Journal of Clinical and Translational Endocrinology最新文献

{"title":"Body weight and waist circumference are differentially associated with the response to L-thyroxine treatment in primary hypothyroidism","authors":"Anders Funkquist ,&nbsp;Stefan Sjöberg ,&nbsp;Henrik Zetterberg ,&nbsp;Stefan Bergman ,&nbsp;Josefine Rosvall ,&nbsp;Per Bjellerup ,&nbsp;Johan Svensson","doi":"10.1016/j.jcte.2026.100440","DOIUrl":"10.1016/j.jcte.2026.100440","url":null,"abstract":"<div><h3>Background</h3><div>Thyroid hormones (TH) and neurotransmitter orexin (ORX) are implicated in the regulation of metabolism. Abdominal weight gain is common in primary hypothyroidism (PH).</div></div><div><h3>Methods</h3><div>Our aim was to investigate whether TH affected peripheral weight gain, waist circumference (WC) and low-density lipoprotein cholesterol (LDL-C), before and 6 months after L-thyroxine substitution therapy. A secondary aim was to investigate the role of ORX.</div></div><div><h3>Results</h3><div>Weight gain was positively correlated with improvement in QoL (r = 0.72, p = 0.003) and with CSF ORX levels in the 15 included patients (r = 0.78, p = 0.001). Increased WC, which was not associated with QoL changes, correlated negatively with free thyroxine levels, after 6 months of treatment, in both CSF (r = -0.71, p = 0.003) and serum (r = -0.64, p = 0.0097). Increased LDL-C correlated negatively with CSF free thyroxine levels after 6 months of treatment (r = -0.74, p = 0.003).</div></div><div><h3>Conclusion</h3><div>The marked correlations with CSF levels of thyroxine and ORX suggest that hypothalamic mechanisms participate in the regulation of WC and weight during L-thyroxine therapy, highlighting the need for individualized treatment of the metabolic disturbances seen in PH.</div></div><div><h3>Short communication</h3><div>Through evaluating the dynamics of body weight and waist circumference during the initial treatment of primary hypothyroidism, a positive correlation was found between orexin levels in CSF and the change in body weight. Furthermore, negative correlations were found between CSF free thyroxine levels and the changes in waist circumference and serum LDL-C levels. These findings emphasize the importance of finding future individualized treatment strategies in primary hypothyroidism, particularly regarding metabolic disturbances.</div></div>","PeriodicalId":46328,"journal":{"name":"Journal of Clinical and Translational Endocrinology","volume":"44 ","pages":"Article 100440"},"PeriodicalIF":3.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147797258","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":"Somatic genomic profiling reveals clinically relevant heterogeneity in RAS-mutant sporadic medullary thyroid carcinoma","authors":"Edoardo Ruggeri ,&nbsp;Simona Censi ,&nbsp;Loris Bertazza ,&nbsp;Andrea Benetti ,&nbsp;Fausto Cortese ,&nbsp;Ilaria Piva ,&nbsp;Cristina Clausi ,&nbsp;Vincenzo Marotta ,&nbsp;Francesca Galuppini ,&nbsp;Alessandra Giannella ,&nbsp;Gianmaria Pennelli ,&nbsp;Maurizio Iacobone ,&nbsp;Mario Vitale ,&nbsp;Giulio Ceolotto ,&nbsp;Susi Barollo ,&nbsp;Caterina Mian","doi":"10.1016/j.jcte.2026.100442","DOIUrl":"10.1016/j.jcte.2026.100442","url":null,"abstract":"<div><h3>Objective</h3><div>Sporadic medullary thyroid carcinoma (sMTC) is predominantly driven by somatic <em>RET</em> or <em>RAS</em> mutations, although the molecular basis of disease heterogeneity remains incompletely understood. Our study aims to characterize molecular heterogeneity in sMTC in order to identify pathways that may improve patient’s stratification and support more personalized clinical management strategies.</div></div><div><h3>Methods</h3><div>Deep targeted next-generation sequencing of 31 neuroendocrine- and cancer-related genes was performed on tumor samples from 94 patients with sMTC to characterize the somatic mutational landscape beyond canonical drivers.