Journal of Endocrinological Investigation最新文献

{"title":"Effects of acarbose and metformin on thyroid function and thyroid hormone sensitivity in type 2 diabetes patients: a post-hoc analysis of the MARCH study.","authors":"Chenyu Zhang, Aihua Liu, Weiping Teng, Wenying Yang, Jing Li, Zhongyan Shan","doi":"10.1007/s40618-024-02463-7","DOIUrl":"10.1007/s40618-024-02463-7","url":null,"abstract":"<p><strong>Purpose: </strong>While metformin is known to regulate thyroid stimulating hormone (TSH) levels, the effects of acarbose on thyroid function remain unreported. Our study was designed to evaluate the impact of acarbose and metformin on thyroid function and thyroid hormone sensitivity in type 2 diabetic patients.</p><p><strong>Methods: </strong>In the MARCH study, 788 patients with type 2 diabetes were randomly assigned to treat with acarbose (300 mg) or metformin (1,500 mg) for 48 weeks. Thyroid function was assessed at baseline, 24 weeks, and 48 weeks, and the thyroid feedback quantile index (TFQI) and parameterized thyroid feedback quantile index (PTFQI) were calculated. Generalized estimating equations adjusted for confounders were used to analyze changes over time.</p><p><strong>Results: </strong>Eighty-four patients with subclinical hypothyroidism (SCH) exhibited a decrease in TSH levels (p = 0.001) with no significant differences between the two treatment groups (p = 0.460). Both TFQI (p = 0.029) and PTFQI (p < 0.001) also decreased over time. Mediation analysis revealed that these change over time were not mediated by BMI (all p < 0.05). Among the 489 euthyroid subjects, no significant changes in TSH levels were observed (p > 0.05). Stratification by baseline TSH levels revealed significant increases in TSH, TFQI, and PTFQI (all p < 0.05) in the normal-low TSH group and significant decreases in PTFQI (all p < 0.05) in the normal-high TSH group after treatment with acarbose and metformin.</p><p><strong>Conclusions: </strong>Acarbose and metformin have similar buffering effects on TSH levels, the TFQI and the PTFQI. In patients with lower TSH levels, acarbose and metformin do not further decrease TSH levels.</p><p><strong>Clinical trial registry number: </strong>ChiCTR-TRC-08000231.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"419-433"},"PeriodicalIF":5.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accelerated biological aging, mediating amino acids, and risk of incident type 2 diabetes: a prospective cohort study.","authors":"Ziteng Zhang, Junxue Wang, Bowei Yu, Ying Sun, Yi Chen, Yingli Lu, Ningjian Wang, Fangzhen Xia","doi":"10.1007/s40618-024-02436-w","DOIUrl":"10.1007/s40618-024-02436-w","url":null,"abstract":"<p><strong>Purpose: </strong>Aging plays an important role in type 2 diabetes mellitus (T2DM). But the association between accelerated biological age and T2DM, and the mechanisms underlying this association remains unclear. Thus, this study aimed to examine the associations of biological aging with T2DM, and explore the potential mediation effect of amino acids.</p><p><strong>Methods: </strong>This prospective cohort study included 95,773 participants in the UK Biobank who were free of diabetes at baseline. Biological age was measured from clinical traits using PhenoAgeAccel. Cox proportional hazard models were used to estimate the hazard ritios (HRs) and 95% confidence intervals (CIs), and mediation analysis was used to explore the mediation effect of amino acids.</p><p><strong>Results: </strong>During a median follow-up of 14.02 years, 6,347 incident T2DM cases were recorded. After multivariable adjustment for sociodemographic characteristics, lifestyle factors, and other risk factors of T2DM, participants with older biological age were at increased risk of incident T2DM (30% increase per standard deviation of PhenoAgeAccel, 95% CI: 28.0-33.0%). Additionally, higher branched chain amino acids (BCAAs) including isoleucine and leucine, aromatic amino acids (AAAs) including phenylalanine and tyrosine, were associated with increased PhenoAgeAccel and risk of incident T2DM; while glutamine and glycine were inversely associated. Alanine, glutamine, glycine, phenylalanine, tyrosine, isoleucine, leucine, and total concentration of branched-chain amnio acids could partially explain the associations between PhenoAgeAccel and T2DM.