Background: Sedentary behavior has emerged as a potential risk factor for various health issues, including hormonal imbalances like testosterone deficiency (TD). However, the relationship between sedentary time and TD remains underexplored, especially with respect to the complex biological mechanisms underlying this association. This study aimed to examine the association between sedentary time and TD in adult males.
Methods: This cross-sectional study analyzed data from the National Health and Nutrition Examination Survey 2011-2016. A total of 6057 male participants aged 20 years and older were included. Sedentary time was categorized into quartiles, and TD was defined as serum testosterone levels below 300 ng/dL. Logistic regression models were employed to assess the association between sedentary time and TD, adjusting for demographic, lifestyle, and health-related covariates. Restricted cubic spline (RCS) analysis and segmented regression were also conducted to explore potential non-linear relationships and thresholds. Subgroup analyses were performed to examine the consistency of associations across various groups.
Results: The analysis revealed a significant positive association between sedentary time and TD. Prolonged sedentary behaviour was consistently associated with higher odds of TD across all models (all p < 0.001). RCS analysis showed a significant non-linear relationship, particularly as sedentary time exceeded 4.5 h per day, with a marked increase in the likelihood of TD (p-non-linear = 0.027). Subgroup analysis indicated that this association was most pronounced in Non-Hispanic Whites, current smokers, and drinkers, and was weaker in individuals with diabetes, where the association lost statistical significance after full adjustment.
Conclusions: This study identifies a significant association between prolonged sedentary behaviour and a higher risk of TD, suggesting that sedentary behavior may play a key role in the development of TD, particularly in specific high-risk populations.
{"title":"Exploring the non-linear association and threshold effect of sedentary behavior on testosterone deficiency.","authors":"Liangchun Cai, Haiping Xie, Wue Li, Chuhui Chen, Ting Li, Lizhen Xu, Yaqian Mao, Jixing Liang, Junping Wen, Gang Chen","doi":"10.1007/s12020-025-04199-7","DOIUrl":"https://doi.org/10.1007/s12020-025-04199-7","url":null,"abstract":"<p><strong>Background: </strong>Sedentary behavior has emerged as a potential risk factor for various health issues, including hormonal imbalances like testosterone deficiency (TD). However, the relationship between sedentary time and TD remains underexplored, especially with respect to the complex biological mechanisms underlying this association. This study aimed to examine the association between sedentary time and TD in adult males.</p><p><strong>Methods: </strong>This cross-sectional study analyzed data from the National Health and Nutrition Examination Survey 2011-2016. A total of 6057 male participants aged 20 years and older were included. Sedentary time was categorized into quartiles, and TD was defined as serum testosterone levels below 300 ng/dL. Logistic regression models were employed to assess the association between sedentary time and TD, adjusting for demographic, lifestyle, and health-related covariates. Restricted cubic spline (RCS) analysis and segmented regression were also conducted to explore potential non-linear relationships and thresholds. Subgroup analyses were performed to examine the consistency of associations across various groups.</p><p><strong>Results: </strong>The analysis revealed a significant positive association between sedentary time and TD. Prolonged sedentary behaviour was consistently associated with higher odds of TD across all models (all p < 0.001). RCS analysis showed a significant non-linear relationship, particularly as sedentary time exceeded 4.5 h per day, with a marked increase in the likelihood of TD (p-non-linear = 0.027). Subgroup analysis indicated that this association was most pronounced in Non-Hispanic Whites, current smokers, and drinkers, and was weaker in individuals with diabetes, where the association lost statistical significance after full adjustment.</p><p><strong>Conclusions: </strong>This study identifies a significant association between prolonged sedentary behaviour and a higher risk of TD, suggesting that sedentary behavior may play a key role in the development of TD, particularly in specific high-risk populations.</p>","PeriodicalId":11572,"journal":{"name":"Endocrine","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-26DOI: 10.1007/s12020-025-04207-w
Jingxin Li, Xiaomin Wang, Jingcheng Wu, Dandan Geng, Fan Li, Yang Liu, Yanhong Shen
Objective: This meta-analysis aimed to compare the efficacy and safety of iGlarLixi with those of insulin glargine for treating type 2 diabetes (T2D).
Methods: A systematic search of PubMed, the Cochrane Library, and EMBASE was conducted to identify randomized controlled trials (RCTs) that compared the use of iGlarLixi with the use of insulin glargine in patients with T2D. The meta-analysis protocol was registered at PROSPERO. The primary outcomes of interest were changes in hemoglobin A1c (HbA1c) and body weight. Risk ratios and mean differences with 95% confidence intervals were calculated using random-effects models.
