Endocrine and Metabolic Science最新文献

{"title":"IPSS does not impact management in Cushing's Disease when a pituitary tumor is visible on MRI","authors":"Michelle D. Lundholm ,&nbsp;Kevin M. Pantalone ,&nbsp;Pratibha PR Rao ,&nbsp;Amir H. Hamrahian ,&nbsp;Varun R. Kshettry ,&nbsp;Pablo Recinos ,&nbsp;Divya Yogi-Morren","doi":"10.1016/j.endmts.2025.100257","DOIUrl":"10.1016/j.endmts.2025.100257","url":null,"abstract":"<div><h3>Purpose</h3><div>There is controversy surrounding the value of inferior petrosal sinus sampling (IPSS) in Cushing's Disease (CD) when there is a visible pituitary lesion on pre-operative imaging. This study compares lateralization results between IPSS and pituitary MRI against surgical localization.</div></div><div><h3>Methods</h3><div>A retrospective chart review was conducted at a tertiary referral center on patients with pathology-confirmed CD between 2003 and 2022, with unilateral pituitary tumor on MRI, and successful pre-operative bilateral IPSS. Bilateral sellar exploration was performed surgically in all cases.</div></div><div><h3>Results</h3><div>Of 32 patients included, all had IPSS results consistent with CD and all lateralized. The median age at diagnosis was 43 years (range 23–69 years) and 88 % were female (<em>N</em> = 28). The median tumor size on MRI was 5 mm (range 3–12 mm). Prolactin adjustment was performed in the interpretation of IPSS in 30 cases (94 %). MRI correctly lateralized 31 tumors (97 %), whereas IPSS correctly lateralized 27 tumors (84 %). Of the 6 cases where MRI and IPSS disagreed on laterality, the operative report was consistent with MRI lateralization in 4 of 6 cases, and midline disease in the remaining 2 cases. There were no cases where IPSS lateralization was correct when MRI lateralization was incorrect.</div></div><div><h3>Conclusion</h3><div>When a tumor is visible on MRI (≥3 mm), IPSS does not add to the accuracy of determining tumor lateralization. Therefore, IPSS does not add to the diagnostic nor therapeutic management for patients with biochemical testing consistent with CD and visible tumor on MRI.</div></div>","PeriodicalId":34427,"journal":{"name":"Endocrine and Metabolic Science","volume":"19 ","pages":"Article 100257"},"PeriodicalIF":0.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482472","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":"Influence of high fructose intake on systemic and cognitive health across developmental stages: A review","authors":"Zinhle Mvelase ,&nbsp;Mluleki Luvuno ,&nbsp;Musa V. Mabandla","doi":"10.1016/j.endmts.2025.100256","DOIUrl":"10.1016/j.endmts.2025.100256","url":null,"abstract":"<div><div>Overconsumption of fructose is a significant medical concern due to its potential adverse effects. In this review article, we critically examine the repercussions of high fructose exposure to increase awareness about the adverse impact of fructose on memory and learning performance, metabolic and systematic parameters with a particular focus on how these manifestations differ among adolescents, children and adults. Chronic intake of high-fructose diets has been consistently associated with impairments in learning and memory functions. These deficits in memory function have been linked to disruptions in insulin signalling pathways in the brain. Scientific evidence further highlights that high fructose intake is attributed to the development of kidney diseases, type 2 diabetes, cardiovascular complications, and an increased risk of Alzheimer's disease. Despite extensive research on fructose's metabolic effects, there are still gaps in understanding its impact on cognitive function and systemic health across different developmental stages.