Melhora dos marcadores sanguíneos inflamatórios em pacientes com hipotireoidismo em tratamento com levotiroxina
Ano de defesa: | 2015 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , , , |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Santa Maria
Centro de Ciências Naturais e Exatas |
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
|
Departamento: |
Bioquímica
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/17560 |
Resumo: | Introduction: Some studies suggest that patients with hypothyroidism have systemic inflammation and increased oxidative stress and consider these factors may contribute to the increased risk of atherosclerosis and atherosclerotic cardiovascular disease in these patients. Few studies have evaluated the effect of treatment of hypothyroidism on inflammatory markers and oxidative stress, with conflicting results. Background: The aim of this study was to investigate the effect of levothyroxine replacement therapy on biomarkers of oxidative stress and systemic inflammation in patients with hypothyroidism. Methods: Patients with recently diagnosed primary hypothyroidism due to Hashimoto´s thyroiditis who were not taking levothyroxine were included. The following blood parameters were measured at pre-treatment, at six and twelve months of levothyroxine: thyroid stimulating hormone (TSH), free thyroxine (FT4), high sensitive C-reactive protein (hs-CRP), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10), interferon gamma (INF-γ), tumor necrosis factor alpha (TNF-α), thiobarbituric acid reactive substances (TBARS), activity of the aminolevulinic acid dehydratase enzyme (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 effect of treatment (at baseline, six and twelve month of follow-up) on the variables mentioned above. The hypothyroidism status (overt or subclinical hypothyroidism) was included as a confounder in all analyses. An additional GEE post hoc analysis was made with intent to compare time by time. Results: There was a significant decrease in TSH levels 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) over treatment (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 significant increase in IL-10 (P<0.0001) and significant decrease of 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 levels over time was found (P<0.284). There was a significant reduction of NP-SH levels (P<0.0001) during follow-up. Conclusions: This study observed reduction of oxidative stress biomarker, reduction of pro-inflammatory cytokines and increase of anti-inflammatory cytokine in hypothyroid patients treated with levothyroxine. These modifications may have clinical relevance because the hypothesis that inflammation and oxidative stress may contribute to the development of atherosclerosis and cardiovascular disease in these patients. |
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Biblioteca Digital de Teses e Dissertações do UFSM |
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2019-07-25T19:23:51Z2019-07-25T19:23:51Z2015-04-17http://repositorio.ufsm.br/handle/1/17560Introduction: Some studies suggest that patients with hypothyroidism have systemic inflammation and increased oxidative stress and consider these factors may contribute to the increased risk of atherosclerosis and atherosclerotic cardiovascular disease in these patients. Few studies have evaluated the effect of treatment of hypothyroidism on inflammatory markers and oxidative stress, with conflicting results. Background: The aim of this study was to investigate the effect of levothyroxine replacement therapy on biomarkers of oxidative stress and systemic inflammation in patients with hypothyroidism. Methods: Patients with recently diagnosed primary hypothyroidism due to Hashimoto´s thyroiditis who were not taking levothyroxine were included. The following blood parameters were measured at pre-treatment, at six and twelve months of levothyroxine: thyroid stimulating hormone (TSH), free thyroxine (FT4), high sensitive C-reactive protein (hs-CRP), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10), interferon gamma (INF-γ), tumor necrosis factor alpha (TNF-α), thiobarbituric acid reactive substances (TBARS), activity of the aminolevulinic acid dehydratase enzyme (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 effect of treatment (at baseline, six and twelve month of follow-up) on the variables mentioned above. The hypothyroidism status (overt or subclinical hypothyroidism) was included as a confounder in all analyses. An additional GEE post hoc analysis was made with intent to compare time by time. Results: There was a significant decrease in TSH levels 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) over treatment (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 significant increase in IL-10 (P<0.0001) and significant decrease of 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 levels over time was found (P<0.284). There was a significant reduction of NP-SH levels (P<0.0001) during follow-up. Conclusions: This study observed reduction of oxidative stress biomarker, reduction of pro-inflammatory cytokines and increase of anti-inflammatory cytokine in hypothyroid patients treated with levothyroxine. These modifications may have clinical relevance because the hypothesis that inflammation and oxidative stress may contribute to the development of atherosclerosis and cardiovascular disease in these patients.Introdução: Alguns estudos sugerem que os pacientes com hipotireoidismo