Results: We included 7 RCTs comprising 2229 men and 1926 women, of whom 2075 (49.94%) were randomized to iGlarLixi. Compared with insulin glargine, iGlarLixi decreased HbA1c (MD: -0.50%; 95% CI: -0.65% to -0.35%; p < 0.00001) and body weight (MD: -1.17 kg; 95% CI: -1.36 kg to -0.98 kg; p < 0.00001) and self-measured plasma glucose (MD: -0.97 mmol/L; 95% CI: -1.27 mmol/L to -0.68 mmol/L; p < 0.00001) and increased the percentage of patients achieving HbA1c < 7% (RR: 1.66; 95% CI: 1.31 to 2.11; p < 0.0001), the percentage of patients achieving HbA1c < 6.5% (RR: 2.11; 95% CI: 1.53 to 2.92; p < 0.00001), and HbA1c < 7.0% without weight gain and/or without severe or blood glucose-confirmed hypoglycemic episodes (RR: 2.18; 95% CI: 1.76 to 2.69; p < 0.00001). However, a higher incidence of gastrointestinal adverse events (RR: 2.02; 95% CI: 1.61 to 2.54; p < 0.00001) and adverse events (RR: 1.08; 95% CI: 1.02 to 1.14; p = 0.008) was associated with iGlarLixi than with insulin glargine.
Conclusions: Compared with insulin glargine, iGlarLixi is superior in reducing blood glucose levels and facilitating weight loss. Nevertheless, its administration is also linked to a heightened occurrence of gastrointestinal and adverse events.
{"title":"Efficacy and safety of iGlarLixi versus insulin glargine in type 2 diabetes: a meta-analysis of randomized controlled trials.","authors":"Jingxin Li, Xiaomin Wang, Jingcheng Wu, Dandan Geng, Fan Li, Yang Liu, Yanhong Shen","doi":"10.1007/s12020-025-04207-w","DOIUrl":"https://doi.org/10.1007/s12020-025-04207-w","url":null,"abstract":"<p><strong>Objective: </strong>This meta-analysis aimed to compare the efficacy and safety of iGlarLixi with those of insulin glargine for treating type 2 diabetes (T2D).</p><p><strong>Methods: </strong>A systematic search of PubMed, the Cochrane Library, and EMBASE was conducted to identify randomized controlled trials (RCTs) that compared the use of iGlarLixi with the use of insulin glargine in patients with T2D. The meta-analysis protocol was registered at PROSPERO. The primary outcomes of interest were changes in hemoglobin A1c (HbA1c) and body weight. Risk ratios and mean differences with 95% confidence intervals were calculated using random-effects models.</p><p><strong>Results: </strong>We included 7 RCTs comprising 2229 men and 1926 women, of whom 2075 (49.94%) were randomized to iGlarLixi. Compared with insulin glargine, iGlarLixi decreased HbA1c (MD: -0.50%; 95% CI: -0.65% to -0.35%; p < 0.00001) and body weight (MD: -1.17 kg; 95% CI: -1.36 kg to -0.98 kg; p < 0.00001) and self-measured plasma glucose (MD: -0.97 mmol/L; 95% CI: -1.27 mmol/L to -0.68 mmol/L; p < 0.00001) and increased the percentage of patients achieving HbA1c < 7% (RR: 1.66; 95% CI: 1.31 to 2.11; p < 0.0001), the percentage of patients achieving HbA1c < 6.5% (RR: 2.11; 95% CI: 1.53 to 2.92; p < 0.00001), and HbA1c < 7.0% without weight gain and/or without severe or blood glucose-confirmed hypoglycemic episodes (RR: 2.18; 95% CI: 1.76 to 2.69; p < 0.00001). However, a higher incidence of gastrointestinal adverse events (RR: 2.02; 95% CI: 1.61 to 2.54; p < 0.00001) and adverse events (RR: 1.08; 95% CI: 1.02 to 1.14; p = 0.008) was associated with iGlarLixi than with insulin glargine.</p><p><strong>Conclusions: </strong>Compared with insulin glargine, iGlarLixi is superior in reducing blood glucose levels and facilitating weight loss. Nevertheless, its administration is also linked to a heightened occurrence of gastrointestinal and adverse events.</p>","PeriodicalId":11572,"journal":{"name":"Endocrine","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-25DOI: 10.1007/s12020-025-04192-0
Anja Wasmuth, Iris van de Loo, Julia Domberg, Birgit Harbeck
Purpose: Patients with adrenal insufficiency (AI) are known to have a higher cardiovascular risk (CVR) than the normal population. In particular arteriosclerosis, coronary heart disease, arterial hypertension, hyperlipoproteinemia as well as metabolic disturbances contribute to the increased morbidity and mortality. Aim of this study was to evaluate known CVR factors along with the quality of care by the treating physicians.
Methods: To this end the medical records of AI patients were screened for CVR factors and the treatment initiated was documented. In addition, a questionnaire evaluating CVR factors was analyzed if available.
Results: In total, 327 AI patients were included in the study. At least 298 of these patients were found to have one or more CVR factors. Ninety-one patients were diagnosed with arterial hypertension, of these 40 patients (44%) still showed increased blood pressure (BP) values. Of all AI patients, about 25% (n = 83) did not have measurements to calculate their BMI, even though obesity is known as a major risk factor for cardiovascular events. Out of 46 patients with diabetes, one-quarter still had increased HbA1c values. Regarding hyperlipoproteinemia, only 2% of AI patients achieved normal lipid values across all parameters (n = 8). Interestingly, at least one lipid variable was untested in 150 patients (46%).
Conclusion: Our study demonstrates (1) the high rate of CVR factors in AI patients, leading to increased morbidity and eventually mortality, (2) AI patients are inadequately monitored and treated for CVR factors, (3) treating physicians should be aware of this risk to minimize complications where possible.
