Familial Dysalbuminemic Hyperthyroxinemia as a Cause for Discordant Thyroid Function Tests

Ting, Matthew Jun Min; Zhang, Rui; Lim, Ee Mun; Ward, Bryan K.; Wilson, Scott G.; Walsh, John P.

doi:10.1210/jendso/bvab012

Cited by 5 publications

(9 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, in our experience, the FT4/ULN ratios of FDH patients with R218H or R218S mutations were lowest in the Abbott platform, indicating the FT4 level detected with the Abbott platform is less affected than with the other two platforms. These results are consistent with those of a recent report in which the FT4 results from the Abbott platform were the least likely to be affected among three automated immunoassays and had the best agreement with LC-MS/MS ( 32 ). Beckman, although as a two-step method, is recorded highest FT4/ULN values; thus, interference is not a problem only exclusive to one-step assays.…”

Section: Discussionsupporting

confidence: 92%

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.

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 92%

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.

View full text Add to dashboard Cite

show abstract

“…Another possible cause of normal TSH levels accompanied by increased thyroid hormone concentrations (T3 and T4) is FDH, which was eventually ruled out in this case, based on three main observations: the normal values of total thyroid hormones, the sudden increase in serum concentrations of thyroid hormones with returning to normal after childbirth and the absence of two of the possible mutations in albumin gene (residue R242 and R222I in exon 7), described in FDH ( 7 , 8 , 9 ).…”

Section: Discussionmentioning

confidence: 90%

“…To better evaluate the TFT pattern, serum total triiodothyronine (TT3) and total thyroxine (TT4) of both the mother and the daughter were measured by Liaison XL (DiaSorin S.p.A., Saluggia, Italy) obtaining normal values (TT3 = 1.42 and 2.50 nmol/L for the mother and the daughter, respectively; RI: 1.18–3.40; TT4 = 78.33 and 90.30 nmol/L for the mother and the daughter, respectively; RI: 57.6–161.3 nmol/L). These results helped to rule out the FDH hypothesis as this autosomal dominant disease is characterized by high serum levels of TT4 as well as FT4 ( 9 ).…”

Section: Case Presentationmentioning

confidence: 84%

“…Genomic DNA of the adult patient was extracted from whole blood using the QIAsymphony DSP DNA mini kit (Qiagen) and the whole of exon 7 was subsequently amplified using the FW 5’-TCTACCTACCACACACACTCT-3’ and RW 5’-TCTACCAACTTGAGCATGCA-3’ primers; cycling conditions were as follows: 95°C for 5 min, 35 cycles of 95°C for 30 s, 60°C for 30 s, 72°C for 30 s and a final extension at 72°C for 5 min. The PCR product of 387 bp was confirmed by gel electrophoresis, purified by Illustra ExoProStar 1-step digestion and subsequently subjected to bidirectional sequencing ( 8 , 9 ).…”

Section: Case Presentationmentioning

confidence: 99%

See 1 more Smart Citation

Thyroid function tests, incongruent internally and with thyroid status, both in a pregnant woman and in her newborn daughter

D’Aurizio

Biasotto

Cipri

et al. 2022

European Thyroid Journal

View full text Add to dashboard Cite

Introduction: Thyroid function tests (TFT) are extensively used in daily clinical practice. Here we described a case of incongruent TFT both in a pregnant woman and in her newborn. Case presentation: A 32-year-old woman, diagnosed with autoimmune thyroiditis during her first pregnancy, was monitored during her second gestation. At week 5+2 days, TSH and FT4 values, (Dimension VISTA 1500, Siemens Healthineers) were within normal limits. At week 19+5 days, TSH remained normal while FT4, increased approximately by 3-fold. FT4 inconsistency was with both TSH and the clinical status, since she continued to be clinically euthyroid. On the same serum sample, thyroid autoantibodies were negative. At week 25+4 days, the patient complained of palpitations and dyspnea, with tachycardia. Even though TSH was normal, high levels of both FT4 and FT3 were interpreted as evidence of thyroid overactivity and methimazole was started. TFT of the pregnant woman continued to be monitored up throughout gestation. Postpartum FT4 and FT3 gradually returned to normal. TFT, performed on daughter’s serum, three days after birth, showed the same inconsistency of her mother but without clinical signs of congenital hyperthyroidism. Based on the clinical and laboratory setting, the presence of circulating autoantibodies against T3 and T4 (THAb) were suspected and demonstrated by radioimmunoprecipitation. Conclusion: Analytical interferences should be supposed when TFT do not fit with the clinical picture and despite their infrequency, THAb must also be considered. To our knowledge, this is the first case describing the passage of THAb to the newborn.

show abstract

“…Refetoff (2020) 35 Ting (2021) 72 , d Jansen (2023) 18 "Soldin method" a Hernández (2021) 61 A dash (−) indicate not covered/reported in publication.…”

Section: Yue (2008) 21mentioning

confidence: 99%

Analysis of free, unbound thyroid hormones by liquid chromatography‐tandem mass spectrometry: A mini‐review of the medical rationale and analytical methods

Westbye,

Aas,

Kelp

et al. 2023

Analytical Science Advances

View full text Add to dashboard Cite

Measurement of hormones is important for the diagnosis and management of endocrine diseases. The thyroid hormones thyroxine (T4) and triiodothyronine (T3) are among the most commonly measured hormones in clinical laboratories, and it is the concentration of free (not bound to proteins) thyroid hormones that is clinically most relevant. Free thyroid hormones are commonly measured using automated immunoassays, however, these are known to produce erroneous results due to interferences for some patients. Measurement of free thyroid hormones using equilibrium dialysis or ultrafiltration combined with liquid chromatography coupled to tandem mass spectrometry (LC‐MS/MS) is considered a more accurate and robust method for free thyroid hormone analysis and overcomes many of the limitations of immunoassays. However, LC‐MS/MS‐based methods are often considered too technically difficult and not amendable to high throughput by clinical chemists and are not offered by many clinical laboratories. This mini‐review aims to make it easier for clinical laboratories to implement LC‐MS/MS‐based measurement of free thyroid hormones. It describes the medical rationale for measuring free thyroid hormones, the benefits of LC‐MS/MS‐based methods with respect to interferences affecting immunoassay‐based methods and physical separation methods. This mini‐review highlights important parameters for ultrafiltration and equilibrium dialysis to obtain physiologically relevant free thyroid hormone concentrations and focuses on methods and devices used in clinical chemistry.

show abstract

Familial Dysalbuminemic Hyperthyroxinemia as a Cause for Discordant Thyroid Function Tests

Cited by 5 publications

References 11 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

Thyroid function tests, incongruent internally and with thyroid status, both in a pregnant woman and in her newborn daughter

Analysis of free, unbound thyroid hormones by liquid chromatography‐tandem mass spectrometry: A mini‐review of the medical rationale and analytical methods

Contact Info

Product

Resources

About