Direct Equilibrium Dialysis Compared with Two Non-dialysis Free T4 Methods in Premature Infants

Deming, Douglas; Rabin, Christopher W.; Hopper, Andrew; Peverini, Ricardo; Vyhmeister, Nidia R.; Nelson, Jerald C.

doi:10.1016/j.jpeds.2007.03.046

Cited by 27 publications

(11 citation statements)

References 40 publications

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“…One may argue against its accuracy in determining FT 4 levels, considering that some TBG-deficient patients were falsely detected to have low FT 4 levels and that the equilibrium dialysis method is the gold standard (15,16). However, it has been difficult to introduce the equilibrium dialysis method in newborn screening because it requires a larger volume serum sample and longer measurement times.…”

Section: Discussionmentioning

confidence: 99%

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Mass screening of newborns for congenital hypothyroidism of central origin by free thyroxine measurement of blood samples on filter paper

Adachi

Soneda

Asakura

et al. 2012

European Journal of Endocrinology

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Objective: To evaluate the effectiveness of mass screening of newborns for congenital hypothyroidism of central origin (CH-C) by measurement of free thyroxine (FT 4 ) and thyroid-stimulating hormone (TSH). Design: Questionnaire-based survey of CH-C patients born between 1999 and 2008 in Kanagawa prefecture, Japan. Methods: TSH and FT 4 levels in dried blood spots on filter paper were measured using ELISA kits, and CH-C was diagnosed at FT 4 levels below a cutoff of 0.7 ng/dl (9.0 pmol/l). Survey results were collated with the database created by the screening organizer.

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Section: Discussionmentioning

confidence: 99%

“…Characteristics of ten patients with CH-C categorized into isolated CH-C (group I; patients [15][16][17][18][19][20][21][22] and those with undetermined pituitary involvement (group U; patients 23 and 24). CH-C in Kanagawa prefecture as 1 in 30 833 births (24/740 003).…”

Section: Tablementioning

confidence: 99%

Mass screening of newborns for congenital hypothyroidism of central origin by free thyroxine measurement of blood samples on filter paper

Adachi

Soneda

Asakura

et al. 2012

European Journal of Endocrinology

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“…For assay of FT4, with the caveat of measurement under conditions of low-binding proteins, direct equilibrium dialysis methods are considered the 'gold standard' 25 as other immunoassays can show bias according to proteinbound TT4, to serum TT4 binding capacity, 26,27 to inherent methodological variation 28 or to comparison to inappropriate reference ranges. 28 To determine the impact of serum TT4 binding capacity on the FT4 measurements, a French study 27 compared the FT4 measured by direct equilibrium 27 Overall, although there was variation within groups, the biases between each of the immunoassays and direct equilibrium dialysis according to serum binding capacity were significant, although generally small for the normal and high serum binding capacity groups, but significant and appreciable with the low serum binding capacity group.…”

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confidence: 99%

“…28 To determine the impact of serum TT4 binding capacity on the FT4 measurements, a French study 27 compared the FT4 measured by direct equilibrium 27 Overall, although there was variation within groups, the biases between each of the immunoassays and direct equilibrium dialysis according to serum binding capacity were significant, although generally small for the normal and high serum binding capacity groups, but significant and appreciable with the low serum binding capacity group. Similarly, the concordance between FT4 measurements with direct equilibrium dialysis and each of the binding capacity groups; for normal and high serum binding capacity groups the range of concordance was between 59 -96% and 66 -90%, respectively, but for the low serum binding capacity group the range was 31-69%.…”

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confidence: 99%

The measurement, definition, aetiology and clinical consequences of neonatal transient hypothyroxinaemia

Williams

Hume

2010

Ann Clin Biochem

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This review focuses on neonatal transient hypothyroxinaemia, a condition characterized by temporary postnatal reductions in concentrations of Total T4 or Free T4, with normal or low concentrations of thyroid stimulating hormone (TSH). There is neither an agreed quantitative definition, nor an agreed mode of measurement for the condition. Transient hypothyroxinaemia is not routinely monitored yet it is thought to affect about 50% of preterm infants; it was thought to be without long-term sequelae but observational studies indicate that neurodevelopment may be compromised. The aetiology of transient hypothyroxinaemia is complex. There are significant contributions from the withdrawal of maternal -placental thyroxine transfer, hypothalamic-pituitary -thyroid immaturity, developmental constraints on the synthesis and peripheral metabolism of iodothyronines and iodine deficiency. It is not possible to distinguish clinically, or from laboratory measurements, whether transient hypothyroxinaemia is an independent condition or simply a consequence of non-thyroidal illness and/or drug usage. An answer to this question is important because studies of thyroid hormone replacement have been instigated, with mixed results. Until the aetiology of transient hypothyroxinaemia is better understood it would seem prudent not to routinely supplement preterm infants with thyroid hormones. Iodine deficiency, non-thyroidal illness and drug usage are the most modifiable risk factors for transient hypothyroxinaemia and are the clear choices for attempts at reducing its incidence. We suggest that transient hypothyroxinaemia in preterm infants is defined as a normal or low TSH concentration in conjunction with a concentration of Total T4, that is 10th percentile of cord Total T4 of the equivalent gestational age had the infant remained in utero.Ann Clin Biochem 2011; 48: 7-22.