</div></div>","PeriodicalId":34427,"journal":{"name":"Endocrine and Metabolic Science","volume":"19 ","pages":"Article 100256"},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482474","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":"Update on thyroid nodules: Characteristics and clinical management","authors":"Elisa Lepore ,&nbsp;Laura Rizza ,&nbsp;Francesca Rota ,&nbsp;Roberto Baldelli","doi":"10.1016/j.endmts.2025.100255","DOIUrl":"10.1016/j.endmts.2025.100255","url":null,"abstract":"<div><div>Thyroid nodules (TNs) represent a highly widespread condition, usually destined to a positive outcome. Nevertheless, making a correct diagnosis is crucially important to ensure an appropriate and tailored strategy of follow up or treatment. Several different techniques allow to gradually characterize TNs by performing cytological and compositional analysis. In addition, collecting data of common risk factors together with recognized features - including microcalcifications, uneven margins, taller-than-wide form - may contribute to indicate a suspected malignancy. By combining all these information and proceeding step by step in the patients' investigation to achieve a diagnosis, physicians can optimize the diagnostic process thus differentiating the small percentage of patients that need surgical intervention, without impacting on those patients with benign TNs. This may result helpful for improving the management of patients with TNs. Instead, in cases of benign TNs that no need neither surgical nor pharmacological treatments, dietary supplementations based on micronutrients involved in thyroid physiology, as iodine or myo-Inositol (myo-Ins), represent a useful tool. Even though evidence from literature sustains a correlation between iodine deficiency and TN occurrence, there are very few studies regarding a possible correlation between myo-Ins deficiency and presence of TNs. Therefore, further investigations aimed to correlate myo-Ins levels with the cytological severity of TNs may add new insights on this topic and improve the diagnostic process that aims to tailored therapies for these patients.</div></div>","PeriodicalId":34427,"journal":{"name":"Endocrine and Metabolic Science","volume":"19 ","pages":"Article 100255"},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482473","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":"Sodium-glucose cotransporter 2 inhibitors in chronic kidney disease: A review of current evidence and clinical implications","authors":"Abdulrahman Saad Alfaiz","doi":"10.1016/j.endmts.2025.100251","DOIUrl":"10.1016/j.endmts.2025.100251","url":null,"abstract":"<div><h3>Background</h3><div>Chronic kidney disease (CKD) is a progressive condition affecting millions worldwide, leading to substantial morbidity, mortality, and healthcare burden. While traditional treatments such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have been the cornerstone of CKD management, newer therapeutic approaches are needed to slow disease progression and improve outcomes. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, initially developed as antihyperglycemic agents, have demonstrated significant renoprotective and cardioprotective effects beyond glucose control.</div></div><div><h3>Objective</h3><div>This review aims to evaluate the current evidence on the efficacy, safety, and clinical implications of SGLT2 inhibitors in CKD, highlighting their mechanisms of action, benefits, limitations, and future research directions.</div></div><div><h3>Methods</h3><div>A comprehensive literature search was conducted in PubMed, Google Scholar, and Medline using keywords related to SGLT2 inhibitors, CKD, and renal outcomes with no time limit. Studies included randomized controlled trials, cohort studies, and case-control studies examining the effects of SGLT2 inhibitors on renal and cardiovascular outcomes in CKD patients. The risk of bias was assessed using standard tools such as the Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool.