RESUMO
Neonatal mouse hearts can regenerate post-injury, unlike adult hearts that form fibrotic scars. The mechanism of thyroid hormone signaling in cardiac regeneration warrants further study. We found that triiodothyronine impairs cardiomyocyte proliferation and heart regeneration in neonatal mice after apical resection. Single-cell RNA-Sequencing on cardiac CD45-positive leukocytes revealed a pro-inflammatory phenotype in monocytes/macrophages after triiodothyronine treatment. Furthermore, we observed that cardiomyocyte proliferation was inhibited by medium from triiodothyronine-treated macrophages, while triiodothyronine itself had no direct effect on the cardiomyocytes in vitro. Our study unveils a novel role of triiodothyronine in mediating the inflammatory response that hinders heart regeneration.
Assuntos
Proliferação de Células , Macrófagos , Monócitos , Miócitos Cardíacos , Regeneração , Tri-Iodotironina , Animais , Regeneração/efeitos dos fármacos , Tri-Iodotironina/farmacologia , Monócitos/metabolismo , Monócitos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Camundongos , Inflamação/metabolismo , Inflamação/patologia , Animais Recém-Nascidos , Coração/efeitos dos fármacos , Coração/fisiopatologia , Camundongos Endogâmicos C57BLRESUMO
Heart failure tends to deteriorate in colder climates, heightening the risk of major adverse cardiovascular events. Brown adipose tissue (BAT) serves as both a thermogenic organ and an atypical site for triiodothyronine (T3) synthesis in response to cold. This study investigates the potential role of BAT in contributing to abdominal aortic constriction (AAC)-induced pathological cardiac remodeling during cold exposure. In this study, we developed a mouse model of pathological cardiac remodeling using AAC. Physical excision of interscapular BAT (iBATx) was performed during cold exposure, and T3 synthesis levels were measured. Additionally, the impact of uncoupling protein 1 (UCP1) knockout on thermogenic function and pathological cardiac remodeling was investigated. In vitro studies were conducted to assess the effect of T3 on cardiomyocyte hypertrophy induced by phenylephrine (PE). Physical removal of interscapular BAT during cold exposure decreased T3 synthesis and mitigated pathological cardiac remodeling. Conversely, UCP1 knockout eliminated thermogenic function during cold exposure, while preserving BAT integrity increased T3 synthesis and exacerbated pathological cardiac remodeling. In vitro, T3 further aggravated cardiomyocyte hypertrophy caused by PE. These findings underscore the distinct effects of physical and functional BAT ablation on pathological cardiac remodeling, primarily through altering T3 levels rather than thermogenesis in cold environments. This research provides new insights into the differential roles of BAT in cardiac health, particularly under cold exposure conditions.
Assuntos
Tecido Adiposo Marrom , Camundongos Knockout , Miócitos Cardíacos , Tri-Iodotironina , Proteína Desacopladora 1 , Remodelação Ventricular , Animais , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/patologia , Tri-Iodotironina/metabolismo , Proteína Desacopladora 1/metabolismo , Proteína Desacopladora 1/genética , Camundongos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Camundongos Endogâmicos C57BL , Masculino , Termogênese , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Cardiomegalia/genética , Temperatura Baixa , Aorta Abdominal/patologia , Aorta Abdominal/metabolismo , Aorta Abdominal/cirurgiaRESUMO
The effect of triiodothyronine (T3) on the phosphorylation of ERK and the occurrence and development of hepatocellular carcinoma (HCC) is controversial and remains to be clarified. In the present study, both in vitro (hepatoma cell lines) and in vivo (wild-type mice [WT] and mouse models of HCC [HrasG12Vand KrasG12Dtransgenic mice (Hras-Tg and Kras-Tg)]) systems were used to investigate the effect of T3 on p-ERK and hepatocarcinogenesis. The results showed that, in vitro, T3 treatment elevated the levels of p-ERK in hepatoma cells within 30 min. However, p-ERK levels returned to normal after 1 h with no significant effects on cellular proliferation or apoptosis. Interestingly, in vivo, T3 induced early rapid and transient activation of ERK and later persistent downregulation of p-ERK in liver tissues of WT. In Hras-Tg, liver weight, liver/body weight ratio, hepatic tumor numbers and sizes were significantly reduced withT3treatment compared with the untreated group. Furthermore, the levels of albumin, HrasG12V, and p-ERK in hepatic precancerous and tumor tissues were all significantly downregulated with T3 treatment; however, the levels of endogenous Hras were not affected. In WT, T3 also induced downregulation of Albumin in liver tissues, but without influence on the expression of endogenous Hras and p-MEK. Especially, the inhibitory effect of T3 on p-ERK and hepatic tumorigenesis and development without influence on the levels of KrasG12D and p-MEK was further confirmed in Kras-Tg. In conclusion, T3 suppresses hepatic tumorigenesis and development by independently and substantially inhibiting the phosphorylation of ERK in vivo.
