Differentiating primary hyperparathyroidism (PHPT), normocalcemic PHPT (NPHPT), and vitamin D deficiency-related secondary hyperparathyroidism (VDSHPT) remains a diagnostic challenge. This study evaluated the utility of biochemical markers in distinguishing these conditions.
Methods
In this cross-sectional study, 437 participants were categorised into PHPT (n = 161), NPHPT (n = 97), VDSHPT (n = 89), and control (n = 90) groups. Serum calcium, phosphate, chloride, PTH, and vitamin D levels were analysed, along with indices such as Ca/P, Cl/P, Ca × Cl/P, and the PF Index (Ca × PTH/P).
Results
Calcium levels were highest in PHPT (2.73 ± 0.17 mmol/L), while phosphate levels were lowest (0.70 ± 0.19 mmol/L) both p < 0.001. PTH levels were significantly elevated in PHPT, NPHPT, and VDSHPT versus controls (p < 0.001). Ca/P ratio was significantly higher in PHPT (4.17 ± 1.21, p < 0.001), as was the Ca × Cl/P ratio (448.5 ± 133.6, p < 0.001). No significant difference was found between NPHPT and VDSHPT groups in Ca/P (p = 0.63) and Ca × Cl/P (p = 0.74) ratios. Ca × Cl/P ratio exhibited the highest diagnostic accuracy for PHPT with a specificity of 89.2% and PPV of 82.2%. Ca/P ratio had the highest sensitivity (77.6%) and an NPV of 86.6%. PF Index (AUC: 0.851, 95% CI: 0.816–0.886) and Cl/P ratio (0.766, 95% CI: 0.711–0.820) showed moderate accuracy. In NPHPT, all markers had high sensitivity but poor specificity (1.6%–23.2%).
Conclusion
The Ca × Cl/P and Ca/P ratios demonstrate substantial diagnostic value for PHPT, while biochemical markers exhibited limited specificity in NPHPT. These findings highlight their role in screening but emphasize the need for additional diagnostic approaches.
{"title":"Biochemical Ratios for Predicting Primary Hyperparathyroidism: Revisiting Simple yet Powerful Diagnostic Tools","authors":"Fatma Tuğçe Şah Ünal, Özgür Demir, Rıfat Emral, Asena Gökçay Canpolat","doi":"10.1111/cen.70052","DOIUrl":"10.1111/cen.70052","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Differentiating primary hyperparathyroidism (PHPT), normocalcemic PHPT (NPHPT), and vitamin D deficiency-related secondary hyperparathyroidism (VDSHPT) remains a diagnostic challenge. This study evaluated the utility of biochemical markers in distinguishing these conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this cross-sectional study, 437 participants were categorised into PHPT (<i>n</i> = 161), NPHPT (<i>n</i> = 97), VDSHPT (<i>n</i> = 89), and control (<i>n</i> = 90) groups. Serum calcium, phosphate, chloride, PTH, and vitamin D levels were analysed, along with indices such as Ca/P, Cl/P, Ca × Cl/P, and the PF Index (Ca × PTH/P).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Calcium levels were highest in PHPT (2.73 ± 0.17 mmol/L), while phosphate levels were lowest (0.70 ± 0.19 mmol/L) both <i>p</i> < 0.001. PTH levels were significantly elevated in PHPT, NPHPT, and VDSHPT versus controls (<i>p</i> < 0.001). Ca/P ratio was significantly higher in PHPT (4.17 ± 1.21, <i>p</i> < 0.001), as was the Ca × Cl/P ratio (448.5 ± 133.6, <i>p</i> < 0.001). No significant difference was found between NPHPT and VDSHPT groups in Ca/P (<i>p</i> = 0.63) and Ca × Cl/P (<i>p</i> = 0.74) ratios. Ca × Cl/P ratio exhibited the highest diagnostic accuracy for PHPT with a specificity of 89.2% and PPV of 82.2%. Ca/P ratio had the highest sensitivity (77.6%) and an NPV of 86.6%. PF Index (AUC: 0.851, 95% CI: 0.816–0.886) and Cl/P ratio (0.766, 95% CI: 0.711–0.820) showed moderate accuracy. In NPHPT, all markers had high sensitivity but poor specificity (1.6%–23.2%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The Ca × Cl/P and Ca/P ratios demonstrate substantial diagnostic value for PHPT, while biochemical markers exhibited limited specificity in NPHPT. These findings highlight their role in screening but emphasize the need for additional diagnostic approaches.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"104 1","pages":"19-26"},"PeriodicalIF":2.4,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353994","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}
Canxiao Li, Shijie Li, Yishen Zhao, Daqi Zhang, Yantao Fu, Le Zhou, Jingting Li, Fang Li, Rui Du, Nan Liang, Hui Sun
<div> <section> <h3> Background</h3> <p>Patients with medium and high-risk papillary thyroid carcinoma (PTC) demonstrate significantly poorer clinical outcomes compared to their low-risk counterparts. However, current prognostic stratification for this patient population remains suboptimal due to the absence of reliable biomarkers. This investigation aims to evaluate the clinical utility and prognostic potential of three hematological inflammatory indices: the platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII) in medium and high-risk PTC cases.</p> </section> <section> <h3> Methods</h3> <p>This study analyzed 1070 PTC patients from the “DTCC study” (2014–2016), a multicenter prospective cohort investigating the initial management of differentiated thyroid cancer (DTC) in China. Preoperative hematological parameters (including PLR, NLR, and SII) and baseline clinical characteristics were evaluated to assess their prognostic significance.