</p><p><strong>Conclusion: </strong>Accelerated biological aging was associated with increased risk of incident T2DM independent of chronological age and may be a risk factor of T2DM, partially mediated by several amino acids.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"435-443"},"PeriodicalIF":5.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The blood pressure-lowering property of subcutaneous semaglutide: a systematic review, meta-analysis, and meta-regression.","authors":"Moein Ala, Mohammadreza Moheb Aleaba","doi":"10.1007/s40618-024-02459-3","DOIUrl":"10.1007/s40618-024-02459-3","url":null,"abstract":"<p><strong>Purpose: </strong>Semaglutide is a glucagon-like peptide (GLP1) receptor agonist with unprecedented weight-lowering and anti-hyperglycemic properties. Recent clinical trials reported that subcutaneous semaglutide can modulate blood pressure; however, its effect on blood pressure widely varied in different studies and different subgroups of patients.</p><p><strong>Methods: </strong>PubMed, Web of Science, Scopus, and the Cochrane Library were systematically searched from the inception to July 18, 2024. Due to high heterogeneity, a random-effects model was adopted to pool data.</p><p><strong>Results: </strong>Twenty clinical trials with 15,312 participants in the placebo group and 18,231 participants in the semaglutide group were included in this study. Subcutaneous semaglutide significantly decreased both systolic (WMD - 3.71 mmHg, 95% CI (-4.29, -3.13), I²: 50.2%) and diastolic (WMD - 1.10 mmHg, 95% CI (-1.58, -0.63), I²: 69.7%) blood pressure. Subgroup analyses indicated that the blood pressure-lowering property of subcutaneous semaglutide was greater among patients without diabetes, with lower baseline hemoglobin A1c (HbA1c), baseline body mass index (BMI) greater than 35 kg/m², dose of semaglutide more than 1 mg/week, baseline systolic blood pressure equal or less than 130 mmHg, weight loss greater than 10 kg, and BMI reduction greater than 3 kg/m². In addition, a treatment length of 50 to 100 weeks was associated with greater blood pressure-lowering effects in subgroup analysis. After adjusting for other factors, meta-regression revealed that placebo-adjusted weight change was independently correlated with the effect of semaglutide on systolic and diastolic blood pressure.</p><p><strong>Conclusion: </strong>Subcutaneous semaglutide can significantly decrease systolic and diastolic blood pressure, particularly in selected groups of patients.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"283-294"},"PeriodicalIF":5.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin-5: an indicator of mild cognitive impairment in patients with type 2 diabetes mellitus - a comprehensive investigation ranging from bioinformatics analysis to clinical research.","authors":"Hui Zhang, Wenwen Zhu, Shufang Yang, Tong Niu, Huzaifa Fareeduddin Mohammed Farooqui, Bing Song, Hongxiao Wang, Sumei Li, Jumei Wang, Linlin Xu, Zhen Zhang, Haoqiang Zhang","doi":"10.1007/s40618-024-02430-2","DOIUrl":"10.1007/s40618-024-02430-2","url":null,"abstract":"<p><strong>Purpose: </strong>Neuroinflammation constitutes an underlying mechanism for cognitive impairment. Here, we endeavor to scrutinize the potential contribution of interleukin-5 (IL-5) towards mild cognitive impairment (MCI), and to assess its diagnostic value for MCI in patients with type 2 diabetes mellitus (T2DM).</p><p><strong>Methods: </strong>RNA-seq was used to explore the potential neuroinflammation factors in the hippocampus of diabetic mice with cognitive decline. Additionally, the promising risk factor was verified in animals. Finally, the association between IL-5 levels and cognitive function and its diagnostic value for MCI were assessed.