Assuntos
Carcinogênese , Carcinoma Hepatocelular , Neoplasias Hepáticas , Tri-Iodotironina , Animais , Tri-Iodotironina/farmacologia , Tri-Iodotironina/metabolismo , Fosforilação , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Humanos , Carcinogênese/metabolismo , Carcinogênese/efeitos dos fármacos , Carcinogênese/genética , Proliferação de Células/efeitos dos fármacos , Camundongos Transgênicos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Linhagem Celular Tumoral , Apoptose , Masculino , Sistema de Sinalização das MAP Quinases/efeitos dos fármacosRESUMO
OBJECTIVE: Hypothyroidism is a common endocrine condition usually managed with levothyroxine (LT4). However, controversy remains around the use of liothyronine (LT3). We aimed to investigate the practices of Australian endocrinologists when managing patients with hypothyroidism, their use of LT3 + LT4 combination therapy and use of thyroid hormones in euthyroid patients. DESIGN AND PARTICIPANTS: Members of the Endocrine Society of Australia (ESA) were invited to participate in an online questionnaire. MEASUREMENTS: We analysed questionnaires that had complete demographic data. RESULTS: Eighty-seven questionnaires fulfilled the criteria. LT4 was used as first line treatment for hypothyroidism by all respondents. Only 45% reported that their patients were dispensed the brand of LT4 that they recommend. LT3 (alone or in combination) was prescribed by 44% in their clinical practice. Although 49% of respondents would consider LT3 + LT4 in patients with normal TSH who had ongoing symptoms of hypothyroidism, the inability of LT4 to restore normal physiology was ranked the least likely explanation for persistent symptoms and only 32% would consider it for themselves if they were diagnosed with hypothyroidism. The majority (55%), in accordance with evidence, would not prescribe thyroid hormone to euthyroid individuals but 39% would consider use in euthyroid female infertility with high levels of thyroid antibodies and 11% in euthyroid patients with a simple goitre growing over time. LT4 use in pregnancy was variable among members. CONCLUSIONS: Australian endocrinologists mostly follow international guidelines when prescribing thyroid hormone therapy and many prescribe combination LT3 and LT4 therapy, particularly for patients who remain symptomatic on LT4 monotherapy. Prescribing practices are largely similar to other countries who have completed similar questionnaires.
Assuntos
Hipotireoidismo , Gravidez , Humanos , Feminino , Austrália , Hipotireoidismo/tratamento farmacológico , Hormônios Tireóideos/uso terapêutico , Tiroxina/uso terapêutico , Tri-Iodotironina/uso terapêutico , Inquéritos e Questionários , Tireotropina/uso terapêuticoRESUMO
Mitochondria provide the energy to keep cells alive and functioning and they have the capacity to influence highly complex molecular events. Mitochondria are essential to maintain cellular energy homeostasis that determines the course of neurological disorders, including traumatic brain injury (TBI). Various aspects of mitochondria metabolism such as autophagy can have long-term consequences for brain function and plasticity. In turn, mitochondria bioenergetics can impinge on molecular events associated with epigenetic modifications of DNA, which can extend cellular memory for a long time. Mitochondrial dysfunction leads to pathological manifestations such as oxidative stress, inflammation, and calcium imbalance that threaten brain plasticity and function. Hence, targeting mitochondrial function may have great potential to lessen the outcomes of TBI.
Assuntos
Lesões Encefálicas Traumáticas , Encéfalo , Metabolismo Energético , Mitocôndrias , Plasticidade Neuronal , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/fisiopatologia , Humanos , Animais , Mitocôndrias/metabolismo , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Encéfalo/patologia , Estresse OxidativoRESUMO
BACKGROUND: Advanced maternal age may affect the intrauterine environment and increase the risk of neurodevelopmental disorders in offspring. Thyroid hormones are critical for fetal neurological development but whether maternal age influences fetal thyroid hormone levels in euthyroid mothers is unknown. OBJECTIVE: This study evaluated the association between cord blood thyroid hormones and maternal age, fetal sex, maternal thyroid function, and other perinatal factors. METHODS: The study population consisted of 203 healthy women with term singleton pregnancies who underwent elective cesarean section. Maternal levels of free T3 (fT3), free T4 (fT4) and TSH before delivery, and cord levels of fT3, fT4 and TSH were measured. Spearman's correlation coefficient and multiple linear regression analyses were performed to determine the correlation between cord thyroid hormone parameters and maternal characteristics. RESULTS: There were no significant differences in maternal serum or cord blood thyroid hormone levels between male and female births. In multivariate linear regression analysis, maternal age and maternal TSH values were negatively associated with the cord blood levels of fT3 in all births, after adjusting for confounding factors. Maternal age was more closely associated with the cord blood levels of fT3 in female than in male births. CONCLUSION: The inverse association between maternal age and cord blood levels of fT3 in euthyroid pregnant women suggested an impact of maternal aging on offspring thyroid function.
