-specific-primer-extension assay; perform 1-year retrospective analysis of Minnesota NBS results comparing metrics between a conventional steroid-based two-tier protocol and a molecular-based multi-tier NBS protocol, applied post-hoc.
CYP21A2 gene sequencing of 103 Minnesota families resulted in a Minnesota-specific panel of 21 pathogenic variants. Centers for Disease Control and Prevention (CDC) created a molecular assay with 100% accuracy and reproducibility. Two-tier steroid-based screening of 68,659 live births during 2015 resulted in 2 false negatives (FNs), 91 FPs, and 1 true positive (TP). A three-tier protocol with a lower 1st-tier steroid cutoff, 2nd-tier 21-variant CYP21A2 panel and 3rd-tier CYP21A2 sequencing would have resulted in 0 FNs, 52 FPs and 3 TPs.
Incorporation of molecular testing could improve the accuracy of CAH NBS, although some distinct challenges of molecular testing may need to be considered before implementation by NBS programs.
Metabolic Syndrome and the Risk of Kidney Stones: a Large-scale Cohort Study from 487,860 UK Biobank participants.
Clinical EndocrinologyWhile some studies have suggested an association between metabolic syndrome and kidney stones, the quality and level of evidence in these studies vary. Whether some individual characteristics and clustering of metabolic syndrome traits increase the risk of kidney stones has not been examined in a large-scale prospective cohort.
We conducted a retrospective analysis of data from a prospective cohort of 487,860 UK Biobank participants who were free from kidney stones at baseline. The presence of metabolic syndrome was based on five criteria: abdominal obesity, high triglyceride levels, low high-density lipoprotein (HDL) cholesterol levels, high blood pressure (HBP), and type 2 diabetes mellitus (T2DM). Cox proportional hazards regression models were used to evaluate the association between metabolic syndrome and risk of kidney stones.
After an average follow-up period of 12.6 years, a total of 5,213 of the 487,860 participants included in the UK Biobank study developed kidney stones. The partial traits of metabolic syndrome, including waist circumference (HR: 1.15, 95% CI: 1.10-1.20), HDL cholesterol (0.66, 0.55-0.79), HBP (1.11, 1.03-1.19) and T2DM (1.14, 1.04-1.21), were independently associated with the occurrence of kidney stones. The clustering of metabolic syndrome is significantly associated with kidney stone formation, and as the number of metabolic syndrome traits increases, the risk of kidney stones gradually increases.
Metabolic syndrome is a significant and independent risk factor for the development of kidney stones. This association suggests that kidney stones may represent a systemic disorder influenced by the interplay of various metabolic risk factors.