</p><p><strong>Results: </strong>In animals, up-regulated IL-5 mRNA and protein levels were detected by RNA-seq and (or) verified experiments in the hippocampus of diabetic db/db mice with cognitive decline, compared to those of db/m mice without diabetes. In human, compared to diabetic patients without MCI, those with MCI demonstrate elevated levels of IL-5. It is natively associated with Montreal Cognitive Assessment (MoCA) scores, reflecting global cognitive function, and positively correlated with Trail Making Test A (TMTA) scores, reflecting information processing speed. Furthermore, an elevated level of IL-5 is identified as a risk factor for MCI, and a factor that influences TMTA scores. Finally, it is recommended that the cut-off value for IL-5 in the diagnosis of MCI is 22.98 pg/mL, with a sensitivity of 68.6% and specificity of 72.9%.</p><p><strong>Conclusions: </strong>IL-5 is considered a risk factor for MCI in T2DM patients and is associated with their performance in information processing speed. Moreover, an elevated level of IL-5 is a plausible biomarker for MCI in T2DM patients.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"401-417"},"PeriodicalIF":5.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FT4 is a novel indicator for risk assessment of severe hypocalcemia following parathyroidectomy.","authors":"Xiao Liu, Weiqian Li, Chuancheng Huang, Zongyu Li","doi":"10.1007/s40618-024-02460-w","DOIUrl":"10.1007/s40618-024-02460-w","url":null,"abstract":"<p><strong>Objective: </strong>To analyze the risk factors associated with the development of severe hypocalcemia (SH) in patients who have undergone parathyroidectomy (PTX).</p><p><strong>Methods: </strong>This research involved patients with chronic kidney disease-secondary hyperparathyroidism who underwent PTX between June 1, 2021, and May 31, 2023. SH was characterized by a serum total calcium (tCa) level below 1.8 mmol/L. This study aimed to analyze differences in preoperative laboratory findings and clinical manifestations between patients with and without SH. Logistic regression analysis was used to identify potential risk factors associated with the development of SH.</p><p><strong>Results: </strong>The incidence of SH was 23% (n = 176). Significant differences were observed in free thyroxine (FT4), free triiodothyronine, alanine aminotransferase, osteocalcin, tCa, alkaline phosphatase (ALP), C-terminal cross-linked telopeptide of type I collagen, and parathyroid hormone between the SH and non-SH groups. The three independent risk factors for SH were tCa [odds ratio (OR) 0.063, 95% confidence interval (95% CI) 0.006-0.663], ALP (OR 1.003, 95% CI 1.001-1.005), and FT4 (OR 0.439, 95%CI 0.310-0.621). The area under the curve, sensitivity, specificity, and overall accuracy of this model were 0.904 (95% CI 0.856-0.952), 46.3%(95% CI 32.0%-61.3%), 94.8% (95% CI 89.7%-97.5%), and 83.5% (95% CI 77.3%-88.3%), respectively.</p><p><strong>Conclusion: </strong>The preoperative level of FT4 plays a crucial role in predicting the risk of SH after PTX. The combined FT4-ALP-tCa model demonstrates the ability to predict SH risk, providing valuable insights for customizing calcium supplementation strategies and improving clinical decision-making.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"369-380"},"PeriodicalIF":5.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spliceosome component TCERG1 regulates the aggressiveness of somatotroph adenoma.","authors":"Kyungwon Kim, Hye Ju Shin, Sang-Cheol Park, Youngsook Kim, Min-Ho Lee, Ju Hyung Moon, Eui Hyun Kim, Eun Jig Lee, Chan Woo Kang, Cheol Ryong Ku","doi":"10.1007/s40618-024-02447-7","DOIUrl":"10.1007/s40618-024-02447-7","url":null,"abstract":"<p><strong>Purpose: </strong>We aimed to identify differentially expressed spliceosome components in growth hormone (GH)-secreting pituitary tumors and investigate their roles in pathogenesis.