apresentam inflamação sistêmica e estresse oxidativo aumentado e consideram que esses fatores podem contribuir para o risco aumentado de aterosclerose e doença cardiovascular aterosclerótica nesses pacientes. Poucos avaliaram o efeito do tratamento do hipotireoidismo sobre marcadores inflamatórios e de estresse oxidativo, com resultados conflitantes. Objetivos: O objetivo desse estudo foi investigar o efeito da terapia de reposição com levotiroxina sobre os marcadores inflamatórios e de estresse oxidativo em pacientes com hipotireoidismo. Métodos: Foram incluídos pacientes com diagnóstico recente de hipotireoidismo, ainda sem tratamento. Foram analisados os seguintes parâmetros sanguíneos, em condições basais, aos 6 e doze meses de tratamento com levotiroxina: hormônio estimulante da tireoide (TSH), tiroxina livre (FT4), proteína C-reativa de alta sensibilidade (hs-CRP), interleucina-1 (IL-1), interleucina-6 (IL-6), interleucina-10 (IL-10), interferon-gama (INF-γ), fator de necrose tumoral alfa (TNF-α), substâncias reativas do ácido tiobarbitúrico (TBARS), atividade da enzima ácido aminolevulínico desidratase (δ-ALA-D), grupos tiois não-proteico e total (NP-SH e T-SH), colesterol total (TC), colesterol lipoproteína de alta densidade (HDL-C), colesterol lipoproteína de baixa densidade (LDL-C) e triglicerídeos (TG). Foi usado o modelo de Equação de Estimativas Generalizadas (GEE) para analisar o efeito do tratamento (basal, aos seis e doze meses de seguimento) sobre as variáveis mencionadas acima. O status do hipotireoidismo (evidente ou subclínico) foi incluído como confundidor em todas as análises. Foi feita análise adicional GEE post hoc para comparação tempo a tempo. Resultados: Houve redução significativa nos níveis de TSH ao longo do tempo (P<0.0001) (níveis iniciais em média 32.4 μIU/mL e 10.5 μIU/mL aos doze meses). Houve aumento significativo do FT4 ao longo do tratamento (P<0.0001) (níveis iniciais basais em média 0,8 ng/dL e 2.7 ng/dL aos 12 meses). Houve modificação significativa nos níveis de interleucinas ao longo do tempo, com aumento significativo da IL-10 (P<0.0001) e redução significativa da IL-1 (P<0.0001), IL-6 (P<0.0001), INF-γ (P<0.0001) e TNF-α (P<0.0001). Não houve diferença significativa nos níveis de hs-CRP ao longo do tempo (P<0.284). Houve redução significativa dos níveis de NP-SH (P<0.0001) durante o acompanhamento. Conclusões: Houve redução de marcador de estresse oxidativo, redução de citocinas pró-inflamatórias e elevação de citocina anti-inflamatória em pacientes com hipotireoidismo em uso de levotiroxina. Essas modificações podem ter relevância clínica devido à hipótese de que inflamação e estresse oxidativo podem contribuir para o desenvolvimento de aterosclerose e doenças cardiovasculares nesses pacientes.porUniversidade Federal de Santa MariaCentro de Ciências Naturais e ExatasPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaUFSMBrasilBioquímicaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessHipotireoidismoInflamaçãoEstresse oxidativoAteroscleroseTireoidite de HashimotoLevotiroxinaHypothyroidism.InflammationOxidative stressAtherosclerosisHashimoto´s thyroiditisLevothyroxineCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAMelhora dos marcadores sanguíneos inflamatórios em pacientes com hipotireoidismo em tratamento com levotiroxinaImprovement of inflammatory mediators in patients with hypothyroidism under levothyroxine treatmentinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisRocha, João Batista Teixeira dahttp://lattes.cnpq.br/3935055744673018Dalla Corte, Cristiane Lenzhttp://lattes.cnpq.br/5296284169605317Nogueira, Cristina Waynehttp://lattes.cnpq.br/2877042401245169Ávila, Daiana Silva dehttp://lattes.cnpq.br/4355211015887363Souza, Diogo Onofre Gomes dehttp://lattes.cnpq.br/9534019126486839http://lattes.cnpq.br/4797974118988345Marchiori, Roseane Cardoso20080000000260027186f63-94dd-4f0f-8181-7ce1b0835009c634a5b1-c94f-4963-856e-71ee558a1f71fbd9b15f-bf0f-47a3-bafb-31f1b6ccdb0403fcea4e-532c-4289-b5c0-2e0fe6d48c4815242f17-0b9b-4669-b305-de826805f2f391e601ed-c514-430b-b92c-eec2e6d38c0breponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALTES_PPGBT_2015_MARCHIORI_ROSEANE.pdfTES_PPGBT_2015_MARCHIORI_ROSEANE.pdfTese de Doutoradoapplication/pdf1705242http://repositorio.ufsm.br/bitstream/1/17560/1/TES_PPGBT_2015_MARCHIORI_ROSEANE.pdf7f3c260d613df2b103026e539f0d9336MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Melhora dos marcadores sanguíneos inflamatórios em pacientes com hipotireoidismo em tratamento com levotiroxina |
dc.title.alternative.eng.fl_str_mv |
Improvement of inflammatory mediators in patients with hypothyroidism under levothyroxine treatment |
title |
Melhora dos marcadores sanguíneos inflamatórios em pacientes com hipotireoidismo em tratamento com levotiroxina |
spellingShingle |
Melhora dos marcadores sanguíneos inflamatórios em pacientes com hipotireoidismo em tratamento com levotiroxina Marchiori, Roseane Cardoso Hipotireoidismo Inflamação Estresse oxidativo Aterosclerose Tireoidite de Hashimoto Levotiroxina Hypothyroidism. Inflammation Oxidative stress Atherosclerosis Hashimoto´s thyroiditis Levothyroxine CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Melhora dos marcadores sanguíneos inflamatórios em pacientes com hipotireoidismo em tratamento com levotiroxina |
title_full |
Melhora dos marcadores sanguíneos inflamatórios em pacientes com hipotireoidismo em tratamento com levotiroxina |
title_fullStr |