</p> </section> <section> <h3> Results</h3> <p>In medium and high-risk PTC patients, PLR ≤ 115.6 predicted increased recurrence risk (OR = 4.579, 95% CI: 1.863–11.255, <i>p</i> = 0.001) and worse disease-free survival (DFS; <i>p</i> = 0.001). Multivariate Cox regression confirmed PLR ≤ 115.6 as an independent prognostic factor for reduced DFS (HR = 3.080, 95% CI: 1.115–8.507, <i>p</i> = 0.030). Notably, this association persisted in intermediate-risk patients. Among high-risk PTC patients, however, SII ≤ 360.9 (rather than PLR) demonstrated stronger predictive value for recurrence (OR = 15.154, 95% CI: 1.873–122.640, <i>p</i> = 0.011). Consistently, multivariate analysis identified SII ≤ 360.9 as an independent risk factor for shorter DFS (HR = 14.399, 95% CI: 1.823–113.730, <i>p</i> = 0.011).</p> </section> <section> <h3> Conclusion</h3> <p>Our findings demonstrate that PLR and SII emerged as risk stratification-specific prognostic biomarkers: PLR independently predicted prognosis in intermediate-risk cases, while SII showed superior predictive value for prognosis in high-risk patients. The differential utility of these indices—PLR for intermediate-risk stratification patients and SII for high-risk stratification patients—highlights their complementary roles in clinical decision-making. As routinely available, cost-effective inflammatory markers, PLR and SII may enhance risk-adapted surveillance strategies, though further validation is warranted to standardize cutoff values and integrate them into existing clinical management systems.</p> </section> <section> <h3> Trial Registration
背景：中高风险甲状腺乳头状癌（PTC）患者的临床预后明显较低风险患者差。然而，由于缺乏可靠的生物标志物，目前对该患者群体的预后分层仍然不理想。本研究旨在评估三个血液学炎症指标：血小板-淋巴细胞比率（PLR）、中性粒细胞-淋巴细胞比率（NLR）和全身免疫-炎症指数（SII）在中高危PTC病例中的临床应用和预后潜力。方法：本研究分析了来自“DTCC研究”（2014-2016）的1070例PTC患者，这是一项研究中国分化型甲状腺癌（DTC）初始治疗的多中心前瞻性队列研究。评估术前血液学参数（包括PLR、NLR和SII）和基线临床特征以评估其预后意义。结果：在中高危PTC患者中，PLR≤115.6预示着复发风险增加（OR = 4.579, 95% CI: 1.863-11.255, p = 0.001）和无病生存期（DFS; p = 0.001）。多因素Cox回归证实PLR≤115.6是DFS降低的独立预后因素（HR = 3.080, 95% CI: 1.115 ~ 8.507, p = 0.030）。值得注意的是，这种关联在中危患者中持续存在。而在高危PTC患者中，SII≤360.9（而不是PLR）对复发的预测价值更强（OR = 15.154, 95% CI: 1.873-122.640, p = 0.011）。多变量分析一致发现SII≤360.9是缩短DFS的独立危险因素（HR = 14.399, 95% CI: 1.823-113.730, p = 0.011）。结论：我们的研究结果表明，PLR和SII是风险分层特异性的预后生物标志物：PLR独立预测中危病例的预后，而SII对高危患者的预后具有优越的预测价值。这些指标（plr用于中危分层患者，SII用于高危分层患者）的差异效用突出了它们在临床决策中的互补作用。作为常规可用的、具有成本效益的炎症标志物，PLR和SII可以增强风险适应监测策略，尽管需要进一步验证以标准化临界值并将其整合到现有的临床管理系统中。试验注册：该试验在ClinicalTrials注册。NCT02638077。
{"title":"Prognostic Value of Hematological Inflammatory Indices (PLR, NLR, SII) in Medium and High-Risk Papillary Thyroid Carcinoma: A Multicenter Cohort Study","authors":"Canxiao Li, Shijie Li, Yishen Zhao, Daqi Zhang, Yantao Fu, Le Zhou, Jingting Li, Fang Li, Rui Du, Nan Liang, Hui Sun","doi":"10.1111/cen.70046","DOIUrl":"10.1111/cen.70046","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Patients with medium and high-risk papillary thyroid carcinoma (PTC) demonstrate significantly poorer clinical outcomes compared to their low-risk counterparts. However, current prognostic stratification for this patient population remains suboptimal due to the absence of reliable biomarkers. This investigation aims to evaluate the clinical utility and prognostic potential of three hematological inflammatory indices: the platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII) in medium and high-risk PTC cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study analyzed 1070 PTC patients from the “DTCC study” (2014–2016), a multicenter prospective cohort investigating the initial management of differentiated thyroid cancer (DTC) in China. Preoperative hematological parameters (including PLR, NLR, and SII) and baseline clinical characteristics were evaluated to assess their prognostic significance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In medium and high-risk PTC patients, PLR ≤ 115.6 predicted increased recurrence risk (OR = 4.579, 95% CI: 1.863–11.255, <i>p</i> = 0.001) and worse disease-free survival (DFS; <i>p</i> = 0.001). Multivariate Cox regression confirmed PLR ≤ 115.6 as an independent prognostic factor for reduced DFS (HR = 3.080, 95% CI: 1.115–8.507, <i>p</i> = 0.030). Notably, this association persisted in intermediate-risk patients. Among high-risk PTC patients, however, SII ≤ 360.9 (rather than PLR) demonstrated stronger predictive value for recurrence (OR = 15.154, 95% CI: 1.873–122.640, <i>p</i> = 0.011). Consistently, multivariate analysis identified SII ≤ 360.9 as an independent risk factor for shorter DFS (HR = 14.399, 95% CI: 1.823–113.730, <i>p</i> = 0.011).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings demonstrate that PLR and SII emerged as risk stratification-specific prognostic biomarkers: PLR independently predicted prognosis in intermediate-risk cases, while SII showed superior predictive value for prognosis in high-risk patients. The differential utility of these indices—PLR for intermediate-risk stratification patients and SII for high-risk stratification patients—highlights their complementary roles in clinical decision-making. As routinely available, cost-effective inflammatory markers, PLR and SII may enhance risk-adapted surveillance strategies, though further validation is warranted to standardize cutoff values and integrate them into existing clinical management systems.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"104 3","pages":"255-269"},"PeriodicalIF":2.4,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307335","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}
To clarify the link between environmental pollution and diabetes risk by focusing on pancreatic β-cells as key targets of environmental insults, with emphasis on the role of endocrine-disrupting chemicals (EDCs) in pancreatic dysfunction and diabetes pathogenesis.
