Detection of 3,5-Diiodothyronine in Sera of Patients with Altered Thyroid Status Using a New Monoclonal Antibody-Based Chemiluminescence Immunoassay

Lehmphul, Ina; Brabant, Georg; Wallaschofski, Henri; Ruchała, Marek; Strasburger, Christian J.; Köhrle, Josef; Wu, Zida

doi:10.1089/thy.2013.0688

Cited by 58 publications

(65 citation statements)

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“…This finding is also in agreement with our previous study, where no correlation between 3,5-T2 and serum T4 and T3 concentrations was observed in healthy or T4-substituted individuals (20). However, since early experimental work suggested an extrathyroidal conversion of 3,5-T2 from T3 also in humans (45), the missing correlation observed within our tight subset does not necessarily exclude a physiological link between both, and further effort is needed for clarification.…”

Section: Figsupporting

confidence: 93%

“…For this purpose, we used a newly developed immunoassay (20), representing the only currently available method to determine serum 3,5-T2 concentrations in humans (26)(27)(28). Our data revealed significant bell-shaped associations of serum 3,5-T2 concentrations with serum glucose concentration and TSH concentrations in the fasting state, pointing toward a versatile role of circulating 3,5-T2 in human metabolism.…”

Section: Discussionmentioning

confidence: 91%

“…Serum 3,5-T2 concentrations were measured with a recently developed monoclonal antibody-based chemiluminescence immunoassay (20). Blood samples were stored for about five years prior to analysis.…”

Section: Figmentioning

confidence: 99%

“…Blood samples were stored for about five years prior to analysis. In the course of assay validation (20), different storage conditions, that is, room temperature, 4°C and -20°C, as well as several freeze-thaw cycles did not disturb 3,5-T2 stability, leading to the assumption that even prolonged storage would not affect the results. The functional sensitivity of the assay was specified as 0.2 nM.…”

Section: Figmentioning

confidence: 99%

“…Expanding these initial findings and questioning former results that reported a wide spectrum of serum 3,5-T2 concentrations over almost two orders of magnitude in rather small groups of analyzed individuals, we now used a newly developed assay (20) to determine serum 3,5-T2 concentrations in a larger healthy study population. The aim of the present study was to analyze associations between serum 3,5-T2 concentrations and metabolic parameters from glucose and lipid metabolism as well as anthropometric measures in a euthyroid population.…”

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confidence: 91%

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Translating Pharmacological Findings from Hypothyroid Rodents to Euthyroid Humans: Is There a Functional Role of Endogenous 3,5-T2?

Pietzner

Lehmphul

Friedrich

et al. 2015

Thyroid

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Background: During the last two decades, it has become obvious that 3,5-diiodothyronine (3,5-T2), a wellknown endogenous metabolite of the thyroid hormones thyroxine (T4) or triiodothyronine (T3), not only represents a simple degradation intermediate of the former but also exhibits specific metabolic activities. Administration of 3,5-T2 to hypothyroid rodents rapidly stimulated their basal metabolic rate, prevented highfat diet-induced obesity as well as steatosis, and increased oxidation of long-chain fatty acids. Objective: The aim of the present study was to analyze associations between circulating 3,5-T2 in human serum and different epidemiological parameters, including age, sex, or smoking, as well as measures of anthropometry, glucose, and lipid metabolism. Methods: 3,5-T2 concentrations were measured by a recently developed immunoassay in sera of 761 euthyroid participants of the population-based Study of Health in Pomerania. Subsequently, analysis of variance and multivariate linear regression analysis were performed. Results: Serum 3,5-T2 concentrations exhibited a right-skewed distribution, resulting in a median serum concentration of 0.24 nM (1st quartile: 0.20 nM; 3rd quartile: 0.37 nM). Significant associations between 3,5-T2 and serum fasting glucose, thyrotropin (TSH), as well as leptin concentrations were detected ( p < 0.05). Interestingly, the association to leptin concentrations seemed to be mediated by TSH. Age, sex, smoking, and blood lipid profile parameters did not show significant associations with circulating 3,5-T2. Conclusion: Our findings from a healthy euthyroid population may point toward a physiological link between circulating 3,5-T2 and glucose metabolism.

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Section: Figsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 91%

Section: Figmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

mentioning

confidence: 91%

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Translating Pharmacological Findings from Hypothyroid Rodents to Euthyroid Humans: Is There a Functional Role of Endogenous 3,5-T2?