</div></div><div><h3>Results</h3><div>Clinical trials have demonstrated that SGLT2 inhibitors, including empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin, significantly reduce CKD progression, lower albuminuria, and decrease the risk of cardiovascular events and all-cause mortality. These effects are observed in both diabetic and non-diabetic populations. Additionally, SGLT2 inhibitors exhibit renoprotective mechanisms such as reducing glomerular hyperfiltration, modulating tubuloglomerular feedback, and exerting anti-inflammatory and antifibrotic properties. However, potential adverse effects, including an initial decline in estimated glomerular filtration rate (eGFR), an increased risk of euglycemic diabetic ketoacidosis, and urinary tract infections, necessitate careful patient selection and monitoring. Emerging studies also explore the role of machine learning in optimizing SGLT2 inhibitor use for personalized treatment approaches.</div></div><div><h3>Conclusion</h3><div>SGLT2 inhibitors have emerged as a transformative addition to CKD management, offering substantial renal and cardiovascular benefits. Despite safety concerns, their advantages outweigh the risks, warranting broader clinical implementation. Future research should focus on refining patient selection, optimizing treatment combinations, and leveraging data science to enhance therapeutic outcomes in CKD patients.</div></div>","PeriodicalId":34427,"journal":{"name":"Endocrine and Metabolic Science","volume":"18 ","pages":"Article 100251"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144229780","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":"Biochemical, laboratory and instrumental diagnostic indicators of early diagnosis of women with gestational diabetes","authors":"Gulchekhra Ikhtiyarova Akmalovna ,&nbsp;Gulrukh Karimova Komilovna ,&nbsp;Guljamal Arstanalievna Subanova ,&nbsp;Nilufar Navruzova Orzijonovna ,&nbsp;Nargiza Narzulloeva Sayfilloevna ,&nbsp;Feruza Oripova Shopulatovna ,&nbsp;Salimova Toxtajan Baxtiyarovna ,&nbsp;Aiganysh Zhoomartovna Rysbaeva ,&nbsp;Fakher Rahim","doi":"10.1016/j.endmts.2025.100252","DOIUrl":"10.1016/j.endmts.2025.100252","url":null,"abstract":"<div><div>Gestational diabetes (GDM) is a type of diabetes that can develop during pregnancy in women who don't have diabetes. We studied the concentration of homocysteine in the blood in two study groups - 36 healthy pregnant women and 68 pregnant women with GDM. The study included biochemical (homocysteine, glucose, creatinine, glycated hemoglobin), hormonal (leptin, C-peptide, 25 (OH) D, and methods of correlation and statistical research. According to the analysis of blood in the case histories of patients in groups, anemia was observed in an average of 61.45 % of patients. Homocysteine is a biomarker that controls the action of folic acid in the body in pregnant women, the reference values of which are in the range of 5.6–16.42 μmol/l, while in healthy women this diagnostic indicator averages 12.98 ± 0.31. The mean homocysteine value in pregnant women with GDM was 42.87 ± 2.26 μmol/l (<em>P</em> ≤ 0.001). Another specific marker in pregnant women with GDM is the study of cholecalciferol, vitamin 25(OH) D. It was found that the level of significance of the difference between the indicators in the group of pregnant women with GDM and in the control group was almost 2 times less. Based on this finding, in future studies, the predictive value of each of these indices in the occurrence of GDM can be examined. It was also found that such indices differ significantly in patients with GDM compared to the control group, although further studies in the broader population are needed to confirm this.</div></div>","PeriodicalId":34427,"journal":{"name":"Endocrine and Metabolic Science","volume":"18 ","pages":"Article 100252"},"PeriodicalIF":0.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169614","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":"Optimizing blood glucose predictions in type 1 diabetes patients using a stacking ensemble approach","authors":"Vincent B. Liu ,&nbsp;Laura Y. Sue ,&nbsp;Oscar Madrid Padilla ,&nbsp;Yingnian Wu","doi":"10.1016/j.endmts.2025.100253","DOIUrl":"10.1016/j.endmts.2025.100253","url":null,"abstract":"<div><h3>Introduction</h3><div>The diabetes pandemic, including 828 million adults worldwide in 2022, would benefit from continued development of novel, effective and accurate blood glucose prediction systems. Using the DiaTrend dataset, this study used stacking machine learning optimized by Grey Wolf Optimizer to construct and assess prediction models for blood glucose levels in type 1 diabetes patients.