Clinical characteristics of familial dysalbuminemic hyperthyroxinemia in Chinese patients and comparison of free thyroxine in three immunoassay methods

Objective Familial dysalbuminemic hyperthyroxinemia (FDH) has not been thoroughly studied in the Chinese population to date. The clinical characteristics of FDH in Chinese patients were summarized, and the susceptibility of common free thyroxine (FT4) immunoassay methods was evaluated. Methods The study included 16 affected patients from eight families with FDH admitted to the First Affiliated Hospital of Zhengzhou University. The published FDH patients of Chinese ethnicity were summarized. Clinical characteristics, genetic information, and thyroid function tests were analyzed. The ratio of FT4 to the upper limit of normal (FT4/ULN) in three test platforms was also compared in patients with R218H ALB mutation from our center. Results The R218H ALB mutation was identified in seven families and the R218S in one family. The mean age of diagnosis was 38.4 ± 19.5 years. Half of the probands (4/8) were misdiagnosed as hyperthyroidism previously. The ratios of serum iodothyronine concentration to ULN in FDH patients with R218S were 8.05–9.74 for TT4, 0.68–1.28 for TT3, and 1.20–1.39 for rT3, respectively. The ratios in patients with R218H were 1.44 ± 0.15, 0.65 ± 0.14, and 0.77 ± 0.18, respectively. The FT4/ULN ratio detected using the Abbott I4000 SR platform was significantly lower than Roche Cobas e801 and Beckman UniCel Dxl 800 Access platforms (P < 0.05) in patients with R218H. In addition, nine Chinese families with FDH were retrieved from the literature, of which eight carried the R218H ALB mutation and one the R218S. The TT4/ULN of approximately 90% of patients (19/21) with R218H was 1.53 ± 0.31; the TT3/ULN of 52.4% of patients (11/21) was 1.49 ± 0.91. In the family with R218S, 45.5% of patients (5/11) underwent TT4 dilution test and the TT4/ULN was 11.70 ± 1.33 and 90.9% (10/11) received TT3 testing and the TT3/ULN was 0.39 ± 0.11. Conclusions Two ALB mutations, R218S and R218H, were found in eight Chinese families with FDH in this study, and the latter may be a high-frequency mutation in this population. The serum iodothyronine concentration varies with different mutation forms. The rank order of deviation in measured versus reference FT4 values by different immunoassays (lowest to highest) was Abbott < Roche < Beckman in the FDH patients with R218H.

[1]  S. Abalı,et al.  Rapid molecular diagnosis of ALB gene variants prevents unnecessary interventions in familial dysalbuminemic hyperthyroxinemia , 2021, Journal of pediatric endocrinology & metabolism : JPEM.

[2]  T. Tagami.  An overview of thyroid function tests in subjects with resistance to thyroid hormone and related disorders. , 2021, Endocrine journal.

[3]  E. Lim,et al.  Familial Dysalbuminemic Hyperthyroxinemia as a Cause for Discordant Thyroid Function Tests , 2021, Journal of the Endocrine Society.

[4]  P. Reynier,et al.  Familial Dysalbuminemic Hyperthyroxinemia: An Underdiagnosed Entity , 2020, Journal of clinical medicine.

[5]  Y. Yuen,et al.  Familial dysalbuminaemic hyperthyroxinaemia with discordant thyroid function test results: two case reports. , 2020, Hong Kong medical journal = Xianggang yi xue za zhi.

[6]  C. Phornphutkul,et al.  Familial Dysalbuminemic Hyperthyroxinemia (FDH), Albumin Gene Variant (R218S), and Risk of Miscarriages in Offspring. , 2020, The American journal of the medical sciences.

[7]  M. Gurnell,et al.  Familial dysalbuminaemic hyperthyroxinaemia interferes with current free thyroid hormone immunoassay methods , 2020, European journal of endocrinology.

[8]  Zengrui Wu,et al.  Free thyroxine concentrations in sera of individuals with Familial Dysalbuminemic Hyperthyroxinemia: a comparison of three methods of measurement. , 2019, Thyroid : official journal of the American Thyroid Association.

[9]  Y. Liu,et al.  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 , 2019, International journal of endocrinology.

[10]  Xianghui He,et al.  Familial dysalbuminemic hyperthyroxinemia associated with thyroid papillary cancer: one case report and review of literature , 2018 .

[11]  O. Janssen,et al.  Directional thyroid hormone distribution via the blood stream to target sites , 2017, Molecular and Cellular Endocrinology.