</p><p><strong>Methods: </strong>We performed transcriptome analysis of 20 somatotroph adenomas and 6 normal pituitary tissues to select dysregulated spliceosome components. Clinical characteristics were analyzed based on gene expression in 64 patients with acromegaly. Proliferation, invasion, and hormonal activity of GH secreting pituitary adenoma cells were investigated.</p><p><strong>Results: </strong>TCERG1 expression was significantly higher in somatotroph adenomas than in normal pituitaries (log2 fold change 0.59, adjusted P = 0.0002^*). Genotype-phenotype analysis revealed that patients with higher TCERG1 expression had lower surgical remission rates than those with lower expression (63.64% vs. 95.45%, P = 0.009^*). TCERG1 expression was significantly higher in groups with cavernous sinus (CS) invasion or Ki67 index over 3 (all P>0.05^*). TCERG1 overexpression led to a 29.60% increase in proliferation (P<0.001^*) and a 249.47% increase in invasion after 48 h in GH3 cells (P = 0.026^*). Conversely, TCERG1 silencing significantly decreased cell proliferation (25.76% at 72 h, P<0.001^*) and invasion (96.87% at 48 h, P = 0.029^*). E-cadherin was decreased, but vimentin was increased in both TCERG1 overexpressed GH3 cells and somatotroph adenomas. And TCERG1 silence reversed the expression of the genes (CDH2, SNAI1, ZEB2, and VIM) in GH3 cells.</p><p><strong>Conclusions: </strong>Spliceosome machinery provide novel insights into the pathogenesis of GH-secreting pituitary tumor and highlight the potential role of TCERG1 as a biomarker for tumor aggressiveness.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"333-344"},"PeriodicalIF":5.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence, risk factors and effect of curative parathyroidectomy on nephrocalcinosis in Asian-Indian patients with symptomatic primary hyperparathyroidism.","authors":"Poonam Kumari, Sheenam Garg, Sanjay Kumar Bhadada, Rimesh Pal, Soham Mukherjee, Shivangani Lohani, Rinki Basoya, Divya Dahiya, Veenu Singla, Ashwani Sood","doi":"10.1007/s40618-024-02464-6","DOIUrl":"10.1007/s40618-024-02464-6","url":null,"abstract":"<p><p>Primary hyperparathyroidism (PHPT) is characterized by inappropriate secretion of parathyroid hormone, causing hypercalcemia and hypercalciuria, leading to renal stone diseases and nephrocalcinosis. The frequency, risk factors, and curative effect on nephrocalcinosis in post-parathyroidectomy have not been identified yet. Therefore, the present study evaluated the clinico-biochemical, radiological parameters and curative effect on nephrocalcinosis. A total of 583 PHPT patients were analysed in four groups viz. Group 1 (PHPT with nephrocalcinosis-98; 16.8%); Group 2 (PHPT with nephrolithiasis-227; 38.9%); Group 3 (PHPT with both nephrolithiasis and nephrocalcinosis-59; 10.1%); and Group 4 (PHPT without renal diseases-199, 34.1%). In the sub-group analysis, younger age (p ≤ 0.05), male gender (p ≤ 0.05), and hematuria (p ≤ 0.005) were significant in Group 1 vs. Group 4. Dysuria and low eGFR were significant in Group 1 vs. Group 2 (p ≤ 0.0005; p ≤ 0.05) and Group 1 vs. Group 4 (p ≤ 0.0005; p ≤ 0.0005). Polyuria (p ≤ 0.05; p ≤ 0.05, p ≤ 0.005), and gravluria (p ≤ 0.05; p ≤ 0.0005, p ≤ 0.005) were frequent in Group 1 vs. other groups. A significant difference was observed in S.Ca and, 24-hrs U.Ca in Group 1 vs. Group 2 {(12.2 (10.8-13.4) vs. 11.2 (10.7-12.4), p ≤ 0.05; 301 (189.5-465) vs. 180 (92.5-323.1), p ≤ 0.05} and Group 1 vs. Group 4 {(12.2 (10.8-13.4) vs. 11.4 (10.7-12.5), p ≤ 0.05 ; 301 (189.5-465) vs. 213 (110-360), p ≤ 0.0005}. Multivariate logistic regression showed gravluria [aOR = 9.2, p = 0.0001], S.Ca (aOR = 1.30, p = 0.003) and, 24-hrs U.Ca (aOR = 1.02, p = 0.042) to be independent predictors of nephrocalcinosis. Pre and post-operative assessment revealed decreased S. Ca levels [(11.9 ± 1.9) vs. (10.5 ± 1.0) mg/dL; p = 0.04] and complete radiological resolution (10.4%) in PHPT with nephrocalcinosis. Therefore, serum calcium, 24-hrs Urinary calcium, and gravluria were independent predictors of nephrocalcinosis with 10.4% showing complete radiological resolution post-operatively.