Analysis of metabolomics profile in hypothyroid patients before and after thyroid hormone replacement
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ORIGINAL ARTICLE
Analysis of metabolomics profile in hypothyroid patients before and after thyroid hormone replacement C. Piras1 · M. Pibiri1 · V. P. Leoni1 · A. Balsamo1 · L. Tronci1 · N. Arisci2 · S. Mariotti2 · L. Atzori1 Received: 13 August 2020 / Accepted: 24 September 2020 © Italian Society of Endocrinology (SIE) 2020
Abstract 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. Keywords Metabolomics · Hypothyroidism · Biomarkers · 1H NMR · Multivariate statistical analysis
Introduction Hypothyroidism (HypoT) is a pathological state resulting from thyroid hormone deficiency. It is clinically characterized by a subtle yet wide spectrum of manifestations [1] reflecting a hypometabolic state, characterized by reduced resting energy expenditure, heat production and basal metabolic rate [2, 3] which are associated with increased cholesterol levels, reduced lipolysis, and reduced gluconeogenesis [4]. More in detail, the thyroid hormones thyroxine (T4) and * S. Mariotti [email protected] 1
Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy
Department of Medical Sciences and Public Health, University of Cagliari, 09042 Monserrato, Italy
2
tri-iodothyronine (T3) have been reported to regulate both glyc
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