Abstract
BackgroundTriiodothyronine (T3) and thyroxine (T4) as the main secretion products of the thyroid affect nearly every human tissue and are involved in a broad range of processes ranging from energy expenditure and lipid metabolism to glucose homeostasis. Metabolomics studies outside the focus of clinical manifest thyroid diseases are rare. The aim of the present investigation was to analyze the cross-sectional and longitudinal associations of urinary metabolites with serum free T4 (FT4) and thyroid-stimulating hormone (TSH).MethodsUrine Metabolites of participants of the population-based studies Inter99 (n = 5620) and Health2006/Health2008 (n = 3788) were analyzed by 1H-NMR spectroscopy. Linear or mixed linear models were used to detect associations between urine metabolites and thyroid function.ResultsCross-sectional analyses revealed positive relations of alanine, trigonelline and lactic acid with FT4 and negative relations of dimethylamine, glucose, glycine and lactic acid with log(TSH). In longitudinal analyses, lower levels of alanine, dimethylamine, glycine, lactic acid and N,N-dimethylglycine were linked to a higher decline in FT4 levels over time, whereas higher trigonelline levels were related to a higher FT4 decline. Moreover, the risk of hypothyroidism was higher in subjects with high baseline trigonelline or low lactic acid, alanine or glycine values.ConclusionThe detected associations mainly emphasize the important role of thyroid hormones in glucose homeostasis. In addition, the predictive character of these metabolites might argue for a potential feedback of the metabolic state on thyroid function. Besides known metabolic consequences of TH, the link to the urine excretion of trigonelline, a marker of coffee consumption, represents a novel finding of this study and given the ubiquitous consumption of coffee requires further research.
Highlights
A normal thyroid function is crucial to maintain physiological actions including growth, development as well as regulation of metabolism and thermogenesis [1, 2]
Lower levels of alanine, dimethylamine, glycine, lactic acid and N,N-dimethylglycine were linked to a higher decline in free T4 (FT4) levels over time, whereas higher trigonelline levels were related to a higher FT4 decline
Bruker BioSpin supports the current study in form of metabolite quantification for the nuclear magnetic resonance (NMR) measurements, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript
Summary
A normal thyroid function is crucial to maintain physiological actions including growth, development as well as regulation of metabolism and thermogenesis [1, 2]. Mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy based metabolomics are used to detect physiological or pathological changes in cells, tissues or body fluids and activity of metabolic pathways. In recent years, these techniques have been used to gain deeper insights in both thyroid cancer progression [5] and THs-mediated regulation of metabolism [6,7,8,9,10,11]. Triiodothyronine (T3) and thyroxine (T4) as the main secretion products of the thyroid affect nearly every human tissue and are involved in a broad range of processes ranging from energy expenditure and lipid metabolism to glucose homeostasis. The aim of the present investigation was to analyze the cross-sectional and longitudinal associations of urinary metabolites with serum free T4 (FT4) and thyroid-stimulating hormone (TSH)
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