medRxiv - Endocrinology最新文献

{"title":"Treatment outcomes with oral anti-hyperglycaemic therapies in people with diabetes secondary to a pancreatic condition (type 3c diabetes): A population-based cohort study","authors":"Rhian Hopkins, Katherine G Young, Nicholas J Thomas, Angus G Jones, Andrew T Hattersley, Beverley M Shields, John M Dennis, Andrew P McGovern, MASTERMIND consortium","doi":"10.1101/2024.07.31.24311262","DOIUrl":"https://doi.org/10.1101/2024.07.31.24311262","url":null,"abstract":"Objectives\u0000Diabetes secondary to a pancreatic condition (type 3c diabetes) affects 5-10% of people with diabetes, but evidence on the efficacy and tolerability of oral therapies in this group are lacking. We aimed to assess short-term treatment outcomes with oral anti-hyperglycaemic therapies in people with type 3c diabetes.\u0000Design\u0000Population-based cohort study.\u0000Setting\u0000UK primary care records (Clinical Practice Research Datalink; 2004-2020), linked hospital records.\u0000Participants\u00007,084 people with a pancreatic condition (acute pancreatitis, chronic pancreatitis, pancreatic cancer, haemochromatosis) preceding diabetes diagnosis (type 3c cohort) initiating an oral glucose-lowering therapy (metformin, sulphonylureas, SGLT2-inhibitors, DPP4-inhibitors, or thiazolidinediones [TZDs]), without concurrent insulin treatment. This cohort was stratified by evidence of pancreatic exocrine insufficiency [PEI] (1,167 with PEI, 5,917 without) and matched to 97,227 type 2 diabetes (T2D) controls. Main outcome measures\u000012-month HbA1c change and treatment discontinuation within 6 months, in the type 3c diabetes cohort compared to T2D controls.\u0000Results\u0000People with type 3c diabetes had a substantial mean HbA1c reduction with oral therapies in those with PEI (9.4 mmol/mol [95%CI 8.9 to 10.0]) and without (12.2 mmol/mol [12.0 to 12.4]). Compared to T2D controls, people with type 3c diabetes without PEI had a similar mean HbA1c reduction (0.7 mmol/mol [0.4 to 1.0] difference) and similar odds of early treatment discontinuation (Odds ratio [OR] 1.08 [0.98 to 1.19]). In contrast, people with type 3c diabetes and PEI had a lower mean HbA1c response (3.5 mmol/mol [2.9 to 4.1] lesser reduction), and greater discontinuation (OR 2.03 [1.73 to 2.36]). Results were largely consistent across type 3c subtypes and individual drug classes.\u0000Conclusions\u0000Oral anti-hyperglycaemic therapies are effective in people with type 3c diabetes, and could provide an important component of glycaemic management. However, the presence of PEI is associated with modestly reduced glycaemic response and reduced tolerability, meaning PEI could identify people that may benefit from closer monitoring after initiating oral therapy.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141865094","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":"Analysis of Frailty in Peritoneal Dialysis Patients Based on Logistic Regression Model and XGBoost Model","authors":"Qi Liu, Guanchao Tong, Qiong Ye","doi":"10.1101/2024.07.29.24311190","DOIUrl":"https://doi.org/10.1101/2024.07.29.24311190","url":null,"abstract":"Purpose: The aim of this study was to establish a model that would enable healthcare providers to use routine follow-up measures of peritoneal dialysis to predict frailty in those patients. Design: A cross-sectional design with Logistic regression and XGBoost machine learning algorithms analysis. Methods: One hundred and twenty-three cases of peritoneal dialysis patients who underwent regular follow-up at our center were included in this study. We use the FRAIL scale to confirm the frailty of the patients. Clinical and Laboratory data were obtained from the peritoneal dialysis registration system. Factors associated with patient Frailty were identified through regularized logistic regression and validated using an XGBoost model. The final selected variables were in-cluded in the unregularized Logistic Regression to construct the model Findings: A total of 123 patients were reviewed in this study, with an average age of 61.58 years, and the median dialysis Duration was 38.5(18.07,60.53) months. 39 patients (31.71%) were female, 54 PD patients (43.9%) were classified as frail. Age, Ferritin, and TCH are the top three im-portant features labeled by the XGBoost. The results are consistent with the regularized logistic regression. Conclusions: In this study, age, total cholesterol, and ferritin are the most important features associated with the frailty in peritoneal dialysis patients. This model can be used to predict frailty status and help health monitoring of peritoneal dialysis patients.