RESUMO
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.
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.
Assuntos
Síndromes do Eutireóideo Doente , Adulto , Estudos de Coortes , Síndromes do Eutireóideo Doente/diagnóstico , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Prognóstico , Tireotropina , Tri-Iodotironina , Tri-Iodotironina ReversaRESUMO
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.
Assuntos
Hipocampo/enzimologia , Hipotireoidismo/enzimologia , Integrina alfaVbeta3/metabolismo , Transdução de Sinais , Tri-Iodotironina Reversa/farmacologia , Animais , Transporte Biológico/efeitos dos fármacos , Cálcio/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Glucose/metabolismo , Glutamato-Amônia Ligase/metabolismo , Ácido Glutâmico/metabolismo , Glutationa/metabolismo , Homeostase/efeitos dos fármacos , Hipotireoidismo/patologia , L-Lactato Desidrogenase/metabolismo , Modelos Biológicos , Simulação de Acoplamento Molecular , Fosforilação/efeitos dos fármacos , Ratos Wistar , Receptores de Glutamato/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transaminases/metabolismoRESUMO
Thyroid hormone (TH) abnormalities are common in patients with diabetes mellitus (DM). These thyroid hormone abnormalities have been associated with inflammatory activity in several conditions but this link remains unclear in DM. We assessed the influence of subclinical inflammation in TH metabolism in euthyroid diabetic patients. Cross-sectional study involving 258 subjects divided in 4 groups: 70 patients with T2DM and 55 patients with T1DM and two control groups of 70 and 63 non-diabetic individuals, respectively. Groups were paired by age, sex, and body mass index (BMI). We evaluated the association between clinical and hormonal variables [thyrotropin, reverse T3 (rT3), total and free thyroxine (T4), and triiodothyronine (T3)] with the inflammation markers C-reactive protein (hs-CRP), serum amyloid A (SAA), and interleukin-6 (IL-6). Serum T3 and free T3 were lower in patients with diabetes (all P < 0.001) compared to the control groups. Interleukin-6 showed positive correlations with rT3 in both groups (P < 0.05). IL-6 was independently associated to FT3/rT3 (B = -0.193; 95% CI -0.31; -0.076; P = 0.002) and FT4/rT3 (B = -0.107; 95% CI -0.207; -0.006; P = 0.039) in the T1DM group. In the T2DM group, SAA (B = 0.18; 95% CI 0.089; 0.271; P < 0.001) and hs-CRP (B = -0.069; 95% CI -0.132; -0.007; P = 0.03) predicted FT3 levels. SAA (B = -0.16; 95% CI -0.26; -0.061; P = 0.002) and IL6 (B = 0.123; 95% CI 0.005; 0.241; P = 0.041) were related to FT4/FT3. In DM, differences in TH levels compared to non-diabetic individuals were related to increased subclinical inflammatory activity and BMI. Altered deiodinase activity was probably involved. These findings were independent of sex, age, BMI, and HbA1c levels.
Assuntos
Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Inflamação/complicações , Doenças da Glândula Tireoide/complicações , Hormônios Tireóideos/sangue , Adulto , Doenças Assintomáticas , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Inflamação/sangue , Inflamação/epidemiologia , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Proteína Amiloide A Sérica/metabolismo , Doenças da Glândula Tireoide/sangue , Doenças da Glândula Tireoide/epidemiologia , Testes de Função Tireóidea , Tri-Iodotironina Reversa/sangue , Adulto JovemRESUMO
There is increasing experimental evidence of the nongenomic action of thyroid hormones mediated by receptors located in the plasma membrane or inside cells. The aim of this work was to characterize the reverse T3 (rT3) action on calcium uptake and its involvement in immature rat Sertoli cell secretion. The results presented herein show that very low concentrations of rT3 are able to increase calcium uptake after 1 min of exposure. The implication of T-type voltage-dependent calcium channels and chloride channels in the effect of rT3 was evidenced using flunarizine and 9-anthracene, respectively. Also, the rT3-induced calcium uptake was blocked in the presence of the RGD peptide (an inhibitor of integrin-ligand interactions). Therefore, our findings suggest that calcium uptake stimulated by rT3 may be mediated by integrin αvß3. In addition, it was demonstrated that calcium uptake stimulated by rT3 is PKC and ERK-dependent. Furthermore, the outcomes indicate that rT3 also stimulates cellular secretion since the cells manifested a loss of fluorescence after 4 min incubation, indicating an exocytic quinacrine release that seems to be mediated by the integrin receptor. These findings indicate that rT3 modulates the calcium entry and cellular secretion, which might play a role in the regulation of a plethora of intracellular processes involved in male reproductive physiology.
