RESUMEN
BACKGROUND: To assess 28-day survival in two pilot groups of septic shock patients with euthyroid sick syndrome (ESS) supplemented with triiodothyronine (T3). METHODS: A total of 95 septic shock patients with ESS were divided according to values of the thyroid hormones into low T3 and low T3T4 groups. Among 48 patients with low T3, 24 (50%) were randomized to T3 for 4 days and 24 (50%) to placebo. Among 47 patients with low T3T4, 24 (51%) were randomized to T3 for 4 days and 23 (49%) to placebo. The analysis included 28-day survival as the primary outcome and laboratory with hemodynamics as the secondary outcomes. Laboratory data were analyzed on the day of admission (T0), on the first (T1), third (T2) and seventh day (T3) with hemodynamics analyzed for the first four days. RESULTS: In the low T3 population, 18 (75%) patients receiving T3 died at day 28 compared with 8 (33.3%) patients receiving placebo (p = 0.004). In the low T3T4 population, 6 (25%) patients receiving T3 died in ICU compared with 12 (52.1%) patients receiving placebo (p = 0.039). Oral T3 treatment increased mean arterial pressure values at day 1, day 3 and day 7 in the low T3T4 population, (p = 0.015, =0.005 and =0.042 respectively), and had no significant effect on these values in the low T3 population. CONCLUSION: T3 supplementation was associated with a low 28-day mortality rate in patients with low T3T4 but with increased mortality in patients with low T3 ESS. These results suggest caution before initiating thyroid supplementation in septic patients. REGISTRATION: ClinTrials.gov (NCT05270798).
Asunto(s)
Síndromes del Eutiroideo Enfermo , Choque Séptico , Humanos , Triyodotironina/uso terapéutico , Choque Séptico/tratamiento farmacológico , Síndromes del Eutiroideo Enfermo/tratamiento farmacológico , Síndromes del Eutiroideo Enfermo/complicaciones , Ensayos Clínicos Controlados Aleatorios como Asunto , Hormonas Tiroideas/uso terapéuticoRESUMEN
BACKGROUND: Although elevated thyrotropin (TSH) is common in older adults, controversy exists over what degree of elevation should be treated with thyroid hormone supplements. Isolated, elevated TSH in this population can be consistent with aging-related adaptations rather than indicative of primary thyroid disease, raising the possibility that thyroid hormone replacement may be harmful. OBJECTIVES: Determine the association between all-cause mortality and levothyroxine use among older adults. DESIGN: Longitudinal observational study. SETTING: Baltimore Longitudinal Study of Aging. PARTICIPANTS: One thousand two hundred and fifty eight community dwelling adult participants aged 65+ with an average of 9 years of follow up. MEASUREMENTS: Thyroid and pituitary hormone levels and thyroid hormone supplementation were determined at each visit. Incident rate ratios (IRR) for all-cause mortality were calculated using time-dependent Poisson regression models to accommodate the varying start times. To isolate the effects of hormone replacement from its effects on TSH, the association between treatment and all-cause mortality was analyzed in participants with stable thyroid function status throughout follow-up (N = 638). RESULTS: Thyroid hormone supplementation was not associated with a significant increase all-cause mortality in the subsequent year in the fully adjusted model (IRR = 1.40, 95% confidence interval (CI) = 0.93-2.12). In a stratified analysis of euthyroid participants, thyroid hormone use was associated with significantly greater mortality, with an adjusted IRR = 1.81 (95% CI = 1.10-2.98). CONCLUSION: The increased mortality associated with thyroid hormone use among the subclass of euthyroid community dwelling older adults is consistent with a model in which TSH elevation can result from a variety of underlying pathophysiologic processes, not all of which should be treated with thyroid hormone supplementation. Clinicians should consider overall clinical status when interpreting an isolated elevated TSH in older adults.
