Identification of Protein Changes in The Urine of Hypothyroid Patients Treated with Thyroxine Using Proteomics Approach

Abstract Background The thyroid gland and thyroid hormones control a multitude of homeostatic functions including the functions kidney related to fluid and electrolyte balance and formation of urine. In the present study we aimed to define changes in the urinary proteome characterizing alterations in thyroid hormone status.Methods An untargeted proteomic approach with network analysis was used to study 9 age-matched subjects with newly diagnosed overt hypothyroidism. Urine was collected from subjects pre and post L-thyroxine treatment. Proteome analysis was performed using two-dimensional difference in gel electrophoresis coupled with mass spectrometry.Results 42 proteins were found to have significant differential abundance (≥1.5-fold change, ANOVA, p ≤ 0.05). 28 proteins were upregulated and 14 proteins were downregulated in the hypothyroid compared to the euthyroid state. The differentially abundant proteins investigated by Ingenuity Pathway Analysis showed involvement of signaling pathways related to MAPK Kinase, VEGF, Pi3 Kinase/Akt, Pkc, and nvolvement of pathway related to amino acid metabolism, molecular transport, small molecule biochemistry.Conclusions The differentially abundant proteins identified revealed their involvement in regulating TH and Tg metabolism. The alterations in levels of identified proteins in indicate a compensatory increase in the regulation of Tg to increase circulating TH levels in the hypothyroid state.