{"title":"Ignored or underestimated - evaluation and treatment of cardiovascular risk factors in patients with adrenal insufficiency.","authors":"Anja Wasmuth, Iris van de Loo, Julia Domberg, Birgit Harbeck","doi":"10.1007/s12020-025-04192-0","DOIUrl":"https://doi.org/10.1007/s12020-025-04192-0","url":null,"abstract":"<p><strong>Purpose: </strong>Patients with adrenal insufficiency (AI) are known to have a higher cardiovascular risk (CVR) than the normal population. In particular arteriosclerosis, coronary heart disease, arterial hypertension, hyperlipoproteinemia as well as metabolic disturbances contribute to the increased morbidity and mortality. Aim of this study was to evaluate known CVR factors along with the quality of care by the treating physicians.</p><p><strong>Methods: </strong>To this end the medical records of AI patients were screened for CVR factors and the treatment initiated was documented. In addition, a questionnaire evaluating CVR factors was analyzed if available.</p><p><strong>Results: </strong>In total, 327 AI patients were included in the study. At least 298 of these patients were found to have one or more CVR factors. Ninety-one patients were diagnosed with arterial hypertension, of these 40 patients (44%) still showed increased blood pressure (BP) values. Of all AI patients, about 25% (n = 83) did not have measurements to calculate their BMI, even though obesity is known as a major risk factor for cardiovascular events. Out of 46 patients with diabetes, one-quarter still had increased HbA1c values. Regarding hyperlipoproteinemia, only 2% of AI patients achieved normal lipid values across all parameters (n = 8). Interestingly, at least one lipid variable was untested in 150 patients (46%).</p><p><strong>Conclusion: </strong>Our study demonstrates (1) the high rate of CVR factors in AI patients, leading to increased morbidity and eventually mortality, (2) AI patients are inadequately monitored and treated for CVR factors, (3) treating physicians should be aware of this risk to minimize complications where possible.</p>","PeriodicalId":11572,"journal":{"name":"Endocrine","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-22DOI: 10.1007/s12020-025-04203-0
José María Jiménez Cassinello, Arturo Vega-Beyhart, María Bernarda Iriarte, Sara Donato, Aura D Herrera-Martínez, Mónica Marazuela, Marta Araujo-Castro
Introduction: Mild autonomous cortisol secretion (MACS) is associated with several cardiometabolic and non-metabolic comorbidities, including osteoporosis, fractures and worse quality of life (QoL).
Methods: We performed a comprehensive review of the literature including articles that reported the association between MACS and osteoporosis, fractures and impact on QoL.
Results: In relation to bone health, several studies reported that the risk of fractures in patients with MACS is discordant with the degree of bone mineral density loss measured per dual X-ray absorptiometry (DXA), suggesting that a reduction in bone quality rather than density contributes to the increased fracture risk. Nevertheless, in general a greater prevalence of vertebral fractures has been described in MACS compared with nonfunctioning adrenal incidentalomas (NFAIs) patients. Regarding QoL, due to the higher burden of comorbidities and the adverse symptoms linked to MACS diagnosis, MACS patients are overall frailer and have worse QoL than patients with NFAIs or the general population. Higher levels of disability related to mental health, middle insomnia and perceived stress have also been described in patients with MACS when compared to NFAIs patients.
Conclusion: MACS patients have a higher prevalence of fractures and osteoporosis, as well as a worse QoL compared to NFAIs and the general population. Thus, both bone health and QoL evaluation should be part of the assessment of patients with MACS diagnosis.
{"title":"Mild autonomous cortisol secretion: impact on bone health and quality of life. A review.","authors":"José María Jiménez Cassinello, Arturo Vega-Beyhart, María Bernarda Iriarte, Sara Donato, Aura D Herrera-Martínez, Mónica Marazuela, Marta Araujo-Castro","doi":"10.1007/s12020-025-04203-0","DOIUrl":"https://doi.org/10.1007/s12020-025-04203-0","url":null,"abstract":"<p><strong>Introduction: </strong>Mild autonomous cortisol secretion (MACS) is associated with several cardiometabolic and non-metabolic comorbidities, including osteoporosis, fractures and worse quality of life (QoL).</p><p><strong>Methods: </strong>We performed a comprehensive review of the literature including articles that reported the association between MACS and osteoporosis, fractures and impact on QoL.</p><p><strong>Results: </strong>In relation to bone health, several studies reported that the risk of fractures in patients with MACS is discordant with the degree of bone mineral density loss measured per dual X-ray absorptiometry (DXA), suggesting that a reduction in bone quality rather than density contributes to the increased fracture risk. Nevertheless, in general a greater prevalence of vertebral fractures has been described in MACS compared with nonfunctioning adrenal incidentalomas (NFAIs) patients. Regarding QoL, due to the higher burden of comorbidities and the adverse symptoms linked to MACS diagnosis, MACS patients are overall frailer and have worse QoL than patients with NFAIs or the general population. Higher levels of disability related to mental health, middle insomnia and perceived stress have also been described in patients with MACS when compared to NFAIs patients.</p><p><strong>Conclusion: </strong>MACS patients have a higher prevalence of fractures and osteoporosis, as well as a worse QoL compared to NFAIs and the general population. Thus, both bone health and QoL evaluation should be part of the assessment of patients with MACS diagnosis.</p>","PeriodicalId":11572,"journal":{"name":"Endocrine","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Obesity is among the important healthcare issues in which there is an abnormal increase in body fat because energy intake is higher than energy expenditure. The Tumor Necrosis Factor (TNF)-alpha overexpression in adipose tissue plays important roles in mediating obesity and insulin resistance. "TNF-related apoptosis-inducing Ligand (TRAIL(TNSF10))", which is a member of the TNF family, is expressed as a Type-II Transmembrane Protein with an effect on the development of obesity and diabetes.