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141865097","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":"Comparison of Different Diagnostic Criteria of 68Ga-Pentixafor PET/CT for the Classification of Primary Aldosteronism","authors":"Shumin Yang, Xiangshuang Zhang, Furong He, Ying Song, Ying Jing, Jinbo Hu, Hang Shen, Aipin Zhang, Wenwen He, Zhengping Feng, Qifu Li, Hua Pang","doi":"10.1101/2024.07.26.24311092","DOIUrl":"https://doi.org/10.1101/2024.07.26.24311092","url":null,"abstract":"Background: 68Ga-Pentixafor positron emission tomography/computed tomography (PET/CT) is an emerging method for the classifying primary aldosteronism (PA). How to use this method for PA classification is still controversial. Methods: A retrospective study was conducted in patients with PA who underwent PET/CT. These patients had a classification diagnosis of unilateral PA (UPA) or bilateral PA (BPA) based on adrenal venous sampling or post-surgical outcomes. Area under the receiver operating characteristic curve (AUC), specificity and sensitivity were used to analyze the accuracy of the lateralization index (LI) based on adrenal maximum standardized uptake value (SUVmax), dominant side SUVmax adjusted by liver, dominant side of SUVmax and visual analysis.\u0000Results: A total of 208 PA patients were included, with 128 UPA and 80 BPA. The AUC for diagnosing UPA using LI and visual analysis were 0.82 [95% CI, 0.77-0.87] and 0.82 (95% CI, 0.76-0.87), respectively, higher than the dominant side of SUVmax [0.72, (95%CI, 0.65-0.78)] and dominant side SUVmax adjusted by liver [0.71, (95%CI, 0.64-0.77)]. Visual analysis showed a sensitivity of 0.73 (95%CI,0.65-0.81) and a specificity of 0.88(95%CI,0.80-0.95). The LI cutoff of 1.50 resulted the highest Youden Index of 0.59, with a sensitivity of 0.68 (95%CI,0.59-0.76) and a specificity of 0.91 (95%CI,0.83-0.96). When the LI cutoff was increased to 1.65, the sensitivity reduced to 0.61 (95%CI,0.53-0.70), while the specificity increased to 0.96 (95%CI,0.89-1.00). Conclusion: Both LI and visual analysis of PET/CT could be used in the classification diagnosis of PA. Nevertheless, visual analysis is more sensitive, and LI is more advantageous in specificity.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141780585","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":"Predicting Type 2 Diabetes Metabolic Phenotypes Using Continuous Glucose Monitoring and a Machine Learning Framework","authors":"Ahmed A. Metwally, Dalia Perelman, Heyjun Park, Yue Wu, Alokkumar Jha, Seth Sharp, Alessandra Celli, Ekrem Ayhan, Fahim Abbasi, Anna L Gloyn, Tracey McLaughlin, Michael Snyder","doi":"10.1101/2024.07.20.24310737","DOIUrl":"https://doi.org/10.1101/2024.07.20.24310737","url":null,"abstract":"Type 2 diabetes (T2D) and prediabetes are classically defined by the level of fasting glucose or surrogates such as hemoglobin A1c. This classification does not take into account the heterogeneity in the pathophysiology of glucose dysregulation, the identification of which could inform targeted approaches to diabetes treatment and prevention and/or predict clinical outcomes. We performed gold-standard metabolic tests in a cohort of individuals with early glucose dysregulation and quantified four distinct metabolic subphenotypes known to contribute to glucose dysregulation and T2D: muscle insulin resistance, beta-cell dysfunction, impaired incretin action, and hepatic insulin resistance. We revealed substantial inter-individual heterogeneity, with 44% of individuals exhibiting dominance in muscle or liver IR, and 16%, 13%, and 9% exhibiting dominance in beta-cell, incretin, or both, respectively. Further, with a frequently-sampled oral glucose tolerance test (OGTT), we developed a novel machine learning framework to predict metabolic subphenotypes using features from the dynamic patterns of the glucose time-series (\"shape of the glucose curve\"). The glucose time-series features identified insulin resistance, beta-cell deficiency, and incretin defect with auROCs of 95%, 89%, and 88%, respectively. These figures are superior to currently-used estimates. The prediction of muscle insulin resistance and beta-cell deficiency were validated using an independent cohort. We then tested the ability of glucose curves generated by a continuous glucose monitor (CGM) worn during at-home OGTTs to predict insulin resistance and beta-cell deficiency, yielding auROC of 88% and 84%, respectively. We thus demonstrate that the prediabetic state is characterized by metabolic heterogeneity, which can be defined by the shape of the glucose curve during standardized OGTT, performed in a clinical research unit or at-home setting using CGM. The use of at-home CGM to identify muscle insulin resistance and beta-cell deficiency constitutes a practical and scalable method by which to risk stratify individuals with early glucose dysregulation and inform targeted treatment to prevent T2D.