Assuntos
Cálcio/metabolismo , Exocitose/efeitos dos fármacos , Integrinas/metabolismo , Células de Sertoli/citologia , Células de Sertoli/metabolismo , Tri-Iodotironina Reversa/farmacologia , Animais , Transporte Biológico/efeitos dos fármacos , Canais de Cálcio/metabolismo , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Canais de Cloreto/metabolismo , Masculino , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Proteína Quinase C/metabolismo , Ratos , Ratos Wistar , Células de Sertoli/efeitos dos fármacos , Fatores de Tempo , Proteína Tumoral 1 Controlada por TraduçãoRESUMO
A síndrome do eutireoidiano doente (SED) é uma entidade caracterizada pela queda das concentrações sanguíneas de triiodotironina nas formas total e livre e aumento da forma reversa. Ocorre principalmente em pacientes portadores de doenças graves e agudas, particularmente dentre aqueles internados em unidade de terapia intensiva. Há descrição desta síndrome em portadores de Diabetes Mellitus, particularmente sob controle glicêmico inadequado. Objetivos: Avaliar as alterações dos hormônios tireoidianos em portadores de DM sob cuidado ambulatorial e a correlação entre concentrações de hormônios tireoidianos e controle glicêmico, presença de complicações crônicas (neuropatia, nefropatia, retinopatia) e marcadores de inflamação sistêmica subclínica, bem como sua relação com presença de eventos cardiovasculares. Metodologia: Estudo transversal avaliando 52 pacientes com diabetes tipo 2 e 52 indivíduos sem diabetes, entre 40 e 75 anos de idade, pareados por sexo, idade e índice de massa corporal. Avaliaram-se dados clínicos e antropométricos, concentrações séricas de hormônios tireoidianos e proteína C reativa, bem como exames laboratoriais que refletem o perfil lipídico e controle glicêmico. Resultados: Cerca de 73% dos pacientes com diabetes e 40% dos indivíduos sem DM apresentaram concentrações séricas diminuídas de T3 total; 25% dos pacientes e apenas 2% dos indivíduos sem DM apresentaram concentrações diminuídas de T3 livre. As concentrações séricas de T3 total (p<0,001), T3 livre (p<0,001) e T4 total (p=0,006) estavam diminuídas em comparação aos de indivíduos sem diabetes. As concentrações de T3 reverso não apresentaram diferença entre os dois grupos. Pacientes com diabetes apresentaram T4 livre mais elevado (p=0,033).
The non-thyroidal illness is an entity characterized by reduced serum levels of total and free triiodothyronine and a rise in its reverse form. It occurs mainly in critically ill patients. There are descriptions of this syndrome in patients with Diabetes Mellitus, especially those under inadequate glycemic control. Objectives: Evaluate the abnormalities in thyroid hormone levels in individuals with diabetes under standard outpatient care and the correlation of thyroid hormone levels with glycemic control, presence of chronic complications (neuropathy, nephropathy and retinopathy) and subclinical systemic inflammation, as well as its relation with the presence of previous cardiovascular events. Methodology: Cross sectional study involving 52 patients with type 2 diabetes and 52 individuals without the diabetes, between 40 and 75 years of age paired by age, gender and body mass index. We evaluated clinical and anthropometric data, serum levels of thyroid hormones and Creactive protein, as well as laboratory parameters that reflect the lipid profile and glycemic control. Results: Approximately 73% of the patients with diabetes and 40% of individuals without diabetes presented reduced serum levels of total T3. Nearly 25% of the patients and only 2% of the individuals without diabetes presented reduced levels of free T3. The levels of total T3 (p<0.001), free T3 (p<0.001) and total T4 (p=0.006) were lower in patients with diabetes compared with those without diabetes. The levels of reverse T3 did not present any difference between both groups. Patients with diabetes presented higher levels of free T4 (p=0.033). The levels of reverse T3 were significantly different only when comparing individuals with previous cardiovascular events with those without this characteristic (p=0.002 for patients with diabetes and p=0.037 for individuals without diabetes). The prevalence of cardiovascular disease was 25%.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , /complicações , Doenças Cardiovasculares/complicações , Síndromes do Eutireóideo Doente/diagnóstico , Citocinas , Nefropatias Diabéticas/complicações , Neuropatias Diabéticas/complicações , Retinopatia Diabética/complicações , Glândula Tireoide , Tri-Iodotironina , Tri-Iodotironina ReversaRESUMO
Steered molecular dynamics simulations of ligand dissociation from Thyroid hormone receptors indicate that dissociation is favored via rearrangements in a mobile part of the LBD comprising H3, the loop between H1 and H2, and nearby beta-sheets, contrary to current models in which the H12 is mostly involved. Dissociation is facilitated in this path by the interaction of the hydrophilic part of the ligand with external water molecules, suggesting strategies to enhance ligand binding affinity.
