RESUMO
BACKGROUND/AIMS: Diastolic dysfunction (DD) and low levels of thyroid hormones (TH) are frequent found in chronic kidney disease; both are associated with all-cause and cardiovascular mortality. However, a link between them has not yet been established. The aim of this study was to analyze DD as a surrogate marker of fibrosis and its association with TH in incident patients on peritoneal dialysis (PD). METHODS: A cross-sectional study with 183 incident patients on PD with preserved ejection fraction was performed. Clinical and demographic data were registered. Serum total and free (t/f) triiodothyronine (T3), thyroxin (T4), and thyroid stimulating hormone levels were determined by RIA kits, albumin and high-sensitivity C-reactive protein by conventional assays. Transthoracic 2D echocardiogram was performed for evaluation of left ventricular (LV) mass and ejection fraction. DD was evaluated using pulsed-wave tissue Doppler imaging. RESULTS: Patients were 43 ± 12, 42% with diabetes mellitus (DM). Some degree of DD was found in 62% of patients; 18% had grade I DD, 8% grade II DD and 36% grade III DD. Patients with grade III DD were more likely to have diabetes, older, high LV mass and low serum albumin, t/fT3 and tT4 levels. In logistic multivariate regression analysis, it was found that diabetes (B = -0.86, 95% CI 0.182-0.992, p < 0.05), hypertension (B = -0.95, 95% CI 0.184-0.817, p = 0.01) and tT3 (B = -1.94, 95% CI 0.023-0.876, p < 0.05) were associated with grade III DD. CONCLUSIONS: High prevalence of grade III DD was found in incident patients on PD. In addition to DM and hypertension, tT3 was found to be an independent risk factor for grade III DD and more studies are needed to understand the reasons as to why this association is present.
Assuntos
Diástole/fisiologia , Diálise Peritoneal/efeitos adversos , Hormônios Tireóideos/deficiência , Disfunção Ventricular Esquerda/etiologia , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/terapia , Fatores de Risco , Disfunção Ventricular Esquerda/epidemiologia , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
This study aimed to investigate whether nitric oxide participates in the cardiovascular function and haemodynamic adaptation to acute haemorrhage in animals with thyroid disorders. Sprague-Dawley rats aged 2months old treated with T3 (hyper, 20µg/100g body weight) or 0.02% methimazole (hypo, w/v) during 28days were pre-treated with N(G) nitro-l-arginine methyl ester (L-NAME) and submitted to 20% blood loss. Heart function was evaluated by echocardiography. Measurements of arterial blood pressure, heart rate, nitric oxide synthase activity and protein levels were performed. We found that hypo decreased fractional shortening and ejection fraction and increased left ventricle internal diameter. Hyper decreased ventricle diameter and no changes in cardiac contractility. Haemorrhage elicited a hypotension of similar magnitude within 10min. Then, this parameter was stabilized at about 30-40min and maintained until finalized, 120min. L-NAME rats showed that the immediate hypotension would be independent of nitric oxide. Nitric oxide synthase inhibition blunted the changes of heart rate induced by blood loss. Hyper and hypo had lower atrial enzyme activity associated with a decreased enzyme isoform in hypo. In ventricle, hyper and hypo had a higher enzyme activity, which was not correlated with changes in protein levels. Haemorrhage induced an increased heart nitric oxide production. We concluded that thyroid disorders were associated with hypertrophic remodelling which impacted differently on cardiac function and its adaptation to a hypovolemia. Hypovolemia triggered a nitric oxide synthase activation modulating the heart function to maintain haemodynamic homeostasis. This involvement depends on a specific enzyme isoform, cardiac chamber and thyroid state.