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Síndromes del Eutiroideo Enfermo/tratamiento farmacológico , Síndromes del Eutiroideo Enfermo/mortalidad , Terapia de Reemplazo de Hormonas/mortalidad , Vida Independiente/estadística & datos numéricos , Tiroxina/uso terapéutico , Anciano , Anciano de 80 o más Años , Baltimore/epidemiología , Causas de Muerte , Femenino , Humanos , Estudios Longitudinales , Masculino , Distribución de PoissonRESUMEN
Non-thyroid disorders may modify thyroid hormone metabolism, resulting in an 'euthyroid sick syndrome'. Studies determining the association of cardiopulmonary bypass to thyroid function showed changes in line with this euthyroid sick syndrome. In some cases, cardiovascular dysfunction after cardiac surgery with cardiopulmonary bypass is comparable to that noticed in hypothyroidism associated with low cardiac output and elevated systemic vascular resistance. Numerous lines of research have proposed that triiodothyronine can behave acutely as a positive inotropic and vasodilator agent. The aim of this review is to present an update on the current literature about in what clinical situations the use of thyroid supplementation during the perioperative period of extracorporeal circulation in the adult and paediatric populations may impact outcome to any appreciable degree. The contribution of thyroid function in patients undergoing a ventricular assist device implantation is additionally reviewed and future study directions are proposed. This is a narrative review, where the search strategy consisted on retrieving the articles through an extensive literature search performed using electronic databases from January 1978 up to September 2019. All controlled trials randomly allocating to perioperative thyroid hormone administration in children and adults undergoing extracorporeal circulation for cardiac surgery were considered. Thyroid hormone supplementation may be recommended particularly in selected paediatric sub-populations. There is currently no firm evidence regarding the benefits of routine use of thyroid hormone administration in cardiac adult patients. Further studies are required to assess the beneficial effect of thyroid hormone on patients with end-stage heart failure supported by ventricular assist devices.
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Síndromes del Eutiroideo Enfermo , Adulto , Puente Cardiopulmonar/efectos adversos , Niño , Suplementos Dietéticos , Síndromes del Eutiroideo Enfermo/tratamiento farmacológico , Síndromes del Eutiroideo Enfermo/etiología , Humanos , Hormonas Tiroideas , TriyodotironinaRESUMEN
WHAT IS KNOWN AND OBJECTIVE: Low levels of serum triiodothyronine (T3) are a strong predictor of mortality and poor prognosis in critical care patients. Few reports, however, have focused on neurocritical patients. The application of hormone replacement therapy (HRT) in the treatment of neurocritical patients with low T3 syndrome remains controversial. We studied the role of low T3 state as a predictor of outcomes in neurocritical patients and examined the effect of HRT on prognosis. METHODS: A retrospective analysis was performed on the data of 32 neurocritical patients with low T3 syndrome who were admitted to the neuro-intensive care unit of Peking Union Medical College Hospital between January 2012 and October 2018. While 18/32 (56.25%) patients received HRT (HRT group; n = 18), 14/32 (43.75%) patients did not receive HRT (non-HRT group; n = 14). Patients were followed up for periods ranging from 3 months to 72 months. Baseline clinical and laboratory data were compared between the two groups using Mann-Whitney U tests or the t tests. Overall survival was assessed by Kaplan-Meier curve and compared by log-rank tests. Univariate and multivariate regression analyses were performed to identify the factors associated with prognosis and estimate the effect of HRT. We also assessed the influence of HRT on final neurological function, using the Glasgow Coma Scale (GCS) and the Glasgow Outcome Scale (GOS) scores. RESULTS AND DISCUSSION: The neurocritical events in our cohort included post-operative complications (n = 18), traumatic brain injury (n = 8) and spontaneous intracerebral haemorrhage (n = 6). Mean GCS score in the cohort was 6.41 (6.44 ± 3.14 in HRT group vs 6.36 ± 2.06 in non-HRT group). A total of 15/32 (46.87%) deaths were recorded (7 in the HRT group, 8 in the non-HRT group). In the HRT group, 15 patients underwent repeat thyroid function tests after completion of HRT; the low T3 situation was corrected in only 5/15 (33.3%) patients. Overall survival was significantly shorter in the non-HRT group than in the HRT group (16.45 months vs 47.47 months; P = .034). In univariate regression analysis, the HRT group has the lower mortality risk than the non-HRT group (HR = 0.301, 95% Cl: 0.094-0.964; P = .043). However, multivariate regression analysis showed no significant difference in mortality risk between the two groups (HR = 0.340 95% CI: 0.099-1.172; P = .087). There was no significant difference in effects of HRT on the short- and long-term neurological function between the groups. WHAT IS NEW AND CONCLUSION: Low T3 syndrome may influence the prognosis of neurocritical patients, attention should be paid to the changes in serum T3 levels during treatment. Although it is unclear to what extent HRT can improve the short or long-term outcomes of neurological function, it can significantly improve the survival rates of neurocritical patients.
