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RESUMO Objetivo: Avaliar a síndrome do doente eutireóideo como fator prognóstico em pacientes na unidade de terapia intensiva, detectar fatores que possam influenciar a mortalidade e desenvolver uma equação para calcular a probabilidade de morte. Métodos: Este foi um estudo de coorte longitudinal, observacional e não concorrente realizado na unidade de terapia intensiva da Fundação Santa Casa de Misericórdia do Pará. Realizou-se coleta de 20mL de sangue em 100 adultos sem endocrinopatia previamente documentada para a dosagem do hormônio estimulante da tireoide, da tetraiodotironina livre, da tri-iodotironina livre e da tri-iodotironina reversa. Resultados: A maioria dos pacientes era do sexo feminino, com idades entre 20 e 29 anos. A maioria dos pacientes que morreram era mais velha (idade mediana de 48 anos), e 97,5% deles possuíam a síndrome do doente eutireóideo. A síndrome do doente eutireóideo esteve relacionada à morte, às comorbidades, à idade e ao tempo de internação (mediana de 7,5 dias) na unidade de terapia intensiva. A baixa dosagem de hormônio estimulante da tireoide estava associada à morte. Os pacientes com dosagem da tri-iodotironina livre menor que 2,9pg/mL tinham maior probabilidade de morrer e, naqueles que morreram, a dosagem de tri-iodotironina reversa era maior que 0,2ng/mL. A tri-iodotironina livre apresentou maior sensibilidade e acurácia, e a tri-iodotironina reversa teve maior especificidade para prever a mortalidade. Com base nos resultados e pontos de corte, desenvolveu-se uma fórmula de regressão logística múltipla para calcular a probabilidade de morte. Conclusão: Sugere-se verificar oportunamente a dosagem da triiodotironina livre e reversa em pacientes graves e aplicar a equação proposta.
ABSTRACT Objective: To assess euthyroid sick syndrome as a prognostic factor in patients in the intensive care unit; to detect factors that may affect mortality; and to develop an equation to calculate death probability. Methods: This was a longitudinal, observational, nonconcurrent cohort study developed in the intensive care unit of Fundação Santa Casa de Misericórdia do Pará. One hundred adults with no prior documented endocrinopathy were submitted to a 20mL blood sample collection for the measurement of thyroid stimulating hormone, free tetraiodothyronine, free triiodothyronine and reverse triiodothyronine. Results: Most patients were female, aged 20 to 29 years. Most patients who died were older (median age of 48 years), and euthyroid sick syndrome was present in 97.5% of them. Euthyroid sick syndrome was related to death, comorbidities, age and length of stay in the intensive care unit (median of 7.5 days). There was an association between lower thyroid stimulating hormone and death. Patients with free triiodothyronine levels below 2.9pg/mL were more likely to die; reverse triiodothyronine rates were above 0.2ng/mL in those who died. Free triiodothyronine had greater sensitivity and accuracy, and reverse triiodothyronine had greater specificity to predict mortality. Based on the results and cutoff points, a multiple logistic regression formula was developed to calculate the probability of death. Conclusion: The main limitation of this study is the fact that it was conducted in a reference hospital for maternal and child care; therefore, there was a greater number of female patients and, consequently, a sampling bias existed. However, opportune measurement of free and reverse triiodothyronine levels in critical patients and application of the proposed equation are suggested.
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Objective:To establish reverse triiodothyronine (rT 3) biological reference interval suitable for laboratory by indirect method. Methods:From April to September 2019, 797 cases (332 males, 465 females, age: 12-95 years) underwent thyroid function, thyroid related antibody and rT 3 tests from hospitalized population in Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine were retrospectively analyzed. The reference individuals with normal thyroid hormone, antibody and without thyroid nodule or goiter were screened as inclusion criteria, and the factors such as acute and chronic diseases or drugs that might affect the values of rT 3 were excluded. Independent sample t test, one-way analysis of variance and least significant difference t test were used to analyze data. The rT 3 reference interval was established by non-parametric sequencing method, and 2.5% and 97.5% percentile values of data distribution were selected as the upper and the lower reference limits. In order to verify the rT 3 reference interval, 20 healthy individuals and 20 inpatients who met the inclusion and exclusion criteria were selected to test rT 3 with a simple random sampling method. Results:A total of 159 reference individuals (66 males, 93 females, age: 23-87 years) were enrolled. The rT 3 values of 23-29( n=4), 30-39( n=18), 40-49( n=29), 50-59( n=43), 60-69( n=40), 70-79( n=19) and over 80( n=6) years old groups were (0.62±0.16), (0.63±0.12), (0.64±0.11), (0.61±0.11), (0.65±0.14), (0.65±0.11) and (0.79±0.10) μg/L, respectively. There was a statistically significant difference in the rT 3 test results among different age groups ( F=2.17, P=0.049). There were statistically significant differences of rT 3 between the individuals over 80 years old and other age groups (all P<0.05), while there were no statistically significant differences among the other groups (all P>0.05). The rT 3 of males and females under 80 years old were (0.62±0.11) and (0.64±0.12) μg/L, respectively, with no significant difference between them ( t=-0.81, P=0.420). The newly established rT 3 reference interval suitable for people above 20 years old and below 80 years old was 0.47-0.92 μg/L, and the lower limit was significantly higher than that of the reference interval in the reagent specification (0.20-0.95 μg/L). The rT 3 range of 20 healthy individuals was 0.57-0.82 μg/L and that of 20 inpatients was 0.48-0.77 μg/L, which were all within the new reference interval. Conclusion:The rT 3 biological reference interval established here has clinical application value, but its applicable range of age still needs to be further improved.
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In the present study we provide evidence that 3,3',5'-triiodothyronine (reverse T3, rT3) restores neurochemical parameters induced by congenital hypothyroidism in rat hippocampus. Congenital hypothyroidism was induced by adding 0.05% propylthiouracil in the drinking water from gestation day 8 and continually up to lactation day 15. In the in vivo rT3 exposure, hypothyroid 12-day old pups were daily injected with rT3 (50 ng/kg body weight) or saline until day 14. In the ex vivo rT3 treatment, hippocampal slices from 15-day-old hypothyroid pups were incubated for 30 min with or without rT3 (1 nM). We found that ex vivo and/or in vivo exposure to rT3 failed in restoring the decreased 14C-glutamate uptake; however, restored the phosphorylation of glial fibrillary acidic protein (GFAP), 45Ca2+ influx, aspartate transaminase (AST), glutamine synthetase (GS) and gamma-glutamate transferase (GGT) activities, as well as glutathione (GSH) levels in hypothyroid hippocampus. In addition, rT3 improved 14C-2-deoxy-D-glucose uptake and lactate dehydrogenase (LDH) activity. Receptor agonists/antagonists (RGD peptide and AP-5), kinase inhibitors of p38MAPK, ERK1/2, CaMKII, PKA (SB239063, PD98059, KN93 and H89, respectively), L-type voltage-dependent calcium channel blocker (nifedipine) and intracellular calcium chelator (BAPTA-AM) were used to determine the mechanisms of the nongenomic rT3 action on GGT activity. Using molecular docking analysis, we found rT3 interaction with αvß3 integrin receptors, nongenomically activating signaling pathways (PKA, CaMKII, p38MAPK) that restored GGT activity. We provide evidence that rT3 is an active TH metabolite and our results represent an important contribution to elucidate the nonclassical mechanism of action of this metabolite in hypothyroidism.