Assuntos
Doenças Cardiovasculares/etiologia , Óxido Nítrico/metabolismo , Doenças da Glândula Tireoide/complicações , Adaptação Fisiológica , Animais , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Ecocardiografia , Hemodinâmica , Hemorragia/fisiopatologia , Hipovolemia/fisiopatologia , Masculino , Distribuição Aleatória , Ratos Sprague-Dawley , Doenças da Glândula Tireoide/diagnóstico por imagem , Doenças da Glândula Tireoide/metabolismo , Doenças da Glândula Tireoide/fisiopatologia , Hormônios Tireóideos/deficiênciaRESUMO
Hypothyroidism has been associated to psychiatric disorder development and tissue oxidative damage. In this study, we evaluated the effect of diphenyl diselenide supplementation on depressive-like behavior triggered by methimazole exposure in female rats. Additionally, thiobarbituric acid reactive substances (TBARS), reactive oxygen species (ROS) and non-protein thiol (NP-SH) levels were analyzed in cerebral cortex, hippocampus and striatum structures of rats. Monoamine oxidase (MAO) activity was evaluated in total brain. Firstly, female rats received methimazole (MTZ) 20mg/100ml in the drinking water for 30days and were evaluated in open-field and forced swimming tests (FST). In this set of experiments, the rats exposed to MTZ presented a depressive-like behavior, which was evidenced by a significant increase in the immobility time when compared to control group. Thereafter, MTZ-induced hypothyroid rats received either a standard or a diet containing 5ppm of diphenyl diselenide, and then they were evaluated monthly in open-field and FST tests during 3months. No alteration on the locomotor performance was observed among the groups. The depressive-like behavior of hypothyroid rats was blunted by diphenyl diselenide supplementation during all experimental periods. The levels of thyroid hormones remained low in MTZ exposed groups until the end of experimental period. The MTZ group had an increase in TBARS and ROS levels that were restored by diphenyl diselenide supplementation. NP-SH content of cerebral structures was not modified by MTZ exposure and/or diphenyl diselenide supplementation. Diphenyl diselenide supplementation restored the MAO B activity that was decreased in MTZ group. In summary, our results show that hypothyroidism induced by MTZ methimazole triggers a depressive-like behavior in female rats and that dietary diphenyl diselenide was able to reduce this effect.
Assuntos
Antidepressivos/uso terapêutico , Derivados de Benzeno/uso terapêutico , Depressão/dietoterapia , Compostos Organosselênicos/uso terapêutico , Animais , Antidepressivos/farmacologia , Derivados de Benzeno/farmacologia , Encéfalo/metabolismo , Depressão/sangue , Depressão/complicações , Feminino , Hipotireoidismo/sangue , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/complicações , Hipotireoidismo/dietoterapia , Resposta de Imobilidade Tônica/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Metimazol , Monoaminoxidase/metabolismo , Atividade Motora/efeitos dos fármacos , Compostos Organosselênicos/farmacologia , Ratos , Espécies Reativas de Oxigênio/metabolismo , Compostos de Sulfidrila/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Hormônios Tireóideos/sangue , Hormônios Tireóideos/deficiênciaRESUMO
Cognitive deficits have been observed in different animal models of adult-onset hypothyroidism. Thus, this study was delineated to evaluate whether diphenyl diselenide, an organoselenium compound with neuroprotective and antioxidant properties, could afford protection against the detrimental effects of hypothyroidism on behavioral parameters. Hypothyroidism condition was induced in female rats by continuous exposure to methimazole (MTZ) at 20 mg/100 ml in the drinking water, during 3 months. MTZ-induced hypothyroid rats were fed with either standard or a diet containing 5 ppm of diphenyl diselenide for 3 months. Behavioral assessments were performed monthly, in the following order: elevated plus maze, open field and Morris water maze. The levels of thyroid hormones in the animals exposed to MTZ were lower than control until the end of experimental period. The rats exposed to MTZ had a significant weight loss from the first month, which was not modified by diphenyl diselenide supplementation. In elevated plus maze test, MTZ exposure caused a reduction on the number of entries of animals in closed arms, which was avoided by diphenyl diselenide supplementation. In Morris water maze, the parameters latency to reach the platform and distance performed to find the escape platform in the test session were significantly greater in MTZ group when compared to control. These cognitive deficits observed in MTZ-induced hypothyroid rats were restored by dietary diphenyl diselenide. The group fed with diphenyl diselenide alone exhibited a better spatial learning and memory capability in some parameters of Morris water maze when compared to the control group. In summary, our data provide evidence of the effectiveness of dietary diphenyl diselenide in improving the performance of control and hypothyroid rats in the water maze test.