</div></div><div><h3>Results</h3><div><em>RET</em> and <em>RAS</em> mutations were detected in 53% and 29% of cases, respectively, while 18% of tumors lacked both alterations. Variant allele frequency (VAF) analysis demonstrated a significant positive correlation between driver mutation burden and tumor size in both <em>RET</em>- and <em>RAS</em>-mutant tumors, supporting the clonal contribution of these alterations. Additional oncogenic variants were identified in genes involved in DNA damage response and epigenetic regulation, including <em>ATM</em> and <em>KMT2A</em>. Notably, within the <em>RAS</em>-mutant subgroup, the presence of co-occurring oncogenic alterations was associated with more advanced T status (T3-T4, <em>p</em> = 0.0181) at diagnosis and lower biochemical cure rates (<em>p</em> = 0.02) at the follow-up compared with tumors harboring isolated <em>RAS</em> mutations, supporting the clinical relevance of extended genomic profiling in <em>RAS</em>-mutant sMTC.</div></div><div><h3>Conclusions</h3><div>Overall, these findings highlight additional oncogenic alterations potentially involved in tumor progression and suggest that extended targeted profiling may provide clinically relevant information on molecular heterogeneity in sMTC, particularly within <em>RAS</em>-mutant tumors.</div></div>","PeriodicalId":46328,"journal":{"name":"Journal of Clinical and Translational Endocrinology","volume":"44 ","pages":"Article 100442"},"PeriodicalIF":3.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147849881","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":"Urinary neutrophil Gelatinase–Associated lipocalin as an early and reliable biomarker of diabetic nephropathy in type 2 diabetes mellitus","authors":"Elham Yousief ,&nbsp;Ikram Hassan Adam ,&nbsp;Tarek Abdelaziem Ramzy ,&nbsp;Ahmed Laymouna","doi":"10.1016/j.jcte.2026.100441","DOIUrl":"10.1016/j.jcte.2026.100441","url":null,"abstract":"<div><h3>Background</h3><div>Early detection of diabetic nephropathy (DN) remains a major clinical challenge. Conventional indicators such as serum creatinine and urinary albumin excretion often identify renal impairment only after significant structural damage has occurred. Increasing evidence suggests that tubular injury may precede glomerular dysfunction in diabetic kidney disease. Neutrophil gelatinase–associated lipocalin (NGAL), a biomarker released from injured renal tubular epithelial cells, has therefore emerged as a potential early indicator of renal injury.</div></div><div><h3>Objective</h3><div>This study aimed to evaluate the diagnostic performance of urinary NGAL as an early biomarker of diabetic nephropathy in patients with type 2 diabetes mellitus and to compare its performance with conventional renal function markers.</div></div><div><h3>Methods</h3><div>A cross-sectional study was conducted including 90 participants: 72 patients with type 2 diabetes mellitus and 18 healthy controls. Diabetic patients were categorized into four stages of nephropathy according to estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR) based on KDIGO criteria. Urinary NGAL concentrations were measured using a sandwich enzyme-linked immunosorbent assay (ELISA). Statistical analysis included correlation analysis, receiver operating characteristic (ROC) curve assessment, and multivariate logistic regression.</div></div><div><h3>Results</h3><div>Urinary NGAL levels increased progressively with the severity of diabetic nephropathy, rising from 49.1 ± 14.2 ng/mL in controls (within the normal reference range &lt; 70 ng/mL) to 547.7 ± 31.7 ng/mL in patients with stage IV disease (p &lt; 0.001). NGAL demonstrated a strong positive correlation with serum creatinine (r = 0.81) and urinary ACR (r = 0.76), and a significant negative correlation with eGFR (r =  − 0.79). ROC curve analysis showed that NGAL exhibited excellent diagnostic performance (AUC = 1.00), outperforming ACR (AUC = 0.97) and serum creatinine (AUC = 0.83). An optimal cutoff value of 107.3 ng/mL provided high sensitivity and specificity for detecting diabetic nephropathy in this cohort.