Methods: The rs781673405, rs1244378045, rs767450259, rs750556128, rs369143448, rs143353036, and rs759369504 polymorphisms of TRAIL, which were determined to play protective roles against diabetes, were evaluated with the RT-qPZR Method in the present study.
Results: It was found that the genotype distribution of TRAIL rs767450259 Polymorphism was significant and the T-Allele had protective effects against diabetic obesity. It was also found that the G-Allele of the rs369143448 Polymorphism had protective roles against diabetic obesity. It was shown that carrying the A-Allele in the rs750556128 Polymorphism might increase the risk of obesity in diabetic patients by 1.3-fold.
Conclusions: The present study makes a significant contribution to the literature data because it is the first to investigate these polymorphisms.
{"title":"Evaluation of rs781673405, rs1244378045, rs767450259, rs750556128, rs369143448, rs143353036, and rs759369504 mutations in terms of polymorphism in diabetic obese and non-diabetic obese individuals.","authors":"Saadet Busra Aksoyer Sezgin, Sermin Durak, Faruk Celik, Varol Guler, Aysegul Sarikaya, Umit Zeybek","doi":"10.1007/s12020-025-04184-0","DOIUrl":"https://doi.org/10.1007/s12020-025-04184-0","url":null,"abstract":"<p><strong>Background: </strong>Obesity is among the important healthcare issues in which there is an abnormal increase in body fat because energy intake is higher than energy expenditure. The Tumor Necrosis Factor (TNF)-alpha overexpression in adipose tissue plays important roles in mediating obesity and insulin resistance. \"TNF-related apoptosis-inducing Ligand (TRAIL(TNSF10))\", which is a member of the TNF family, is expressed as a Type-II Transmembrane Protein with an effect on the development of obesity and diabetes.</p><p><strong>Methods: </strong>The rs781673405, rs1244378045, rs767450259, rs750556128, rs369143448, rs143353036, and rs759369504 polymorphisms of TRAIL, which were determined to play protective roles against diabetes, were evaluated with the RT-qPZR Method in the present study.</p><p><strong>Results: </strong>It was found that the genotype distribution of TRAIL rs767450259 Polymorphism was significant and the T-Allele had protective effects against diabetic obesity. It was also found that the G-Allele of the rs369143448 Polymorphism had protective roles against diabetic obesity. It was shown that carrying the A-Allele in the rs750556128 Polymorphism might increase the risk of obesity in diabetic patients by 1.3-fold.</p><p><strong>Conclusions: </strong>The present study makes a significant contribution to the literature data because it is the first to investigate these polymorphisms.</p>","PeriodicalId":11572,"journal":{"name":"Endocrine","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-11DOI: 10.1007/s12020-025-04173-3
Carla Columbu, Domenico Rendina, Luigi Gennari, Flavia Pugliese, Vincenzo Carnevale, Antonio Stefano Salcuni, Iacopo Chiodini, Claudia Battista, Patrizia Tabacco, Vito Guarnieri, Giuseppe Guglielmi, Cristina Eller-Vainicher, Cristiana Cipriani, Antonello Cuttitta, Gianpaolo De Filippo, Fernanda Velluzzi, Alberto Falchetti, Salvatore Minisola, Afredo Scillitani, Fabio Vescini
Purpose: Parathyroid hormone controls calcium and phosphate metabolism. The latter is also regulated by both FGF23 and 1-25(OH)2VitaminD. The polymorphic variant c.716 C > T of the FGF23 gene was previously found to be associated with renal phosphate leak/nephrolithiasis. The aim of our research is to study the metabolism of phosphate in a cohort of patients with primary hyperparathyroidism (PHPT) and its impact on bone and kidney.
Methods: We have retrospectively compared a large sample of sporadic PHPT patients (339) with historical comparison cohort (HCC 503: Olivetti Study Group and Siena Osteoporosis Study). Moreover, in 51 PHPT patients, phosphate metabolism indexes were also revaluated at least 2 years after surgical cure. The variant c.716 C > T of the FGF23 gene was genotyped in patients and in a small sample of the control group.
