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Erzsébet Toldy - One of the best experts on this subject based on the ideXlab platform.
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Serum Thyroglobulin antibody levels within or near to the reference range may interfere with Thyroglobulin measurement
Biochemia medica, 2012Co-Authors: Zoltan Locsei, István Szabolcs, Károly Rácz, Gábor L. Kovács, Dóra Horváth, Erzsébet ToldyAbstract:High concentration of Thyroglobulin antibodies (TgAb) is a major limiting factor of Thyroglobulin measurements in patients with differentiated thyroid cancer. We investigated whether Thyroglobulin antibody added to serum samples could interfere with the Thyroglobulin assay. Thyroglobulin levels in serum samples with different concentrations of Thyroglobulin were measured by electrochemiluminescence immunoassay before and after the addition of increasing concentrations of Thyroglobulin antibody using the secondary calibrator solution of the Thyroglobulin assay kit containing sheep Thyroglobulin antibody to reach Thyroglobulin antibody levels within or near to the reference range. Thyroglobulin and Thyroglobulin antibody concentrations were also measured in 134 serum samples from 27 patients after thyroid ablation. There was a strong negative association (slope = -1.179) between Thyroglobulin antibody and Thyroglobulin concentrations in samples with added Thyroglobulin antibody (beta = -0.86; P < 0.001). Changes in Thyroglobulin concentrations were described mathematically as loss of Thyroglobulin% = -0.2408 x Ln(Thyroglobulin antibody IU/ml) + 0.1944. Thyroglobulin concentrations were significantly lower than those calculated from experiments with added Thyroglobulin antibody in 26/134 samples from patients after thyroid ablation. We conclude that if the same TgAb interference exists in the presence of naturally occurring human TgAb, our observation may prove to be useful during follow-up of patients with differentiated thyroid cancer. However, further studies are needed to explore the clinical relevance of Thyroglobulin antibody levels within or near to the reference range in monitoring these patients.
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Szérumtireoglobulin és tireoglobulin-antitest együttesmeghatározásának jelentősége a differenciált pajzsmirigy-karcinómás betegek gondozása során = The significance of simultaneous measurement of serum Thyroglobulin and Thyroglobulin antibody during
2011Co-Authors: Zoltán Lőcsei, Károly Rácz, Dóra Horváth, Erzsébet ToldyAbstract:A differencialt pajzsmirigy-karcinomas betegek gondozasaban a szerumtireoglobulin alapvető tumormarker. A tireoglobulin teljes hianyat nem lehet bizonyitani immunanalitikai modszerekkel, ha a beteg szerumaban tireoglobulin ellen kepződő autoantitest van jelen, ami differencialt pajzsmirigy-karcinomaban szenvedő betegek kozel 20%-aban előfordul. Ezert a szakmai ajanlasok csak a tireoglobulin-autoantitest mennyisegenek ismereteben javasoljak a szerumtireoglobulin-lelet ertekeleset. A tireoglobulin-autoantitest normalis szintje nem zarja ki a zavaro hatast, ugyanis nem ismert, hogy mekkora antitest-koncentracional nem kell antitest-interakcioval szamolnunk. Ebben a tekintetben nem kovetkezetesek az irodalmi ajanlasok, mivel ritkan tesznek kulonbseget a tireoglobulinautoantitest-negativitas es az alacsony, de meg merhető antitestszint kozott. Ezert nem egyertelmű, hogy az alacsony antitestszintek mennyire befolyasoljak a tireoglobulin kimutathatosagat. A szerzők az irodalmi adatok es szakmai ajanlasok tukreben tekintik at a szerumtireoglobulin- es tireoglobulinautoantitest-vizsgalat preanalitikai es analitikai korlatait, es sajat eredmenyeik alapjan javaslatot tesznek a tireoglobulinmeghatarozas diagnosztikai pontossaganak novelesere. Orv. Hetil., 2011, 152, 743–752. | Serum Thyroglobulin is an essential marker during the follow-up of patients with differentiated thyroid carcinoma. Demonstration of the total absence of Thyroglobulin is not possible by immunoanalytic methods if Thyroglobulin antibody is present in serum samples that occur in almost 20% of patients with differentiated thyroid carcinoma. Therefore, current guidelines recommend estimation of Thyroglobulin levels only if quantitative level of Thyroglobulin antibody is known. However, normal Thyroglobulin antibody level fails to exclude interference with the antibody, because antibody concentration within the normal range may interfere with the Thyroglobulin assay. In this respect recommendations are not consistent because they distinguish only occasionally cases with normal and those with non-detectable serum Thyroglobulin level. In addition, the possible impact of normal Thyroglobulin antibody level on the Thyroglobulin assay has not been entirely explored. Authors review literature data and current guidelines on the analytical and preanalytical limitations of the Thyroglobulin and Thyroglobulin antibody measurements. On the basis of their own studies, authors make recommendation for improvement of the diagnostic accuracy of the Thyroglobulin measurement. Orv. Hetil., 2011, 152, 743–752.