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141780590","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":"A ONECUT1 regulatory, non-coding region in pancreatic development and diabetes","authors":"Sarah Merz, Valerie Senee, Anne Philippi, Franz Oswald, Mina Shaigan, Marita Fuehrer, Cosima Drewes, Chantal Allgoewer, Rupert Oellinger, Martin Heni, Anne Boland, Jean-Francois Deleuze, Franziska Birkhofer, Eduardo G Gusmao, Martin Wagner, Meike Hohwieler, Markus Breunig, Roland Rad, Reiner Siebert, David Alexander Christian Messerer, Ivan Gesteira Costa Filho, Fernando Alvarez, Cecile Julier, Sandra Heller, Alexander Kleger","doi":"10.1101/2024.07.23.24310605","DOIUrl":"https://doi.org/10.1101/2024.07.23.24310605","url":null,"abstract":"In a patient with permanent neonatal syndromic diabetes clinically similar to cases with ONECUT1 biallelic mutations, we identified a disease-causing deletion located upstream of ONECUT1. Through genetic, genomic and functional studies we identified a crucial regulatory region acting as an enhancer of ONECUT1 specifically during pancreatic development. This enhancer region contains a low-frequency variant showing strong association with type 2 diabetes and other glycemic traits, thus extending the contribution of this region to common forms of diabetes. Clinical relevance is provided by experimentally tailored therapy options for patients carrying ONECUT1 coding or regulatory mutations.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141780591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of polyunsaturated fatty acids with cholelithiasis risk and the role of plasma lipid mediators: insights from NHANES 2017-2020 and Mendelian randomization","authors":"Yuxuan Chen, Wei Chen, Jin Qian, Xuanchen Jin, Congying Wang, Yihu Zheng","doi":"10.1101/2024.07.22.24310765","DOIUrl":"https://doi.org/10.1101/2024.07.22.24310765","url":null,"abstract":"Abstract\u0000Background & aims\u0000Previous studies have suggested a potential link between polyunsaturated fatty acid (PUFA) intake and the risk of cholelithiasis. Omega–3 fatty acids, a key subfamily of PUFAs, have been identified in observational studies as playing a role in lipid regulation and potentially serving as a protective factor against cholelithiasis. In this study, we aim to investigate this association further by analyzing data from the 2017 – 2020 National Health and Nutrition Examination Survey (NHANES) and conducting Mendelian randomization (MR) analyses.\u0000Methods\u0000We employed weighted multivariate–adjusted logistic regression analyses to examine the association between PUFAs and cholelithiasis risk using data from NHANES 2017 – 2020. Additionally, a two–sample Mendelian randomization (MR) study was conducted utilizing pooled data from Genome-Wide Association Studies (GWAS) to establish the causal relationship between PUFAs and cholelithiasis. Following this, we performed two–step MR mediation analyses to investigate the mediating role of plasma lipids in the pathway, focusing on the strongly positive subfamily of PUFAs, Omega–3, in relation to plasma circulating lipids and cholelithiasis.\u0000Results\u0000Our observational study in NHANES included 7,527 participants. Weighted multivariate–adjusted logistic regression analyses initially revealed a negative association between PUFAs, their subclasses, and cholelithiasis. However, this association became nonsignificant after adjusting for multiple covariates. In contrast, MR analyses identified a significant negative association between PUFAs (OR=0.75 [95% CI, 0.58~0.98]) and Omega–3 (OR=0.79 [95% CI, 0.7~0.9]) and the risk of cholelithiasis. Specifically, Omega–3 was associated with a reduced risk of developing cholelithiasis (OR=0.77 [95% CI, 0.65~0.91]), possibly due to the upregulation of LDL–C levels (Beta=0.24 [95% CI, 0.1~0.38]). This upregulation of LDL–C subsequently lowered the risk of cholelithiasis (OR=0.77 [95% CI, 0.65~0.91]), with the mediating effect of LDL–C accounting for 28% of the overall association.\u0000Conclusions\u0000Both cross–sectional observational analyses and Mendelian randomization (MR) analyses demonstrated a negative correlation between polyunsaturated fatty acids (PUFAs) and cholelithiasis. Omega–3 fatty acids seem to play a key role in this association by increasing plasma LDL–C levels, which in turn may help reduce the risk of cholelithiasis.