</div></div><div><h3>Conclusion</h3><div>Urinary NGAL appears to be a sensitive biomarker of renal tubular injury and may allow earlier identification of diabetic nephropathy compared with conventional markers. Incorporation of NGAL measurement into clinical evaluation may improve early detection of diabetic kidney disease, although larger prospective studies are required to confirm these findings.</div></div>","PeriodicalId":46328,"journal":{"name":"Journal of Clinical and Translational Endocrinology","volume":"44 ","pages":"Article 100441"},"PeriodicalIF":3.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147797256","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":"Increased cytokine production capacity and persistent inflammation after achieving remission of Cushing’s syndrome","authors":"Pepijn van Houten ,&nbsp;Annenienke C. van de Ven ,&nbsp;Antonius E. van Herwaarden ,&nbsp;Mihai G. Netea ,&nbsp;Martin Jaeger ,&nbsp;Romana T. Netea-Maier","doi":"10.1016/j.jcte.2026.100443","DOIUrl":"10.1016/j.jcte.2026.100443","url":null,"abstract":"<div><div>Endogenous Cushing’s syndrome (CS) is characterized by chronic hypercortisolism. After achieving remission, morbidity remains increased and quality of life remains impaired. Moreover, the incidence of inflammatory disorders increases after remission of CS. Despite these immune-mediated clinical consequences, the course of innate immune cell function after remission of CS is poorly known. In this study we aimed to assess changes in innate immune cell function and systemic inflammatory markers after achieving remission of CS. Blood samples were collected from nine CS patients (six adrenal CS and three Cushing’s disease) at diagnosis and after achieving remission and fully tapering off glucocorticoid suppletion. Peripheral blood mononuclear cell (PBMC) cellularity and monocyte-derived cytokine responses upon 24 h of <em>ex vivo</em> stimulation were compared between at diagnosis and after achieving remission. Changes in circulating inflammation-related proteins were assessed by proximity extension assay proteomics and ELISA. After achieving remission of CS, the PBMC fraction showed higher percentages of lymphocytes and lower percentages of monocytes. Production of pro-inflammatory cytokines IL-6 and IL-8 by monocytes after 24 h of stimulation with microbial stimuli was higher after achieving remission, while production of anti-inflammatory cytokines IL-10 and IL-1Ra was lower. Proteomic analysis of plasma identified seven inflammation-related proteins with increased expression and eleven proteins with decreased expression after achieving remission. Concentrations of circulating IL-6, IL-8 and CRP did not change after remission. In conclusion, increased pro-inflammatory cytokine production by monocytes and persistent systemic inflammation could partially explain increased morbidity and incidence of inflammatory disorders after achieving remission of CS.</div></div>","PeriodicalId":46328,"journal":{"name":"Journal of Clinical and Translational Endocrinology","volume":"44 ","pages":"Article 100443"},"PeriodicalIF":3.