</div></div><div><h3>Methods</h3><div>The DiaTrend dataset includes 27,561 days of continuous glucose monitoring and 8220 days of insulin pump data for 54 patients with type 1 diabetes. Grey Wolf optimization was used to tune and evaluate three machine learning algorithms – Random Forest, LSTM, GRU – for blood glucose predictions, whose predictions were then combined into an XGBoost stacking ensemble meta-learner.</div></div><div><h3>Results</h3><div>This study looked at three baseline algorithms for predicting blood glucose levels. Machine learning models Random Forest, LSTM, and GRU served as baselines, with MAE, RMSE, and MARD values. GRU had the best predictive accuracy of the initial models. Grey Wolf optimization contributed to achieving optimal baseline model results. Stacking ensemble learning via XGBoost meta-learner (MAE = 10.65, RMSE = 14.59, MARD = 6.98) achieved higher performance than the baseline models.</div></div><div><h3>Conclusion</h3><div>The GRU method with Grey Wolf optimization outperformed the other models with the lowest MAE, RMSE, and MARD, but the Stacked XGBoost model fared best. These findings emphasize the need to improve parameter selection with approaches such as Grey Wolf or stacking ensemble methods to achieve accurate blood glucose predictions. These prediction models can aid in the continued development of monitoring devices, and algorithms for these devices, which contain alert systems for impending abnormal blood glucose levels, allowing for timely diabetes self-management.</div></div>","PeriodicalId":34427,"journal":{"name":"Endocrine and Metabolic Science","volume":"18 ","pages":"Article 100253"},"PeriodicalIF":0.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169615","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":"Impending thyroid storm in a case of Down syndrome with burr hole surgery: A case report","authors":"Ayyesha Yuanita ,&nbsp;Hermina Novida","doi":"10.1016/j.endmts.2025.100250","DOIUrl":"10.1016/j.endmts.2025.100250","url":null,"abstract":"<div><h3>Introduction</h3><div>An accidental injury requiring surgery in a patient with Down syndrome (DS) and hyperthyroidism is an uncommon case, in which thyroid hormone control plays a crucial role in successful surgery.</div></div><div><h3>Case presentation</h3><div>An Indonesian woman, 33 years old, suffered an accidental brain injury and gradually lost consciousness. She was born with DS and had no prior medical consultation. At the emergency room, she was diagnosed with hyperthyroidism and an acute subdural hematoma. According to the Burch-Wartofsky (BW) score, the examination revealed an impending thyroid storm (40 points). Management of hyperthyroidism aims to avoid the thyroid storm before, during, and after double burr hole drainage, which is treated with glucocorticoid and antithyroid drugs. She was followed up for 6 months after surgery and had considerable improvement.</div></div><div><h3>Conclusion</h3><div>Management of hyperthyroidism have a crucial role in DS patient with burr hole drainage to improve surgical outcomes, control of cardiac output, and minimize thyroid storm.</div></div>","PeriodicalId":34427,"journal":{"name":"Endocrine and Metabolic Science","volume":"18 ","pages":"Article 100250"},"PeriodicalIF":0.