Familial Dysalbuminemic Hyperthyroxinemia that was Inappropriately Treated with Thiamazole Due to Pseudo-thyrotoxic Symptoms

Fukaishi, Takahiro; Sekiguchi, Yoshihiro; Hara, Yuki

doi:10.2169/internalmedicine.8619-16

Cited by 6 publications

(5 citation statements)

References 16 publications

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“…Euthyroid hyperthyroxinemia is a major characteristic of FDH and usually detected during a routine health examination ( 11 , 12 ) or by the presence of vague signs and symptoms possibly associated with thyroid dysfunction such as palpitation, weight loss, tremors, and anxiety ( 10 , 13 ). In the present study, approximately 50% of probands complained of persistent or paroxysmal palpitation, of which two probands were diagnosed with paroxysmal atrial fibrillation.…”

Section: Discussionmentioning

confidence: 99%

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

Zhao

Zhou²,

Huang³

et al. 2023

Front. Endocrinol.

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ObjectiveFamilial 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.MethodsThe 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.ResultsThe 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.ConclusionsTwo 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.

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Section: Discussionmentioning

confidence: 99%

“…It is also reported in Korean and Chinese populations ( 7 , 21 ). R218P is the only mutation found to date in the Japanese population, mostly from Aomori prefecture ( 1 , 13 , 22 ). However, the R218P mutation is not unique to Japan, as it has also been found in a Caucasian family from Switzerland ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

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

Zhao

Zhou²,

Huang³

et al. 2023

Front. Endocrinol.

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“…An antithyroid treatment may be inappropriately indicated in patients with FDH based on an increased FT4 result (10). However, the decision to initiate antithyroid treatment should incorporate TSH results and clinical symptoms.…”

Section: Discussionmentioning

confidence: 99%

Questionable High Free T4 Concentrations: When Confirming against an Alternative Method Is Not Enough

et al. 2022

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A 60-year old male was referred to the Endocrinology Department due to confusing results of thyroid tests during a routine medical check-up. The asymptomatic patient presented with increased free thyroxine (FT4) concentrations, and thyroid-stimulating hormone (TSH) and total thyroxine (T4) concentrations within the reference range (Table 1), with no tachycardia, distal tremor, visual impairment, or any other symptoms of thyrotoxicosis. He presented with a 10-kg weight gain over the previous few months (body mass index 27.7 kg/m 2 ), which was attributed to changes in dietary and exercise habits due to the mobility restraints related to control of COVID-19 dissemination. Physical examination revealed neither goiter nor signs of orbitopathy, and there was no personal or family history of thyroid disorders. His usual medications were hydroxyzine, zopiclone, famotidine, and clonazepam. The patient's clinical condition could not explain the high FT4 results with TSH within the reference range, which opened the possibility to consider unusual clinical situations.Initial results were confirmed in a new sample, so his endocrinologist consulted the biochemistry laboratory because of this lack of consistency with clinical presentation. Analytical records revealed similar results in 2016. Additionally, the patient provided analytical results from an outside laboratory, performed 2 months earlier using a different test method (Table 1, Lab 2),

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“…For example, a variant in familial hyperthyroxinemia dysalbuminemia can modify the affinity of ALB for thyroxine (T4), inducing assay artifacts (falsely elevated T4L), which can lead to misdiagnosis and possibly to overtreatment. 2 , 3 Conjugation of growth hormone with this ALB variant was associated with improved pharmacokinetics of growth hormone therapy. 4 A better understanding of ALB variants may thus lead to the development of potentially new therapeutic approaches.…”

Section: Introductionmentioning

confidence: 99%

Human serum albumin variants in China: a molecular epidemiological investigation and literature review

Lin

et al. 2021

J Int Med Res

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Background Bisalbuminemia is a hereditary and/or acquired abnormality characterized by a double albumin (ALB) band on serum protein electrophoresis. However, there have been no epidemiological investigations of ALB variants in Chinese populations. Methods This retrospective study examined 71,963 unrelated subjects from five provinces in southern China. ALB variants were screened by cellulose acetate electrophoresis at pH 8.6 and ALB mutations were confirmed by polymerase chain reaction-DNA sequencing. Results The average incidence of inherited bisalbuminemia in the southern Chinese population was 0.0264% (19/71,963). Thirteen cases showed slow and six showed fast genetic variants on cellulose acetate electrophoresis. Four kinds of ALB variants were identified: proalbumin Lille (p.Arg23His), ALB Castel di Sangro (p.Lys560Glu), ALB Fukuoka-1 (p.Asp587Asn), and a novel ALB Wuxi (p.Lys562Glu). The gene frequency of ALB variants in the Wuxi region (0.126%, 13/10,297) was significantly higher than in other regions in southern China, and 90.9% (10/11) of cases of proalbumin Lille were also found in the Wuxi region. Conclusions This study provides the first report of the detailed prevalence and molecular characterization of ALB variants in southern China. Compared with other areas of China, Wuxi had a different pattern of ALB variants and a high prevalence of proalbumin Lille.

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Familial Dysalbuminemic Hyperthyroxinemia that was Inappropriately Treated with Thiamazole Due to Pseudo-thyrotoxic Symptoms

Cited by 6 publications

References 16 publications

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

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

Questionable High Free T4 Concentrations: When Confirming against an Alternative Method Is Not Enough

Human serum albumin variants in China: a molecular epidemiological investigation and literature review

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