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147849880","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":"Systemic MOTS-c levels are increased in adults with obesity in association with metabolic dysregulation and remain unchanged after weight loss","authors":"Se-Hee Yoon ,&nbsp;Fei Yuan ,&nbsp;Xiangyang Zhu ,&nbsp;Hui Tang ,&nbsp;Dilbar Abdurakhimoova ,&nbsp;James Krier ,&nbsp;Alfonso Eirin ,&nbsp;Amir Lerman ,&nbsp;Pinchas Cohen ,&nbsp;Lilach O Lerman","doi":"10.1016/j.jcte.2025.100429","DOIUrl":"10.1016/j.jcte.2025.100429","url":null,"abstract":"<div><h3>Introduction</h3><div>MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) is a mitochondrial-derived peptide and regulator of metabolic homeostasis. Although its role in glucose and lipid metabolism is emerging, changes in circulating MOTS-c with obesity remain unclear. We hypothesized that circulating MOTS-c concentrations would be altered in obese vs. lean adults in associations with altered metabolic and inflammatory markers.</div></div><div><h3>Methods</h3><div>Circulating MOTS-c levels, metabolic parameters, and inflammatory markers were compared between 22 lean controls and 32 obese participants scheduled for bariatric surgery. Longitudinal changes in weight, MOTS-c levels, and metabolic markers were also analyzed in 10 of the obese patients before and 6 months after bariatric surgery. Additionally, adipose tissue MOTS-c expression was assessed by immunofluorescence in lean kidney donors (n = 6) and obese (n = 14) subjects.</div></div><div><h3>Results</h3><div>Circulating MOTS-c levels were significantly higher in obese compared to lean individuals (273 ± 56 vs. 223 ± 50 pg/mL; <em>P</em> &lt; 0.01). BMI and HOMA-IR independently predicted elevated MOTS-c levels (<em>P</em> = 0.035 and <em>P</em> = 0.032, respectively). MOTS-c showed a biphasic relationship with HOMA-IR, rising sharply above HOMA-IR of ∼ 6.6 mmol/L×µU/mL. Adipose tissue MOTS-c did not differ between the groups or correlate with circulating MOTS-c. Despite significant BMI improvements post-surgery (<em>P</em> &lt; 0.001), circulating MOTS-c levels remained unchanged (<em>P</em> = 0.913).</div></div><div><h3>Conclusion</h3><div>Circulating MOTS-c levels are elevated in obesity, exhibiting a nonlinear relationship with BMI and insulin resistance. MOTS-c may represent a compensatory metabolic response in obesity and insulin-resistant states, highlighting its potential as a clinical biomarker. This preliminary exploratory study warrants validation in larger and independent cohorts.</div></div>","PeriodicalId":46328,"journal":{"name":"Journal of Clinical and Translational Endocrinology","volume":"43 ","pages":"Article 100429"},"PeriodicalIF":3.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926261","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":"Remnant cholesterol inflammatory index and MASLD in U.S. adults: mediation role of triglyceride-glucose index","authors":"Qiqi Hang ,&nbsp;Ting Xu ,&nbsp;Jiajie Guo ,&nbsp;Ruixuan Li ,&nbsp;Kang Zhao ,&nbsp;Yinnig Guo ,&nbsp;Lu Shao ,&nbsp;Hanfei Zhu ,&nbsp;Qin Xu ,&nbsp;Minghui Ji","doi":"10.1016/j.jcte.2025.100427","DOIUrl":"10.1016/j.jcte.2025.100427","url":null,"abstract":"<div><h3>Background</h3><div>Metabolic dysfunction–associated steatotic liver disease (MASLD) is driven by dyslipidemia and chronic inflammation. We proposed a novel biomarker, the Remnant Cholesterol Inflammatory Index (RCII), and evaluated its association with MASLD, considering mediation via insulin resistance (TyG index).</div></div><div><h3>Methods</h3><div>In 3,232 U.S. adults from NHANES 2015–2020 (709 with MASLD), participants were divided into RCII tertiles. Multivariable logistic regression, restricted cubic splines, threshold analysis, subgroup interaction tests, ROC curves, XGBoost SHAP, and mediation analysis were used to assess relationships and mechanisms.</div></div><div><h3>Results</h3><div>Compared with the lowest tertile, the highest RCII tertile had an OR of 9.578 (95 % CI 6.420–14.291; <em>P</em> &lt; 0.001) for MASLD. A nonlinear association was identified, with a stronger slope below RCII = 3.640 (1-unit increase associated with 76.1 % higher odds). Significant interaction was observed by smoking status. In SHAP ranking, RCII was the sole lipid-class feature among the top five predictors. ROC showed AUC = 0.747 for RCII versus 0.732 for RC, both outperforming TC/LDL-C. TyG index mediated 32.4 % of RCII’s total effect on MASLD (<em>P</em> &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>RCII is a robust lipid–inflammation marker that outperforms conventional lipids in predicting MASLD. Its association is partly mediated by insulin resistance, supporting RCII’s use in MASLD risk stratification and early prevention.