Assuntos
Modelos Químicos , Receptores dos Hormônios Tireóideos/química , Tri-Iodotironina Reversa/química , Tri-Iodotironina/análogos & derivados , Simulação por Computador , Ligantes , Estrutura Molecular , Receptores dos Hormônios Tireóideos/efeitos dos fármacos , Relação Estrutura-Atividade , Fatores de Tempo , Tri-Iodotironina/química , Tri-Iodotironina/farmacologia , Tri-Iodotironina Reversa/farmacologiaRESUMO
Heart failure (HF) is frequently associated with euthyroid "sick" syndrome (low T3 and elevated rT3). We investigated if altered thyroid hormone in HF could affect expression of the TH receptor (TRalpha1), and alpha and beta myosin heavy chains (alpha-MHC, beta-MHC). HF was provoked in rats by aortic stenosis. We showed that rT3 generated from liver and kidney deiodination significantly increased and T3 decreased in HF; there was significantly higher TRalpha1 expression, no alpha-MHC expression, but beta-MHC expression. Changes in TRalpha could be compensating for low T3 from HF.
Assuntos
Síndromes do Eutireóideo Doente/metabolismo , Regulação da Expressão Gênica/fisiologia , Insuficiência Cardíaca/metabolismo , Tri-Iodotironina Reversa/metabolismo , Tri-Iodotironina/deficiência , Animais , Síndromes do Eutireóideo Doente/complicações , Síndromes do Eutireóideo Doente/genética , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/genética , Ventrículos do Coração/metabolismo , Masculino , Cadeias Pesadas de Miosina/biossíntese , Cadeias Pesadas de Miosina/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estatísticas não Paramétricas , Receptores alfa dos Hormônios Tireóideos/biossíntese , Receptores alfa dos Hormônios Tireóideos/genética , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Tri-Iodotironina/metabolismoRESUMO
Nuclear factor-kappaB (NF-kappaB) DNA binding, tumor necrosis factor-alpha (TNF-alpha) expression, and parameters related to liver oxidative stress and Kupffer cell function were assessed in control rats and in animals given 3,3',5-triiodothyronine (T3) (0.1 mg T3/kg) and/or lindane (50 mg/kg; 4 h after T3). Liver NF-kappaB DNA binding and serum TNF-alpha levels were enhanced by the combined T3-lindane administration after 16-22 h, effects that were lower than those elicited by the separate treatments and coincided with increased hepatic TNF-alpha mRNA levels. Thyroid calorigenesis occurred independently of lindane, whereas T3, lindane and T3-lindane groups showed liver glutathione (GSH) depletion, with higher protein carbonyl levels in lindane and T3-lindane groups. Carbon-induced O2 consumption/carbon uptake ratios were not altered by T3 or lindane compared to controls, whereas combined T3-lindane administration elicited a 92% diminution with enhancement in the sinusoidal efflux of lactate dehydrogenase (LDH). In conclusion, depression of T3- or lindane-induced liver NF-kappaB activation and TNF-alpha expression occurred after their combined treatment, effects that correlate with the impairment of the respiratory burst activity of Kupffer cells and exacerbation of liver injury.
