ArticleThe Journal of clinical endocrinology and metabolism2014
A novel albumin gene mutation (R222I) in familial dysalbuminemic hyperthyroxinemia.
Article in The Journal of clinical endocrinology and metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- 2026 ETA guideline on interference in immunoassay measurements used in assessment of thyroid function.European thyroid journal · 2026Guideline
- Familial dysalbuminemic hyperthyroxinemia: 2 Indian cases with a novelJCEM case reports · 2026Article
- Coexistence of familial dysalbuminemic hyperthyroixinemia and papillary thyroid carcinoma: a rare case report and diagnostic challenge.Therapeutic advances in endocrinology and metabolism · 2025Article
- Clinical characteristics of familial dysalbuminemic hyperthyroxinemia in Chinese patients and comparison of free thyroxine in three immunoassay methods.Frontiers in endocrinology · 2023Article
- Clinical Consequences of Variable Results in the Measurement of Free Thyroid Hormones: Unusual Presentation of a Family with a Novel Variant in theEuropean thyroid journal · 2021Article
- Clinical recognition and evaluation of patients with inherited serum thyroid hormone-binding protein mutations.Journal of endocrinological investigation · 2020Review
- The Differential Diagnosis of Discrepant Thyroid Function Tests: Insistent Pitfalls and Updated Flow-Chart Based on a Long-Standing Experience.Frontiers in endocrinology · 2020Article
- Free Thyroxine Concentrations in Sera of Individuals with Familial Dysalbuminemic Hyperthyroxinemia: A Comparison of Three Methods of Measurement.Thyroid : official journal of the American Thyroid Association · 2020Article
- A 2019 update on TSH-secreting pituitary adenomas.Journal of endocrinological investigation · 2019Review
- A Chinese Family with Familial Dysalbuminemic Hyperthyroxinemia (FDH) due to R242H Mutation on Human Albumin Gene: Reevaluating the Role of FDH in Patients with Asymptomatic Hyperthyroxinemia.International journal of endocrinology · 2019Article
- Assessing the clinical and molecular diagnosis of inherited forms of impaired sensitivity to thyroid hormone from a single tertiary center.Endocrine · 2018Article
- Effect of Albumin Polymorphism on Thyroid Hormones: A Case Report and Literature Review.Cureus · 2018Article
- Central hypothyroidism - a neglected thyroid disorder.Nature reviews. Endocrinology · 2017Review
- Familial Dysalbuminemic Hyperthyroxinemia that was Inappropriately Treated with Thiamazole Due to Pseudo-thyrotoxic Symptoms.Internal medicine (Tokyo, Japan) · 2017Article
- First Report of Familial Dysalbuminemic Hyperthyroxinemia With an ALB Variant.Annals of laboratory medicine · 2017Article
- Clinical, Genetic, and Protein Structural Aspects of Familial Dysalbuminemic Hyperthyroxinemia and Hypertriiodothyroninemia.Frontiers in endocrinology · 2017Review
- Familial Dysalbuminemic Hyperthyroxinemia in a Japanese Man Caused by a Point Albumin Gene Mutation (R218P).Japanese clinical medicine · 2016Article
- Inherited defects of thyroxine-binding proteins.Best practice & research. Clinical endocrinology & metabolism · 2015Review
Corrections and comments
- Erratum issuedCorrigenda.2015
Authors and funding
19 authors at 11 institutions in 2 countries.
Funding
Abstract
contextFamilial dysalbuminemic hyperthyroxinemia, characterized by abnormal circulating albumin with increased T4 affinity, causes artefactual elevation of free T4 concentrations in euthyroid individuals.
objectiveFour unrelated index cases with discordant thyroid function tests in different assay platforms were investigated. DESIGN AND
resultsLaboratory biochemical assessment, radiolabeled T4 binding studies, and ALB sequencing were undertaken. (125)I-T4 binding to both serum and albumin in affected individuals was markedly increased, comparable with known familial dysalbuminemic hyperthyroxinemia cases. Sequencing showed heterozygosity for a novel ALB mutation (arginine to isoleucine at codon 222, R222I) in all four cases and segregation of the genetic defect with abnormal biochemical phenotype in one family. Molecular modeling indicates that arginine 222 is located within a high-affinity T4 binding site in albumin, with substitution by isoleucine, which has a smaller side chain predicted to reduce steric hindrance, thereby facilitating T4 and rT3 binding. When tested in current immunoassays, serum free T4 values from R222I heterozygotes were more measurably abnormal in one-step vs two-step assay architectures. Total rT3 measurements were also abnormally elevated.
conclusionsA novel mutation (R222I) in the ALB gene mediates dominantly inherited dysalbuminemic hyperthyroxinemia. Susceptibility of current free T4 immunoassays to interference by this mutant albumin suggests likely future identification of individuals with this variant binding protein.
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