Assuntos
Derivados de Benzeno/administração & dosagem , Hipotireoidismo/fisiopatologia , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/fisiopatologia , Fármacos Neuroprotetores/administração & dosagem , Compostos Organosselênicos/administração & dosagem , Hormônios Tireóideos/deficiência , Administração Oral , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Modelos Animais de Doenças , Feminino , Alimentos Formulados , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/complicações , Transtornos da Memória/etiologia , Ratos , Ratos WistarRESUMO
Introducción: El hipotiroidismo subclínico se conoce desde 1970, cursa a menudo en forma asintomática o con signos clínicos indefinidos, de los cuales, la falla reproductiva es uno de ellos. Y su prevalencia en la literatura es muy variable. Material y métodos: Se realizó un estudio prospectivo, apareado, directo, no ciego, no experimental, de 59 mujeres en edad reproductiva, que por un año buscaron embarazo sin conseguirlo, en las que se descartó otras causas de falla reproductiva, tiempo que fue desde marzo del año 2000 hasta diciembre de 2005. Se les busco sistemáticamente hipotiroidismo subclínico y posteriormente se les inició tratamiento con hormona tiroidea, observándolas por un periodo de un año, registrándose si se obtenía o no una gestación. Resultados: en nuestro grupo de estudio de las 59 mujeres incluídas, al cabo de un año de iniciado el tratamiento con hormona tiroidea se consiguió gestación en 15 de ellas (el 25.42 por ciento). Al analizar dicho resultado mediante metodología estadística, para nuestra apareada, se obtuvo una diferencia estadísticamente significativa, dando una p=0.0001093. Conclusiones: consideramos que el hipotiroidismo subclínico debe ser buscado rutinariamente en personas que buscan fertilidad y no tienen otra causa de falla reproductiva que impida conseguir el embarazo. Los resultados obtenidos con tratamiento hormonal tiroideo adecuado, en este pequeño grupo de pacientes, logró conseguir el 25.42 por ciento de gestaciones. Situación que abre la posibilidad de ampliar ésta actitud a un grupo mayor de pacientes en un contexto semejante.
Assuntos
Humanos , Adulto , Feminino , Adulto Jovem , Hipotireoidismo/diagnóstico , Hipotireoidismo/terapia , Infertilidade Feminina/etiologia , Infertilidade Feminina/terapia , Análise Química do Sangue , Hipotireoidismo/complicações , Hormônios Tireóideos/deficiência , Hormônios Tireóideos/uso terapêutico , Resultado do Tratamento , Taxa de GravidezRESUMO
OBJECTIVE: To present relevant and updated information on the status of hypothyroidism in the pediatric population (newborn infants to adolescents). SOURCES: Original and review articles and books containing relevant updated data. SUMMARY OF THE FINDINGS: This review addressed data on the etiopathogeny of hypothyroidism and on the importance of screening for congenital hypothyroidism to assure early diagnosis and treatment of the newborn. We point out the difficulties experienced in the handling of subclinical hypothyroidism; we also address the importance of diagnosing autoimmune Hashimoto's thyroiditis, the high incidence of the disease among adolescents, mainly females, and the occurrence of a severe neurological condition, Hashimoto's encephalopathy. We indicate situations in which severe hypothyroidism may lead to puberty disorders (precocious or delayed puberty) and describe the importance of transcription factors in thyroid embryogenesis. Diagnostic and therapeutic criteria are also addressed. CONCLUSION: Thyroid hormones are necessary for normal growth and development since fetal life. Insufficient production or inadequate activity on the cellular or molecular level lead to hypothyroidism. These hormones are necessary for the development of the brain in the fetus and in the newborn infant. Neonatologists and pediatricians deal with child development issues in their practice, and many of these issues start during intrauterine life. Currently, with neonatal screening, neonatologists and pediatricians can prevent irreversible damage through early treatment. They should also be alert for dysfunctions such as subclinical hypothyroidism and Hashimoto's thyroiditis, which may provoke damage not only to growth, but also to the neurological and psychological development of these children and adolescents.
