Clinica Chimica Acta最新文献

{"title":"End-tidal carbon monoxide levels as a point-of-care biomarker for the early detection of hemolytic disease in Chinese neonates","authors":"Ge Yang ,&nbsp;Kun Zhang ,&nbsp;Li Deng ,&nbsp;Huijuan Liu ,&nbsp;Xinrui Fu ,&nbsp;Yue Hu ,&nbsp;Xiaodan Yan ,&nbsp;Xiaoyun Zhou ,&nbsp;Wei Luo ,&nbsp;Siyao Wang ,&nbsp;Xiaotong Ye ,&nbsp;Tianlang Zhang ,&nbsp;Fan Li ,&nbsp;Zhuanxia Huo ,&nbsp;Yan Jiang ,&nbsp;Shan Zeng ,&nbsp;Dehua Wu ,&nbsp;Yuan Yuan ,&nbsp;Huayan Zhang","doi":"10.1016/j.cca.2025.120368","DOIUrl":"10.1016/j.cca.2025.120368","url":null,"abstract":"<div><h3>Objective</h3><div>Hemolytic disease of newborn (HDN) is a leading risk factor for severe neonatal hyperbilirubinemia. While end-tidal carbon monoxide (CO) corrected for ambient CO (ETCOc) reflects the endogenous rate of bilirubin production, there remain translational gaps in understanding the link between ETCOc and HDN. We aimed to evaluate ETCOc levels as an indicator of increased bilirubin production in HDN.</div></div><div><h3>Methods</h3><div>This secondary analysis of the HEME (Hyperbilirubinemia risk Evaluation and Management by ETCOc) trial included near-term/term neonates (≥35 weeks’ gestation, birth weight ≥ 2000 g) with transcutaneous bilirubin (TcB) levels &gt; 40th percentile within 72 h of birth. Infants diagnosed with HDN, defined as the presence of ABO HDN and/or glucose-6-phosphate dehydrogenase (G6PD) deficiency, were compared with those without HDN. ETCOc was measured within the first 7 days of life (DOL).</div></div><div><h3>Results</h3><div>Of 2500 infants studied, 171 (6.8%) were diagnosed with HDN. ETCOc levels within 72 h of birth were significantly higher in HDN cases compared with controls. ETCOc percentiles within 7 DOL showed trends with fluctuations. Each 1 ppm incremental increase in ETCOc was each significantly associated with odds ratios of 3.90 (95 %CI 2.89–5.29), 2.72 (95 %CI 1.89–3.92), and 2.47 (95 %CI 1.21–5.02) of developing HDN early after life (<span><math><mo>≤</mo></math></span> 72 h).</div></div><div><h3>Conclusion</h3><div>Early postnatal ETCOc was strongly associated with increased risk of HDN in newborns of Southern China. Our findings highlight the potential of ETCOc as a noninvasive point of care biomarker for early hemolysis identification. Integration of ETCOc measurements into existing screening protocols could refine risk stratification and guide timely interventions, particularly in regions with a high prevalence of HDN.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"575 ","pages":"Article 120368"},"PeriodicalIF":3.2,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144084415","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}

{"title":"A proof-of-concept practical approach for achieving equivalent results from non-harmonized measurement methods while awaiting harmonization: The CA 125 example","authors":"Hikmet Can Çubukçu ,&nbsp;Oğuzhan Zengi ,&nbsp;Hamit Hakan Alp ,&nbsp;Murat Cihan ,&nbsp;Kamil Taha Uçar ,&nbsp;Marc Thelen ,&nbsp;Mauro Panteghini","doi":"10.1016/j.cca.2025.120355","DOIUrl":"10.1016/j.cca.2025.120355","url":null,"abstract":"<div><h3>Background</h3><div>Laboratory test results are crucial for clinical decisions, yet inconsistencies arise when measurements are not harmonized due to the lack of suitable higher-order references. This study introduces an approach to improve result comparability across different measurement systems, applicable until full metrological harmonization of the measurand is achieved.</div></div><div><h3>Methods</h3><div>A linear transformation formula was developed, utilizing the 2.5th and 97.5th percentiles of data from source and target methods, to adjust source method results. The feasibility of this formula was tested using carbohydrate antigen 125 (CA 125) data from two commercial assays provided by Roche Diagnostics and Abbott Diagnostics. Method comparison statistics, including difference plots and Passing-Bablok regression, were used to evaluate the transformation’s effectiveness before and after adjustment. A web application, “Result Transformer,” was developed to facilitate the application of the transformation process.</div></div><div><h3>Results</h3><div>Prior to transformation, the median relative difference between the Roche and Abbott CA 125 assays was 37.7% (95% CI: 34.5–40.8%), exceeding acceptable bias. Passing-Bablok regression yielded a slope of 1.450 (95% CI: 1.400–1.485) and an intercept of −0.83 kU/L (95% CI: −1.50 to −0.29). After adjustment using the proposed approach, the median relative difference decreased to 6.0% (95% CI: 4.3–7.7%), falling within the desirable acceptable bias goal. The slope and intercept of the regression equation improved to 1.075 (95% CI: 1.039–1.102) and −0.12 kU/L (95% CI: −0.71 to 0.19), respectively.</div></div><div><h3>Conclusion</h3><div>The proposed transformation method effectively improved the comparability of results from different assays, permitting a more consistent test result interpretation during patient follow-up.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"575 ","pages":"Article 120355"},"PeriodicalIF":3.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144072243","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}