Assuntos
Sangue Fetal , Idade Materna , Tri-Iodotironina , Humanos , Feminino , Adulto , Masculino , Gravidez , Sangue Fetal/química , Sangue Fetal/metabolismo , Recém-Nascido , Tri-Iodotironina/sangue , Fatores Sexuais , Testes de Função Tireóidea , Tireotropina/sangueRESUMO
PURPOSE: Vertebral fractures (VFs), the hallmark of skeletal fragility, have been reported as an emerging complication in patients with pituitary diseases associated with hormonal excess and/or deficiency, independently from bone mineral density. Non-functioning pituitary adenoma (NFPA) is amongst the most frequent pituitary adenomas; however, skeletal health in this context has never been investigated. We aimed at assessing the prevalence and the determinants of morphometric VFs in patients with NFPA. METHODS: We enrolled 156 patients (79 M/77F, mean age 55.75 ± 12.94 years) at admission in Neurosurgery Unit before trans-sphenoidal surgery and compared them with an age and sex-matched control group of subjects with neither history/risk factors for secondary osteoporosis nor pituitary disorders. We performed a vertebral morphometric evaluation of the thoracic spine on pre-operative X-ray images (MTRx) and collected biochemical, demographic, and clinical data from the entire cohort. RESULTS: The prevalence of thoracic VFs in patients with NFPA was significantly higher than the control group (26.3% vs. 10.3%; p < 0.001). In the NFPA group, 20 patients (48.8% of the fractured patients) showed multiple VFs, 14 (34.1% of them) showed moderate/severe VFs. Patients with VFs were significantly older and had lower serum free triiodothyronine (fT3) levels than non-fractured ones (p = 0.002 and p = 0.004; respectively). The prevalence of secondary male hypogonadism was higher among men with VFs as compared to those with no VFs (72% vs. 48.1%; p = 0.047). Consistently, total testosterone levels in males were significantly lower in fractured patients than in non-fractured ones (p = 0.02). The prevalence of gonadotroph adenomas was significantly higher among patients with VFs (p = 0.02). In multiple logistic regression analysis, older age and lower serum fT3 levels were independent factors predicting the risk for VFs. CONCLUSIONS: For the first time, we reported a high prevalence of thoracic radiological VFs in patients with NFPAs. Our data should prompt clinicians to proceed with a clinical bone fragility evaluation already during the diagnostic work-up, particularly in those with concomitant hypogonadism, or in those with older age and/or with lower fT3.
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Neoplasias Hipofisárias , Fraturas da Coluna Vertebral , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/complicações , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Idoso , Prevalência , Adulto , Adenoma/diagnóstico por imagem , Adenoma/epidemiologia , Adenoma/patologia , Densidade Óssea , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/patologia , Fatores de RiscoRESUMO
TSH-secreting pituitary adenoma (TSHoma) is the rarest functioning pituitary tumor, with an increasing incidence over the last decades. Diagnosis is often delayed, exposing patients to a high risk of developing chronic complications of long-standing hyperthyroidism. Although thyroid hormone excess is a recognized cause of secondary osteoporosis, very few studies have investigated skeletal damage in patients with TSHoma, with data limited to bone turnover markers (BTM) and a study on the prevalence of radiological vertebral fractures (VFs) incidentally detected on chest X-ray, whereas data on bone mineral density (BMD) are anecdotal. Bone resorption is increased in TSHoma compared to controls, whereas few case reports described osteoporosis and spine fractures as early complications of TSHoma. A high prevalence of morphometric VFs was described in TSHoma compared to nonfunctioning pituitary adenoma (NFPA). Patients with fracture were older and had higher free thyroxine (fT4) levels than patients without fracture. In this specific setting, treatment with somatostatin receptor ligands seems to have a protective role on fracture risk. Based on this evidence, a comprehensive osteometabolic evaluation should be performed in all patients with TSHoma, including assessment of BTM, measurement of BMD, and morphometric evaluation of VFs, both at diagnosis and then during follow-up, particularly in patients at high risk for fragility fractures.