Assuntos
Hexaclorocicloexano/toxicidade , Inseticidas/toxicidade , Células de Kupffer/efeitos dos fármacos , Células de Kupffer/fisiologia , NF-kappa B/farmacologia , Tri-Iodotironina Reversa/farmacologia , Fator de Necrose Tumoral alfa/biossíntese , Animais , Adutos de DNA , Feminino , Estresse Oxidativo , Consumo de Oxigênio , Ratos , Ratos Sprague-Dawley , Tri-Iodotironina Reversa/administração & dosagemRESUMO
AIM: To compare serum concentrations of thyroid hormones--T4, T3, free T4 (FT4) and reverse T3 (rT3)--and thyroid-stimulating hormone (TSH) found in the umbilical cord blood of term newborns with and without asphyxia and those found in their arterial blood collected between 18 and 24 h after birth. A further aim of the study was to assess the association between severity of hypoxic-ischemic encephalopathy and altered thyroid hormone and TSH levels, and between mortality and FT4 levels in the arterial blood of newborns between 18 and 24 h of life. METHODS: A case-control study was carried out. The case group comprised 17 term newborns (Apgar score < or = 3 and < or = 5 at the first and fifth minutes; umbilical cord blood pH < or = 7.15) who required bag and mask ventilation for at least one minute immediately after birth. The control group consisted of 17 normal, term newborns (Apgar score > or = 8 and > or = 9 at the first and fifth minutes; umbilical cord blood pH > or = 7.2). Cord blood and arterial blood samples were collected immediately after birth and 18 to 24 h after birth, respectively, and were used in the blood gas analysis and to determine serum concentrations of T4, T3, FT4, rT3 and TSH by radioimmunoassay. All newborns were followed-up until hospital discharge or death. RESULTS: Gestational age, birthweight, sex, size for gestational age, mode of delivery and skin color (white and non-white) were similar for both groups. No differences were found in mean levels of cord blood TSH, T4, T3 and FT4 between the groups. In the samples collected 18 to 24 h after birth, mean levels of TSH, T4, T3 and FT4 were significantly lower in the asphyxiated group than in the control group. Mean concentrations of arterial TSH, T4 and T3 between 18 and 24 h of life were lower than concentrations found in the cord blood analysis in asphyxiated newborns, but not in controls. In addition, asphyxiated newborns with moderate/severe hypoxic-ischemic encephalopathy presented significantly lower mean levels of TSH, T4, T3 and FT4 than those of controls. None of the asphyxiated newborns with FT4 > or = 2.0 ng/dl died; 6 out of the 11 asphyxiated newborns with FT4 < 2.0 ng/dl died. CONCLUSIONS: Serum concentrations of TSH, T4, T3 and FT4 are lower in asphyxiated newborns than in normal newborns between 18 and 24 h of life; this suggests central hypothyroidism secondary to asphyxia. Asphyxiated newborns with moderate/severe hypoxic-ischemic encephalopathy present a greater involvement of the thyroid function and consequently a greater risk of death.
Assuntos
Asfixia Neonatal/sangue , Asfixia Neonatal/complicações , Sangue Fetal/química , Hipóxia-Isquemia Encefálica/sangue , Hipóxia-Isquemia Encefálica/etiologia , Doenças da Glândula Tireoide/sangue , Doenças da Glândula Tireoide/etiologia , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina Reversa/sangue , Tri-Iodotironina/sangue , Asfixia Neonatal/mortalidade , Estudos de Casos e Controles , Feminino , Humanos , Hipóxia-Isquemia Encefálica/mortalidade , Mortalidade Infantil , Recém-Nascido , Masculino , Valor Preditivo dos Testes , Fatores de Risco , Índice de Gravidade de Doença , Doenças da Glândula Tireoide/mortalidade , Fatores de TempoRESUMO
Thyroid hormones (THs), primarily 3,3',5-triiode-(L)-thyronine (T(3)), have been clearly established as natural inducers of apoptosis during metamorphosis of anuran embryos. We decided to use this phenomenon to test the hypothesis that, prior to genomic activation, T(3) has acute actions in the neuromuscular junction (NMJ) of the tail of amphibian embryos. We detected a dramatic increase in the production of miniature end-plate currents (MEPCs) 2-5 min after continuous application of T(3) (250 nM) using focal recordings under voltage clamp. Furthermore, this increase in the spontaneous release of neurotransmitter, evaluated by the MEPC frequency, was maintained for several hours. Reverse-T(3), the "inhibitory" form of THs, prevented this increase in MEPC frequency, suggesting that this is probably a highly specific action of T(3). In addition, the elevation in MEPC frequency induced by T(3) was unchanged in the presence or absence of extracellular calcium. The T(3)-mediated increase in MEPC frequency was blocked by niflumic acid, a nonsteroidal antinflammatory fenamate used to prevent the apoptotic volume decrease observed in many systems. The present study demonstrated that T(3) induces a remarkable nongenomic action in the NMJ of the tadpole tail at pre- and promatamorphic stages.
