title: Improvement of blood inflammatory marker levels in patients with hypothyroidism under levothyroxine treatment.
abstract: BACKGROUND
  There are several specific inflammatory and oxidative correlates among patients with hypothyroidism, but most studies are cross-sectional and do not evaluate the change in parameters during the treatment. The aim of this study was to investigate the effect of levothyroxine replacement therapy on biomarkers of oxidative stress (OS) and systemic inflammation in patients with hypothyroidism.
  
  
  METHODS
  In this prospective open-label study, 17 patients with recently diagnosed primary hypothyroidism due to Hashimoto's thyroiditis who were not taking levothyroxine were included. The following parameters were measured before and at 6 and 12 months of levothyroxine treatment with an average dose of 1.5 to 1.7 μg/kg/day: thyroid-stimulating hormone (TSH), free thyroxine (FT4), high-sensitivity C-reactive protein (hs-CRP), interleukin 1 (IL-1), IL-6, IL-10, interferon gamma (INF-γ), tumor necrosis factor alpha (TNF-α), thiobarbituric acid-reactive substances (TBARS), activity of aminolevulinic acid dehydratase (δ-ALA-D), nonprotein and total thiol (NP-SH and T-SH) groups, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). Generalized estimating equation (GEE) modeling was used to analyze the effects of LRT (at pre-treatment, 6 months and 12 months) on those variables. The hypothyroidism status (i.e., overt or subclinical hypothyroidism) was included as a confounder in all analyses. An additional GEE post hoc analysis was made to compare time points.
  
  
  RESULTS
  There was a significant decrease in TSH over time (P < 0.0001), (initial levels were on average 32.4 μIU/mL and 10.5 μIU/mL at 12 months). There was a significant increase in FT4 (P < 0.0001) (initial levels were on average 0,8 ng/dL and 2.7 ng/dL at 12 months). There were significant changes in interleukin levels over time, with a significant increase in IL-10 (P < 0.0001) and significant decreases in IL-1 (P < 0.0001), IL-6 (P < 0.0001), INF-γ (P < 0.0001) and TNF-α (P < 0.0001). No significant difference in hs-CRP over time was observed (P < 0.284). There was a significant reduction in NP-SH (P < 0.0001).
  
  
  CONCLUSIONS
  This study observed significant changes in the inflammatory profile in hypothyroid patients under treatment, with reduction of pro-inflammatory cytokines and elevation of anti-inflammatory cytokine. In these patients, a decrease in low-grade chronic inflammation may have clinical relevance due to the known connection between chronic inflammation, atherosclerosis and cardiovascular events.
authors.affiliation: Departamento de Clinica Médica, Centro de Ciencias da Saude, Universidade Federal de Santa Maria, Av. Roraima n° 1000, Cidade Universitaria, Camobi, Santa Maria, RS, Brazil. rcmarchiori@gmail.com.
authors.forename: Roseane C
authors.initials: RC
authors.lastname: Marchiori
authors.affiliation: Departamento de Clinica Médica, Centro de Ciencias da Saude, Universidade Federal de Santa Maria, Av. Roraima n° 1000, Cidade Universitaria, Camobi, Santa Maria, RS, Brazil. lap.trevobranco@gmail.com.
authors.forename: Luiz A F
authors.initials: LA
authors.lastname: Pereira
authors.affiliation: Serviço de Metodos Graficos, Hospital Universitario de Santa Maria, Universidade Federal de Santa Maria, Av. Roraima n° 1000, Cidade Universitaria, Camobi, Santa Maria, RS, Brazil. alexandre.cardio@gmail.com.
authors.forename: Alexandre A
authors.initials: AA
authors.lastname: Naujorks
authors.affiliation: Departamento de Genetica, Instituto de Biociencias, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves, 9500, Porto Alegre, Brazil. rovaris.diego@gmail.com.
authors.forename: Diego L
authors.initials: DL
authors.lastname: Rovaris
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Centro de Ciencias Naturais e Exatas, Universidade Federal de Santa Maria, Av. Roraima n° 1000, Cidade Universitaria, Camobi, Santa Maria, RS, Brazil. daiameinerz@hotmail.com.
authors.forename: Daiane F
authors.initials: DF
authors.lastname: Meinerz
authors.affiliation: Ciencias da Saude, Universidade Luterana do Brasil (ULBRA), campus Santa Maria, BR 287, Km 252, Trevo Maneco Pedroso, Boca do Monte, Santa Maria, RS, Brazil, Cx. Postal 21834. marta.duarte@ulbra.br.
authors.forename: Marta M M F
authors.initials: MM
authors.lastname: Duarte
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Centro de Ciencias Naturais e Exatas, Universidade Federal de Santa Maria, Av. Roraima n° 1000, Cidade Universitaria, Camobi, Santa Maria, RS, Brazil. jbtrocha@yahoo.com.br.
authors.forename: João B T
authors.initials: JB
authors.lastname: Rocha
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000276:immunology; D002097:C-Reactive Protein / Q000276:immunology; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D050031:Hashimoto Disease / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007375:Interleukin-1 / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D007453:Iodide Peroxidase / Q000276:immunology; D008297:Male; D008875:Middle Aged; D000623:Porphobilinogen Synthase / Q000378:metabolism; D011446:Prospective Studies; D013438:Sulfhydryl Compounds / Q000097:blood; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013967:Thyroiditis, Autoimmune / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood / Q000627:therapeutic use*; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D001323:Autoantibodies; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D007375:Interleukin-1; D015850:Interleukin-6; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; C006606:anti-thyroglobulin; D016753:Interleukin-10; D007371:Interferon-gamma; D013972:Thyrotropin; D002097:C-Reactive Protein; D007453:Iodide Peroxidase; D000623:Porphobilinogen Synthase; D013974:Thyroxine