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szerumtireoglobulin es tireoglobulin antitest egyuttesmeghatarozasanak jelentősege a differencialt pajzsmirigy karcinomas betegek gondozasa soran the significance of simultaneous measurement of serum Thyroglobulin and Thyroglobulin antibody during th
2011Co-Authors: Zoltán Lőcsei, Károly Rácz, Dóra Horváth, Erzsébet ToldyAbstract:A differencialt pajzsmirigy-karcinomas betegek gondozasaban a szerumtireoglobulin alapvető tumormarker. A tireoglobulin teljes hianyat nem lehet bizonyitani immunanalitikai modszerekkel, ha a beteg szerumaban tireoglobulin ellen kepződő autoantitest van jelen, ami differencialt pajzsmirigy-karcinomaban szenvedő betegek kozel 20%-aban előfordul. Ezert a szakmai ajanlasok csak a tireoglobulin-autoantitest mennyisegenek ismereteben javasoljak a szerumtireoglobulin-lelet ertekeleset. A tireoglobulin-autoantitest normalis szintje nem zarja ki a zavaro hatast, ugyanis nem ismert, hogy mekkora antitest-koncentracional nem kell antitest-interakcioval szamolnunk. Ebben a tekintetben nem kovetkezetesek az irodalmi ajanlasok, mivel ritkan tesznek kulonbseget a tireoglobulinautoantitest-negativitas es az alacsony, de meg merhető antitestszint kozott. Ezert nem egyertelmű, hogy az alacsony antitestszintek mennyire befolyasoljak a tireoglobulin kimutathatosagat. A szerzők az irodalmi adatok es szakmai ajanlasok tukreben tekintik at a szerumtireoglobulin- es tireoglobulinautoantitest-vizsgalat preanalitikai es analitikai korlatait, es sajat eredmenyeik alapjan javaslatot tesznek a tireoglobulinmeghatarozas diagnosztikai pontossaganak novelesere. Orv. Hetil., 2011, 152, 743–752. | Serum Thyroglobulin is an essential marker during the follow-up of patients with differentiated thyroid carcinoma. Demonstration of the total absence of Thyroglobulin is not possible by immunoanalytic methods if Thyroglobulin antibody is present in serum samples that occur in almost 20% of patients with differentiated thyroid carcinoma. Therefore, current guidelines recommend estimation of Thyroglobulin levels only if quantitative level of Thyroglobulin antibody is known. However, normal Thyroglobulin antibody level fails to exclude interference with the antibody, because antibody concentration within the normal range may interfere with the Thyroglobulin assay. In this respect recommendations are not consistent because they distinguish only occasionally cases with normal and those with non-detectable serum Thyroglobulin level. In addition, the possible impact of normal Thyroglobulin antibody level on the Thyroglobulin assay has not been entirely explored. Authors review literature data and current guidelines on the analytical and preanalytical limitations of the Thyroglobulin and Thyroglobulin antibody measurements. On the basis of their own studies, authors make recommendation for improvement of the diagnostic accuracy of the Thyroglobulin measurement. Orv. Hetil., 2011, 152, 743–752.
Henry B. Burch - One of the best experts on this subject based on the ideXlab platform.
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Serum Thyroglobulin measurement. Utility in clinical practice.