RESUMO
Achieving endothermic homeothermy is a critical aspect of avian development. In pre-homeothermic altricial nestlings, variation in parental brooding behavior results in variable exposure of nestlings to cooling, with consequences for the developing endocrine system. Nestlings facing repeated cooling challenges may benefit from upregulation of thyroid hormone secretion, allowing for earlier onset of thermoregulatory capability to mitigate the potentially negative effects of exposure to non-optimal temperatures during development. We examined the effects of (1) a single cooling challenge on thyroid hormone secretion in pre-homeothermic nestlings, and (2) repeated cooling challenges prior to the onset of homeothermy on nestling growth and thyroid hormone secretion prior to fledging. We found that pre-homeothermic eastern bluebird nestlings exposed to a single cooling challenge increased circulating triiodothyronine (T3), demonstrating that the thyroid system can be activated by cooling early in life. However, we found no consequences of repeated cooling during the first week of life on nestling growth or baseline T3 levels prior to fledging. This work addresses how the nestling hypothalamic-pituitary-thyroid axis responds to acute cooling challenges prior to the development of endothermic homeothermy; future work will confirm whether such responses allow nestlings to hasten the onset of physiological thermoregulation when conditions demand it.
Assuntos
Corticosterona , Aves Canoras , Animais , Aves Canoras/fisiologia , Temperatura Baixa , Temperatura , Tri-IodotironinaRESUMO
OBJECTIVE: Functional hypothalamic amenorrhea (FHA) is one of the foremost manifestations in anorexia nervosa (AN), but a subset of patients have menses despite marked weight loss and underweight. The aim of our study was to investigate parameters potentially influencing FHA in AN. DESIGN AND METHODS: In this observational retrospective study, we selected 114 female patients with AN who completed a 12 months semi-residential rehabilitation program and a subsequent 12 months outpatient follow-up. We divided our sample into three groups: "Group 0" patients who experienced FHA and recovered their menses, "Group 1" persistent FHA, "Group 2" never experienced FHA, and looked for clinical and hormonal correlations. RESULTS: At the enrollment, the BMI was higher in Group 2 than in Group 1 (p = 0.0202), but the last follow-up weight was higher in Group 1 (p < 0.0001) despite persistent amenorrhea. At logistic regression, the higher BMI at which patients experienced amenorrhea was the main prediction factor for persistent FHA. Notwithstanding comparable leptin levels at admission, they improved significantly at discharge only in Groups 0 and 2 (p = 0.0054 and p = 0.0104, respectively). FT3 at admission was significantly higher in Group 2 than in Group 0 (p = 0.0249). CONCLUSIONS: FHA does not correlate strictly with body weight variations in AN patients, indicating a multifactorial origin, likely including an individual predisposition. Higher FT3 levels identify patients who continue having menses at extremely low BMI. AN patients with persistent FHA constitute a subgroup in whom estroprogestins should be considered after significant weight recovery to prevent prolonged tissue hypoestrogenism.
Assuntos
Anorexia Nervosa , Doenças Hipotalâmicas , Feminino , Humanos , Amenorreia , Estudos Retrospectivos , Peso CorporalRESUMO
PURPOSE: Thyroid function is closely related to the prognosis of cardiovascular diseases. This study aimed to explore the predictive value of thyroid hormones for adverse cardiovascular outcomes in left ventricular noncompaction (LVNC). METHODS: This longitudinal cohort study enrolled 388 consecutive LVNC patients with complete thyroid function profiles and comprehensive cardiovascular assessment. Potential predictors for adverse outcomes were thoroughly evaluated. RESULTS: Over a median follow-up of 5.22 years, primary outcome (the combination of cardiovascular mortality and heart transplantation) occurred in 98 (25.3%) patients. For secondary outcomes, 75 (19.3%) patients died and 130 (33.5%) patients experienced major adverse cardiovascular events (MACE). Multivariable Cox analysis identified that free triiodothyronine (FT3) was independently associated with both primary (HR 0.455, 95%CI 0.313-0.664) and secondary (HR 0.547, 95%CI 0.349-0.858; HR 0.663, 95%CI 0.475-0.925) outcomes. Restricted cubic spline analysis illustrated that the risk for adverse outcomes increased significantly with the decline of serum FT3. The LVNC cohort was further stratified according to tertiles of FT3 levels. Individuals with lower FT3 levels in the tertile 1 group suffered from severe cardiac dysfunction and remodeling, resulting in higher incidence of mortality and MACE (Log-rank P < 0.001). Subgroup analysis revealed that lower concentration of FT3 was linked to worse prognosis, particularly for patients with left atrial diameter ≥ 40 mm or left ventricular ejection fraction ≤ 35%. Adding FT3 to the pre-existing risk score for MACE in LVNC improved its predictive performance. CONCLUSION: Through the long-term investigation on a large LVNC cohort, we demonstrated that low FT3 level was an independent predictor for adverse cardiovascular outcomes.