Assuntos
Hipotireoidismo/diagnóstico , Hipotireoidismo/terapia , Hormônios Tireóideos/fisiologia , Adolescente , Criança , Desenvolvimento Infantil/fisiologia , Pré-Escolar , Hipotireoidismo Congênito/diagnóstico , Feminino , Doença de Hashimoto/diagnóstico , Humanos , Hipotireoidismo/etiologia , Lactente , Recém-Nascido , Masculino , Triagem Neonatal , Hormônios Tireóideos/deficiênciaRESUMO
OBJETIVO: Apresentar dados relevantes e atualizados referentes ao quadro de hipotireoidismo do recém-nascido ao adolescente. FONTES DE DADOS: Artigos, revisões e livros contendo informações atualizadas e de interesse. SÍNTESE DOS DADOS:Esta revisão aborda dados sobre etiopatogenia do hipotireoidismo. A triagem para o hipotireoidismo congênito é importante para o diagnóstico e tratamento precoce do recém-nascido. Aponta as dificuldades na conduta do hipotireoidismo subclínico. Destaca a importância do diagnóstico da tireoidite auto-imune de Hashimoto, sua alta incidência entre os adolescentes, principalmente meninas, e a existência de um quadro neurológico grave, a encefalopatia de Hashimoto. Aponta para situações em que o hipotireoidismo grave pode levar a distúrbios da puberdade com situações de precocidade e retardo puberal. Descreve a importância dos fatores de transcrição na embriogênese da tireóide. Critérios diagnósticos e terapêuticos são abordados. CONCLUSÃO: Os hormônios tireoidianos são necessários para o crescimento e desenvolvimento normal desde a vida fetal. Sua produção insuficiente ou sua ação inadequada em nível celular ou molecular levam ao hipotireoidismo. Esses hormônios são necessários para o desenvolvimento do cérebro na vida fetal e pós-natal. Neonatologistas e pediatras deparam-se com problemas do desenvolvimento da criança, muitos dos quais já começam em vida intra-uterina. Atualmente, com a triagem neonatal, neonatologistas e pediatras podem evitar danos irreversíveis com tratamento precoce. Também devem estar atentos para disfunções como as do hipotireoidismo subclínico e tireoidite de Hashimoto, que podem provocar danos não só no crescimento, mas também no desenvolvimento neurológico e psicológico destas crianças e adolescentes.
OBJECTIVE:To present relevant and updated information on the status of hypothyroidism in the pediatric population (newborn infants to adolescents). SOURCES: Original and review articles and books containing relevant updated data. SUMMARY OF THE FINDINGS: This review addressed data on the etiopathogeny of hypothyroidism and on the importance of screening for congenital hypothyroidism to assure early diagnosis and treatment of the newborn. We point out the difficulties experienced in the handling of subclinical hypothyroidism; we also address the importance of diagnosing autoimmune Hashimoto's thyroiditis, the high incidence of the disease among adolescents, mainly females, and the occurrence of a severe neurological condition, Hashimoto's encephalopathy. We indicate situations in which severe hypothyroidism may lead to puberty disorders (precocious or delayed puberty) and describe the importance of transcription factors in thyroid embryogenesis. Diagnostic and therapeutic criteria are also addressed. CONCLUSION: Thyroid hormones are necessary for normal growth and development since fetal life. Insufficient production or inadequate activity on the cellular or molecular level lead to hypothyroidism. These hormones are necessary for the development of the brain in the fetus and in the newborn infant. Neonatologists and pediatricians deal with child development issues in their practice, and many of these issues start during intrauterine life. Currently, with neonatal screening, neonatologists and pediatricians can prevent irreversible damage through early treatment. They should also be alert for dysfunctions such as subclinical hypothyroidism and Hashimoto's thyroiditis, which may provoke damage not only to growth, but also to the neurological and psychological development of these children and adolescents.