Endocrinology and metabolism clinics of North America, 2001Co-Authors: Javier I. Torréns, Henry B. BurchAbstract:Serum Thyroglobulin measurement has greatly facilitated the clinical management of patients with differentiated thyroid cancer and a variety of other thyroid disorders. Thyroglobulin autoantibodies remain a significant obstacle to the clinical use of Thyroglobulin measurement. The interpretation of any given Thyroglobulin value requires the careful synthesis of all pertinent clinical and laboratory data available to the clinician. The diagnostic use of rhTSH-stimulated Thyroglobulin levels has greatly facilitated the follow-up of low-risk patients with thyroid cancer. Although the measurement of Thyroglobulin mRNA from peripheral blood is likely to affect the future management of these patients, it is expected that serum Thyroglobulin measurement will continue to have a principal role in the care of patients with differentiated thyroid cancer.
Volker Herzog - One of the best experts on this subject based on the ideXlab platform.
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Cysteine proteinases mediate extracellular prohormone processing in the thyroid.
Biological chemistry, 2001Co-Authors: Klaudia Brix, Martin Linke, Carmen Tepel, Volker HerzogAbstract:Thyroglobulin, the precursor of thyroid hormones, is extracellularly stored in a highly condensed and covalently cross-linked form. Solublization of Thyroglobulin is facilitated by cysteine proteinases like cathepsins B and K which are proteolytically active at the surface of thyroid epithelial cells. The cysteine proteinases mediate the processing of Thyroglobulin by limited extracellular proteolysis at the apical plasma membrane, thereby rapidly liberating thyroxine. The trafficking of cysteine proteinases in thyroid epithelial cells includes their targeting to lysosomes where they become maturated before being transported to the apical plasma membrane and, thus, into the extracellular follicle lumen. We propose that thyroid stimulating hormone regulates extracellular proteolysis of Thyroglobulin in that it enhances the rate of exocytosis of lysosomal proteins at the apical plasma membrane. Later, thyroid stimulating hormone upregulates Thyroglobulin synthesis and its secretion into the follicle lumen for subsequent compaction by covalent cross-linking. Hence, cycles of Thyroglobulin proteolysis and Thyroglobulin deposition might result in the regulation of the size of the luminal content of thyroid follicles. We conclude that the biological significance of extracellularly acting cysteine proteinases of the thyroid is the rapid utilization of Thyroglobulin for the maintenance of constant thyroid hormone levels in vertebrate organisms.
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Extrathyroidal release of thyroid hormones from Thyroglobulin by J774 mouse macrophages.
Journal of Clinical Investigation, 1994Co-Authors: Klaudia Brix, Volker HerzogAbstract:Thyroglobulin appears in the circulation of vertebrates at species-specific concentrations. We have observed that the clearance of Thyroglobulin from the circulation occurs in the liver by macrophages. Here we show that the thyroid hormones T3 and T4 were released by incubation of mouse macrophages (J774) with Thyroglobulin. Thyroid hormone release was a fast process, with an initial rate of approximately 20 pmol T4/mg per min and approximately 0.6 pmol T3/mg per min, indicating that macrophages preferentially release T4. The bulk of released thyroid hormones appeared after 5 min of incubation of macrophages with Thyroglobulin, whereas degradation of the protein was detectable only after several hours. During internalization of Thyroglobulin, endocytic vesicles and endosomes were reached at 5 min and lysosomes at 60 min. T4 release started extracellularly by secreted proteases and continued along the endocytic pathway of Thyroglobulin, whereas T3 release occurred mainly intracellularly when Thyroglobulin had reached the lysosomes. This shows that the release of both hormones occurred at distinct cellular sites. Our in vitro observations suggest that macrophages in situ represent an extrathyroidal source for thyroid hormones from circulating Thyroglobulin.
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Endocytosis of Thyroglobulin is not mediated by mannose-6-phosphate receptors in thyrocytes. Evidence for low-affinity-binding sites operating in the uptake of Thyroglobulin.