Melhora dos marcadores sanguíneos inflamatórios em pacientes com hipotireoidismo em tratamento com levotiroxina |
title_full_unstemmed |
Melhora dos marcadores sanguíneos inflamatórios em pacientes com hipotireoidismo em tratamento com levotiroxina |
title_sort |
Melhora dos marcadores sanguíneos inflamatórios em pacientes com hipotireoidismo em tratamento com levotiroxina |
author |
Marchiori, Roseane Cardoso |
author_facet |
Marchiori, Roseane Cardoso |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Rocha, João Batista Teixeira da |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/3935055744673018 |
dc.contributor.referee1.fl_str_mv |
Dalla Corte, Cristiane Lenz |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/5296284169605317 |
dc.contributor.referee2.fl_str_mv |
Nogueira, Cristina Wayne |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/2877042401245169 |
dc.contributor.referee3.fl_str_mv |
Ávila, Daiana Silva de |
dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/4355211015887363 |
dc.contributor.referee4.fl_str_mv |
Souza, Diogo Onofre Gomes de |
dc.contributor.referee4Lattes.fl_str_mv |
http://lattes.cnpq.br/9534019126486839 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/4797974118988345 |
dc.contributor.author.fl_str_mv |
Marchiori, Roseane Cardoso |
contributor_str_mv |
Rocha, João Batista Teixeira da Dalla Corte, Cristiane Lenz Nogueira, Cristina Wayne Ávila, Daiana Silva de Souza, Diogo Onofre Gomes de |
dc.subject.por.fl_str_mv |
Hipotireoidismo Inflamação Estresse oxidativo Aterosclerose Tireoidite de Hashimoto Levotiroxina |
topic |
Hipotireoidismo Inflamação Estresse oxidativo Aterosclerose Tireoidite de Hashimoto Levotiroxina Hypothyroidism. Inflammation Oxidative stress Atherosclerosis Hashimoto´s thyroiditis Levothyroxine CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
Hypothyroidism. Inflammation Oxidative stress Atherosclerosis Hashimoto´s thyroiditis Levothyroxine |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Introduction: Some studies suggest that patients with hypothyroidism have systemic inflammation and increased oxidative stress and consider these factors may contribute to the increased risk of atherosclerosis and atherosclerotic cardiovascular disease in these patients. Few studies have evaluated the effect of treatment of hypothyroidism on inflammatory markers and oxidative stress, with conflicting results. Background: The aim of this study was to investigate the effect of levothyroxine replacement therapy on biomarkers of oxidative stress and systemic inflammation in patients with hypothyroidism. Methods: Patients with recently diagnosed primary hypothyroidism due to Hashimoto´s thyroiditis who were not taking levothyroxine were included. The following blood parameters were measured at pre-treatment, at six and twelve months of levothyroxine: thyroid stimulating hormone (TSH), free thyroxine (FT4), high sensitive C-reactive protein (hs-CRP), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10), interferon gamma (INF-γ), tumor necrosis factor alpha (TNF-α), thiobarbituric acid reactive substances (TBARS), activity of the aminolevulinic acid dehydratase enzyme (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 effect of treatment (at baseline, six and twelve month of follow-up) on the variables mentioned above. The hypothyroidism status (overt or subclinical hypothyroidism) was included as a confounder in all analyses. An additional GEE post hoc analysis was made with intent to compare time by time. Results: There was a significant decrease in TSH levels 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) over treatment (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 significant increase in IL-10 (P<0.0001) and significant decrease of 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 levels over time was found (P<0.284). There was a significant reduction of NP-SH levels (P<0.0001) during follow-up. Conclusions: This study observed reduction of oxidative stress biomarker, reduction of pro-inflammatory cytokines and increase of anti-inflammatory cytokine in hypothyroid patients treated with levothyroxine. These modifications may have clinical relevance because the hypothesis that inflammation and oxidative stress may contribute to the development of atherosclerosis and cardiovascular disease in these patients. |
publishDate |
2015 |
dc.date.issued.fl_str_mv |
2015-04-17 |
dc.date.accessioned.fl_str_mv |
2019-07-25T19:23:51Z |
dc.date.available.fl_str_mv |
2019-07-25T19:23:51Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/17560 |
url |
http://repositorio.ufsm.br/handle/1/17560 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
200800000002 |
dc.relation.confidence.fl_str_mv |
600 |
dc.relation.authority.fl_str_mv |
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dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Bioquímica |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações do UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
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Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
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UFSM |
reponame_str |
Biblioteca Digital de Teses e Dissertações do UFSM |
collection |
Biblioteca Digital de Teses e Dissertações do UFSM |
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repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
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1793239982714912768 |