{"title":"Continuous glucose monitoring: Minimally and non-invasive technologies","authors":"Jeong Eun Lee ,&nbsp;Badrinathan Sridharan ,&nbsp;Daehun Kim ,&nbsp;Yeongho Sung ,&nbsp;Jin Hyeong Park ,&nbsp;Hae Gyun Lim","doi":"10.1016/j.cca.2025.120358","DOIUrl":"10.1016/j.cca.2025.120358","url":null,"abstract":"<div><div>This paper highlights technological advancements in non-invasive blood glucose monitoring against the backdrop of increasing global prevalence of diabetes. Traditional monitoring methods, primarily invasive methods face limitations in providing continuous glucose level data, which is essential for effective and timely diagnosis of disease stage and for determining the optimal therapeutic strategy. Recent non-invasive technologies encompass optical, acoustic, electromagnetic, and chemical approaches. These technologies exploit the intrinsic properties of glucose, such as its optical absorption coefficients, to offer promising avenues for less intrusive blood glucose monitoring. Despite these advancements, challenges in achieving high accuracy persist due to interference from substances like water and other blood components. This underlines the need for sophisticated algorithms and sensor designs for accurate glucose estimation. Further research is required to integrate various sensing techniques and advanced data processing to enhance accuracy and user-friendliness. In conclusion, while significant progress has been made, developing a reliable, convenient, and accessible method for non-invasive glucose monitoring is crucial for transforming diabetes management and improving patients’ quality of life.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"575 ","pages":"Article 120358"},"PeriodicalIF":3.2,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144084413","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}

{"title":"Plasma protein biomarkers for long COVID-19: Predictors of symptom severity and mortality risk","authors":"Kaleem Maqsood ,&nbsp;Shaaf Ahmad ,&nbsp;Azeem Saeed ,&nbsp;Nabila Roohi","doi":"10.1016/j.cca.2025.120350","DOIUrl":"10.1016/j.cca.2025.120350","url":null,"abstract":"<div><h3>Introduction</h3><div>Long COVID-19 is marked by persistent symptoms beyond the acute phase, necessitating a deeper understanding of mortality risk factors for effective management. Plasma proteins hold promise as prognostic markers, offering insights into disease progression and aiding in mortality risk assessment.</div></div><div><h3>Method</h3><div>A total of 240 patients and 89 healthy controls were enrolled for this study. Two months post-COVID follow-up, patients were categorized as survivors (n = 212) and non-survivors (n = 28). Plasma samples underwent 2-dimensional Gel Electrophoresis (2DE) for protein separation, followed by LC-MS/MS for protein identification, and validation was performed using ELISA. Proteomic data analysis was conducted using Mascot version 2.3.02 and Samespots software 4.5.1. Statistical analyses were carried out using GraphPad Prism and IBM SPSS.</div></div><div><h3>Results</h3><div>LC-MS/MS identified fibrinogen (Spot 14; 52.15 kDa/5.32 pI; protein score 2293) and haptoglobin (Spot 08; 45.86 kDa/6.56 pI; protein score 453) as prospective predictive biomarkers. ELISA results confirmed increased plasma levels of fibrinogen and haptoglobin in severe cases (P &lt; 0.001 for both) and non-survivors (P &lt; 0.01 and P &lt; 0.0086, respectively). ROC analysis showed haptoglobin had moderate predictive power for mortality (AUC = 0.68; P = 0.0025), surpassing fibrinogen (AUC = 0.62; P = 0.0374).</div></div><div><h3>Conclusion</h3><div>Plasma fibrinogen and haptoglobin are promising biomarkers for assessing disease severity and mortality risk in long COVID. These findings highlight their potential for prognostic applications, warranting further research into their mechanistic roles in COVID-19 and broader clinical implications.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"575 ","pages":"Article 120350"},"PeriodicalIF":3.2,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071008","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}

