Avaliação do metabolismo dos hormônios tireoidianos nas células imunológicas durante a fase aguda do paciente crítico : uma coorte prospectiva

• Ano de defesa: 2024
• Autor(a) principal: Oliveira, Thaliane Carvalho
• Orientador(a): Wajner, Simone Magagnin
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Palavras-chave em Português: Testes de função tireóidea; Metabolismo; Hormônios tireóideos; Cuidados críticos; Sistema imunitário
• Palavras-chave em Inglês: Deiodinases; Metabolism; Thyroid hormone
• Link de acesso: http://hdl.handle.net/10183/277098

Dysregulation of types 2 and 3 deiodinases (D2 and D3) alter the metabolism of thyroid hormones in the nonthyroidal illness syndrome (NTIS). Altered function of these enzymes in peripheral blood cells can be one of the factors that leads to this syndrome. The effect of oxidative stress, the colocalization and D2 and D3 expression in cells extracted and purified from ill patients is unknown. Objective: Evaluate the presence and variations of D2 and D3 expression in intensive care patients' neutrophils and monocytes admitted in ICU due to any disease. Methods: Ninety-six patients admitted to ICU due to any cause had their blood collected at admission and after seven days. Cells from whole blood were separated by different cell gradients and purified by flow cytometry. The total carbonyl, sulfhydryl contents, and GSH were redox balance parameters. D2 and D3 expression and colocalization were determined with RNAscope, real-time PCR and immunofluorescence. Cellular T3 levels were measured. Results: The formation of carbonyls, a marker of oxidative damage to proteins, was increased in all patients (all P<0.0001), and sulfhydryl and GSH were diminished (P<0.001). Expression of DIO2 and DIO3 was augmented in neutrophils and monocytes from alive and deceased patients, and its localization in the cell and colocalization of D2 and D3 strikingly different between both groups. Immunofluorescence showed diminished D2 protein and distinct enzyme distribution in both cell types. Levels of D3 protein were high, and we also observed different distributions of the enzyme in the cells. T3 levels on each type of cell were different and related to fate. The different crosstalk of D2 and D3 in neutrophils and monocytes provides a novel mechanism to explain the reduction in T3 levels in ill patients. Further, distinct enzyme distribution is correlated with prognosis. These new results illuminate NTIS pathophysiology and might represent an easy prognosis tool.