Results: In PHPT patients we found higher levels of serum calcium, PTH, alkaline phosphatase, beta-C-terminal telopeptide (CTx), urinary calcium, while serum phosphate, 25OH-VitaminD, maximal tubular renal phosphate reabsorption adjusted for glomerular filtration rate (TmPO4/GFR) were lower than what was found in HCC. In PHPT patients fibroblast growth factor 23 (FGF23) levels were higher than in controls. Patients with kidney stones carried the 716 T allele more frequently than patients without it (χ2 7.20, p = 0.027). In PHPT patients revaluated at least 2 years after surgery, we observed a significant reduction of 1-25(OH)2VitaminD and FGF23. According to the median of serum phosphate levels, PHPT patients were subdivided into two subgroups: ≤2.8 mg/dL and > 2.8 mg/dL. The lowest phosphate group had a significantly higher serum calcium, PTH, 1-25(OH)2VitaminD, urinary calcium and a higher prevalence of kidney stones than in the highest phosphate group. The rate of males in the lowest phosphate group was significantly higher than in the highest phosphate group.
Conclusion: Our study shows that the regulators of phosphate metabolism in PHPT patients are higher than controls and they significantly reduce after surgical cure. PHPT patients with low serum phosphate have a worse biochemical and clinical phenotype.
{"title":"Phosphate metabolism in primary hyperparathyroidism: a real-life long-term study.","authors":"Carla Columbu, Domenico Rendina, Luigi Gennari, Flavia Pugliese, Vincenzo Carnevale, Antonio Stefano Salcuni, Iacopo Chiodini, Claudia Battista, Patrizia Tabacco, Vito Guarnieri, Giuseppe Guglielmi, Cristina Eller-Vainicher, Cristiana Cipriani, Antonello Cuttitta, Gianpaolo De Filippo, Fernanda Velluzzi, Alberto Falchetti, Salvatore Minisola, Afredo Scillitani, Fabio Vescini","doi":"10.1007/s12020-025-04173-3","DOIUrl":"https://doi.org/10.1007/s12020-025-04173-3","url":null,"abstract":"<p><strong>Purpose: </strong>Parathyroid hormone controls calcium and phosphate metabolism. The latter is also regulated by both FGF23 and 1-25(OH)<sub>2</sub>VitaminD. The polymorphic variant c.716 C > T of the FGF23 gene was previously found to be associated with renal phosphate leak/nephrolithiasis. The aim of our research is to study the metabolism of phosphate in a cohort of patients with primary hyperparathyroidism (PHPT) and its impact on bone and kidney.</p><p><strong>Methods: </strong>We have retrospectively compared a large sample of sporadic PHPT patients (339) with historical comparison cohort (HCC 503: Olivetti Study Group and Siena Osteoporosis Study). Moreover, in 51 PHPT patients, phosphate metabolism indexes were also revaluated at least 2 years after surgical cure. The variant c.716 C > T of the FGF23 gene was genotyped in patients and in a small sample of the control group.</p><p><strong>Results: </strong>In PHPT patients we found higher levels of serum calcium, PTH, alkaline phosphatase, beta-C-terminal telopeptide (CTx), urinary calcium, while serum phosphate, 25OH-VitaminD, maximal tubular renal phosphate reabsorption adjusted for glomerular filtration rate (TmPO4/GFR) were lower than what was found in HCC. In PHPT patients fibroblast growth factor 23 (FGF23) levels were higher than in controls. Patients with kidney stones carried the 716 T allele more frequently than patients without it (χ<sup>2</sup> 7.20, p = 0.027). In PHPT patients revaluated at least 2 years after surgery, we observed a significant reduction of 1-25(OH)<sub>2</sub>VitaminD and FGF23. According to the median of serum phosphate levels, PHPT patients were subdivided into two subgroups: ≤2.8 mg/dL and > 2.8 mg/dL. The lowest phosphate group had a significantly higher serum calcium, PTH, 1-25(OH)<sub>2</sub>VitaminD, urinary calcium and a higher prevalence of kidney stones than in the highest phosphate group. The rate of males in the lowest phosphate group was significantly higher than in the highest phosphate group.</p><p><strong>Conclusion: </strong>Our study shows that the regulators of phosphate metabolism in PHPT patients are higher than controls and they significantly reduce after surgical cure. PHPT patients with low serum phosphate have a worse biochemical and clinical phenotype.</p>","PeriodicalId":11572,"journal":{"name":"Endocrine","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-11DOI: 10.1007/s12020-025-04165-3
Zixia Tao, Zheng Ding, Bomin Guo, Youben Fan, Xianzhao Deng
Purpose: Locally advanced thyroid cancer (LATC) has gained increased attention, yet factors influencing invasion patterns and their prognostic impact remain poorly understood.
Methods: Patients with LATC were identified from the Surveillance, Epidemiology, and End Results (SEER) program. Invasion patterns were visualized using bar graphs. Kaplan-Meier method and log-rank test analyzed outcomes by different invasion sites. Multivariable Cox regression analysis was conducted to adjust confounding factors and establish a new site-based risk stratification.
Results: Papillary thyroid carcinoma (PTC) predominantly invaded esophagus or larynx (21.0%) and trachea (26.3%), while follicular thyroid carcinoma/oncocytic thyroid carcinoma (FTC/OTC) mainly invaded blood vessel (31.3%). Anaplastic thyroid carcinoma (ATC) exhibited the highest rate of trachea invasion (33.3%) and multi-invasion (8.1%). Age, tumor size significantly influenced the proportion of trachea invasion (p < 0.001). Locally advanced PTC patients with different invasion sites demonstrated significantly different prognoses: 10-year OS rate of each invasion site was: parathyroid or nerve (82.5%), bone or skeletal muscle (76.6%), esophagus or larynx (68.7%), blood vessel (58.0%), trachea (57.5%), multi-invasion (26.8%). Based on multivariable Cox regression, a novel site-based risk stratification was established for locally advanced PTC patients, with trachea invasion (HR = 1.83, p < 0.001), blood vessel invasion (HR = 2.64, p < 0.001), and multi-invasion (HR = 2.76, p < 0.001) categorized as medium and high risk of mortality, respectively, demonstrating better discrimination than 8th AJCC staging system.