{"title":"Development and evaluation of a novel non-competitive MAGLUMI estradiol chemiluminescence immunoassay","authors":"Yueying Wang ,&nbsp;Yun Zhang ,&nbsp;Zhonggang Fang ,&nbsp;Ran Xu ,&nbsp;Qiang Luo ,&nbsp;Jian Liu ,&nbsp;Yixiong Yao ,&nbsp;Wenhai Liang ,&nbsp;Ruiwei Gan ,&nbsp;Tinghua Li ,&nbsp;Zhifang Lin","doi":"10.1016/j.cca.2025.120356","DOIUrl":"10.1016/j.cca.2025.120356","url":null,"abstract":"<div><div>Estradiol is a key estrogen, and measuring its circulating levels is essential for evaluating ovarian function, monitoring follicular development, and assessing reproductive health. In several patient samples, estradiol levels can be extremely low, surpassing the detection capabilities of current competitive immunoassays. This research introduces a non-competitive MAGLUMI estradiol chemiluminescence immunoassay (CLIA) that utilizes a two-step sandwich approach to quantify estradiol levels. The sandwich-based detection system for estradiol was established by preparing monoclonal antibodies for estradiol-primary antibody immune complexes. To optimize the performance of the reagents, we screened the ideal feeding ratios of the primary antibody to magnetic beads and the secondary antibody to ABEI, and then determined the best reaction system. The novel system exhibited higher sensitivity and precision compared to competitive assays. Besides superiority in limit of blank (LoB, 1.0 × 10⁻³ μg/L), limit of detection (LoD, 5.0 × 10⁻³ μg/L), limit of quantification (LoQ, 9.3 × 10⁻³ μg/L) and coefficient of variation for reproducibility (CV, 3.15 %∼9.47 %). The cross-reactivity with estrone, estriol, fulvestrant, abemaciclib and estradiol valerate is notably minimized. Meanwhile, the quantification result of this system strongly correlates with LC-MS/MS (y = 1.008x + 0.8949, R² = 0.981). In conclusion, the non-competitive reagents developed in this study for estradiol detection outperform existing competitive reagents, providing more reliable results for clinical applications.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"575 ","pages":"Article 120356"},"PeriodicalIF":3.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068623","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}

{"title":"Evaluating monocyte distribution width in pediatric emergency care","authors":"Luisa Agnello ,&nbsp;Caterina Maria Gambino ,&nbsp;Fabio Del Ben ,&nbsp;Concetta Scazzone ,&nbsp;Carmelinda Cavallaro ,&nbsp;Claudia Colomba ,&nbsp;Marcello Ciaccio","doi":"10.1016/j.cca.2025.120357","DOIUrl":"10.1016/j.cca.2025.120357","url":null,"abstract":"<div><h3>Background</h3><div>Pediatric sepsis remains a major global health challenge, complicated by age-related variability in presentation and diagnostic uncertainty. Monocyte Distribution Width (MDW), a measure of monocyte anisocytosis automatically reported with complete blood count, has shown promise as an early biomarker for sepsis in adults. However, its clinical utility in pediatric patients remains unclear. In this study, we explored the usefulness of MDW in pediatric patients presenting to the emergency department (ED).</div></div><div><h3>Methods</h3><div>We conducted a retrospective observational study of pediatric patients (&lt;18 years) who presented to the ED for any cause. Patients were categorized into four groups: controls (no infection), infection, sepsis, and shock. MDW values were compared across groups and stratified by age (≤6 years and &gt; 6 years). A receiver operating characteristic (ROC) curve analysis was performed to assess MDW diagnostic performance.</div></div><div><h3>Results</h3><div>A total of 393 patients were enrolled: 117 controls, 183 with infection, 88 with sepsis, and 5 with shock. Overall, MDW values increased with disease severity, peaking in patients with shock. However, significant overlap was observed between infection and sepsis groups, particularly in children ≤ 6 years, where MDW was elevated even in controls. In children &gt; 6 years, MDW showed a clearer stepwise increase across disease categories. ROC analysis revealed an AUC of 0.73 for distinguishing infected from non-infected patients at a cutoff of 24.</div></div><div><h3>Conclusions</h3><div>MDW is a readily accessible biomarker that may aid in identifying pediatric patients with infection in emergency settings.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"575 ","pages":"Article 120357"},"PeriodicalIF":3.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143947397","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}