Methods
This narrative review synthesises recent research on EDCs, focusing on their effects on β-cells. The literature search included studies in English on EDCs, diabetes, and β-cell function, utilising Boolean operators to refine the search.
Results
EDCs impair β-cell function through mechanisms such as oxidative stress, mitochondrial damage, and epigenetic changes. These pollutants disrupt insulin synthesis, secretion, and β-cell survival, which is distinct from their general metabolic effects. Additionally, EDCs may interact synergistically with traditional diabetes risk factors, such as high-fat diets, amplifying the risk of diabetes.
Conclusion
Environmental pollutants play a significant role in β-cell dysfunction and diabetes, offering new directions for research and prevention.
{"title":"Environmental Endocrine-Disrupting Chemicals, Pancreatic β-Cells, and Type 2 Diabetes Mellitus","authors":"Yan-li Zhao, Yang Ou","doi":"10.1111/cen.70050","DOIUrl":"10.1111/cen.70050","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To clarify the link between environmental pollution and diabetes risk by focusing on pancreatic β-cells as key targets of environmental insults, with emphasis on the role of endocrine-disrupting chemicals (EDCs) in pancreatic dysfunction and diabetes pathogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This narrative review synthesises recent research on EDCs, focusing on their effects on β-cells. The literature search included studies in English on EDCs, diabetes, and β-cell function, utilising Boolean operators to refine the search.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>EDCs impair β-cell function through mechanisms such as oxidative stress, mitochondrial damage, and epigenetic changes. These pollutants disrupt insulin synthesis, secretion, and β-cell survival, which is distinct from their general metabolic effects. Additionally, EDCs may interact synergistically with traditional diabetes risk factors, such as high-fat diets, amplifying the risk of diabetes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Environmental pollutants play a significant role in β-cell dysfunction and diabetes, offering new directions for research and prevention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"104 2","pages":"79-91"},"PeriodicalIF":2.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.70050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Prerna Dogra, Lana Šambula, Jasmine Saini, Matthew T. Drake, Shobana Athimulam, Stylianos Tsagarakis, Dimitra A. Vassiliadi, Vasiliki Antonopoulou, Rohit Nathani, Catherine D. Zhang, Natalia Genere, Urszula Ambroziak, Joanna Hubska, Raul G. Garcia, Mohamed Bassiony, Bahaa H. Salama, Elizabeth J. Atkinson, Vanessa Fell, Darko Kastelan, Joseph J. Larson, Irina Bancos
Objective
Data on bone health in patients with mild autonomous cortisol secretion (MACS) are limited and heterogenous. We sought to assess the prevalence of osteoporosis and symptomatic fragility fractures in patients with adrenal adenomas and hypercortisolism, and explore associations with the degree of cortisol excess and frailty.
Design
This multicenter cross -sectional study involved prospective enrollment of adults with nonfunctioning adrenal adenomas (NFA), MACS, Cushing syndrome (CS) and referent subjects without adrenal disorders during the study period (January 2019–September 2022). All participants completed a bone health questionnaire at enrollment and had dual-energy X-ray absorptiometry bone mineral density assessment within 12-months. Final analyses were adjusted for age, sex, body mass index, smoking status, alcohol use.
Results
Participants included 117 with NFA (median age 62 years, 80% women), 191 with MACS (median age 63 years, 74% women), 62 with CS (median age 50 years, 92% women), and 101 referent subjects (median age 59 years, 47% women). Both patients with CS (OR: 3.0, 95% CI: 1.1–8.3) and MACS (OR: 2.2, 95% CI: 1.9–4.9) had a higher prevalence of osteoporosis when compared to referents. Among patients with MACS, only those with post 1-mg dexamethasone suppression test (post-1mg-DST) cortisol > 83 nmol/L had a higher prevalence of osteoporosis when compared to referents (OR: 3.2, 95% CI: 1.4–7.5) and NFA (OR: 2.2, 95% CI: 1.1–4.4). For clinical fragility fractures, only patients with CS showed an increased prevalence when compared to referents (OR: 6.1, 95% CI: 1.7–26.4) and NFA (OR: 3.8, 95% CI: 1.3–11.2). Prevalence of clinical fragility fractures was similar to referents in patients with MACS (OR: 1.8, 95% CI: 0.6–6.9) and NFA (OR: 1.5, 95% CI: 0.4–6.1), and was not associated with post-1mg-DST cortisol or frailty in the MACS and NFA groups.
Conclusion
Patients with CS, and those with MACS and post-1mg-DST cortisol > 83 nmol/L, exhibited a higher burden of osteoporosis. However, only CS was associated with an elevated risk of symptomatic fragility fractures.