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"381-392"},"PeriodicalIF":5.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the relationship between cognitive impairment and brain white matter tracts using diffusion tensor imaging in patients with prolactinoma.","authors":"Mustafa Duru, Ahmet Numan Demir, Ahmet Oz, Osman Aykan Kargin, Ali Tarik Altunc, Oznur Demirel, Serdar Arslan, Osman Kizilkilic, Burc Cagri Poyraz, Pinar Kadioglu","doi":"10.1007/s40618-024-02442-y","DOIUrl":"10.1007/s40618-024-02442-y","url":null,"abstract":"<p><strong>Background: </strong>Cognitive impairment is known to occur in patients with prolactinoma, but the underlying mechanism is unclear.</p><p><strong>Objective: </strong>To evaluate cognitive function in patients with prolactinoma and to investigate the basis of possible cognitive impairment in brain white matter changes using diffusion tensor imaging (DTI).</p><p><strong>Methods: </strong>37 consecutive patients with prolactinoma and 37 healthy controls of similar age, sex, and education were enrolled in the study. Hormone levels were determined in all participants, comprehensive neuropsychological testing was performed, and DTI was used to reconstruct and evaluate white matter tracts.</p><p><strong>Results: </strong>In patients with prolactinoma, short- and long-term visual and verbal memory, attention, concentration, and executive and language functions were impaired compared to the healthy group. When comparing the DTI results, lower fractional anisotropy (FA) values were found in the patients' right uncinate fasciculus (R-UF), indicating neuronal damage. After applying the Bonferroni correction, the two groups had no significant difference in 42 tracts (p > 0.0012 for all). A positive correlation was found between poor FA scores on the R-UF and low scores on long-term memory, category and letter fluency tests. In addition, patients with hypoprolactinemia had the worst short-term memory scores, while normoprolactinemia had the best scores. Also, the poorer R-UF FA values were found in the patients with hypoprolactinemia and the highest in those with normoprolactinemia.</p><p><strong>Conclusion: </strong>This study is the first to investigate reasons for cognitive dysfunction in patients with prolactinoma by DTI. No significant structural changes were found in brain tracts of patients with prolactinoma. Still, there may be a link between potential damage in the R-UF and cognitive dysfunction, and further research is needed. In addition, the results showed that the development of hypoprolactinemia is associated with cognitive dysfunction and emphasized that overtreatment should be avoided.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"345-355"},"PeriodicalIF":5.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic value of total, free and lipoprotein fraction-bound plasma mitotane levels in advanced adrenocortical carcinoma: a prospective study of the ENDOCAN-COMETE-Cancer network.","authors":"M Faron, A Naman, J Delahousse, S Hescot, J Hadoux, F Castinetti, D Drui, P Renoult-Pierre, R Libe, L Lamartina, S Leboulleux, A Al-Ghuzlan, M Lombès, A Paci, E Baudin","doi":"10.1007/s40618-024-02439-7","DOIUrl":"10.1007/s40618-024-02439-7","url":null,"abstract":"<p><strong>Purpose: </strong>Mitotane is the only approved treatment for metastatic adrenocortical carcinoma (ACC). Monitoring plasma levels is recommended, but its predictive value is insufficient.</p><p><strong>Methods: </strong>This prospective study of the French ENDOCAN-COMETE network aimed to investigate the prognostic role of plasma mitotane levels pharmacokinetics and free or bound to lipoprotein fraction measurements during six consecutive months. Lipoprotein fractions were isolated by ultracentrifugation, and mitotane level was determined by HPLC-UV. Total, free, and lipoprotein fraction bound plasma mitotane were monitored every two months for six months with morphological assessment. The primary endpoint was overall survival (OS).