Distinct urinary metabolic profiles associated with serum TSH and FT4 concentrations

Abstract

Thyroid hormones (THs) affect virtually all tissues and are essential for maintaining energy metabolism, cellular growth and development. Their release depends on a complex feedback regulation including thyrotropin (TSH), offering a unique individual set point compared with a broad interindividual variance. Keeping in mind that crucial role for intermediary metabolism, the aims of the present study were two-pronged. Firstly to screen the urine metabolome for associations with serum TSH and free thyroxine (FT4) concentrations and secondly, in an attempt to join their metabolic associations and taking into account a tight individual set point, to analyze the relations with the ratio log(TSH)/FT4. Therefore, the urine metabolome of 3327 participants of the population-based Study of Health in Pomerania was characterized by 1H-NMR spectroscopy. Multivariate linear and multinomial logistic regression models were used to detect associations between metabolites and THs. We observed different association patterns for serum TSH or FT4 concentrations. Urine metabolites associated with FT4 included various amino acids as well as citrate, formate and ethanolamine, whereas members of tyrosine metabolism were associated with TSH. Despite not significant, overlap existed towards glycine and ethanolamine. The log(TSH)/FT4 ratio mirrored many of the detected associations and further revealed new associated metabolites/ratios including glycine and succinate. Our findings confirmed metabolic consequences of TH actions, thereby emphasizing the need for distinct interpretation of associations related to serum TSH (hypothalamic-pituitary feedback) or FT4 (tissue specific action) concentrations. In particular, the log(TSH)/FT4 ratio joined their metabolic impact, probably offering a new prospect for thyroid function characterization.