Assuntos
Hormônios Tireóideos , Humanos , Masculino , Feminino , Prognóstico , Pessoa de Meia-Idade , Hormônios Tireóideos/sangue , Seguimentos , Estudos Longitudinais , Miocárdio Ventricular não Compactado Isolado/diagnóstico , Miocárdio Ventricular não Compactado Isolado/sangue , Adulto , Tri-Iodotironina/sangueRESUMO
OBJECTIVE: The study aimed to assess whether thyroid hormone (TH) sensitivity is related to visceral fat area (VFA) and visceral obesity in euthyroid subjects with type 2 diabetes (T2D). METHODS: 750 euthyroid patients with T2D were enrolled. A VFA of 80 cm2 or more was considered visceral obesity. Central TH sensitivity was conducted using thyrotrophic thyroxine resistance index (TT4RI), thyrotropin index (TSHI), and thyroid feedback quantile-based index (TFQI). Free triiodothyronine to free thyroxine (FT3/FT4) was utilized for assessing peripheral TH sensitivity. RESULTS: The subjects had a mean age of 51.5 ± 11.1 years, and 540 (72.0%) of them were men. In multivariable regression analyses, there was a positive correlation of FT3/FT4 tertile with visceral obesity, after full adjustment for confounding variables (P < 0.05). The middle and highest FT3/FT4 tertiles were correlated with a 134% [95% CI (1.24, 4.44)] and 98% [95% CI (1.04, 3.78)] higher prevalence of visceral obesity than the lowest tertile, respectively. Conversely, elevated TFQI levels were linked to a decreased prevalence of visceral obesity. Stratified analysis revealed that these associations were particularly pronounced in participants who are neither overweight nor obese and those aged less than 60 years (all P < 0.05). CONCLUSIONS: Higher TH sensitivity is correlated with visceral obesity and elevated VFA in euthyroid patients with T2D, particularly among those younger than 60 years and individuals who are neither overweight nor obese.
Assuntos
Diabetes Mellitus Tipo 2 , Obesidade Abdominal , Tiroxina , Tri-Iodotironina , Humanos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Masculino , Pessoa de Meia-Idade , Feminino , Obesidade Abdominal/sangue , Obesidade Abdominal/complicações , Adulto , Tri-Iodotironina/sangue , Tiroxina/sangue , Hormônios Tireóideos/sangue , Gordura Intra-Abdominal/metabolismo , Tireotropina/sangueRESUMO
We and other investigators reported that mild TSH suppression with levothyroxine (LT4) was needed to achieve normal free triiodothyronine (FT3) levels and metabolic euthyroid state in athyreotic patients. Consequently, management methods based on thyroid tissue volume have been implemented for patients receiving LT4 at the Kuma Hospital. This retrospective study examined the composition of the thyroid hormone measurement items (serum-free thyroxine [FT4], FT3, and FT4 + FT3) in patients receiving LT4 monotherapy. According to the etiology of hypothyroidism, 36% of the 25,523 patients included in this study underwent total thyroidectomy (TT). Thirteen percent and 14% had undergone 131I treatment for hyperthyroidism (RIT) and partial thyroidectomy (PT), respectively. Moreover, 37% of patients had received non-invasive treatment (NIT). The proportion of patients who underwent only FT3 measurements was higher (TT, 93%; RIT, 61%) in the first two groups, whereas the proportion of patients who underwent only FT4 measurements was higher (PT, 50%; NIT, 65%) in the remaining two groups. Only FT3 measurements were performed in 58% of patients. Only FT4 measurements were performed in 34% of patients. The serum TSH levels were suppressed in nearly half of the patients (46%). Thus, FT3 was the major thyroid hormone measured in patients receiving LT4 treatment, and the serum TSH levels were suppressed in nearly half of the patients. This may be attributed to the management guidelines at our hospital, a specialized facility for thyroid disease, wherein half of the patients present are athyreotic or have atrophic thyroid glands after TT or RIT.