Conclusion: This study is the first to utilize population-based cohort to reveal factors influencing invasion sites and their prognostic differences. This study also proposed a new site-based risk stratification that builds upon 8th AJCC T staging for locally advanced PTC patients, which may facilitate more tailored clinical management strategies.
{"title":"Influence factors and survival outcomes of different invasion sites in locally advanced thyroid cancer and new site-based risk stratification system.","authors":"Zixia Tao, Zheng Ding, Bomin Guo, Youben Fan, Xianzhao Deng","doi":"10.1007/s12020-025-04165-3","DOIUrl":"https://doi.org/10.1007/s12020-025-04165-3","url":null,"abstract":"<p><strong>Purpose: </strong>Locally advanced thyroid cancer (LATC) has gained increased attention, yet factors influencing invasion patterns and their prognostic impact remain poorly understood.</p><p><strong>Methods: </strong>Patients with LATC were identified from the Surveillance, Epidemiology, and End Results (SEER) program. Invasion patterns were visualized using bar graphs. Kaplan-Meier method and log-rank test analyzed outcomes by different invasion sites. Multivariable Cox regression analysis was conducted to adjust confounding factors and establish a new site-based risk stratification.</p><p><strong>Results: </strong>Papillary thyroid carcinoma (PTC) predominantly invaded esophagus or larynx (21.0%) and trachea (26.3%), while follicular thyroid carcinoma/oncocytic thyroid carcinoma (FTC/OTC) mainly invaded blood vessel (31.3%). Anaplastic thyroid carcinoma (ATC) exhibited the highest rate of trachea invasion (33.3%) and multi-invasion (8.1%). Age, tumor size significantly influenced the proportion of trachea invasion (p < 0.001). Locally advanced PTC patients with different invasion sites demonstrated significantly different prognoses: 10-year OS rate of each invasion site was: parathyroid or nerve (82.5%), bone or skeletal muscle (76.6%), esophagus or larynx (68.7%), blood vessel (58.0%), trachea (57.5%), multi-invasion (26.8%). Based on multivariable Cox regression, a novel site-based risk stratification was established for locally advanced PTC patients, with trachea invasion (HR = 1.83, p < 0.001), blood vessel invasion (HR = 2.64, p < 0.001), and multi-invasion (HR = 2.76, p < 0.001) categorized as medium and high risk of mortality, respectively, demonstrating better discrimination than 8th AJCC staging system.</p><p><strong>Conclusion: </strong>This study is the first to utilize population-based cohort to reveal factors influencing invasion sites and their prognostic differences. This study also proposed a new site-based risk stratification that builds upon 8th AJCC T staging for locally advanced PTC patients, which may facilitate more tailored clinical management strategies.</p>","PeriodicalId":11572,"journal":{"name":"Endocrine","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-11DOI: 10.1007/s12020-025-04186-y
Adnan Haider, Jesse Sundar, Albert Beckers, Hermine Mohr, Atsuko Kasajima, Natalia S Pellegata, Patrick Pétrossians, Adrian F Daly
Purpose: Multiple endocrine neoplasia type 5 (MEN5) is an emerging syndrome of endocrine and non-endocrine tumors caused by germline pathogenic variants or genomic rearrangements of the MAX gene. Although MAX variants are predominantly associated with pheochromocytoma-paraganglioma (PPGL) risk, there are a growing number of associated tumors in other organs, including pituitary adenomas. We characterized the clinical presentation of various tumors in an extensive new kindred with a novel germline pathogenic variant of MAX.
Methods: Clinical, genetic, pathological, radiological and hormonal investigations to identify and characterize disease status related to germline MAX gene sequence status.
Results: We identified a novel germline pathological variant in exon 4 of the MAX gene, c.228delG, which was predicted to lead to a truncated protein (p.Asn78Thrfs*92). The propositus had developed pituitary gigantism due to a mixed growth hormone-prolactin secreting pituitary macroadenoma, which was controlled after two surgeries, medical therapy and radiotherapy. He subsequently developed bilateral and recurrent pheochromocytomas and following his death, an extra-adrenal myelolipoma was identified that was negative on MAX immunohistochemistry. An extensive history of pheochromocytomas or uncontrolled hypertension was present in the kindred and multiple affected and unaffected carriers of the c.228delG MAX pathogenic variant were characterized.
Conclusion: We report the first case of pituitary gigantism in association with a pathogenic variant in the MAX gene, and characterize myeloplipoma as a new disease-association in MEN5. Increased awareness of MEN5 as a clinical entity and comprehensive screening of MAX pathogenic variant carriers can help to identify rare disease associations beyond PPGL.