European journal of biochemistry, 1992Co-Authors: Peter Lemansky, Volker HerzogAbstract:Thyroglobulin, the major secretory product of thyrocytes, is the macromolecular precursor of thyroid hormones. After its synthesis, Thyroglobulin follows a complex secretion, storage and recapture pathway to lysosomes. Porcine Thyroglobulin was shown to carry the mannose 6-phosphate-(Man6P)-recognition marker on its N-linked glycans. Since the cation-independent Man6P receptor could also be found on the apical plasma membrane of porcine thyrocytes, we examined the significance of the Man6P signal for the transport of Thyroglobulin. Here, we present data implying that Man6P receptors are not relevant for endocytosis of Thyroglobulin in thyrocytes. Instead, we provide evidence for the existence of specific, low-affinity-binding sites for Thyroglobulin on the apical plasma membrane of thyrocytes responsible for endocytosis of Thyroglobulin. Binding studies with intact, polar-organized porcine thyrocytes grown on collagen-coated filters revealed cooperative and saturable binding of Thyroglobulin to the apical-plasma-membrane domain at relatively high concentrations of Thyroglobulin (20 μM). These observations show that low-affinity interactions between Thyroglobulin and the apical plasma membrane play a key role in endocytosis of Thyroglobulin and hormone formation in the thyroid. The data in this publication have been published as an abstract [Lemansky, P. and Herzog, V. (1991) J. Cell Biol. 115, 261a].
Tom Dembinski - One of the best experts on this subject based on the ideXlab platform.
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Thyroglobulin and anti-Thyroglobulin assays in thyroid cancer monitoring
Clinical Biochemistry, 2009Co-Authors: John Krahn, Tom DembinskiAbstract:Abstract Objectives To compare four methods for Thyroglobulin (Tg) quantitation and three methods for detection and quantitation of Thyroglobulin antibodies (Tg–Ab). We also wanted to explore the premise that Thyroglobulin antibodies, as determined by commercially available assays, interfere with Thyroglobulin assays in a predictable way. Methods Split sample method comparisons were run on all the methods for both the Thyroglobulin and anti-Thyroglobulin assays. In addition to this, samples from patients that had disseminated thyroid cancer but had low serum Thyroglobulin concentrations and high Thyroglobulin antibodies were further studied. These studies involved doing recovery studies (or antibody inhibition studies). Results There was good agreement between methods for quantitation of Thyroglobulin with slopes ranging from 0.77 to 1.23 although closer agreement was expected as the assays are all calibrated to the same reference standard (CRM 457). The situation for the Thyroglobulin antibody assays is significantly worse, and the rate of antibody positivity ranged from 9–21% in this group of patients although there was agreement in only 6%. Different reference standards are used for the Tg–Ab assays we investigated. The Tg–Ab data did not lend itself to traditional linear regression analysis as the data showed wide scatter. Conclusions There is good agreement between the four Thyroglobulin assays compared in this study. The linear regression analysis shows that there is proportional error present between the methods that is greater than 50%. This study is unable to demonstrate any difference in assay values based on the amount of anti-thyrogobulin present in the specimen. The agreement between different anti-Thyroglobulin assays is very poor. This finding is very problematic since it makes it difficult to generalize any literature reports of interference. All the Thyroglobulin assays appear to be suitable for monitoring patients with thyroid cancer, provided that the differences in calibration are taken into account. Differences in calibration between different assays need to be taken into account when changing assays. Conversely, the anti-Thyroglobulin assays are virtually useless since there appears to be very little agreement between the three assays studied and no evidence of assay interference in the measurements of Thyroglobulin.
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Thyroglobulin and anti-Thyroglobulin assays in thyroid cancer monitoring.