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141780586","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":"Fecal microbiome predicts treatment response after the initiation of semaglutide or empagliflozin uptake","authors":"Annabel Klemets, Ingrid Reppo, Kertu Liis Krigul, Vallo Volke, Oliver Aasmets, Elin Org","doi":"10.1101/2024.07.19.24310611","DOIUrl":"https://doi.org/10.1101/2024.07.19.24310611","url":null,"abstract":"Background. The gut microbiome has been shown to be affected by the use of many human-targeted medications, and the interaction can be bidirectional. This has been clearly demonstrated for type 2 diabetes medications that have been in clinical use for several decades. However, the bidirectional effects of novel type 2 diabetes drugs semaglutide, empagliflozin, and the gut microbiome have yet to be clearly described. Objective. We investigate the effect of semaglutide and empagliflozin initiation on the gut microbiome of type 2 diabetes patients. In addition, we analyze whether the pre-treatment gut microbiome can predict the treatment efficacy. Methods. Gut microbiome fecal samples donated at four timepoints (Baseline, Month 1, Month 3; Month 12) were studied using 16S ribosomal RNA gene sequencing and analysis. Subjects additionally donated plasma and urine samples for quantitative measurement of clinical markers before treatment initiation and at Months 3 and 12. Repeated measures ANOVA paired with paired t-tests were used to analyze the effects of drug initiation on the gut microbiome. Pearson correlation was used to identify microbial features associated with the change in clinical parameters. Results. Semaglutide and empagliflozin use is associated with changes in the gut microbiome after treatment initiation, but changes in microbial diversity were not detected. The baseline gut microbiome predicted changes in glycohemoglobin for semaglutide and empagliflozin users. Conclusion. Our findings suggest that semaglutide and empagliflozin impact the gut microbial community during treatment. In addition, the baseline gut microbiome can predict semaglutide treatment effects.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141746449","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":"Determinants of glycemic control among persons living with type 2 diabetes mellitus attending a district hospital in Ghana","authors":"ALEXANDER ADJEI, KENNEDY TETTEY COFFIE BRIGHTSON, MICHAEL MATEY MENSAH, JEMIMA OSEI, MOSES DRAH, CLEMENT TETTEH NARH, KWABENA ASARE, FRANCIS ANTO","doi":"10.1101/2024.07.18.24310634","DOIUrl":"https://doi.org/10.1101/2024.07.18.24310634","url":null,"abstract":"Background\u0000Diabetes mellitus is a growing public health emergency with prevalence in sub-Sahara Africa expected to experience the highest increase by 2045. The cornerstone of diabetes management is glycemic control, a complex process with different contributing factors. This study determines the level of glycemic control and the associated individual factors among type 2 diabetes mellitus (T2DM) patients.\u0000Methods\u0000A cross-sectional descriptive study was conducted at the Shai-Osudoku District Hospital from October to December 2022. A structured questionnaire was used to collect data on socio-demographic characteristics, lifestyle modifications, co-morbidities, adherence to medication and diet regimens and duration of diabetes. Anthropometric and glycated hemoglobin (HbA1c) measurements were taken. Chi-squared and multivariate logistic regression analyses were carried out to determine factors associated with glycemic control at 95% confidence levels.\u0000Results\u0000A total of 227 patients participated in this study. The majority of the participants were females (77.97%) and the mean (+SD) age was 60.76 + 12.12 years. Good glycemic control (HbA1c < 7%) among the participants was 38.77% (n=88) and the median HbA1c was 7.5% (IQR: 6.5% to 9.4%). Significant factors associated with good glycemic control were eating healthy meals (AOR: 4.78, 95% CI: 1.65, 13.88: p=0.004), oral hypoglycemic agents alone (AOR: 15.71, 95% CI: 1.90, 129.44: p=0.010) and those with previously good glycemic control (AOR: 4.27, 95% CI: 2.16, 8.43: <0.001). Conclusion\u0000This study showed low levels of good glycemic control among T2DM patients at the primary care level in Ghana. Healthy eating, oral hypoglycemic agents and those with previously normal HbA1c were associated with glycemic control.