Pietzner

Lehmphul

Friedrich

et al. 2015

Thyroid

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Mass spectrometry in the diagnosis of thyroid disease and in the study of thyroid hormone metabolism

Borsò

Agretti

Zucchi

2020

Mass Spectrometry Reviews

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The importance of thyroid hormones in the regulation of development, growth, and energy metabolism is well known. Over the last decades, mass spectrometry has been extensively used to investigate thyroid hormone metabolism and to discover and characterize new molecules involved in thyroid hormones production, such as thyrotropin-releasing hormone. In the earlier period, the quantification methods, usually based on gas chromatography-mass spectrometry, were complicated and time consuming. They were mainly focused on basic research, and were not suitable for clinical diagnostics on a routine basis. The development of the modern mass spectrometers, mainly coupled to liquid chromatography, enabled simpler sample preparation procedures, and the accurate quantification of thyroid hormones, of their precursors, and of their metabolites in biological fluids, tissues, and cells became feasible. Nowadays, molecules of physiological and pathological interest can be assayed also for diagnostic purposes on a routine basis, and mass spectrometry is slowly entering the clinical laboratory. This review takes stock of the advancements in the field of thyroid metabolism that were carried out with mass spectrometry, with special focus on the use of this technique for the quantification of molecules involved in thyroid diseases. | INTRODUCTIONThyroid hormones (TH), namely triiodothyronine (3,5, 3′-triiodothyronine, T 3 ) and thyroxine (3,5,3′,5′-tetraiodothyronine, T 4 ), regulate development, energy metabolism, and growth, and their blood levels are controlled by complex central and peripheral signals mainly mediated by hypothalamic thyrotropin-releasing hormone (TRH) and pituitary thyrotropin (thyroid-stimulating hormone, TSH). The hypothalamic-pituitary-thyroid axis determines the set

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Thyroid Hormones and Derivatives: Endogenous Thyroid Hormones and Their Targets

Köhrle

2018

Methods in Molecular Biology

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More than a century after the discovery of L-Thyroxine, the main thyroid hormone secreted solely by the thyroid gland, several metabolites of this iodinated, tyrosine-derived ancestral hormone have been identified. These are utilized as hormones during development, differentiation, metamorphosis, and regulation of most biochemical reactions in vertebrates and their precursor species. Among those metabolites are the thyromimetically active 3,3',5-Triiodo-L-thyronine (T3) and 3,5-Diiodo-L-thronine, reverse-T3 (3,3',5'-Triiodo-L-thyronine) with still unclear function, the recently re-discovered thyronamines (e.g., 3-Iodo-thyronamine), which exert in part T3-antagonistic functions, the thyroacetic acids (e.g., Tetrac and Triac), as well as various sulfated or glucuronidated metabolites of this panel of iodinated signaling compounds. In the blood most of these hydrophobic metabolites are tightly bound to the serum distributor proteins thyroxine binding globulin (TBG), transthyretin (TTR), albumin or apolipoprotein B100. Cellular import and export of these charged, highly hydrophobic amino acid derivatives requires a number of cell-membrane transporters or facilitators such as MCT8 or MCT10 and members of the OATP and LAT families of transporters. Depending on their structure, the thyroid hormone metabolites exert their cellular action by binding and thus modulating the function of various receptors systems (e.g., ανβ3 integrin receptor and transient receptor potential channels (TRPM8) of the cell membrane), in part linked to intracellular downstream kinase signaling cascades, and several isoforms of membrane-associated, mitochondrial or nuclear thyroid hormone receptors (TR), which are members of the c-erbA family of ligand-modulated transcription factors. Intracellular deiodinase selenoenzymes, which obligatory are membrane integrated enzymes, ornithine decarboxylase and monoamine oxidases control local availability of biologically active thyroid hormone metabolites. Inactivation of thyroid hormone metabolites occurs mainly by deiodination, sulfation or glucuronidation, reactions which favor their renal or fecal elimination.

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Detection of 3,5-Diiodothyronine in Sera of Patients with Altered Thyroid Status Using a New Monoclonal Antibody-Based Chemiluminescence Immunoassay

Cited by 58 publications

References 48 publications

Translating Pharmacological Findings from Hypothyroid Rodents to Euthyroid Humans: Is There a Functional Role of Endogenous 3,5-T2?

Translating Pharmacological Findings from Hypothyroid Rodents to Euthyroid Humans: Is There a Functional Role of Endogenous 3,5-T2?

Mass spectrometry in the diagnosis of thyroid disease and in the study of thyroid hormone metabolism

Thyroid Hormones and Derivatives: Endogenous Thyroid Hormones and Their Targets

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