</div></div>","PeriodicalId":46328,"journal":{"name":"Journal of Clinical and Translational Endocrinology","volume":"43 ","pages":"Article 100427"},"PeriodicalIF":3.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926260","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":"Continuous glucose monitoring reveals high prevalence of hyperglycaemia in patients prior to pancreatic surgery: A pilot study","authors":"Heleen Driessens ,&nbsp;Josephine A.C. Woldring ,&nbsp;Maarten W. Nijkamp ,&nbsp;Peter R. van Dijk ,&nbsp;Joost M. Klaase","doi":"10.1016/j.jcte.2025.100426","DOIUrl":"10.1016/j.jcte.2025.100426","url":null,"abstract":"<div><h3>Aims</h3><div>Patients with pancreatic tumours are at increased risk of diabetes mellitus (DM) and hyperglycaemia and a subsequent higher risk of developing postoperative complications. Continuous glucose monitoring (CGM) can be used to assess the prevalence of hyperglycaemia in pancreatic surgery patients.</div></div><div><h3>Methods</h3><div>This single-centre observational pilot study (2023–2025) included 15 patients with DM type 2 or new onset DM (HbA1c ≥ 48 mmol/mol (6.5 %)) undergoing pancreatic surgery. Blinded CGM was performed for 2 weeks preoperatively and 2 weeks perioperatively. Primary outcome was time above range (TAR)(glucose &gt; 10.0 mmol/l (180.2 mg/dl)) as a percentage of total CGM wear time. Secondary outcomes were time below and in range, glucose metrics, difference in preoperative HbA1c and patient satisfaction regarding CGM wear.</div></div><div><h3>Results</h3><div>In total, 5 patients had new-onset DM, 6 suboptimal controlled DM (HbA1c ≥ 53 mmol/mol (7.0 %)) and 4 optimal controlled DM (HbA1c &lt; 53 mmol/mol (7.0 %)) at baseline. Median preoperative TAR (&gt;10.0 mmol/L (180.2 mg/dl)) was highest in the suboptimal controlled DM group (59.7 % [35.1–68.6]), compared to 7.9 % [0.9–19.4] in the optimal controlled and 16.7 % [7.7–23.7] in the new-onset DM group. Perioperatively, the optimal controlled DM group had the highest TAR (26.7 % [11.3–49.0]) while the new-onset and suboptimal controlled DM group had TARs of 4.6 % [1.2–9.6] and 16.3 % [11.5–23.4], respectively.</div></div><div><h3>Conclusions</h3><div>Blinded CGM revealed frequent pre- and perioperative hyperglycaemia and high inter-individual variability in TAR among patients with (new-onset) DM undergoing pancreatic surgery. These findings support the need for stricter and more individualized glucose monitoring. This could optimize preoperative glucose management and thereby possibly reduce postoperative complications.</div></div>","PeriodicalId":46328,"journal":{"name":"Journal of Clinical and Translational Endocrinology","volume":"43 ","pages":"Article 100426"},"PeriodicalIF":3.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145685823","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":"Implementation of a Best Practice Advisory to alert inpatient providers of necessary discharge prescriptions for insulin and supplies for patients with diabetes","authors":"Michelle D. Lundholm ,&nbsp;Allison Weathers ,&nbsp;Shannon Knapp ,&nbsp;Pratibha P.R. Rao","doi":"10.1016/j.jcte.2025.100428","DOIUrl":"10.1016/j.jcte.2025.100428","url":null,"abstract":"<div><h3>Background</h3><div>Medication discrepancies and omissions at hospital discharge are a common, preventable source of harm for patients with diabetes. Ensuring accurate prescriptions for insulin and diabetes supplies is critical for safe transitions of care. We aimed to evaluate the impact of a Best Practice Advisory (BPA) integrated into the electronic medical record (EMR) on the accuracy of diabetes-related discharge prescriptions.