RESUMO
Subclinical hyperthyroidism (SHyper) is defined as normal levels of free thyroxine (fT4) and free triiodothyronine (fT3) with suppressed levels of TSH. Previous studies have reported the individual pathophysiology of endogenous SHyper patients and athyreotic patients receiving TSH suppression therapy with levothyroxine; however, apparently no studies have compared the two conditions. Five-hundred-forty untreated endogenous SHyper patients and 1,024 patients receiving TSH suppression therapy who underwent total thyroidectomy for papillary thyroid carcinoma were sampled. Thyroid hormone profiles and peripheral indices related to thyrotoxicosis were investigated in endogenous SHyper patients, athyreotic patients receiving TSH suppression therapy, and healthy participants. Endogenous SHyper patients showed significantly higher thyroid hormone levels (fT4 [p < 0.001] and fT3 [p < 0.001]), and peripheral indices showed a significant tendency towards thyrotoxicosis (strong TSH suppression: alkaline phosphatase [ALP, p < 0.001], creatinine [Cre, p < 0.001], pulse rate [p < 0.05]; and mild TSH suppression: Cre [p < 0.05]) than healthy participants. In contrast, athyreotic patients receiving TSH suppression therapy showed a significant tendency towards thyrotoxicosis than healthy participants only when TSH was strongly suppressed (fT3 [p < 0.001] and Cre [p < 0.001]). Endogenous SHyper patients showed significantly higher fT3 levels (p < 0.001) than athyreotic patients receiving TSH suppression therapy; however, there was a significant tendency towards thyrotoxicosis only when TSH was strongly suppressed (ALP [p < 0.05] and pulse rate [p < 0.05]). The effects of endogenous SHyper and TSH suppression therapy on target organ function are different. Although the serum thyroid hormone profile is similar to that of the thyrotoxic state, athyreotic patients receiving TSH suppression therapy with mildly suppressed serum TSH levels are not thyrotoxic.
Assuntos
Hipertireoidismo , Tireoidectomia , Tireotropina , Tiroxina , Tri-Iodotironina , Humanos , Hipertireoidismo/sangue , Hipertireoidismo/fisiopatologia , Hipertireoidismo/complicações , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Tiroxina/uso terapêutico , Tiroxina/sangue , Tri-Iodotironina/sangue , Tireotropina/sangue , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/fisiopatologia , Neoplasias da Glândula Tireoide/complicações , Tireotoxicose/sangue , Tireotoxicose/fisiopatologia , Tireotoxicose/complicações , Testes de Função Tireóidea , Idoso , Câncer Papilífero da Tireoide/sangue , Câncer Papilífero da Tireoide/fisiopatologia , Câncer Papilífero da Tireoide/complicaçõesRESUMO
BACKGROUND: Idiopathic pulmonary fibrosis (IPF), an interstitial lung disease, is characterized by the exacerbation of progressive pulmonary fibrosis (PF). IPF primarily affects older individuals and can lead to respiratory failure. This study aimed to assess the effects of triiodothyronine (T3) treatment on the lung microbiome of mice with PF. METHODS: Mice were perfused with bleomycin (BLM) to establish a PF model. Using a randomized design, 40 female specific pathogen-free (SPF) C57BL6/N mice were divided into four groups: saline, saline + T3, BLM, and BLM + T3. Histological morphology was assessed through Hematoxylin and Eosin staining as well as Masson's Trichrome staining. For the identification of lung bacteria, 16S rRNA gene sequencing was employed. An Enzyme-Linked Immunosorbent Assay was used to measure total T3 (TT3), free T3 (FT3, and reverse T3 (rT3) levels in the peripheral serum. RESULTS: T3 treatment ameliorated BLM-induced lung fibrosis and structural damage. The microbiome experienced a decrease in the abundance of Proteobacteria, Bacteroides, and Actinomycetes and an increase in the abundance of Firmicutes when exposed to BLM; however, T3 treatment reversed this effect. The four groups showed no significant difference in alpha microbiome diversity (P > 0.05). Serum concentrations of TT3 and FT3 were positively correlated with microbiome abundance (P < 0.05). Administration of T3 enhanced the microbiota in PF without affecting the diversity and biological functions of the microbiome (P > 0.05). CONCLUSION: The administration of T3 demonstrated a favorable impact on the lung microbiota of mice afflicted with PF, thereby partially substantiating the potential role of T3 as a therapeutic agent in the management of PF.
