Euthyroid hyperthyroxinemia: relevance of albumin and transthyretin genetic variations in a single centre experience

IF 3.2 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta Pub Date : 2025-05-09 DOI:10.1016/j.cca.2025.120354

Ilaria Piva , Barollo Susi , Censi Simona , Bertazza Loris , Ruggeri Edoardo , Cristina Clausi , Alfonso Massimiliano Ferrara , Annalisa Stefani , Monica Maria Mion , Martina Montagnana , Caterina Mian

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引用次数: 0

Abstract

Objectives

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 albumin (ALB), transthyretin (TTR) and thyroxine binding globulin (TBG) genes. Our study aimed to evaluate the frequency of inherited conditions affecting thyroid hormones transport proteins, associated with EH.

Methods

We retrospectively enrolled 42 patients with EH who underwent genetic testing for ALB and TTR mutations. A control group of 58 patients, having normal thyroid function tests, negative for ALB and TTR mutations, was selected. Direct sequencing of exons 1,2,3,4 of TTR gene (NM_000371.4), exon 7 of ALB gene (NM_000477.7) was performed.

Results

In 42 patients with EH, ALB p.R218H (c.653G > A) variant was found in 20 subjects (47.6 %); 7 subjects (16.7 %) had TTR gene variants; 15 patients (35.7 %) were wild-type for ALB and TTR genetic testing. FT4 concentration was not dependent on the presence of sequence variants. We compared thyroid hormones levels of all carriers of ALB and TTR variants, including relatives positive for ALB and TTR variants, with 58 controls negative for ALB and TTR mutation. We observed a statistically significant difference between fT4 levels according to mutational status, being fT4 in ALB-mutated: 24.47 ± 2.58 pmol/L, in TTR-mutated: 20.65 ± 3.75 pmol/L; in controls: 14.50 ± 1.65 pmol/L (mean ± 1 standard deviation) (p < 0.000001).

Conclusions

After exclusion of secondary causes, genetic variation in thyroid hormones transport proteins is a common cause of EH.

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甲状腺功能亢进血症：白蛋白和转甲状腺素遗传变异在单一中心经验的相关性

目的甲状腺亢进症（EH）是指总T4 （TT4）高、总T3 （TT3）变、内源性游离T4 （fT4）和游离T3 （fT3）在参考区间内、TSH正常、无甲状腺疾病的一种疾病。EH可能是由于白蛋白（ALB）、转甲状腺素（TTR）和甲状腺素结合球蛋白（TBG）基因的遗传改变。我们的研究旨在评估与EH相关的影响甲状腺激素转运蛋白的遗传性疾病的频率。方法回顾性纳入42例EH患者，进行ALB和TTR突变基因检测。选择58例甲状腺功能检查正常，ALB和TTR突变阴性的患者作为对照组。对TTR基因（NM_000371.4）外显子1,2,3,4和ALB基因（NM_000477.7）外显子7进行直接测序。结果42例EH患者中，ALB p.R218H (c.653G >；A) 20例（47.6%）出现变异；TTR基因变异7例（16.7%）；ALB和TTR基因检测为野生型15例（35.7%）。FT4浓度不依赖于序列变异的存在。我们比较了所有ALB和TTR变异携带者的甲状腺激素水平，包括ALB和TTR变异阳性的亲属，58名ALB和TTR突变阴性的对照。我们观察到不同突变状态下fT4水平的差异有统计学意义，alb突变组fT4为24.47±2.58 pmol/L， ttr突变组fT4为20.65±3.75 pmol/L；对照组：14.50±1.65 pmol/L（平均值±1标准差）(p <；0.000001)。结论排除继发原因后，甲状腺激素转运蛋白的遗传变异是EH的常见原因。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinica Chimica Acta 医学-医学实验技术

CiteScore

10.10

自引率

2.00%

发文量

1268

审稿时长

23 days

期刊介绍： The Official Journal of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Clinica Chimica Acta is a high-quality journal which publishes original Research Communications in the field of clinical chemistry and laboratory medicine, defined as the diagnostic application of chemistry, biochemistry, immunochemistry, biochemical aspects of hematology, toxicology, and molecular biology to the study of human disease in body fluids and cells. The objective of the journal is to publish novel information leading to a better understanding of biological mechanisms of human diseases, their prevention, diagnosis, and patient management. Reports of an applied clinical character are also welcome. Papers concerned with normal metabolic processes or with constituents of normal cells or body fluids, such as reports of experimental or clinical studies in animals, are only considered when they are clearly and directly relevant to human disease. Evaluation of commercial products have a low priority for publication, unless they are novel or represent a technological breakthrough. Studies dealing with effects of drugs and natural products and studies dealing with the redox status in various diseases are not within the journal''s scope. Development and evaluation of novel analytical methodologies where applicable to diagnostic clinical chemistry and laboratory medicine, including point-of-care testing, and topics on laboratory management and informatics will also be considered. Studies focused on emerging diagnostic technologies and (big) data analysis procedures including digitalization, mobile Health, and artificial Intelligence applied to Laboratory Medicine are also of interest.