{"title":"Expanding the phenotype of multiple endocrine neoplasia type 5 (MEN5): Pituitary gigantism, myelolipoma and familial pheochromocytoma due to a germline pathogenic MAX variant.","authors":"Adnan Haider, Jesse Sundar, Albert Beckers, Hermine Mohr, Atsuko Kasajima, Natalia S Pellegata, Patrick Pétrossians, Adrian F Daly","doi":"10.1007/s12020-025-04186-y","DOIUrl":"https://doi.org/10.1007/s12020-025-04186-y","url":null,"abstract":"<p><strong>Purpose: </strong>Multiple endocrine neoplasia type 5 (MEN5) is an emerging syndrome of endocrine and non-endocrine tumors caused by germline pathogenic variants or genomic rearrangements of the MAX gene. Although MAX variants are predominantly associated with pheochromocytoma-paraganglioma (PPGL) risk, there are a growing number of associated tumors in other organs, including pituitary adenomas. We characterized the clinical presentation of various tumors in an extensive new kindred with a novel germline pathogenic variant of MAX.</p><p><strong>Methods: </strong>Clinical, genetic, pathological, radiological and hormonal investigations to identify and characterize disease status related to germline MAX gene sequence status.</p><p><strong>Results: </strong>We identified a novel germline pathological variant in exon 4 of the MAX gene, c.228delG, which was predicted to lead to a truncated protein (p.Asn78Thrfs*92). The propositus had developed pituitary gigantism due to a mixed growth hormone-prolactin secreting pituitary macroadenoma, which was controlled after two surgeries, medical therapy and radiotherapy. He subsequently developed bilateral and recurrent pheochromocytomas and following his death, an extra-adrenal myelolipoma was identified that was negative on MAX immunohistochemistry. An extensive history of pheochromocytomas or uncontrolled hypertension was present in the kindred and multiple affected and unaffected carriers of the c.228delG MAX pathogenic variant were characterized.</p><p><strong>Conclusion: </strong>We report the first case of pituitary gigantism in association with a pathogenic variant in the MAX gene, and characterize myeloplipoma as a new disease-association in MEN5. Increased awareness of MEN5 as a clinical entity and comprehensive screening of MAX pathogenic variant carriers can help to identify rare disease associations beyond PPGL.</p>","PeriodicalId":11572,"journal":{"name":"Endocrine","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-10DOI: 10.1007/s12020-025-04178-y
Meng Wang, Yinghao Guo, Gang Wang, Xiaolei Li, Luming Zheng, Qingqing He
Background: The safety and feasibility of transoral endoscopic thyroidectomy vestibular approach in pediatric patients has been clinically proven, and its cosmetic results have been recognized by children and their families. However, there are no reports on using transoral robotic in pediatric thyroid surgery. In this study, we report the experience of 5 cases of transoral vestibular robotic thyroidectomy in treating of thyroid disease in children.
Patients and methods: Retrospective analysis of clinical data of five children who underwent robotic thyroid surgery via the TOVRT in our hospital from February 2021 to April 2023, including operation time, tumor diameter, postoperative hospitalization time, and surgical complications. All five patients were operated on by the same team, and the postoperative pathological results were all follicular adenoma of thyroid. The children had a strong desire for cosmetic surgery, and their families voluntarily chose the robotic surgical system for their surgery.
Results: All five patients underwent unilateral thyroid lobectomy without conversion to open surgery. All patients were female, with a mean BMI of (19.63 ± 1.79) kg/m2 and the mean age was (14.40 ± 2.33) years. The average operation time was (52.00 ± 5.10) mins, the average tumor diameter was (41.60 ± 8.41) mm, and the average postoperative hospital stay was (3.60 ± 0.49) days. There were no complications such as hypoparathyroidism, recurrent laryngeal nerve injury, genioglossal nerve injury, or skin necrosis.
Conclusion: The transoral vestibular robotic thyroidectomy is safe and feasible, providing a new treatment option for pediatric thyroid diseases that require surgical treatment.