{"title":"Method comparison and re-calibration of three top-used immunoassays and one LC-MS/MS assay for four core cerebrospinal fluid biomarkers of Alzheimer’s disease: an explorative study for harmonization","authors":"Yutong Zou ,&nbsp;Xiaoli Ma ,&nbsp;Chenhui Mao ,&nbsp;Shanshan Chu ,&nbsp;Tianyi Wang ,&nbsp;Wei Jin ,&nbsp;Yifei Wang ,&nbsp;Songlin Yu ,&nbsp;Jing Gao ,&nbsp;Ling Qiu","doi":"10.1016/j.cca.2025.120352","DOIUrl":"10.1016/j.cca.2025.120352","url":null,"abstract":"<div><h3>Background</h3><div>We aimed to compare the analytical performance of four assays, for measuring β-amyloid 1–42 (Aβ1-42), β-amyloid 1–40 (Aβ1-40), total tau, and p-tau181 in cerebrospinal fluid (CSF) and evaluate the clinical performance for the diagnosis of Alzheimer’s disease (AD).</div></div><div><h3>Methods</h3><div>The measured concentrations and analytical performance, including precision, linearity, and accuracy of four assays were compared. The discriminative accuracy for amyloid positron emission tomography (PET) status based on different assays was evaluated.</div></div><div><h3>Results</h3><div>The measurements of the four biomarkers based on the four assays demonstrated favorable agreement, while still significantly different. For the discrimination of PET status, the ratio of Aβ1-42/p-tau181 showed better diagnostic performance than other biomarkers, with liquid chromatography tandem-mass spectrometry (LC-MS/MS) and Lumipulse G assays performing better when combining all biomarkers for each assay.</div></div><div><h3>Conclusions</h3><div>It is crucial to promote the harmonization and standardization of pre-analytical and measurement procedures to achieve consistent and comparable results in different assays and laboratories.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"575 ","pages":"Article 120352"},"PeriodicalIF":3.2,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984978","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}

{"title":"Comparability evaluation of serum and plasma cytokine levels by multiplex bead-based flow cytometry","authors":"Xiaoran Feng ,&nbsp;Wenrong Zou ,&nbsp;Pan Li ,&nbsp;Kai Guo ,&nbsp;Yating Ma ,&nbsp;Gaofeng Hu ,&nbsp;Jian Kang ,&nbsp;Xinjian Yu ,&nbsp;Mingting Peng","doi":"10.1016/j.cca.2025.120351","DOIUrl":"10.1016/j.cca.2025.120351","url":null,"abstract":"<div><h3>Background and aims</h3><div>Serum and plasma are the most common matrices for cytokine assays. Nevertheless, there is a lack of comparability evaluation for cytokine levels in two matrices based on multiplex bead-based flow cytometry. The study aimed to evaluate the comparability of IL-6, IL-8, and IL-10 serum- and plasma-based measurement results using flow cytometry.</div></div><div><h3>Materials and methods</h3><div>The serum and EDTA-K₂ plasma were collected from three cohorts of hematologic malignancy patients (n = 66, 75, and 37, respectively) to evaluate comparability of IL-6, IL-8, and IL-10 measurement results using QuantoBio 14-plex cytokine kit on the BeamCyte-1026 flow cytometry. The Passing-Bablok regression was performed between serum- and plasma-based levels of cytokines. Additionally, the relative deviation of cytokine measurement results from the two matrices was compared with the allowable limits from the China National External Quality Assessment cytokine program.</div></div><div><h3>Results</h3><div>The results revealed a relatively high correlation in IL-6, IL-8, and IL-10 levels between serum and plasma, with correlation coefficients of 0.966, 0.924, and 0.985, respectively. However, the comparability in the two matrices was unsatisfactory. Compared to plasma, the relative deviation of IL-6, IL-8, and IL-10 in serum was 74.8 %, −29.3 %, and 46.5 %, respectively, and only 20 % (IL-6), 31 % (IL-8), and 38 % (IL-10) of samples met allowable limits.</div></div><div><h3>Conclusions</h3><div>Poor comparability was found between serum- and plasma-based measurement results. Moreover, given the great potential of cytokine profiling in diagnosing and treating diseases, there is an urgent need to develop accurate and consistent processing of samples of cytokine assays to improve the accuracy and reproducibility of results and ensure the specimen’s fitness for purpose.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"575 ","pages":"Article 120351"},"PeriodicalIF":3.2,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143947396","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}