Assuntos
Metamorfose Biológica/fisiologia , Junção Neuromuscular/efeitos dos fármacos , Cauda/inervação , Tri-Iodotironina Reversa/farmacologia , Tri-Iodotironina/farmacologia , Acetilcolina/metabolismo , Animais , Cálcio/metabolismo , Canais de Cloreto/antagonistas & inibidores , Espaço Extracelular/metabolismo , Técnicas In Vitro , Larva , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Junção Neuromuscular/metabolismo , Junção Neuromuscular/fisiologia , Neurotransmissores/metabolismo , Ácido Niflúmico/farmacologia , Técnicas de Patch-Clamp , Rana catesbeiana , Cauda/efeitos dos fármacos , Cauda/fisiologia , Tri-Iodotironina/antagonistas & inibidoresRESUMO
Revisar a fisiologia e a disfuncao tireoidiana no feto e no recem-nascido. Fontes pesquisadas: literatura das bases de...
Assuntos
Humanos , Recém-Nascido , Doenças da Glândula Tireoide/patologia , Glândula Tireoide/fisiopatologia , Tri-Iodotironina , Feto , Glândula Tireoide/fisiologia , Recém-Nascido , Recém-Nascido Prematuro , Tiroxina , Tri-Iodotironina ReversaRESUMO
OBJECTIVE: The aim of the present study was to compare the effects of iopanoic acid (IOP) or a saturated solution of potassium iodide (SSKI) administration to patients with toxic diffuse goiters (TDG). DESIGN: Patients with TDG are treated with thionamides and high doses of iodine preoperatively. In this study, two types of preoperative drug regimens were used: propylthiouracil or methimazole plus SSKI for 10-15 days (n=8) or IOP for 7 days (n=6). METHODS: Serum thyroid hormones (total and free thyroxine (T(4)), total tri-iodothyronine (T(3)) and reverse T(3) (rT(3)), were evaluated after 7 days of either SSKI or IOP treatment, and after 10-15 days of SSKI administration. During thyroidectomy, samples of thyroid gland were obtained to evaluate thyroperoxidase and thyroid H(2)O(2)-generating activities. RESULTS: Serum total T(3) was significantly decreased after 7 days of either treatment, and serum rT(3) was significantly increased in IOP-treated patients. Serum total and free T(4) were unaffected by 7 days of IOP treatment, but decreased after 7 days of SSKI treatment, although significantly diminished levels were only reached after a further 3-8 days of SSKI administration. During both drug regimens, serum TSH remained low (SSKI: 0.159+/-0.122; IOP: 0.400+/-0.109 microU/ml). Thyroperoxidase activity was significantly lower in thyroid samples from patients treated with SSKI for 10-15 days than in the thyroid glands from IOP-treated patients. However, thyroid H(2)O(2) generation was inhibited in samples from patients treated with either IOP or SSKI. CONCLUSIONS: We show herein that IOP treatment can be effective in the management of hyperthyroidism and that this drug inhibits thyroid NADPH oxidase activity, just as previously described for SSKI, probably due to its iodine content.