{"title":"Bone Health in Patients With Adrenal Adenomas and Hypercortisolism: A Multicenter Cross-Sectional Study","authors":"Prerna Dogra, Lana Šambula, Jasmine Saini, Matthew T. Drake, Shobana Athimulam, Stylianos Tsagarakis, Dimitra A. Vassiliadi, Vasiliki Antonopoulou, Rohit Nathani, Catherine D. Zhang, Natalia Genere, Urszula Ambroziak, Joanna Hubska, Raul G. Garcia, Mohamed Bassiony, Bahaa H. Salama, Elizabeth J. Atkinson, Vanessa Fell, Darko Kastelan, Joseph J. Larson, Irina Bancos","doi":"10.1111/cen.70048","DOIUrl":"10.1111/cen.70048","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Data on bone health in patients with mild autonomous cortisol secretion (MACS) are limited and heterogenous. We sought to assess the prevalence of osteoporosis and symptomatic fragility fractures in patients with adrenal adenomas and hypercortisolism, and explore associations with the degree of cortisol excess and frailty.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design</h3>\u0000 \u0000 <p>This multicenter cross -sectional study involved prospective enrollment of adults with nonfunctioning adrenal adenomas (NFA), MACS, Cushing syndrome (CS) and referent subjects without adrenal disorders during the study period (January 2019–September 2022). All participants completed a bone health questionnaire at enrollment and had dual-energy <i>X</i>-ray absorptiometry bone mineral density assessment within 12-months. Final analyses were adjusted for age, sex, body mass index, smoking status, alcohol use.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Participants included 117 with NFA (median age 62 years, 80% women), 191 with MACS (median age 63 years, 74% women), 62 with CS (median age 50 years, 92% women), and 101 referent subjects (median age 59 years, 47% women). Both patients with CS (OR: 3.0, 95% CI: 1.1–8.3) and MACS (OR: 2.2, 95% CI: 1.9–4.9) had a higher prevalence of osteoporosis when compared to referents. Among patients with MACS, only those with post 1-mg dexamethasone suppression test (post-1mg-DST) cortisol > 83 nmol/L had a higher prevalence of osteoporosis when compared to referents (OR: 3.2, 95% CI: 1.4–7.5) and NFA (OR: 2.2, 95% CI: 1.1–4.4). For clinical fragility fractures, only patients with CS showed an increased prevalence when compared to referents (OR: 6.1, 95% CI: 1.7–26.4) and NFA (OR: 3.8, 95% CI: 1.3–11.2). Prevalence of clinical fragility fractures was similar to referents in patients with MACS (OR: 1.8, 95% CI: 0.6–6.9) and NFA (OR: 1.5, 95% CI: 0.4–6.1), and was not associated with post-1mg-DST cortisol or frailty in the MACS and NFA groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Patients with CS, and those with MACS and post-1mg-DST cortisol > 83 nmol/L, exhibited a higher burden of osteoporosis. However, only CS was associated with an elevated risk of symptomatic fragility fractures.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"104 2","pages":"103-112"},"PeriodicalIF":2.4,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243804","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}
Hyponatremia remains a common and life-threatening complication in children with traumatic brain injury, subarachnoid haemorrhage, brain tumours and post neurosurgical states, yet distinguishing its two primary neurogenic etiologies—syndrome of inappropriate antidiuretic hormone secretion (SIADH) and cerebral/renal salt wasting (C/RSW)—remains difficult. Misdiagnosis may result in inappropriate treatment strategies with a significant risk of morbidity. While adult studies suggest diagnostic roles for fractional excretion of uric acid (FEurate), fractional excretion of phosphate (PEphosphate) and NT-proBNP level, no paediatric-specific guidelines or reference thresholds currently exist.
Objective
To evaluate the diagnostic accuracy of FEurate, FEphosphate and NT-proBNP in distinguishing C/RSW from SIADH in hyponatremic children with neurologic conditions.
Data Sources
A comprehensive literature search was performed across PubMed, Embase, Web of Science, Scopus and the Cochrane Library.
Study Selection and Data Extraction
Eligible studies included RCTs, systematic reviews, meta-analysis and prospective/retrospective studies involving paediatric patients diagnosed with SIADH or C/RSW using any of the three biomarkers. Systematic reviews were appraised using AMSTAR 2. Two reviewers independently assessed eligibility and extracted data.
Results
Out of 69 identified studies, there were only two prospective paediatric cohort studies reported on the use of biomarkers in C/RSW versus SIADH syndromes.
Limitation
Findings are limited by the absence of paediatric-specific cut-off values.
Conclusions
Current evidence suggests that FEurate, FEphosphate and NT-proBNP may provide diagnostic clues, but each biomarker has limitations related to assay variability, age-dependent reference ranges, comorbidities and confounding medications. FEurate response to sodium correction appears most useful, though serial measurements are often required.
背景：低钠血症仍然是创伤性脑损伤、蛛网膜下腔出血、脑肿瘤和神经外科后状态的儿童常见且危及生命的并发症，但区分其两种主要神经源性病因-抗利尿激素分泌不当综合征（SIADH）和脑/肾盐消耗(C/RSW)-仍然很困难。误诊可能导致不适当的治疗策略和显著的发病率风险。虽然成人研究表明，部分排泄尿酸（FEurate）、部分排泄磷酸盐（PEphosphate）和NT-proBNP水平具有诊断作用，但目前尚无儿科特异性指南或参考阈值。目的：评价FEurate、FEphosphate和NT-proBNP对神经系统疾病低钠血症儿童C/RSW与SIADH的诊断准确性。数据来源：通过PubMed， Embase, Web of Science， Scopus和Cochrane Library进行了全面的文献检索。研究选择和数据提取：符合条件的研究包括随机对照试验、系统评价、荟萃分析和前瞻性/回顾性研究，涉及使用三种生物标志物中的任何一种诊断为SIADH或C/RSW的儿科患者。采用AMSTAR 2对系统评价进行评价。两名审稿人独立评估合格性并提取数据。结果：在69项已确定的研究中，只有两项前瞻性儿科队列研究报告了生物标志物在C/RSW与SIADH综合征中的应用。局限性：研究结果因缺乏儿科特异性临界值而受到限制。结论：目前的证据表明，FEurate、FEphosphate和NT-proBNP可能提供诊断线索，但每种生物标志物在测定变异性、年龄相关参考范围、合共病和混杂药物方面都有局限性。虽然通常需要连续测量，但对钠校正的低反应似乎是最有用的。
{"title":"Diagnostic Utility of Fractional Excretion of Urate, Urinary Phosphate and Brain Natriuretic Peptide in Distinguishing Cerebral/Renal Salt Wasting From SIADH in Neurologically Ill Children: A Systematic Review","authors":"Farahnak Assadi","doi":"10.1111/cen.70049","DOIUrl":"10.1111/cen.70049","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hyponatremia remains a common and life-threatening complication in children with traumatic brain injury, subarachnoid haemorrhage, brain tumours and post neurosurgical states, yet distinguishing its two primary neurogenic etiologies—syndrome of inappropriate antidiuretic hormone secretion (SIADH) and cerebral/renal salt wasting (C/RSW)—remains difficult. Misdiagnosis may result in inappropriate treatment strategies with a significant risk of morbidity. While adult studies suggest diagnostic roles for fractional excretion of uric acid (FEurate), fractional excretion of phosphate (PEphosphate) and NT-proBNP level, no paediatric-specific guidelines or reference thresholds currently exist.