{"title":"Limitations of hemolysis-based correction for potassium measurement in hemolyzed whole blood samples","authors":"Laura Pighi,&nbsp;Gian Luca Salvagno,&nbsp;Giuseppe Lippi","doi":"10.1016/j.cca.2025.120353","DOIUrl":"10.1016/j.cca.2025.120353","url":null,"abstract":"","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"574 ","pages":"Article 120353"},"PeriodicalIF":3.2,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935812","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}

{"title":"Euthyroid hyperthyroxinemia: relevance of albumin and transthyretin genetic variations in a single centre experience","authors":"Ilaria Piva ,&nbsp;Barollo Susi ,&nbsp;Censi Simona ,&nbsp;Bertazza Loris ,&nbsp;Ruggeri Edoardo ,&nbsp;Cristina Clausi ,&nbsp;Alfonso Massimiliano Ferrara ,&nbsp;Annalisa Stefani ,&nbsp;Monica Maria Mion ,&nbsp;Martina Montagnana ,&nbsp;Caterina Mian","doi":"10.1016/j.cca.2025.120354","DOIUrl":"10.1016/j.cca.2025.120354","url":null,"abstract":"<div><h3>Objectives</h3><div>Euthyroid Hyperthyroxinemia (EH) is a condition consisting of high total T4 (TT4), variable total T3 (TT3), endogenous free T4 (fT4) and free T3 (fT3) within the reference interval, normal TSH, absence of thyroid disease. EH may be due to genetic alterations of <em>albumin (ALB)</em>, <em>transthyretin (TTR)</em> and <em>thyroxine binding globulin (TBG)</em> genes. Our study aimed to evaluate the frequency of inherited conditions affecting thyroid hormones transport proteins, associated with EH.</div></div><div><h3>Methods</h3><div>We retrospectively enrolled 42 patients with EH who underwent genetic testing for <em>ALB</em> and <em>TTR</em> mutations. A control group of 58 patients, having normal thyroid function tests, negative for <em>ALB</em> and <em>TTR</em> mutations, was selected. Direct sequencing of exons 1,2,3,4 of <em>TTR</em> gene (NM_000371.4), exon 7 of <em>ALB</em> gene (NM_000477.7) was performed.</div></div><div><h3>Results</h3><div>In 42 patients with EH, <em>ALB</em> p.R218H (c.653G &gt; A) variant was found in 20 subjects (47.6 %); 7 subjects (16.7 %) had <em>TTR</em> gene variants; 15 patients (35.7 %) were wild-type for <em>ALB</em> and <em>TTR</em> genetic testing. FT4 concentration was not dependent on the presence of sequence variants. We compared thyroid hormones levels of all carriers of <em>ALB</em> and <em>TTR</em> variants, including relatives positive for <em>ALB</em> and <em>TTR</em> variants, with 58 controls negative for <em>ALB</em> and <em>TTR</em> mutation. We observed a statistically significant difference between fT4 levels according to mutational status, being fT4 in <em>ALB</em>-mutated: 24.47 ± 2.58 pmol/L, in <em>TTR</em>-mutated: 20.65 ± 3.75 pmol/L; in controls: 14.50 ± 1.65 pmol/L (mean ± 1 standard deviation) (p &lt; 0.000001).</div></div><div><h3>Conclusions</h3><div>After exclusion of secondary causes, genetic variation in thyroid hormones transport proteins is a common cause of EH.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"574 ","pages":"Article 120354"},"PeriodicalIF":3.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143943464","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}