Assuntos
Bócio/tratamento farmacológico , Peróxido de Hidrogênio/metabolismo , Iodeto Peroxidase/metabolismo , Ácido Iopanoico/uso terapêutico , Iodeto de Potássio/uso terapêutico , Glândula Tireoide/efeitos dos fármacos , Adolescente , Adulto , Cálcio/farmacologia , Inibidores Enzimáticos/uso terapêutico , Feminino , Bócio/cirurgia , Humanos , Masculino , NADP/farmacologia , NADPH Oxidases/antagonistas & inibidores , NADPH Oxidases/metabolismo , Iodeto de Potássio/administração & dosagem , Glândula Tireoide/enzimologia , Glândula Tireoide/metabolismo , Tireoidectomia , Tiroxina/sangue , Tri-Iodotironina/sangue , Tri-Iodotironina Reversa/sangueRESUMO
OBJECTIVE: The effects of GH therapy on thyroid function among previous reports have shown remarkable discrepancies, probably due to differences in hormone assay methods, degree of purification of former pituitary-derived GH preparations, dosage schedules, diagnostic criteria, patient selection, duration of treatment and study design. These considerations motivated us to investigate whether and how GH replacement therapy changes serum thyroid hormone levels, including the much less studied rT3 levels, in a group of unequivocally GH-deficient children receiving long-term recombinant human GH therapy. PATIENTS AND DESIGN: Twenty clinically and biochemically euthyroid children were studied in two therapeutic conditions: on GH replacement therapy for at least 6 months and without GH replacement, either before GH was started or after GH was withdrawn for 30-60 days. Eight patients were on thyroxine replacement treatment and thyroxine doses were kept constant during the study. Blood was collected before and after 15, 20 and 60 minutes of TRH administration in both therapeutic conditions (with GH and without GH). MEASUREMENTS: Concentrations of thyroid hormone levels were determined only in sera obtained before TRH administration. FT4, T3 and TSH were measured by immunoflourimetric assays and rT2 was measured by immunoradioassay. RESULTS: Patients were classified into two groups, according to basal TSH levels: group I (TSH > 0.4 mU/l, n = 12) and group II (on thyroxine and TSH < 0.05 mU/l, n = 8). In both groups, serum FT4 levels decreased (17. 0 +/- 1.1 vs. 14.3 +/- 0.9 mU/l, P < 0.001, and 18.0 +/- 1.7 vs. 14. 2 +/- 1.7 mU/l, P < 0.01, respectively), serum T3 levels increased (1.8 +/- 0.1 vs. 2.4 +/- 0.2 nmol/l, P < 0.001, and 1.9 +/- 0.3 vs. 2.4 +/- 0.2 nmol/l, P < 0.05, respectively), and serum rT3 levels decreased (0.35 +/- 0.03 vs. 0.25 +/- 0.03 nmol/l, P < 0.01, and 0. 48 +/- 0.06 vs. 0.34 +/- 0.06 nmol/l, P < 0.01, respectively). Basal (3.2 +/- 0.50 vs. 2.6 +/- 0.72 mU/l, P = 0.28, paired t-test), TRH-stimulated peak TSH levels (13.9 +/- 5.3 vs. 15.9 +/- 8.0 mU/l, P = 0.35, paired t-test) and TRH-stimulated TSH secretion, expressed as area under the curve (609 +/- 97 vs. 499 +/- 53 mU/l.minutes-1, P = 0.15, paired t-test), remained unchanged during GH replacement in group I patients. Low serum FT4 and high serum T3 levels were observed in only one patient each, but low serum rT3 levels were found in six patients (four in group I and two in group II) during GH replacement. CONCLUSIONS: These results show that long-term GH replacement therapy in children with unequivocal GHD significantly decreases serum FT4 and rT3 levels and increases serum T3 levels; that these changes are independent of TSH and result from increased peripheral conversion of T4 to T3 and that GH replacement therapy in GH deficient children does not induce hypothyroidism, but simply reveals previously unrecognized cases whose serum FT4 values fall in the low range during GH replacement.
Assuntos
Transtornos do Crescimento/etiologia , Hormônio do Crescimento/administração & dosagem , Hormônio do Crescimento/deficiência , Terapia de Reposição Hormonal , Hormônios Tireóideos/sangue , Adolescente , Adulto , Criança , Feminino , Seguimentos , Transtornos do Crescimento/sangue , Transtornos do Crescimento/tratamento farmacológico , Humanos , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/diagnóstico , Masculino , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Tri-Iodotironina Reversa/sangueRESUMO
The kinetic characterization of the outer-ring deiodination pathway using rT(3) (rT(3)-ORD) in male, female, and pregnant female livers of an endemic lizard, Sceloporus grammicus, is reported. The ORD pathway does not have the characteristics of deiodinase type II; it is exclusively carried out by deiodinase type I (DI). DI enzymatic activity in lizard liver contains one of the highest activities reported in vertebrates. This activity is sexually dimorphic, with males presenting the highest activity during the reproductive season. The properties of this enzyme correspond to those described in mammals, such as specificity for rT(3), susceptibility to inhibition by 6-n-propyl-2-thiouracil and gold-thioglucose, cofactor requirement, and kinetic pattern. Unlike other vertebrates, the lizard DI exhibits conspicuous stability in the thermal range of 15 to 42 degrees C and in the pH range of 5.0 to 9.0. Male true kinetic constants exhibit a direct correlation with temperature. This is in agreement with short-term adaptation to microenvironmental changes and the feasible expression of enzymatic forms/variants which, together, endow this lizard species with a greater adaptation to natural daily ambient thermal fluctuations.