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To evaluate the diagnostic accuracy of FEurate, FEphosphate and NT-proBNP in distinguishing C/RSW from SIADH in hyponatremic children with neurologic conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Data Sources</h3>\u0000 \u0000 <p>A comprehensive literature search was performed across PubMed, Embase, Web of Science, Scopus and the Cochrane Library.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Study Selection and Data Extraction</h3>\u0000 \u0000 <p>Eligible studies included RCTs, systematic reviews, meta-analysis and prospective/retrospective studies involving paediatric patients diagnosed with SIADH or C/RSW using any of the three biomarkers. Systematic reviews were appraised using AMSTAR 2. Two reviewers independently assessed eligibility and extracted data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Out of 69 identified studies, there were only two prospective paediatric cohort studies reported on the use of biomarkers in C/RSW versus SIADH syndromes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Limitation</h3>\u0000 \u0000 <p>Findings are limited by the absence of paediatric-specific cut-off values.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Current evidence suggests that FEurate, FEphosphate and NT-proBNP may provide diagnostic clues, but each biomarker has limitations related to assay variability, age-dependent reference ranges, comorbidities and confounding medications. FEurate response to sodium correction appears most useful, though serial measurements are often required.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"104 1","pages":"3-9"},"PeriodicalIF":2.4,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.70049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laura Kariola, Tero Varimo, Mitja Lääperi, Hanna Huopio, Sirpa Tenhola, Raimo Voutilainen, Jorma Toppari, Silja Kosola, Päivi J. Miettinen, Olli Raitakari, Marko Elovainio, Taneli Raivio, Matti Hero
Objective
In boys, constitutional delay of growth and puberty (CDGP) has been associated with diverse negative psychosocial effects. Albeit alleviating distress is one of the main reasons for inducing pubertal development, the impact of puberty-promoting treatment on psychosocial wellbeing is under-researched. Our objective was to investigate the impact of puberty-promoting therapies on the behavioural patterns as defined by the temperament characteristics emotionality, activity, and sociability (EAS) in boys with CDGP.
Design
The study is a randomized, controlled, open-label trial.
Patients
Thirty boys were randomized to receive either aromatase inhibitor letrozole (2.5 mg/day) (n = 15) or intramuscular testosterone (1 mg/kg/every 4 weeks) (n = 15) for 6 months and followed up to 12 months. To compare our results with healthy peers, an age- and postal-code matched, and a national reference population were collected.
Measurements
Temperament characteristics were evaluated with a standardized and validated questionnaire at 0-, 6-, and 12-month visits.
Results
In comparison to local peers, boys with CDGP were more withdrawn (p = 0.02) and experienced less anger (p = 0.02) and fear (p = 0.02). Compared to both local and national controls, there was a significant difference in emotionality, CDGP boys being less negatively emotional than peers (p = 0.04). Sociability was higher in the Lz-group in comparison to the T-group both after the 6-month treatment period (−0.48, 95% CI: 0.89; −0.08, p = 0.019) and at 12-month follow-up (−0.72, CI: 95%, −1.12; −0.32, p = 0.001).
Conclusion
Overall, boys with CDGP exhibited a generally docile temperament. The administration of puberty-promoting treatments did not result in any adverse psychosocial effects on the temperament characteristics assessed.
{"title":"Puberty-Promoting Treatment and Psychosocial Well-Being in Boys With Constitutional Delay of Puberty: A Randomized Controlled Trial","authors":"Laura Kariola, Tero Varimo, Mitja Lääperi, Hanna Huopio, Sirpa Tenhola, Raimo Voutilainen, Jorma Toppari, Silja Kosola, Päivi J. Miettinen, Olli Raitakari, Marko Elovainio, Taneli Raivio, Matti Hero","doi":"10.1111/cen.70039","DOIUrl":"10.1111/cen.70039","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>In boys, constitutional delay of growth and puberty (CDGP) has been associated with diverse negative psychosocial effects. Albeit alleviating distress is one of the main reasons for inducing pubertal development, the impact of puberty-promoting treatment on psychosocial wellbeing is under-researched. Our objective was to investigate the impact of puberty-promoting therapies on the behavioural patterns as defined by the temperament characteristics emotionality, activity, and sociability (EAS) in boys with CDGP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design</h3>\u0000 \u0000 <p>The study is a randomized, controlled, open-label trial.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients</h3>\u0000 \u0000 <p>Thirty boys were randomized to receive either aromatase inhibitor letrozole (2.5 mg/day) (<i>n</i> = 15) or intramuscular testosterone (1 mg/kg/every 4 weeks) (<i>n</i> = 15) for 6 months and followed up to 12 months. To compare our results with healthy peers, an age- and postal-code matched, and a national reference population were collected.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Measurements</h3>\u0000 \u0000 <p>Temperament characteristics were evaluated with a standardized and validated questionnaire at 0-, 6-, and 12-month visits.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In comparison to local peers, boys with CDGP were more withdrawn (<i>p</i> = 0.02) and experienced less anger (<i>p</i> = 0.02) and fear (<i>p</i> = 0.02). Compared to both local and national controls, there was a significant difference in emotionality, CDGP boys being less negatively emotional than peers (<i>p</i> = 0.04). Sociability was higher in the Lz-group in comparison to the T-group both after the 6-month treatment period (−0.48, 95% CI: 0.89; −0.08, <i>p</i> = 0.019) and at 12-month follow-up (−0.72, CI: 95%, −1.12; −0.32, <i>p</i> = 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Overall, boys with CDGP exhibited a generally docile temperament. The administration of puberty-promoting treatments did not result in any adverse psychosocial effects on the temperament characteristics assessed.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"104 2","pages":"139-146"},"PeriodicalIF":2.4,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.70039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jessyka Krause Meneses, Daniella Araujo Muniz, Débora Moroto, João Roberto Maciel Martins, Carolina Castro Porto Silva Janovsky
Objective
To investigate the association between health literacy levels and biochemical control of hypothyroidism, measured by serum TSH and free thyroxine (FT4) levels, in patients receiving levothyroxine (L-T4) therapy.