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123577","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":"l-carnitine protects against bile acid-induced mitochondrial dysfunction and IGF-1 impairment in hepatocyte cultures","authors":"Wafa'a Alqabandi,&nbsp;Maira Alsaeid,&nbsp;Gursev Dhaunsi","doi":"10.1016/j.endmts.2025.100249","DOIUrl":"10.1016/j.endmts.2025.100249","url":null,"abstract":"<div><h3>Background and aims</h3><div>Excessive amounts of bile acids (ΒΑ) exert hepatotoxic effects. We investigated the effects of glycochenodeoxycholic acid (GCDC) on mitochondrial function and insulin-like growth factor-1 (IGF-1) activity in hepatocytes and also examined if <span>l</span>-carnitine (CRNT) has any protective role.</div></div><div><h3>Methods</h3><div>Primary hepatocyte cultures were treated with 0–100 μM GCDC with or without 5 mM <span>l</span>-carnitine (CRNT). DNA synthesis was measured by bromodeoxyuridine incorporation assay. Enzymic activities of carnitine palmitoyltransferase-1 (CPT-1), cytochrome <em>c</em> oxidase (CcO) and medium chain-acylCoA dehydrogenase (MCAD), were measured in hepatocyte homogenates. Expression of peroxisome proliferator activated receptor gamma coactivator 1-α (PGC-1α) and IGF-1 receptor (IGF-1R) was detected by RT- PCR and Western blot analysis, respectively<em>.</em></div></div><div><h3>Results</h3><div>Treatment with GCDC significantly decreased the enzymatic activity of MCAD, CPT-1 and CcO (<em>P</em> &lt; 0.01), and mitochondrial ATP content. Additionally, GCDC significantly increased malondialdehyde (MDA) levels in mitochondria and downregulated PGC-1α (<em>p</em> &lt; 0.01). Furthermore, the IGF-1-induced DNA synthesis and IGF-1R gene expression were also notably reduced in GCDC-treated hepatocytes. However, co-treatment with 5 mM CRNT markedly abrogated the GCDC-induced impairment of CcO activity and PGC-1α downregulation, while it had no effect on MCAD activity. In addition, CRNT treatment also restored the enzymatic activity of CPT-1 and the gene expression levels of IGF-1 in GCDC-treated hepatocytes (<em>p</em> &lt; 0.05).</div></div><div><h3>Conclusions</h3><div>GCDC-induced hepatotoxic effects could be triggered by mitochondrial dysfunction and impairment of IGF-1 activity. CRNT has potential beneficial effects against ΒΑ-induced cytotoxicity via enhancing the CPT-1 and CcO enzyme activities, and ATP production in addition to upregulation of PGC-1α and IGF-1R.</div></div>","PeriodicalId":34427,"journal":{"name":"Endocrine and Metabolic Science","volume":"18 ","pages":"Article 100249"},"PeriodicalIF":0.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144117051","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":"The correlation between COVID-19 severity and elevated level of serum glucose","authors":"Zahraa Q. Ali ,&nbsp;Nawar S. Mohammed ,&nbsp;Hussam H. Muhammed","doi":"10.1016/j.endmts.2025.100248","DOIUrl":"10.1016/j.endmts.2025.100248","url":null,"abstract":"<div><div>The collision of COVID-19 and type 2 diabetes (T2D) highlights T2D as the second most prevalent comorbidity in COVID-19. This infection exacerbates complications in diabetics. It elevates blood glucose through excessive glucocorticoid and catecholamine release. This hyperglycemia triggers pro-inflammatory monocytes, heightens platelet reactivity, and amplifies cardiovascular deaths in diabetics. This cross-sectional study, conducted at Private Nursing Home Hospital in Baghdad, focused on 143 COVID-19 patients diagnosed via RNA detection in nasopharyngeal secretions using PCR from May to August 2021. The patients, aged 18 to 76, had no prior history of diabetes upon admission. An 86-member control group, free from COVID-19 and diabetes history, aged 20 to 73, was also included. BMI, platelet count, WBC, ESR, RBG, and serum levels of the alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels were measured. The results revealed statistically highly differences in RBG between the two groups (<em>p</em>-value = 0.001), and significant variations in the Mean ± SD values of ALT and AST enzyme levels, as well as in WBC and ESR, when comparing COVID patients to non-COVID patients. In summary, our findings show a positive correlation between admission hyperglycemia and the risk of severe COVID-19, emphasizing the significance of monitoring and managing blood glucose levels. Effective glycemic control could aid in mitigating COVID-19 progression and is integral to comprehensive treatment. These glucose-related changes and COVID-19 impact on the pancreas may contribute to the development of T2D.