Assuntos
Iodeto Peroxidase/metabolismo , Fígado/enzimologia , Lagartos/metabolismo , Animais , Aurotioglucose/farmacologia , Ditiotreitol/farmacologia , Inibidores Enzimáticos/farmacologia , Feminino , Concentração de Íons de Hidrogênio , Iodeto Peroxidase/antagonistas & inibidores , Cinética , Masculino , Gravidez , Propiltiouracila/farmacologia , Estações do Ano , Caracteres Sexuais , Temperatura , Tri-Iodotironina Reversa/metabolismoRESUMO
To investigate the role of type II 5'-deiodinase (5'D-II) in the expression of mitochondrial uncoupling protein (UCP) in brown adipose tissue (BAT), we injected intact male rats with reverse (r) 3,5,3'-triiodothyronine (T3; 100 micrograms. 100 g body wt-1. day-1), an inhibitor of 5'D-II, for 2-5 days. UCP decreased by approximately 20% in rats kept at 28 degreesC and failed to increase during cold exposure (4 degreesC). Next, thyroxine treatment (1-10 micrograms. 100 g body wt-1. day-1) increased nuclear T3 in rats kept at 28 or 4 degreesC. In these rats, nuclear T3 correlated positively with UCP. In addition, T3 (1-50 micrograms. 100 g body wt-1. day-1) given to intact rats (5-15 days; 28 degreesC) induced an approximately twofold increase in UCP. In these T3-treated animals, the interscapular BAT thermal response to norepinephrine infusion also correlated positively with T3 dose and UCP content. Treatment with propranolol or reserpine failed to block the T3 induction of UCP (approximately 1.8- and approximately 2.3-fold). The results emphasize the importance of local 5'D-II and reveal an independent role of T3 in the expression of UCP.
Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Proteínas de Transporte/metabolismo , Proteínas de Membrana/metabolismo , Sistema Nervoso Simpático/fisiologia , Tri-Iodotironina/farmacologia , Tecido Adiposo Marrom/inervação , Tecido Adiposo Marrom/fisiologia , Antagonistas Adrenérgicos/farmacologia , Animais , Regulação da Temperatura Corporal/efeitos dos fármacos , Regulação da Temperatura Corporal/fisiologia , Núcleo Celular/metabolismo , Temperatura Baixa , Inibidores Enzimáticos/farmacologia , Iodeto Peroxidase/antagonistas & inibidores , Canais Iônicos , Isoenzimas/antagonistas & inibidores , Masculino , Proteínas Mitocondriais , Norepinefrina/farmacologia , Ratos , Ratos Wistar , Receptores dos Hormônios Tireóideos/metabolismo , Tiroxina/farmacologia , Tri-Iodotironina/metabolismo , Tri-Iodotironina Reversa/farmacologia , Proteína Desacopladora 1RESUMO
Growth hormone (GH) gene expression was examined in male Wistar rats (200 g) subjected to different manipulations of thyroid status. Thyroidectomy followed by 10 days of treatment with 0.03% methimazole added to drinking water caused a marked decrease in GH mRNA levels estimated by Northern Blot analysis. T3 administration (100 micrograms/100 g body weight, ip, twice daily) to euthyroid rats for one week caused a substantial increase in GH mRNA levels. In another set of experiments, thyroidectomized methimazole-treated rats were killed at different times after a single T3 injection (100 micrograms/100 g body weight, ip). T3 induced a prompt response in GH gene expression by 15 min that reached a maximum after 1 h, remaining so up to 4 h. We conclude that in the rat, GH gene expression is highly dependent on thyroid hormones. Because of the rapidity of the response, the effect is probably mediated by a transcriptional mechanism.