Methods
We conducted a cross-sectional study at the Thyroid Disorders Outpatient Clinic, Escola Paulista de Medicina, Universidade Federal de São Paulo (EPM/UNIFESP), between April and December 2024. The protocol was approved by the institutional ethics committee (CAAE: 76540423.5.0000.5505), and all participants provided written informed consent. Adult patients aged 18–65 years with primary hypothyroidism on levothyroxine (L-T4) therapy were screened; 274 met eligibility criteria after exclusions. Health literacy was assessed using the Brazilian-Portuguese Newest Vital Sign (NVS), administered face-to-face by trained staff. Demographic and clinical data, including comorbidities, L-T4 dose, TSH, and FT4 levels, were extracted from electronic records. Biochemical analyses were performed using electrochemiluminescence immunoassays. Statistical analyses included ANOVA, χ² tests, and generalised linear regression, with significance set at p < 0.05.
Results
Among 274 patients included in the final analysis, health literacy was inversely associated with serum TSH levels, and this association remained significant in fully adjusted models. A marginal trend was observed for FT4, but it did not reach statistical significance after adjustment. Patients with lower literacy scores required higher levothyroxine doses per kilogram, suggesting less efficient treatment control. No significant differences in comorbidities were observed across literacy strata.
Conclusions
Limited health literacy was independently associated with poorer biochemical control of hypothyroidism, reflected by higher TSH concentrations and greater levothyroxine dose requirements. These findings reinforce health literacy as a modifiable determinant of treatment success. Incorporating literacy-sensitive strategies—such as plain-language counselling, teach-back techniques, and visual aids—into routine care may help stabilise TSH, optimise levothyroxine therapy, and improve long-term outcomes in this population.
目的：探讨健康素养水平与接受左旋甲状腺素（L-T4）治疗的患者血清TSH和游离甲状腺素（FT4）水平与甲状腺功能减退症生化控制的关系。方法：我们于2024年4月至12月在圣保罗联邦大学（EPM/UNIFESP）的Escola Paulista de Medicina甲状腺疾病门诊进行了一项横断面研究。本方案经机构伦理委员会（CAAE: 76540423.5.0000.5505）批准，所有受试者提供书面知情同意。筛选18 ~ 65岁成人原发性甲状腺功能减退患者接受左旋甲状腺素（L-T4）治疗；274例在排除后符合资格标准。健康素养评估采用巴西-葡萄牙最新生命体征（NVS），由训练有素的工作人员面对面管理。从电子记录中提取人口统计学和临床数据，包括合并症、L-T4剂量、TSH和FT4水平。生化分析采用电化学发光免疫分析法。统计分析包括方差分析、χ 2检验和广义线性回归，显著性设置为p。结果：在最终分析的274例患者中，健康素养与血清TSH水平呈负相关，并且这种关联在完全调整模型中仍然显著。FT4有边际趋势，但调整后无统计学意义。识字分数较低的患者每公斤需要较高的左旋甲状腺素剂量，这表明治疗控制效率较低。在不同文化水平的人群中，共病发生率无显著差异。结论：健康素养有限与甲状腺功能减退的生化控制较差独立相关，反映在较高的TSH浓度和较高的左旋甲状腺素剂量要求上。这些发现强化了健康素养作为治疗成功的可改变决定因素的作用。将对读写能力敏感的策略——如通俗易懂的语言咨询、反馈技术和视觉辅助——纳入常规护理中，可能有助于稳定TSH，优化左旋甲状腺素治疗，并改善这一人群的长期预后。
{"title":"The Influence of Health Literacy on the Control of Hypothyroidism in Patients Under Levothyroxine Treatment","authors":"Jessyka Krause Meneses, Daniella Araujo Muniz, Débora Moroto, João Roberto Maciel Martins, Carolina Castro Porto Silva Janovsky","doi":"10.1111/cen.70047","DOIUrl":"10.1111/cen.70047","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To investigate the association between health literacy levels and biochemical control of hypothyroidism, measured by serum TSH and free thyroxine (FT4) levels, in patients receiving levothyroxine (L-T4) therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a cross-sectional study at the Thyroid Disorders Outpatient Clinic, Escola Paulista de Medicina, Universidade Federal de São Paulo (EPM/UNIFESP), between April and December 2024. The protocol was approved by the institutional ethics committee (CAAE: 76540423.5.0000.5505), and all participants provided written informed consent. Adult patients aged 18–65 years with primary hypothyroidism on levothyroxine (L-T4) therapy were screened; 274 met eligibility criteria after exclusions. Health literacy was assessed using the Brazilian-Portuguese Newest Vital Sign (NVS), administered face-to-face by trained staff. Demographic and clinical data, including comorbidities, L-T4 dose, TSH, and FT4 levels, were extracted from electronic records. Biochemical analyses were performed using electrochemiluminescence immunoassays. Statistical analyses included ANOVA, χ² tests, and generalised linear regression, with significance set at <i>p</i> < 0.05.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 274 patients included in the final analysis, health literacy was inversely associated with serum TSH levels, and this association remained significant in fully adjusted models. A marginal trend was observed for FT4, but it did not reach statistical significance after adjustment. Patients with lower literacy scores required higher levothyroxine doses per kilogram, suggesting less efficient treatment control. No significant differences in comorbidities were observed across literacy strata.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Limited health literacy was independently associated with poorer biochemical control of hypothyroidism, reflected by higher TSH concentrations and greater levothyroxine dose requirements. These findings reinforce health literacy as a modifiable determinant of treatment success. Incorporating literacy-sensitive strategies—such as plain-language counselling, teach-back techniques, and visual aids—into routine care may help stabilise TSH, optimise levothyroxine therapy, and improve long-term outcomes in this population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"104 2","pages":"167-174"},"PeriodicalIF":2.4,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.70047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexander Spiers, Supitcha Patjamontri, Rachel B. Smith, Chen Shen, Mireille B. Toledano, S. Faisal Ahmed
Introduction
Urinary gonadotropins measurement is a noninvasive method for evaluation of pubertal development and may have utility in population studies.