</div></div><div><h3>Methods</h3><div>This quality improvement initiative was implemented across seven hospitals within a large health system. The BPA was triggered in the EMR discharge navigator for patients evaluated by a Diabetes Care and Education Specialist (DCES), prompting providers to review and order recommended diabetes medications and supplies. BPA utilization data were collected from February to December 2022. A retrospective chart review of 100 consecutive eligible patients discharged in December 2022 seen by DCES was assessed for prescription accuracy and supply provision.</div></div><div><h3>Results</h3><div>The BPA was triggered 6,714 times for 2,266 patient encounters over 11 months. Among 100 reviewed patients (mean age 57 years, 58 % male, 76 % type 2 diabetes), insulin prescription accuracy at discharge was 99 %, and 88 % received all recommended diabetes supplies. Only 1 % of patients contacted the hospital post discharge for additional supplies, suggesting most omissions were clinically appropriate.</div></div><div><h3>Conclusions</h3><div>Integration of a BPA into the EMR significantly improved the accuracy and completeness of diabetes-related discharge prescriptions. This low-cost, sustainable digital intervention enhances patient safety and care quality, and represents a scalable model for improving discharge practices in inpatient settings.</div></div>","PeriodicalId":46328,"journal":{"name":"Journal of Clinical and Translational Endocrinology","volume":"43 ","pages":"Article 100428"},"PeriodicalIF":3.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926259","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":"Identification of novel and recurrent mutations in nicotinamide nucleotide transhydrogenase (NNT) underlying familial glucocorticoid deficiency-type 4 in multiple Saudi families","authors":"Ibrahim Al Alwan ,&nbsp;Raja Hussain Ali ,&nbsp;Muhammad Umair ,&nbsp;Imran Ali Khan ,&nbsp;Nada Alotaibi ,&nbsp;Essra Aloyouni ,&nbsp;Deemah Alwadaani ,&nbsp;Latifah Alayyar ,&nbsp;Shahad Haddad ,&nbsp;Shahad Alawaji ,&nbsp;Saleh Althenayyan ,&nbsp;Ahmed Alfaidi ,&nbsp;Manal Algattan ,&nbsp;Ali S. Alquraishi ,&nbsp;Abdullah Alzaben ,&nbsp;Haifa Alfaraidi ,&nbsp;Beshaier Almulhem ,&nbsp;Mohammed Almannai ,&nbsp;Majid Alfadhel","doi":"10.1016/j.jcte.2026.100433","DOIUrl":"10.1016/j.jcte.2026.100433","url":null,"abstract":"<div><h3>Background</h3><div>Familial glucocorticoid deficiency (FGD; MIM: 614736) is a genetic disease of glucocorticoid insufficiency, with autosomal recessive mode of inheritance. The FGD is genetically heterogeneous disorder that involves multiple genes related to the pathway that regulates the signaling from pituitary to the adrenal cortex, or the specific redox reactions in mitochondria. The phenotypic spectrum for FGD is also diverse with considerable variability in clinical features. Among the genetic determinants of this disease, pathogenic mutations in <em>NNT</em> gene results in Familial glucocorticoid deficiency type 4. Here we report three consanguineous families with single nucleotide variants in <em>NNT</em> that manifest as familial glucocorticoid deficiency in multiple family members.</div></div><div><h3>Method</h3><div>Prospective cohort of three families from different tribes were identified with clinical diagnosis of familial glucocorticoid deficiency (FGD). Whole exome sequencing (WES) done for affected family members followed by validation of discovered variant by Sanger sequencing and subsequent functional studies including quantitative PCR analysis and protein Modelling.