Assuntos
Expressão Gênica , Hormônio do Crescimento/genética , Hormônios Tireóideos/fisiologia , Animais , Northern Blotting , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Hormônios Tireóideos/genética , Hormônios Tireóideos/metabolismo , Fatores de Tempo , Transcrição Gênica , Tri-Iodotironina Reversa/administração & dosagemRESUMO
Growth hormone (GH) gene expression was examined in male Wistar rats (200 g) subjected to different manipulations of thyroid status. Thyroidectomy followed by 10 days of treatment with 0.03 methimazole added to drinking water caused a marked decrease in GH mRNA levels estimated by Northern Blot analysis. T3 administration (100 micrograms/100 g body weight, ip, twice daily) to euthyroid rats for one week caused a substantial increase in GH mRNA levels. In another set of experiments, thyroidectomized methimazole-treated rats were killed at different times after a single T3 injection (100 micrograms/100 g body weight, ip). T3 induced a prompt response in GH gene expression by 15 min that reached a maximum after 1 h, remaining so up to 4 h. We conclude that in the rat, GH gene expression is highly dependent on thyroid hormones. Because of the rapidity of the response, the effect is probably mediated by a transcriptional mechanism.
Assuntos
Animais , Masculino , Ratos , Expressão Gênica , Hormônio do Crescimento , Hormônios Tireóideos/fisiologia , Northern Blotting , Hormônios Tireóideos/genética , Hormônios Tireóideos/metabolismo , Ratos Wistar , RNA Mensageiro , Fatores de Tempo , Transcrição Gênica , Tri-Iodotironina ReversaRESUMO
Os autores investigam o funcionamento da tireóide em 43 crianças com síndrome de Down e 48 controles em faixas etárias entre três meses e 18 anos, através de dosagens séricas de T3 livre (T3L), T4 L livre (T4L), tireotropina (TSH), T3 reverso (rT3) e anticorpos antimicrossomais (AcAM) e antitireoglobulina (AcAT). A idade óssea e as habilidades intelectuais também foram estimadas. Das 43 crianças com síndrome de Down, uma tinha hipotireoidismo clínico e em 12 havia hipotireoidismo subclíníco (27,9 por cento). A percentagem de AcAM titulável no grupo dos Down foi de 37,2 por cento. Em 25,6 por cento dos pacientes submetidos a radiografia de maos e punhos havia retardo na idade óssea. As médias hormonais dos casos de síndrome de Down sem disfunçao tireóidea detectável, quando comparadas às dos controles, mostraram-se significativamente mais elevadas quanto ao TSH e mais reduzidas quanto ao rT3. É possível que o déficit relativo de rT3 na síndrome de Down, confirmado neste trabalho, represente tao somente mais uma manifestaçao do hipotireoidismo. O rendimento intelectual dos casos de síndrome de Down com hipotireoidismo exclusivamente subclínico revelou-se comparável ao daqueles sem alteraçoes hormonais, embora o paciente com hipotireoidismo clínico mostrasse importante déficit mental. Crianças com síndrome de Down têm elevado risco de desenvolver hipotireoidismo, devendo portanto ser submetidas a estudos laboratoriais especializados, objetivando a prevençao de danos progressivos à funçao intelectual.
Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Glândula Tireoide/fisiologia , Síndrome de Down/fisiopatologia , Anticorpos/sangue , Desenvolvimento Ósseo , Desenvolvimento Infantil , Hipertireoidismo/sangue , Hipertireoidismo/fisiopatologia , Hipotireoidismo/sangue , Hipotireoidismo/fisiopatologia , Inteligência , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina Reversa/sangue , Tri-Iodotironina/sangueRESUMO
O conhecimento do teor de hormônios tireoidianos no leite de mulheres em uso de medicação substitutiva com levotiroxina sódica é importante para risco de exposição dos lactentes à ingestão de quantidades excessivas desses hormônios. Estudou-se a concentração de tiroxina (T4), Triiodo tironina (T3) e Triiodotironina reversa (rT3) e os títulos de anticorpos anti-tireoidianos no soro e leite de nutrizes em uso continuado de levotiroxina sódica e de um grupo controle sem usar qualquer medicação. As dosagens foram realizadas entre o quinto e o sétimo dia após o parto e os níveis séricos dos hormônios nãodiferiram significativamente entre os dois grupos ...Esses resultados permitem conckluir que nutrizes em tratamento substitutivo com as doses habituais de levotiroxina não transferem quantidades suprafisiológicas de T4 e T3 para os seus lactentes.