Objectives
To investigate the utility of urinary gonadotropins as a noninvasive biomarker of puberty in boys and girls.
Methods
School-based adolescent cohort study with two time points for collecting school time urine samples and self-reported assessment of puberty through the Pubertal Development Scale (PDS) approximately 2 years apart. FSH and LH were measured by two-site sandwich immunoassay and corrected for creatinine excretion.
Results
A total of 941 samples from 741 girls and 1198 samples from 899 boys aged between 11 and 16 years were analysed. Samples were collected at a median age of 12.3 years (range 11.1, 13.2) and 14.2 years (13.4, 15.7). The annual change for uLH:FSH ratio was +0.028 (95% [0.021, 0.035]) and +0.035 (95% [0.027, 0.043]) in girls and boys, respectively. In a subgroup analysis of 59 samples from girls and 233 samples from boys, collected within 90 days of a PDS, were analysed for correlations with self-reported pubertal development. In girls, uLH:FSH ratio showed positive correlations with self-report breast development (r = 0.29), self-report menarchal status(r = 0.35), composite PDS score (r = 0.39) and PDS-derived pubertal categories (r = 0.45). In boys, uLH:FSH revealed negligible correlations with self-reported pubertal development, PDS composite score and PDS-derived pubertal categories.
Conclusions
An increase in urinary LH:FSH ratio is associated with an increase in self-reported pubertal development in adolescent girls and represents a valid noninvasive biomarker of puberty in population studies.
{"title":"Urinary Gonadotropins as Markers of Puberty in Girls and Boys During Late Childhood and Adolescence: Evidence From the SCAMP Cohort","authors":"Alexander Spiers, Supitcha Patjamontri, Rachel B. Smith, Chen Shen, Mireille B. Toledano, S. Faisal Ahmed","doi":"10.1111/cen.70045","DOIUrl":"10.1111/cen.70045","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Urinary gonadotropins measurement is a noninvasive method for evaluation of pubertal development and may have utility in population studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To investigate the utility of urinary gonadotropins as a noninvasive biomarker of puberty in boys and girls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>School-based adolescent cohort study with two time points for collecting school time urine samples and self-reported assessment of puberty through the Pubertal Development Scale (PDS) approximately 2 years apart. FSH and LH were measured by two-site sandwich immunoassay and corrected for creatinine excretion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 941 samples from 741 girls and 1198 samples from 899 boys aged between 11 and 16 years were analysed. Samples were collected at a median age of 12.3 years (range 11.1, 13.2) and 14.2 years (13.4, 15.7). The annual change for uLH:FSH ratio was +0.028 (95% [0.021, 0.035]) and +0.035 (95% [0.027, 0.043]) in girls and boys, respectively. In a subgroup analysis of 59 samples from girls and 233 samples from boys, collected within 90 days of a PDS, were analysed for correlations with self-reported pubertal development. In girls, uLH:FSH ratio showed positive correlations with self-report breast development (r = 0.29), self-report menarchal status(r = 0.35), composite PDS score (r = 0.39) and PDS-derived pubertal categories (r = 0.45). In boys, uLH:FSH revealed negligible correlations with self-reported pubertal development, PDS composite score and PDS-derived pubertal categories.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>An increase in urinary LH:FSH ratio is associated with an increase in self-reported pubertal development in adolescent girls and represents a valid noninvasive biomarker of puberty in population studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"104 1","pages":"27-38"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.70045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sweating and flushing are normal physiological processes, but may be the presenting feature of endocrine disease and are a frequent reason for referral from primary care. The most common endocrinopathies causing sweating include excursions of blood glucose, hypogonadism and thyroid dysfunction. Rarer pathologies include phaeochromocytoma or paraganglioma (PPGL), neuroendocrine tumours (NETs), and medullary thyroid carcinoma, which present with a constellation of symptoms that require a clinical index of suspicion. The pre-test probability of sweating being caused by rare endocrinopathies is significantly increased in the context of a family history of known tumour-predisposing germline mutations. Primary hyperhidrosis may have a hypothalamic basis and should be referred for consideration of neurological disease. Where no endocrine pathology is found, managing patient expectations, considering potential causes such as medication and non-endocrine diseases, and involving other clinicians with a pragmatic approach to symptom improvement are important aspects of the consultation in patients with sweating and flushing.
