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In The Journal of clinical endocrinology and metabolism

CONTEXT : Clinical hypothyroidism (CH) and subclinical hypothyroidism (SCH) have been linked to various metabolic co-morbidities but the underlying metabolic alterations remain unclear. Metabolomics may provide metabolic insights into the pathophysiology of hypothyroidism.

OBJECTIVE : To explore metabolic alterations in SCH and CH and identify potential metabolite biomarkers for the discrimination of SCH and CH from euthyroid individuals.

METHODS : Plasma samples from a cohort of 126 human subjects including 45 patients with CH, 41 patients with SCH, and 40 euthyroid controls were analyzed by high-resolution mass spectrometry-based metabolomics. Data were processed by multivariate principal components analysis and orthogonal partial least squares discriminant analysis. Correlation analysis was performed by a Multivarate Linear Regression analysis. Unbiased Variable selection in R algorithm and three machine learning models were utilized to develop prediction models based on potential metabolite biomarkers.

RESULTS : The plasma metabolomic patterns in SCH and CH groups were significantly different from those of control groups, while metabolite alterations between SCH and CH groups were dramatically similar. Pathway enrichment analysis found that SCH and CH had a significant impact on primary bile acid biosynthesis, steroid hormone biosynthesis, lysine degradation, tryptophan metabolism, and purine metabolism. 65 metabolites were found significantly associated with levels of thyrotropin, free thyroxine, thyroid peroxidase antibody, or thyroglobulin antibody. Seventeen metabolic biomarkers were successfully selected and validated to differentiate three groups.

CONCLUSION : SCH and CH have significantly altered metabolic patterns associated with hypothyroidism, and metabolomics coupled with machine learning algorithms can be used to develop diagnostic models based on selected metabolites.

Shao Feifei, Li Rui, Guo Qian, Qin Rui, Su Wenxiu, Yin Huiyong, Tian Limin


Biomarkers, Clinical hypothyroidism, Free thyroxine, Metabolomics, Subclinical hypothyroidism, Thyrotropin