Assuntos
Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Hipotireoidismo/diagnóstico , Hipotireoidismo/terapia , Hormônios Tireóideos/fisiologia , Desenvolvimento Infantil/fisiologia , Hipotireoidismo Congênito/diagnóstico , Doença de Hashimoto/diagnóstico , Hipotireoidismo/etiologia , Triagem Neonatal , Hormônios Tireóideos/deficiênciaRESUMO
Myelination depends on the proper differentiation of oligodendrocytes and several factors may influence this event. For instance, thyroid hormone (T3) affects the timing of differentiation and regulates the expression of several enzymes involved in the synthesis of complex lipids and in the expression of some myelin structural proteins. We investigated the effect of T3 deficiency on oligodendroglial differentiation and in the distribution of oligodendrocyte/myelin proteins 2'3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and myelin basic protein (MBP). Oligodendroglial-enriched cultures were obtained from cerebra of neonate rats grown in a modified medium. The T3-deficient status was induced by using medium devoid of T3. We observed a delay, in T3-deficient cultures, in oligodendroglial maturation characterized by less extensive processes and membrane vellum than in controls. In control cultures, CNPase immunoreactivity was punctated, showing cell bodies and processes at earlier stages and redistribution to cytoskeleton vein-like structures in later stages. In T3-deficient cultures, CNPase remained in a punctated pattern and only at 10 days in vitro we observed CNPase redistribution to the presumptive cytoskeleton vein-like structures. MBP in control cultures was distributed through the whole cell body and processes whereas in T3-deficient cultures, MBP immunoreactivity was concentrated in the perinuclear region. These results reinforce the hypothesis that T3 is an important factor in oligodendrocyte differentiation, particularly regarding the distribution of myelin proteins.
Assuntos
2',3'-Nucleotídeo Cíclico Fosfodiesterases/metabolismo , Diferenciação Celular/fisiologia , Proteína Básica da Mielina/metabolismo , Oligodendroglia/metabolismo , Hormônios Tireóideos/deficiência , Análise de Variância , Animais , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Citoesqueleto/metabolismo , Embrião de Mamíferos , Feminino , Imuno-Histoquímica/métodos , Oligodendroglia/efeitos dos fármacos , Gravidez , Ratos , Ratos Wistar , Fatores de TempoRESUMO
A crise tireotóxica é uma condição clínica, grave, resultante da exacerbação abrupta do estado hipertireóideo, na qual ocorre descompensação de um ou mais órgãos. Incide com maior freqüência em pacientes com doença de Graves, apesar de poder ocorrer em pacientes , com adenoma tóxico ou bócio multinodular tóxico. A apresentação clínica mais comum inclui febre (geralmente >38,5 GRAUSC), taquicardia (desproporcional à febre), disfunções gastrointestinais (náuseas, vômitos, diarréia e em casos graves, icterícia), anormalidades neurológicas (variando de confusão a apatia e coma) e hipertensão, seguida de hipotensão e choque. Apesar de ser rara, o diagnóstico precoce e o tratamento agressivo são necessários para evitar o desfecho fatal, que ocorre em 10 por cento a 75 por cento dos pacientes hospitalizados