{"title":"Clinical Question: How to Approach a Patient Presenting With Sweating and Flushing","authors":"J. Sellicks, A. Morrison, M. J. Levy","doi":"10.1111/cen.70041","DOIUrl":"10.1111/cen.70041","url":null,"abstract":"<div>\u0000 \u0000 <p>Sweating and flushing are normal physiological processes, but may be the presenting feature of endocrine disease and are a frequent reason for referral from primary care. The most common endocrinopathies causing sweating include excursions of blood glucose, hypogonadism and thyroid dysfunction. Rarer pathologies include phaeochromocytoma or paraganglioma (PPGL), neuroendocrine tumours (NETs), and medullary thyroid carcinoma, which present with a constellation of symptoms that require a clinical index of suspicion. The pre-test probability of sweating being caused by rare endocrinopathies is significantly increased in the context of a family history of known tumour-predisposing germline mutations. Primary hyperhidrosis may have a hypothalamic basis and should be referred for consideration of neurological disease. Where no endocrine pathology is found, managing patient expectations, considering potential causes such as medication and non-endocrine diseases, and involving other clinicians with a pragmatic approach to symptom improvement are important aspects of the consultation in patients with sweating and flushing.</p>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"103 6","pages":"783-786"},"PeriodicalIF":2.4,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184638","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}
João Vitor Martins Bernal, Juan Carlos Sánchez-Delgado, Noemi Marchini de Souza Couto, Adriana Marcela Jácome-Hortúa, Victor Barbosa Ribeiro, Kelly Yoshida de Melo, Lucas Dalvit Ferreira, Annick Beatriz Oliveira Dias de Macedo, Hugo Celso Dutra de Souza
Objective
Women with polycystic ovary syndrome (PCOS) exhibit cardiovascular autonomic imbalance, an important predictor of mortality. Physical exercise is an intervention known to enhance cardiovascular autonomic modulation in various populations. However, it remains unclear whether these benefits extend to women with PCOS, given that specific pathophysiological characteristics may influence autonomic adaptations. Therefore, this review aimed to synthesize the available evidence to improve understanding of this topic.
Design
Systematic review and meta-analysis.
Methods
A systematic search of CENTRAL, Embase, PubMed, Scopus, and Web of Science was conducted, followed by a snowball search to ensure comprehensive coverage of relevant randomized and non-randomized clinical trials. Random-effects meta-analyses were performed to quantitatively summarize the effects of exercise interventions on autonomic cardiovascular regulation in this population. The certainty of evidence was assessed using the GRADEpro tool.
Results
Five studies were selected, including 316 women with PCOS (214 in the exercise group and 102 in the control group). The meta-analysis indicated that aerobic exercise reduces the percentage of sequences with three consecutive cardiac cycles without significant variations (mean difference [MD = −6.13; 95% CI = −8.56 to −3.71, p < 0.001; I2 = 0%; moderate-certainty evidence) and increase the percentage of sequences with three consecutive cardiac cycles with two different variations (MD = 7.16; 95% CI = 4.61 to 9.72; p < 0.001; I2 = 8%; moderate-certainty evidence) and the root mean square of successive differences (MD = 12.84; 95% CI = 2.66 to 23.03; p = 0.01; I2 = 52%; low-certainty evidence).
Conclusion
The benefits of aerobic exercise on cardiovascular autonomic modulation appear to extend to women with PCOS, increasing vagal modulation and reducing sympathetic modulation. However, further studies are needed to strengthen the evidence and clarify the effects of other exercise modalities.
{"title":"Effects of Physical Exercise on Cardiovascular Autonomic Modulation in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis","authors":"João Vitor Martins Bernal, Juan Carlos Sánchez-Delgado, Noemi Marchini de Souza Couto, Adriana Marcela Jácome-Hortúa, Victor Barbosa Ribeiro, Kelly Yoshida de Melo, Lucas Dalvit Ferreira, Annick Beatriz Oliveira Dias de Macedo, Hugo Celso Dutra de Souza","doi":"10.1111/cen.70042","DOIUrl":"10.1111/cen.70042","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Women with polycystic ovary syndrome (PCOS) exhibit cardiovascular autonomic imbalance, an important predictor of mortality. Physical exercise is an intervention known to enhance cardiovascular autonomic modulation in various populations. However, it remains unclear whether these benefits extend to women with PCOS, given that specific pathophysiological characteristics may influence autonomic adaptations. Therefore, this review aimed to synthesize the available evidence to improve understanding of this topic.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design</h3>\u0000 \u0000 <p>Systematic review and meta-analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic search of CENTRAL, Embase, PubMed, Scopus, and Web of Science was conducted, followed by a snowball search to ensure comprehensive coverage of relevant randomized and non-randomized clinical trials. Random-effects meta-analyses were performed to quantitatively summarize the effects of exercise interventions on autonomic cardiovascular regulation in this population. The certainty of evidence was assessed using the GRADEpro tool.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Five studies were selected, including 316 women with PCOS (214 in the exercise group and 102 in the control group). The meta-analysis indicated that aerobic exercise reduces the percentage of sequences with three consecutive cardiac cycles without significant variations (mean difference [MD = −6.13; 95% CI = −8.56 to −3.71, <i>p</i> < 0.001; <i>I</i><sup>2</sup> = 0%; moderate-certainty evidence) and increase the percentage of sequences with three consecutive cardiac cycles with two different variations (MD = 7.16; 95% CI = 4.61 to 9.72; <i>p</i> < 0.001; <i>I</i><sup>2</sup> = 8%; moderate-certainty evidence) and the root mean square of successive differences (MD = 12.84; 95% CI = 2.66 to 23.03; <i>p</i> = 0.01; <i>I</i><sup>2</sup> = 52%; low-certainty evidence).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The benefits of aerobic exercise on cardiovascular autonomic modulation appear to extend to women with PCOS, increasing vagal modulation and reducing sympathetic modulation. However, further studies are needed to strengthen the evidence and clarify the effects of other exercise modalities.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":"103 6","pages":"765-782"},"PeriodicalIF":2.4,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.70042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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