Analysis of metabolomics profile in hypothyroid patients before and after thyroid hormone replacement

Purpose: The serum metabolic changes occurring during the transition from hypothyroidism to euthyroidism are not known. This study aimed to determine the metabolomic profile in hypothyroid patients before (HypoT0) and after (HypoT1) euthyroidism achieved through levothyroxine (L-T4) treatment. Methods: Eighteen patients with overt primary hypothyroidism were recruited for the study. All patients were treated with L-T4 to achieve euthyroidism. Thyrotropin (TSH), free thyroxine (FT4), free triiodothyronine (FT3) and metabolomics profiles were measured before and after 3 months of treatment. The euthyroid control group consisted of 28 healthy volunteers. Metabolomics analysis was performed using Nuclear Magnetic Resonance (NMR) spectroscopy. Results: 1H NMR-based metabolomics profiling of patients with newly diagnosed hypothyroidism (HypoT0) showed significantly higher levels of citrate, creatinine, glycerol, myo-inositol and serine, and lower levels of proline and taurine compared to controls. Interestingly, some metabolic changes were persistent three months after pharmacological treatments, despite normal serum TSH and thyroid hormone concentrations (HypoT1). When an Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) model was built to evaluate possible differences in the metabolic profile between HypoT0 and HypoT1, the data obtained were not significantly different. Conclusion: These results suggest that metabolic changes in the patients with hypothyroidism may persist after normalization of serum levels of FT3, FT4, and TSH, which currently represent the gold standard in laboratory testing for diagnosis and evaluation of thyroid pathology. So, the metabolomics approach may contribute to integrate classical hormone assays and to determine the euthyroid status achievement with greater efficacy.