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Bleomicina , Modelos Animais de Doenças , Pulmão , Camundongos Endogâmicos C57BL , Microbiota , RNA Ribossômico 16S , Tri-Iodotironina , Animais , Camundongos , Tri-Iodotironina/sangue , Tri-Iodotironina/farmacologia , Microbiota/efeitos dos fármacos , Pulmão/patologia , Pulmão/microbiologia , Feminino , RNA Ribossômico 16S/genética , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/microbiologia , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/microbiologiaRESUMO
BACKGROUND: Malaria parasites have a devastating effect on the infected host. However, there is a paucity of data on the effect of Plasmodium falciparum on thyroid hormones. METHODS: This case-control study (1:1) involved children <16 years of age with uncomplicated malaria. Hematological parameters were determined using the URIT-5380 hematology analyzer (China). Later, levels of thyroid hormones, namely free triiodothyronine (fT3), free tetraiodothyronine (fT4), and thyroid-stimulating hormone (TSH), were determined using human ELISA kits (DiaSino ELISA kit, Zhengzhou, China). RESULTS: Ninety children with malaria and ninety matched control group were studied. Overall, compared to the control group, lower TSH (3.43 ± 1.25 vs. 3.84 ± 1.34, p = 0.035) and elevated levels of fT3 levels (5.85 ± 1.79 vs. 3.89 ± 1.19, p < 0.001) were observed in patients with malaria. However, fT4 levels were comparable between cases and control group (16.37 ± 2.81 vs 17.06 ± 3.5, p = 0.150). Free T3 levels were significantly higher in children <10 years (p < 0.001) and higher among male children with malaria (p < 0.001). Overall, there was a significant positive relationship between parasite counts and fT3 (R = 0.95, p < 0.001). Furthermore, body temperature was positively correlated with fT3 (R = 0.97, p < 0.001). CONCLUSIONS: Isolated fT3 thyrotoxicosis was observed in falciparum malaria, especially in children <10 years and male malaria patients, independent of TSH. This observation could explain the severity of malaria in children.
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Malária , Tri-Iodotironina , Criança , Humanos , Masculino , Tireotropina , Plasmodium falciparum , Tiroxina , Estudos de Casos e Controles , Hormônios TireóideosRESUMO
BACKGROUND: In systemic inflammatory conditions, inflammatory cytokines can cause low thyroid hormone levels. There are no reports discussing the relation between thyroid hormone levels and response to treatment for Kawasaki disease. METHODS: We investigated 67 patients who underwent treatment in the acute phase of Kawasaki disease. We divided patients into two groups based on their response to initial intravenous immunoglobulin (IVIG) treatment: the responder group (n = 40), and the non-responder group (n = 27). The serum levels of the thyroid hormones free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were compared before and after treatment in all patients, and between responder and non-responder groups. RESULTS: The FT3, FT4, and TSH levels were low before the initial treatment and increased significantly after treatment (p < 0.05). The FT3, FT4, and TSH levels before treatment were significantly lower in the non-responder group than in the responder group (p < 0.05). Logistic regression analysis suggested that the addition of pre-treatment FT4 values to Gunma score was useful in predicting treatment failure. CONCLUSIONS: Thyroid hormone and TSH levels were lower in the non-responder group than in the responder group in the initial IVIG treatment for Kawasaki disease. This study suggests that Kawasaki disease in the acute phase is associated with low thyroid hormone levels and TSH. It is possible that these hormone levels predict response to the initial IVIG.
Assuntos
Síndrome de Linfonodos Mucocutâneos , Tiroxina , Humanos , Tiroxina/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Hormônios Tireóideos , TireotropinaRESUMO
OBJECTIVE: This study aimed to investigate the changes in thyroid hormones in the serum of patients with polycystic ovary syndrome (PCOS) and their correlation with insulin resistance. DESIGN: This is a retrospective study. PARTICIPANTS: 84 patients having insulin resistance and 76 patients without insulin resistance were included. 90 women without history of PCOS were selected as a healthy control group. SETTINGS: This study was conducted at Shijiazhuang Fourth Hospital. METHODS: Blood samples were collected from each group on days 3-5 of their menstrual cycle, and their triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) levels were analyzed and compared between groups. RESULTS: We investigated the changes of serum thyroid hormones in patients with PCOS and their correlation with insulin resistance. We found that serum levels of T3 and T4 were significantly decreased, while TSH levels were significantly increased in PCOS patients compared with HCs. Moreover, we found that patients with insulin resistance had significantly lower levels of serum T3 and T4 and higher levels of TSH compared to those PCOS participants without insulin resistance. LIMITATIONS: This study was a retrospective and single-center study, which had selection bias, information bias, and confounding variables may affect the accuracy and reliability of the conclusion. CONCLUSIONS: Insulin resistance negative correlates with their serum T3, T4, and positive correlates with their TSH levels. Our results develop a combined test model with the serum T3, T4, and TSH levels for the clinical diagnosis of insulin resistance in PCOS women.
