DIAGNOSIS OF ENDOCRINE DISEASE: How reliable are free thyroid and total T3 hormone assays?

Welsh, Kerry J.; Soldin, Steven J.

doi:10.1530/eje-16-0193

Cited by 98 publications

(73 citation statements)

References 59 publications

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“…Limitations of this study include the specialized patient population with multiple transplant patients. Nonetheless, the results of this investigation contribute to the multiple studies (reviewed in (4, 5)) highlighting inaccuracies with common immunoassay platforms in several patient populations.…”

Section: Discussionmentioning

confidence: 89%

“…However, a number of studies have shown discrepancies in free and total thyroid hormone measurement by immunoassay when compared to a reference method such as liquid chromatography-tandem mass spectrometry (LC-MSMS) in several populations (reviewed in (4, 5)). Multiple studies have shown falsely normal values for TT3, FT, and FT4 by immunoassays that are below the reference interval when measured by reference LC-MSMS in a number of patient populations (3, 6–8).…”

Section: Introductionmentioning

confidence: 99%

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Assessment of thyroid function in intensive care unit patients by liquid chromatography tandem mass spectrometry methods

Welsh

Stolze

et al. 2017

Clinical Biochemistry

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Objectives Patients with non-thyroidal illness syndrome have many abnormalities in thyroid hormone tests. Such patients have medical comorbidities associated with low serum proteins and are on multiple medications that interfere with thyroid hormone measurement by immunoassay platforms. It is unknown if these thyroid hormone measurements reflect physiologic conditions or if they are artifacts of testing methodology. Methods Fifty patients were selected from the intensive care unit (ICU) from our institution. Total and free thyroid hormones in plasma were measured by gold standard liquid chromatography-tandem mass spectrometry (LC-MSMS). The results were compared to the Roche Cobas 6000. Patient medical comorbidities and binding protein levels were assessed. Results Concentrations of total 3,5,5'-triidothyronine (TT3) and total thyroxine (TT4) were significantly more likely to be low by LC-MSMS compared to immunoassay. Free 3,5,5'-triidothyronine (FT3) levels were similar by immunoassay and LC-MSMS. However, FT4 concentrations were mildly elevated for many patients when measured by ultrafiltration LC-MSMS (19/50, 38%) compared to 1/50 (2%) when measured by immunoassay (p = 0.0001). Decreased albumin and thyroxine binding globulin were common and patients were on an average of 11.7 ± 5.0 medications, all factors known to interfere with results found on immunoassays. Conclusions Marked discrepancies in thyroid hormone measurement were noted between reference LC-MSMS and a common immunoassay platform. It is hypothesized that T4 binding to low affinity albumin is displaced by several drugs, raising concentrations of FT4 by LC-MSMS compared to immunoassay, and that the immunoassay values are falsely decreased due to low binding proteins in our patient population.

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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Assessment of thyroid function in intensive care unit patients by liquid chromatography tandem mass spectrometry methods

Welsh

Stolze

et al. 2017

Clinical Biochemistry

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“…The gold standard for measurement of free thyroid hormones (fT 3 and fT 4 ) is a method involving a separation step of bound from free thyroid hormone, classically a dialysis method ( 62 ) or recently the LC/MS method; but none of these methods are widely available. In our study, free thyroid hormones were measured by an immunoassay.…”

Section: Discussionmentioning

confidence: 99%

“…In our study, free thyroid hormones were measured by an immunoassay. Immunoassays can both overestimate and underestimate free thyroid hormone concentrations depending on the platform used for the assay ( 62 ). However, there is no reason to suspect that a potential overestimation of free T 3 and free T 4 serum concentrations should be biased in relation to the exposure to UV filters and thereby might not have affected the results.…”

Section: Discussionmentioning

confidence: 99%

Maternal exposure to UV filters: associations with maternal thyroid hormones, IGF-I/IGFBP3 and birth outcomes