{"title":"Transoral vestibular robotic thyroidectomy in pediatric thyroid disease: 5 case reports.","authors":"Meng Wang, Yinghao Guo, Gang Wang, Xiaolei Li, Luming Zheng, Qingqing He","doi":"10.1007/s12020-025-04178-y","DOIUrl":"https://doi.org/10.1007/s12020-025-04178-y","url":null,"abstract":"<p><strong>Background: </strong>The safety and feasibility of transoral endoscopic thyroidectomy vestibular approach in pediatric patients has been clinically proven, and its cosmetic results have been recognized by children and their families. However, there are no reports on using transoral robotic in pediatric thyroid surgery. In this study, we report the experience of 5 cases of transoral vestibular robotic thyroidectomy in treating of thyroid disease in children.</p><p><strong>Patients and methods: </strong>Retrospective analysis of clinical data of five children who underwent robotic thyroid surgery via the TOVRT in our hospital from February 2021 to April 2023, including operation time, tumor diameter, postoperative hospitalization time, and surgical complications. All five patients were operated on by the same team, and the postoperative pathological results were all follicular adenoma of thyroid. The children had a strong desire for cosmetic surgery, and their families voluntarily chose the robotic surgical system for their surgery.</p><p><strong>Results: </strong>All five patients underwent unilateral thyroid lobectomy without conversion to open surgery. All patients were female, with a mean BMI of (19.63 ± 1.79) kg/m<sup>2</sup> and the mean age was (14.40 ± 2.33) years. The average operation time was (52.00 ± 5.10) mins, the average tumor diameter was (41.60 ± 8.41) mm, and the average postoperative hospital stay was (3.60 ± 0.49) days. There were no complications such as hypoparathyroidism, recurrent laryngeal nerve injury, genioglossal nerve injury, or skin necrosis.</p><p><strong>Conclusion: </strong>The transoral vestibular robotic thyroidectomy is safe and feasible, providing a new treatment option for pediatric thyroid diseases that require surgical treatment.</p>","PeriodicalId":11572,"journal":{"name":"Endocrine","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-10DOI: 10.1007/s12020-025-04188-w
Jiabo Qin, Haoran Ding, Weijun Jing, Yudong Qiu, Jianfeng Sang
Objective: To compare the differences among patients with papillary thyroid carcinoma (PTC) whose right lateral lymph node biopsy results indicating positive (pN1b) or negative lymph node metastasis (pN0 or pN1a) so as to explore whether there is a high risk of long-term metastasis in right lateral lymph node among patients who are classified as pN0 or pN1a at present. Only those whose preoperative ultrasound result indicating lymph node metastasis in the right lateral region (cN1b) are included. Meanwhile, to establish predictive models to help clinicians distinguish high-risk and low-risk populations and adopt different follow-up strategies.
Methods: A retrospective analysis was conducted on clinical data of patients who underwent right neck side area biopsy or dissection (cN1b) at the Affiliated Drum Tower Hospital, Medical School of Nanjing University from January 2017 to August 2022 to establish a predictive model. The model will then be validated on patients who undergo right neck lateral area biopsy or clearance from September 2022 to August 2023. Data including demographic characteristics, pathological results, and laboratory examinations were collected. The predictive model was established and evaluated by SPSS 26.0 and R 4.3.1.
Result: This study includes a total of 316 patients diagnosed with papillary thyroid carcinoma and with preoperative ultrasound indicating lymph node metastasis in the neck lateral compartment (cN1b), who were treated at the Affiliated Drum Tower Hospital, Medical School of Nanjing University from January 2017 to August 2023. The training set included 264 patients, and the validation set included 52 patients.The area under the ROC curve for the prediction model is 0.83, with a diagnostic optimal threshold of 0.595. At this threshold, the model achieves a sensitivity of 81.6% and a specificity of 75.2%. Similar results were obtained when utilizing the model on the validation set.
Conclusion: There are distinct disparities in demographics, pathological result, and laboratory examinations that can differentiate between high-risk and low-risk populations for lymph node metastasis in the right lateral region. These differences can be effectively identified by developing predictive models.
{"title":"Prediction model for lymph node metastasis in the right lateral region of papillary thyroid carcinoma.","authors":"Jiabo Qin, Haoran Ding, Weijun Jing, Yudong Qiu, Jianfeng Sang","doi":"10.1007/s12020-025-04188-w","DOIUrl":"https://doi.org/10.1007/s12020-025-04188-w","url":null,"abstract":"<p><strong>Objective: </strong>To compare the differences among patients with papillary thyroid carcinoma (PTC) whose right lateral lymph node biopsy results indicating positive (pN1b) or negative lymph node metastasis (pN0 or pN1a) so as to explore whether there is a high risk of long-term metastasis in right lateral lymph node among patients who are classified as pN0 or pN1a at present. Only those whose preoperative ultrasound result indicating lymph node metastasis in the right lateral region (cN1b) are included. Meanwhile, to establish predictive models to help clinicians distinguish high-risk and low-risk populations and adopt different follow-up strategies.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on clinical data of patients who underwent right neck side area biopsy or dissection (cN1b) at the Affiliated Drum Tower Hospital, Medical School of Nanjing University from January 2017 to August 2022 to establish a predictive model. The model will then be validated on patients who undergo right neck lateral area biopsy or clearance from September 2022 to August 2023. Data including demographic characteristics, pathological results, and laboratory examinations were collected. The predictive model was established and evaluated by SPSS 26.0 and R 4.3.1.</p><p><strong>Result: </strong>This study includes a total of 316 patients diagnosed with papillary thyroid carcinoma and with preoperative ultrasound indicating lymph node metastasis in the neck lateral compartment (cN1b), who were treated at the Affiliated Drum Tower Hospital, Medical School of Nanjing University from January 2017 to August 2023. The training set included 264 patients, and the validation set included 52 patients.The area under the ROC curve for the prediction model is 0.83, with a diagnostic optimal threshold of 0.595. At this threshold, the model achieves a sensitivity of 81.6% and a specificity of 75.2%. Similar results were obtained when utilizing the model on the validation set.</p><p><strong>Conclusion: </strong>There are distinct disparities in demographics, pathological result, and laboratory examinations that can differentiate between high-risk and low-risk populations for lymph node metastasis in the right lateral region. These differences can be effectively identified by developing predictive models.</p>","PeriodicalId":11572,"journal":{"name":"Endocrine","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}