</div></div><div><h3>Results</h3><div>The screening of entire coding region of the genomes of probands in each family revealed three distinct mutations, including one novel missense variant (c.1067 C &gt; T; p.Thr356Ile), classified as variant of uncertain significance (VUS; Class-3) and two recurrent variants (c.1025 T &gt; C; p.Val342Ala and c.98dup; p.Leu33Phefs*13), classified as pathogenic [Class-I]. Computational protein modelling of these mutations (c.98dup and c.1025 T &gt; C) suggests atypical changes in the structure of the mutant proteins that likely disrupt the physiological role of NNT in mitochondria of adrenal cortex.</div></div><div><h3>Conclusion</h3><div>The exome sequencing genetically characterized the autosomal recessive sub-type 4 of hereditary glucocorticoid deficiency in families showing the features of cortisol deficiency, including the development of hypoglycemia and adrenal crisis. This strongly supports the pathogenicity of these variants. In addition, this suggests importance of mitochondrial function in post developmental maintenance of cortisol significance in terms of cellular metabolism, carried out by NNT protein. Identifying individuals with hereditary glucocorticoid deficiency is essential to start life-saving glucocorticoid replacement.</div></div>","PeriodicalId":46328,"journal":{"name":"Journal of Clinical and Translational Endocrinology","volume":"43 ","pages":"Article 100433"},"PeriodicalIF":3.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146173241","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":"Effects of cyclic yoga on selected metabolic and hepatic parameters in diabetic women with fatty liver diseases: A clinical trial","authors":"Zahra Bayat ,&nbsp;Seyedeh Soolmaz Mahdioun ,&nbsp;Houshang Nemati ,&nbsp;Fatemeh Rezvan Madani ,&nbsp;Mehrali Rahimi ,&nbsp;Hanieh Dehghan ,&nbsp;Rozita Naseri ,&nbsp;Seyed Mehdi Goosheh","doi":"10.1016/j.jcte.2026.100431","DOIUrl":"10.1016/j.jcte.2026.100431","url":null,"abstract":"<div><h3>Aims</h3><div>Type 2 diabetes mellitus and non-alcoholic fatty liver disease increase cardiometabolic risk. This randomized controlled trial assessed the effects of cyclic yoga, a structured asana sequence, on anthropometric, glycemic, lipid, and hepatic parameters in overweight women with both conditions.</div></div><div><h3>Methods</h3><div>Forty overweight women (mean age 50.5 ± 5.5 years) with type 2 diabetes and non-alcoholic fatty liver disease were randomized to either an eight-week cyclic yoga intervention (three sessions/week) or a control group maintaining usual activities. Pre- and post-intervention, fasting blood glucose, glycated hemoglobin, insulin resistance, lipid profile, liver enzymes (alanine aminotransferase, aspartate aminotransferase), anthropometric parameters were measured and analyzed using repeated measures analysis of variance.</div></div><div><h3>Results</h3><div>The cyclic yoga group showed significant reductions in fasting blood glucose, glycated hemoglobin, insulin resistance, triglycerides, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, weight, body mass index, hip circumference, waist circumference, with increased high-density lipoprotein cholesterol compared to control group.</div></div><div><h3>Conclusions</h3><div>Cyclic yoga appears to improve glycemic control, lipid profiles, liver enzymes, and anthropometric indices in women with type 2 diabetes mellitus and non-alcoholic fatty liver disease. These findings suggest that cyclic yoga may be a safe, practical, and cost-effective complementary therapy to improve metabolic and hepatic health in this high-risk population, although larger and longer term studies are warranted.</div></div>","PeriodicalId":46328,"journal":{"name":"Journal of Clinical and Translational Endocrinology","volume":"43 ","pages":"Article 100431"},"PeriodicalIF":3.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077938","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}