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141743686","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":"Is aging acceleration mediating the association between hemoglobin glycation index and cardiovascular disease?","authors":"Na Liu, Yun Li, Mengying Li, Yi Wang, Bo Li, Yongqiang Lian, Jianfang Fu, Xiaomiao Li, Jie Zhou","doi":"10.1101/2024.07.11.24310308","DOIUrl":"https://doi.org/10.1101/2024.07.11.24310308","url":null,"abstract":"Background: The potential factors beyond HbA1c that increase the risk of cardiovascular disease and age more quickly in people with diabetes are not yet clear. This study sought to determine the prospective associations between discrepancies in observed and predicted HbA1c levels, also known as the hemoglobin glycation index (HGI), and cardiovascular disease risk. Additionally, the interactions of HGI with accelerated aging in relation to cardiovascular disease risk were evaluated.\u0000Method: This cross-sectional study included 9167 adults from the National Health and Nutrition Examination Survey 1999-2010. The HGI is used to assess individual blood glucose variability, and phenotypic age acceleration is employed to evaluate accelerated aging. Regression analysis, restricted cubic spline and mediation analysis explore the potential roles of phenotypic age acceleration in the relationship between HGI and CVD mortality.\u0000Results: Among the 9167 eligible participants (aged 20 years or older), 4390 (47.9%) were males, and the median (IQR) age was 48.0 (15.0) years; 4403 (48.0%) had prediabetes and diabetes, and 985 (10.7%) had cardiovascular disease. Restricted cubic splines showed that the association between HGI and CVD risk was nonlinear (p < 0.001). The greater the negative value of the HGI was, the greater the risk of CVD, and the association was independent of age, sex and HbA1c. Mediation analyses confirmed that phenotypic age acceleration acted as a mediator in the association between HGI and CVD risk (mediated effect: OR, 68.7%, 95% CI: 36.4%-153%, P=0.002).\u0000Conclusion and Relevance: The HGI serves as a robust biomarker for assessing the acceleration of aging, regardless of HbA1c levels, and is associated with increased susceptibility to cardiovascular disease, particularly among individuals characterized by negative HGI.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141612362","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":"Free cortisol and free 21-deoxycortisol in the clinical evaluation of congenital adrenal hyperplasia","authors":"Bas P.H. Adriaansen, Agustini Utari, Andre J. Olthaar, Rob C.B.M. van der Steen, Karijn J. Pijnenburg-Kleizen, Lizanne Berkenbosch, Paul N. Span, Fred C.G.J. Sweep, Hedi L. Claahsen - van der Grinten, Antonius E. van Herwaarden","doi":"10.1101/2024.07.11.24310065","DOIUrl":"https://doi.org/10.1101/2024.07.11.24310065","url":null,"abstract":"Context: Some patients with classic congenital adrenal hyperplasia (CAH) survive without glucocorticoid treatment. Increased precursor concentrations in these patients might lead to higher free (biological active) cortisol concentrations by influencing the cortisol-protein binding. In 21-hydroxylase deficiency (21OHD), the most common CAH form, accumulated 21-deoxycortisol (21DF), a precursor steroid, may further increase glucocorticoid activity. Both mechanisms could explain the low occurrence of symptoms in some untreated classic CAH patients.\u0000Objective: Establishment and validation of an LC-MS/MS method for (free) cortisol and (free) 21DF to quantify these steroids in untreated patients with classic CAH (n=29), non-classic CAH (NCCAH, n=5), other forms of adrenal insufficiency (AI, n=3), and controls (n=11) before and 60 minutes after Synacthen administration. Results: Unstimulated total cortisol levels of untreated classic CAH patients (median 109 nmol/L) were lower compared to levels in untreated NCCAH patients (249 nmol/L, p=0.010) and controls (202 nmol/L, p=0.016), but free cortisol concentrations were similar. Basal free 21DF levels were high in 21OHD patients (median 5.32 nmol/L) and undetectable in AI patients and controls (<0.19 nmol/L). After Synacthen administration, free concentrations of 21DF -but not cortisol- increased only in patients with 21OHD.\u0000Conclusions: Free cortisol levels were similar in classic CAH compared to controls and NCCAH patients, suggesting a comparable availability of cortisol. Additionally, 21OHD patients produce high levels of the glucocorticoid 21DF, possibly explaining the low occurrence of symptoms in some classic 21OHD patients. Free cortisol and (free) 21DF levels should be considered in the clinical evaluation of adrenal insufficiency in patients with CAH.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141612365","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}