[12]  M. Galliano,et al.  Clinical, Genetic, and Protein Structural Aspects of Familial Dysalbuminemic Hyperthyroxinemia and Hypertriiodothyroninemia , 2017, Front. Endocrinol..

[13]  C. Ahn,et al.  Two case reports , 2017, Medicine.

[14]  Tomoaki Tanaka,et al.  SEVEN FAMILIAL DYSALBUMINEMIC HYPERTHYROXINEMIA CASES IN THREE UNRELATED JAPANESE FAMILIES AND HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY ANALYSIS OF THE THYROXINE BINDING PROFILE. , 2017, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[15]  Y. Hara,et al.  Familial Dysalbuminemic Hyperthyroxinemia that was Inappropriately Treated with Thiamazole Due to Pseudo-thyrotoxic Symptoms , 2017, Internal medicine.

[16]  H. Itoh,et al.  A case of familial dysalbuminemic hyperthyroxinemia (FDH) in Japan: FDH as a possible differential diagnosis of syndrome of inappropriate secretion of thyroid-stimulating hormone (SITSH). , 2017, Endocrine journal.

[17]  C. Ki,et al.  First Report of Familial Dysalbuminemic Hyperthyroxinemia With an ALB Variant , 2016, Annals of Laboratory Medicine.

[18]  S. Refetoff,et al.  Inherited defects of thyroxine-binding proteins. , 2015, Best practice & research. Clinical endocrinology & metabolism.

[19]  S. Refetoff,et al.  Familial dysalbuminemic hyperthyroxinemia in a 4-year-old girl with hyperactivity, palpitations and advanced dental age: how gold standard assays may be misleading , 2015, Journal of pediatric endocrinology & metabolism : JPEM.

[20]  V. Cody,et al.  A novel mutation in the Albumin gene (R218S) causing familial dysalbuminemic hyperthyroxinemia in a family of Bangladeshi extraction. , 2014, Thyroid : official journal of the American Thyroid Association.

[21]  J. Schwabe,et al.  A Novel Albumin Gene Mutation (R222I) in Familial Dysalbuminemic Hyperthyroxinemia , 2014, The Journal of clinical endocrinology and metabolism.

[22]  S. Refetoff,et al.  The syndromes of reduced sensitivity to thyroid hormone. , 2013, Biochimica et biophysica acta.

[23]  F. Sweep,et al.  Spuriously high free thyroxine values in familial dysalbuminemic hyperthyroxinemia. , 2011, Clinical chemistry.

[24]  M. Serdar,et al.  Comparison of Three Methods for Measurement of , 2010 .

[25]  Y. Dou,et al.  [A family with familial dysalbuminaemic hyperthyroxinaemia]. , 2005, Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics.

[26]  K. L. Choi,et al.  A Chinese family with familial dysalbuminaemic hyperthyroxinaemia. , 2003, Hong Kong medical journal = Xianggang yi xue za zhi.

[27]  R. Weiss,et al.  Familial dysalbuminemic hyperthyroxinemia in a Swiss family caused by a mutant albumin (R218P) shows an apparent discrepancy between serum concentration and affinity for thyroxine. , 2000, The Journal of clinical endocrinology and metabolism.

[28]  L. Braverman,et al.  A point mutation in the albumin gene in a Chinese patient with familial dysalbuminemic hyperthyroxinemia. , 1999, European journal of endocrinology.

[29]  S. Refetoff,et al.  Familial dysalbuminemic hypertriiodothyroninemia: a new, dominantly inherited albumin defect. , 1998, The Journal of clinical endocrinology and metabolism.

[30]  D. Jameson,et al.  Mutations in a Specific Human Serum Albumin Thyroxine Binding Site Define the Structural Basis of Familial Dysalbuminemic Hyperthyroxinemia* , 1996, The Journal of Biological Chemistry.

[31]  Y. Hayashi,et al.  An identical missense mutation in the albumin gene results in familial dysalbuminemic hyperthyroxinemia in 8 unrelated families. , 1994, Biochemical and biophysical research communications.

[32]  M. Mandel,et al.  A point mutation in the human serum albumin gene results in familial dysalbuminaemic hyperthyroxinaemia. , 1994, Journal of medical genetics.

[33]  G. Arévalo.  Prevalence of familial dysalbuminemic hyperthyroxinemia in serum samples received for thyroid testing. , 1991, Clinical chemistry.

[34]  L. Braverman,et al.  Effect of chloride on serum thyroxine binding in familial dysalbuminemic hyperthyroxinemia. , 1984, The Journal of clinical endocrinology and metabolism.