</div></div>","PeriodicalId":34427,"journal":{"name":"Endocrine and Metabolic Science","volume":"18 ","pages":"Article 100248"},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144107676","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":"CRF1 receptor antagonists in congenital adrenal hyperplasia: A systematic review and meta-analysis of phase 2 open-label and phase 3 clinical trials","authors":"Mir wajid Majeed ,&nbsp;Emma Finnegan ,&nbsp;Mariano Gallo Ruelas ,&nbsp;Marco Quirós ,&nbsp;Marina Barbosa da Silva ,&nbsp;Issa Salha ,&nbsp;Catalina Herrán-Fonseca ,&nbsp;Helen Michaela de Oliveira ,&nbsp;Melissa Chacón Quirós ,&nbsp;Raheel Ahmed ,&nbsp;Zainab Humayun ,&nbsp;Tajamul Hussain Shah ,&nbsp;Mohammad Ashraf Ganie","doi":"10.1016/j.endmts.2025.100247","DOIUrl":"10.1016/j.endmts.2025.100247","url":null,"abstract":"<div><h3>Introduction</h3><div>Classical Congenital Adrenal Hyperplasia (CAH) due to 21 hydroxylase deficiency is a rare autosomal recessive disorder. Recent clinical trials indicate that type 1 Corticotropin-releasing hormone receptor OR CRFR1 receptor OR CRF1 antagonists could provide a new treatment option for CAH. Hence, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of these drugs in patients with CAH.</div></div><div><h3>Methods</h3><div>Medline, Embase, and Cochrane Library were searched for eligible studies. Analysis of Phase 2b and Phase 3 clinical trials was carried out. Mean percent changes and event numbers were pooled to perform a single-arm meta-analysis. Binary data was pooled from Phase 3 clinical trials. Statistical analysis was performed using RStudio version 4.1.2 (R Foundation for Statistical Computing), under a random-effects model. Heterogeneity was assessed using I² statistics.</div></div><div><h3>Results</h3><div>From Phase 2 clinical trials, pooled efficacy data from studies with CRF1 antagonists resulted in a mean decrease from baseline levels in adrenocorticotropic hormone (ACTH) -57.86 %; 95 % CI -71.15 to −44.58 %; I² = 0 %), 17-OHP (17-hydroxyprogesterone) (Mean − 40.01 %;95 % CI -66.31 to −13.71 %; I² = 66 %) and androstenedione (−39.24 %; 95 % CI -62.77 to −15.70 %; I² = 78 %). Overall, 71 % (95 % CI 53.91 % to 85.39 %) of the included patients experienced adverse events of any grade, with no significant difference between drug-type subgroups (<em>P</em> = 0.83). In Phase 3 trials, compared to placebo, CRF1 receptor antagonists resulted in a significant reduction of 17-OHP (MD: −6049.40 ng/dL; 95 % CI: −6665.23 to −5433.58 ng/dL; <em>p</em> &lt; 0.01; I² = 0 %), androstenedione levels (MD: −313.58 ng/dL; 95 % CI: −400.14 to −227.02 ng/dL; p &lt; 0.01; I² = 0 %) and need for glucocorticoid dose reduction (MD: −20.37 %; 95 % CI: −26.73 % to −14.00 %; p &lt; 0.01; I² = 47 %) No statistically significant difference was found between the two groups with respect to treatment emergent adverse effects 1.02 (95 % CI: 0.91 to 1.15; <em>p</em> = 0.72; I² = 0 %) or treatment discontinuation 3.28 (95 % CI: 0.41 to 26.51; <em>p</em> = 0.27; I² = 0 %).</div></div><div><h3>Conclusion</h3><div>CRF1 antagonists, especially Crinecerfont, are promising in the treatment of CAH. Phase 2b and Phase 3 clinical trials of CRF1 antagonists involving Crinecerfont demonstrated consistent results supporting its efficacy and safety. These studies showed significant reductions in ACTH, 17-OHP and androstenedione levels, as well as a decreased need for glucocorticoid doses, with no notable difference in adverse effects compared to placebo.</div></div>","PeriodicalId":34427,"journal":{"name":"Endocrine and Metabolic Science","volume":"18 ","pages":"Article 100247"},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169616","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}