RESUMO
Specific pediatric populations have exhibited disparate responses to triiodothyronine (T3) repletion during and after cardiopulmonary bypass (CPB). Objective: To determine if T3 supplementation improves outcomes in children undergoing CPB. We searched randomized controlled trials (RCT) evaluating T3 supplementation in children aged 0-3 years undergoing CPB between 1/1/2000 and 1/31/2022. We calculated Hazard ratios (HR) for time to extubation (TTE), ICU length of stay (LOS), and hospital LOS. 5 RCTs met inclusion criteria with available patient-level data. Two were performed in United States (US) and 3 in Indonesia with 767 total subjects (range 29- 220). Median (IQR) age 4.1 (1.6, 8.0) months; female 43%; RACHS-1 scores: 1-1%; 2-55%; 3-27%; 4-13%; 5-0.1%; 6-3.9%; 54% of subjects in US vs 46% in Indonesia. Baseline TSH and T3 were lower in Indonesia (p < 0.001). No significant difference occurred in TTE between treatment groups overall [HR 1.09 (CI, 0.94-1.26)]. TTE numerically favored T3-treated patients aged 1-5 months [HR 1.24 (CI, 0.97-1.60)]. TTE HR for the Indonesian T3 group was 1.31 (CI, 1.04-1.65) vs. 0.95 (CI, 0.78-1.15) in US. The ICU LOS HR for the Indonesian T3 group was 1.19 vs. 0.89 in US (p = 0.046). There was a significant T3 effect on hospital LOS [HR 1.30 (CI, 1.01-1.67)] in Indonesia but not in US [HR 0.99 (CI, 0.78-1.23)]. T3 supplementation in children undergoing CPB is simple, inexpensive, and safe, showing benefit in resource-limited settings. Differences in effects between settings likely relate to depression in baseline thyroid function often associated with malnutrition.
Assuntos
Ponte Cardiopulmonar , Tri-Iodotironina , Humanos , Tri-Iodotironina/sangue , Lactente , Pré-Escolar , Tempo de Internação/estatística & dados numéricos , Suplementos Nutricionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Indonésia , Recém-Nascido , FemininoRESUMO
This study aimed to evaluate and compare the physiological performance of different genetic groups of sheep, by physiological variables and serum hormone levels, in a hot weather environment. Thirty sheep from five genetic groups were used: Santa Inês (SI), ½ Dorper + ½ Santa Inês (DO), ½ Ilê de France + ½ Santa Inês (IF), ½ Suffolk + ½ Santa Inês (SK), and ½ Texel + ½ Santa Inês (TX). The readings and records of physiological parameters (respiratory rate (RR), rectal temperature (RT), auricular cavity temperature (ACT), and surface temperature (ST)) were carried out at 7:00 am, 1:00 pm, and 7:00 pm, in 12 non-consecutive days. The collections of blood samples for hormone analysis (triiodothyronine (T3), thyroxine (T4), and cortisol (CORT)) is in four consecutive days. The environmental conditions of the experimental period caused a thermal discomfort in the sheep, but not a state of thermal stress. The thermolysis mechanisms, sensitive (ST and ACT) and latent (RR) processes, were enough to maintain their homeostasis (RT). The results showed that crossbred breeds presented a higher metabolism and were more efficient at dissipating heat through thermolysis than the SI breed. The crossbred breeds were efficient at dissipating heat through the elevation of body surface temperature and respiratory rate, mainly SK and TX, i.e., crossbred breeds, despite the wool cover, used thermoregulatory mechanisms that promoted lower variation of RT. The analysis of variance showed significant effects (P < 0.05) to the time factor in the responses of T4 and T3, and to the breed factor in the responses of CORT, T4, and T3. We did not observe interaction between the factors to any of the hormonal variables. Therefore, we can state that the effect of time was independent of breed and vice versa. Thyroid hormones presented lower blood concentration in the mornings (4.03 ± 0.82, T4; 65.08 ± 10.6, T3), increasing their concentration in the afternoon (4.60 ± 1.03, T4; 70.16 ± 14.17, T3). The thyroid hormones presented a normal circadian rhythm, with the exception of SK. Air temperature (AT) showed greater correlation with physiological variables than enthalpy (H) did, in the experimental conditions. However, H showed correlation with T4 and T3. The adaptive profile of the genetic groups under study are different, but the IF genetic group showed better performance under environmental conditions.