Krause

Frederiksen

Sundberg

et al. 2018

Endocrine Connections

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BackgroundSeveral chemical UV filters/absorbers ('UV filters' hereafter) have endocrine-disrupting properties in vitro and in vivo. Exposure to these chemicals, especially during prenatal development, is of concern.ObjectivesTo examine maternal exposure to UV filters, associations with maternal thyroid hormone, with growth factor concentrations as well as to birth outcomes.MethodsProspective study of 183 pregnant women with 2nd trimester serum and urine samples available. Maternal concentrations of the chemical UV filters benzophenone-1 (BP-1) and benzophenone-3 (BP-3) in urine and 4-hydroxy-benzophenone (4-HBP) in serum were measured by liquid chromatography–tandem mass spectrometry (LC–MS/MS). The relationships between 2nd trimester maternal concentrations of the three chemical UV filters and maternal serum concentrations of thyroid hormones and growth factors, as well as birth outcomes (weight, height, and head and abdominal circumferences) were examined.ResultsPositive associations between maternal serum concentrations of 4-HBP and triiodothyronine (T3), thyroxine (T4), insulin-like growth factor I (IGF-I) and its binding protein IGFBP3 were observed in mothers carrying male fetuses. Male infants of mothers in the middle 4-HBP exposure group had statistically significantly lower weight and shorter head and abdominal circumferences at birth compared to the low exposure group.ConclusionsWidespread exposure of pregnant women to chemical UV filters and the possible impact on maternal thyroid hormones and growth factors, and on fetal growth, calls for further studies on possible long-term consequences of the exposure to UV filters on fetal development and children’s health.

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“…However, various practical and technical issues related to above-mentioned challenges of TH physiology and pathophysiology hampered rapid progress and success in quantification of total and free THM concentrations. While meanwhile several laboratories developed procedures to accurately determine total T4 and total T3 in human plasma or serum and largely agree on concentrations ranges (25,(67)(68)(69)(70)(71)(72)(73), this consensus has not been achieved yet for most of the other TH metabolites, which occur at much lower concentrations. Analytical procedures typically work well with buffer solutions, in vitro reaction mixtures, as well as with samples of "simple" matrix composition, while reported concentrations in human or experimental animal serum, plasma, and tissue show wide variations and marked insufficiencies in terms of method validation, standardization, and quality assessment parameters [see (23,24,74)].…”

Section: Alternative Lc-ms-based Approaches Are Needed To Determine Cmentioning

confidence: 99%

3,5-T2—A Janus-Faced Thyroid Hormone Metabolite Exerts Both Canonical T3-Mimetic Endocrine and Intracrine Hepatic Action

et al. 2020

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Structural formula of the "Janus-faced" THM 3,5-diiodo-L-thyronine (left), which has the same 3,5-iodine substitution pattern as its putative precursors L-T4 and L-T3 at the tyrosyl-ring, but lacks the iodine substitution in 3 ′-position of the phenolic ring which is essential for binding classical T3-receptors and conveying canonical and non-canonical thyromimetic effects. The roman god Janus symbolized "duality" and "jani" were ceremonial gateways in ancient Rome typically used for symbolically auspicious entrances or exits. Janus-face (right) source: This image comes from the 4th edition of Meyers Konversationslexikon (1885-90). The copyrights have expired and this image is in the public domain. Wikimedia, Meyers_b9_s0153_b1.png. HYPOTHESES AND THEORY a. 3,5-T2 is an endogenous metabolite of thyroid hormones T4 and T3 b. 3,5-T2 might represent the precursor of 3-iodothyronamine c. 3,5-T2 acts like T3 via canonical activation of T3 receptors albeit with lower potency d. 3,5-T2 exerts actions distinct from those of thyromimetically active T3 i) via mitochondrial targets ii) by its intrahepatic accumulation iii) by its intracrine mode of action e. 3,5-T2 formation and action might be altered in patients on T4 replacement therapy and causes adverse effects if abused.

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DIAGNOSIS OF ENDOCRINE DISEASE: How reliable are free thyroid and total T3 hormone assays?

Cited by 98 publications

References 59 publications

Assessment of thyroid function in intensive care unit patients by liquid chromatography tandem mass spectrometry methods

Assessment of thyroid function in intensive care unit patients by liquid chromatography tandem mass spectrometry methods

Maternal exposure to UV filters: associations with maternal thyroid hormones, IGF-I/IGFBP3 and birth outcomes

3,5-T2—A Janus-Faced Thyroid Hormone Metabolite Exerts Both Canonical T3-Mimetic Endocrine and Intracrine Hepatic Action

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