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Lesiones Traumáticas del Encéfalo/complicaciones , Hemorragia Cerebral/complicaciones , Cuidados Críticos , Síndromes del Eutiroideo Enfermo/tratamiento farmacológico , Terapia de Reemplazo de Hormonas , Tiroxina/uso terapéutico , Adulto , Anciano , Síndromes del Eutiroideo Enfermo/diagnóstico , Síndromes del Eutiroideo Enfermo/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Glándula Tiroides/fisiopatologíaRESUMEN
Cardiovascular diseases are the leading cause of death worldwide. Heart failure is the terminal manifestation of cardiovascular diseases, and its morbidity and mortality remain high. The prevalence of heart failure with preserved ejection fraction (HFpEF) among heart failure patients remains uncertain. However, recent studies have found that it ranged from 40 to 71%. There is still no effective treatment for HFpEF. Thyroid hormones (TH) have central regulatory actions in the cardiovascular system, particularly in the heart. Changes in plasmatic or tissue thyroid hormone levels are associated with significant alterations in cardiovascular function. A significant proportion of patients with heart failure presents some form of thyroid dysfunction including hypothyroidism, hyperthyroidism, and low T3 syndrome. Furthermore, thyroid hormones can vary at a local level independently of the serum TH levels. This may lead to local cardiac hypothyroidism in heart failure. Based on these findings and the role that TH play in cardiovascular regulation, they were proposed as a potential target for heart failure therapy. Several clinical and experimental studies have shown beneficial effects of TH supplementation. Data from epidemiological studies supports a higher risk of heart failure and a worse prognosis in heart failure patients with low levels of TH. In addition, animal studies and small clinical studies suggest that TH supplementation may improve cardiac function in heart failure. Although further studies are needed to evaluate the safety and efficacy of TH in this context, the available evidence suggests that TH modulation is a promising therapeutic approach to heart failure.
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Síndromes del Eutiroideo Enfermo/metabolismo , Insuficiencia Cardíaca/metabolismo , Hipertiroidismo/metabolismo , Hipotiroidismo/metabolismo , Miocitos Cardíacos/metabolismo , Glándula Tiroides/metabolismo , Hormonas Tiroideas/metabolismo , Animales , Modelos Animales de Enfermedad , Síndromes del Eutiroideo Enfermo/tratamiento farmacológico , Síndromes del Eutiroideo Enfermo/epidemiología , Síndromes del Eutiroideo Enfermo/fisiopatología , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/fisiopatología , Humanos , Hipertiroidismo/tratamiento farmacológico , Hipertiroidismo/epidemiología , Hipertiroidismo/fisiopatología , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/epidemiología , Hipotiroidismo/fisiopatología , Pronóstico , Factores de Riesgo , Transducción de Señal , Volumen Sistólico , Glándula Tiroides/fisiopatología , Hormonas Tiroideas/uso terapéutico , Función Ventricular IzquierdaRESUMEN
Thyroid hormone is integral for normal function, yet during illness, circulating levels of the most active form (triiodothyronine [T3]) decline. Whether this is an adaptive response in critical illness or contributes to progressive disease has remained controversial. This review outlines the basis of thyroid hormone changes during critical illness and considers the evidence regarding T3 replacement.