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“…Bruce Wilcox 1* and Jerald C. Nelson 2 There have been, and continue to be, reports of discordant free thyroxine (T 4 ) 3 measurements when different free-T 4 methods are applied to the same serum samples (1)(2)(3)(4). Our laboratory has attempted to identify some of the factors that contribute to these disparities.…”

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confidence: 99%

Counterpoint: Legitimate and Illegitimate Tests of Free-Analyte Assay Function: We Need to Identify the Factors That Influence Free-Analyte Assay Results

Wilcox¹,

Nelson

2009

Clinical Chemistry

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There have been, and continue to be, reports of discordant free thyroxine (T 4 ) 3 measurements when different free-T 4 methods are applied to the same serum samples (1-4 ). Our laboratory has attempted to identify some of the factors that contribute to these disparities.There are 4 separate components of serum T 4 : free T 4 , albumin-bound T 4 , transthyretin-bound T 4 , and thyroxine-binding globulin (TBG)-bound T 4 . Free T 4 is the one component that moves across semipermeable membranes during equilibrium dialysis and ultrafiltration. As Midgley and Christofides point out, the gold standard free-T 4 methods are designed to measure this component.We applied analog-type methods and an equilibrium-dialysis/immunoassay gold standard method to carefully prepared solutions in which we varied these 4 components of serum T 4 . This equilibrium-dialysis method agrees closely with a liquid chromatographytandem mass spectrometry method applied to serum ultrafiltrates (4 ). We also applied this equilibrium dialysis/immunoassay and a group of 7 analog-type free-T 4 assays to solutions of T 4 that did not include T 4 -binding proteins (5 ); that is, the only form of T 4 was free T 4 . The analog-type assays required 28-to 588-fold higher concentrations of free T 4 than the equilibrium dialysis/immunoassay to generate similar assay results. These results highlight the widely differing characteristics of the antibodies used in these assays. Midgley and Christofides state that analog-type methods are not suitable for application to "pure" analyte solutions. We understand that they are not suitable for the measurement of free T 4 in the absence of protein-bound T 4 ; however, we are not persuaded that applying any assay to the substance it reports is inappropriate, when the goal is to identify the factors that influence assay results.When albumin, transthyretin, and TBG are held constant and the total T 4 concentration is varied, the concentrations of free T 4 , albumin-bound T 4 , transthyretin-bound T 4 , TBG-bound T 4 , and total T 4 are aligned with one another. That is, they are proportionate covariables. In a recent experiment, the total T 4 concentration was varied while albumin, transthyretin, and TBG concentrations were within the reference interval and constant. Seven analog-type free-T 4 assays were applied to these T 4 solutions. Analog-type free-T 4 estimates correlated closely with dialyzable T 4 concentrations (Fig. 1). This result prompts a question: What happens to analog-type free-T 4 estimates when these 5 T 4 components are not aligned?In a previous study, albumin, transthyretin, TBG, and total-T 4 concentrations were proportionate covariables, and dialyzable T 4 was held constant (6 ). Five analog-type free-T 4 assays were applied. Free-T 4 estimates obtained with analog-type assays reflected the concentrations of T 4 -binding proteins and total T 4 . They did not reflect the fixed dialyzable T 4 concentration. These data are direct evidence that total T 4 and/or T 4 -binding proteins influence such as...

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Direct Equilibrium Dialysis Compared with Two Non-dialysis Free T4 Methods in Premature Infants

Cited by 27 publications

References 40 publications

Mass screening of newborns for congenital hypothyroidism of central origin by free thyroxine measurement of blood samples on filter paper

Mass screening of newborns for congenital hypothyroidism of central origin by free thyroxine measurement of blood samples on filter paper

The measurement, definition, aetiology and clinical consequences of neonatal transient hypothyroxinaemia

Counterpoint: Legitimate and Illegitimate Tests of Free-Analyte Assay Function: We Need to Identify the Factors That Influence Free-Analyte Assay Results

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