</p><p><strong>Results: </strong>21 patients with metastatic ACC were included. Median overall survival was 23 months. The median free mitotane level per patient was 12% (± 7%), and the majority (88%) was bound to lipoprotein fractions. Several pharmacokinetics measures of total mitotane were related to OS: first level at one month (p = 0.026), mean level (p = 0.055), and area under the curve (AUC) (p = 0.048), with higher exposure associated to longer OS. Free mitotane (not bounded) and mitotane bounded to lipoprotein subfraction added no prognostic values. The relationship between the mitotane level and OS suggested a minimum \"effective\" threshold of 10-15 mg/L or an area under the curve above 100 mg/L/month with no individualized maximum value.</p><p><strong>Conclusion: </strong>This prospective study did not identify any added prognostic value of free mitotane level over the total level. Early total mitotane level measurements (before 3-6 months) were related to OS with a higher and faster exposure related to more prolonged survival.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"357-367"},"PeriodicalIF":5.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Areas of uncertainty on the diagnosis, treatment, and follow-up of hypophosphatemia in adults: an Italian Delphi consensus.","authors":"Iacopo Chiodini, Daniela d'Angela, Alberto Falchetti, Luigi Gennari, Nazzarena Malavolta, Laura Masi, Antonio Migliore, Massimiliano Orso, Barbara Polistena, Domenico Rendina, Alfredo Scillitani, Federico Spandonaro, Giuseppe Vezzoli, Fabio Vescini","doi":"10.1007/s40618-024-02458-4","DOIUrl":"10.1007/s40618-024-02458-4","url":null,"abstract":"<p><strong>Purpose: </strong>The study aimed to present the results of a Delphi consensus involving Italian experts focusing on the management of hypophosphatemia in adults.</p><p><strong>Methods: </strong>A multidisciplinary advisory board of nine physicians, experts in hypophosphatemia management, was established. Next, a literature search was performed to identify international guidelines, consensus, and clinical pathways, which were later presented to the advisory board. Collaboratively, the advisory board and authoring team selected key statements for the consensus process and focused on areas of uncertainty related to the management of hypophosphatemia. The advisory board also indicated the experts to be invited to participate in the consensus process. The Delphi method was employed to reach a consensus.</p><p><strong>Results: </strong>The literature search yielded one guideline, five consensus documents, and one clinical pathway. While our search strategy aimed to identify documents on the management of all types of hypophosphatemia, most of the guidelines and consensus documents retrieved focused on X-linked hypophosphatemia. The consensus process focused on 11 key issues, achieving strong convergence (over 70% consensus) in the first Delphi round for 8 out of the 11 statements. Three statements proceeded to the second round, with strong agreement reached for two. Notably, consensus was not reached for the statement concerning the measurement of fibroblast growth factor 23 for diagnostic purposes.</p><p><strong>Conclusion: </strong>The study revealed that the community of clinical experts is well-informed and in agreement regarding hypophosphatemia management. It emphasized the importance of developing clear national guidance documents to support clinicians and multidisciplinary teams in patient management. These documents are crucial not only for healthcare professionals but also for those responsible for defining pathways and services, facilitating a more accurate management of hypophosphatemic patients.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"257-267"},"PeriodicalIF":5.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}