Clinical biochemistry, 2009Co-Authors: John Krahn, Tom DembinskiAbstract:To compare four methods for Thyroglobulin (Tg) quantitation and three methods for detection and quantitation of Thyroglobulin antibodies (Tg-Ab). We also wanted to explore the premise that Thyroglobulin antibodies, as determined by commercially available assays, interfere with Thyroglobulin assays in a predictable way. Split sample method comparisons were run on all the methods for both the Thyroglobulin and anti-Thyroglobulin assays. In addition to this, samples from patients that had disseminated thyroid cancer but had low serum Thyroglobulin concentrations and high Thyroglobulin antibodies were further studied. These studies involved doing recovery studies (or antibody inhibition studies). There was good agreement between methods for quantitation of Thyroglobulin with slopes ranging from 0.77 to 1.23 although closer agreement was expected as the assays are all calibrated to the same reference standard (CRM 457). The situation for the Thyroglobulin antibody assays is significantly worse, and the rate of antibody positivity ranged from 9-21% in this group of patients although there was agreement in only 6%. Different reference standards are used for the Tg-Ab assays we investigated. The Tg-Ab data did not lend itself to traditional linear regression analysis as the data showed wide scatter. There is good agreement between the four Thyroglobulin assays compared in this study. The linear regression analysis shows that there is proportional error present between the methods that is greater than 50%. This study is unable to demonstrate any difference in assay values based on the amount of anti-Thyroglobulin present in the specimen. The agreement between different anti-Thyroglobulin assays is very poor. This finding is very problematic since it makes it difficult to generalize any literature reports of interference. All the Thyroglobulin assays appear to be suitable for monitoring patients with thyroid cancer, provided that the differences in calibration are taken into account. Differences in calibration between different assays need to be taken into account when changing assays. Conversely, the anti-Thyroglobulin assays are virtually useless since there appears to be very little agreement between the three assays studied and no evidence of assay interference in the measurements of Thyroglobulin.
Peter Arvan - One of the best experts on this subject based on the ideXlab platform.
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The role of Thyroglobulin in thyroid hormonogenesis
Nature Reviews Endocrinology, 2019Co-Authors: Cintia E. Citterio, Héctor M. Targovnik, Peter ArvanAbstract:The first definitive evidence of a complete TG gene appears with the development of the vertebrates, and once appearing in evolution, the entire structure of Thyroglobulin, as well as its ability to be secreted, has been retained thereafter. The synthesis of T_3 and T_4 within Thyroglobulin involves oxidative coupling between iodinated tyrosine residues on Thyroglobulin. The main T_3-forming site within Thyroglobulin couples a mono-iodotyrosine donor at the antepenultimate residue of one monomer with a di-iodotyrosine acceptor in the same residue of the apposed monomer within a dimer. Post-translational modifications of Thyroglobulin include phosphorylation for which the secretory pathway kinase FAM20C has been implicated. TSH stimulation of thyrocytes promotes post-translational modifications that can alter Thyroglobulin structure in a way that favours T_3 formation upon iodination, whereas defects in TSH-mediated stimulation result in Thyroglobulin with diminished capacity to form T_3. 167 TG mutations exist that can cause congenital hypothyroidism; although the disease is usually inherited as an autosomal recessive trait, patients with congenital hypothyroidism bearing monoallelic mutations of TG have recently been reported. In humans, the thyroid hormones T_3 and T_4 are synthesized in the thyroid gland in a process that crucially involves the iodoglycoprotein Thyroglobulin. The overall structure of Thyroglobulin is conserved in all vertebrates. Upon Thyroglobulin delivery from thyrocytes to the follicular lumen of the thyroid gland via the secretory pathway, multiple tyrosine residues can become iodinated to form mono-iodotyrosine (MIT) and/or di-iodotyrosine (DIT); however, selective tyrosine residues lead to preferential formation of T_4 and T_3 at distinct sites. T_4 formation involves oxidative coupling between two DIT side chains, and de novo T_3 formation involves coupling between an MIT donor and a DIT acceptor. Thyroid hormone synthesis is stimulated by TSH activating its receptor (TSHR), which upregulates the activity of many thyroid gene products involved in hormonogenesis. Additionally, TSH regulates post-translational changes in Thyroglobulin that selectively enhance its capacity for T_3 formation — this process is important in iodide deficiency and in Graves disease. 167 different mutations, many of which are newly discovered, are now known to exist in TG (encoding human Thyroglobulin) that can lead to defective thyroid hormone synthesis, resulting in congenital hypothyroidism. T_3 and T_4 are synthesized in the thyroid gland in a process that involves the iodoglycoprotein Thyroglobulin. In this Review, we consider the role of Thyroglobulin in thyroid hormonogenesis from evolutionary, biochemical, molecular, cellular and physiological angles.