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Corticoesteroides/uso terapéutico , Cuidados Críticos/métodos , Enfermedad Crítica/terapia , Síndromes del Eutiroideo Enfermo/tratamiento farmacológico , Síndromes del Eutiroideo Enfermo/fisiopatología , Triyodotironina/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Síndromes del Eutiroideo Enfermo/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Cardiopulmonary bypass in cardiac surgery produces systemic inflammatory response and catabolic state. Severe stress frequently causes abnormalities in thyroid hormones in the absence of primary thyroid disease, defined as sick euthyroid syndrome (SES). MATERIALS AND METHODS: Supplementation therapy with thyroid and anabolic hormones in combination with an adequate nutritional support has been used to improve outcome in critically ill patient after cardiac surgery. RESULTS: Administration of thyroid and anabolic hormones significantly improved patient's condition. CONCLUSIONS: Supplementation therapy with thyroid and anabolic hormones in combination with an adequate nutritional support could be used to improve hemodynamics, achieve transition to anabolic metabolism and enhance recovery, which could eventually help for a reduction in post-operative morbidity and mortality.
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Procedimientos Quirúrgicos Cardíacos/efectos adversos , Síndromes del Eutiroideo Enfermo/tratamiento farmacológico , Testosterona/uso terapéutico , Tiroxina/uso terapéutico , Anciano , Aorta/cirugía , Aneurisma de la Aorta/cirugía , Femenino , Terapia de Reemplazo de Hormonas , Humanos , Testosterona/sangre , Tiroxina/sangreRESUMEN
AIM: Non-thyroidal illness syndrome (NTIS) is common among patients with advanced chronic kidney disease (CKD) and is strongly associated with poor prognosis. However, it remains unclear in how to correct this disorder and this study aimed to evaluate the effectiveness of sodium bicarbonate (SB) and N-acetyl-cysteine (NAC) for correcting NTIS status. METHODS: Patients with CKD stage 3-4 were single-blind, placebo-controlled treated with placebo, SB, or NAC for 18 weeks. The primary end points were the correction of NTIS and the occurrence of end-stage renal disease (ESRD). The secondary point was the change in estimated glomerular filtration rate (eGFR) after the follow-up. RESULTS: The Kaplan-Meier survival analysis showed significant lower correcting ratio of NTIS in control group compared with SB group [Hazard ratio (HR) 0.19, 95 % confidence interval (CI) 0.04-0.89, p = 0.035] and NAC group (HR 0.09, 95 % CI 0.02-0.38, p = 0.001), and increased ESRD risk in control group than in SB group (HR 1.97, 95 % CI 1.02-3.84, p = 0.045) and NAC group (HR 5.50, 95 % CI 2.23-13.57, p < 0.001). The Cox regression analysis demonstrated significantly different effectiveness of placebo, SB and NAC on NTIS correction and ESRD risk, p < 0.05, respectively. Variance analysis displayed a greater reduction in eGFR in controls than in SB (p = 0.044) and NAC group (p < 0.001). CONCLUSION: SB and NAC are effective in promoting the recovery from NTIS status and delaying the deterioration of renal function in advanced CKD patients.
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Acetilcisteína/uso terapéutico , Síndromes del Eutiroideo Enfermo/tratamiento farmacológico , Riñón/efectos de los fármacos , Insuficiencia Renal Crónica/tratamiento farmacológico , Bicarbonato de Sodio/uso terapéutico , Acetilcisteína/efectos adversos , Distribución de Chi-Cuadrado , China , Progresión de la Enfermedad , Síndromes del Eutiroideo Enfermo/diagnóstico , Síndromes del Eutiroideo Enfermo/etiología , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Estimación de Kaplan-Meier , Riñón/fisiopatología , Fallo Renal Crónico/etiología , Fallo Renal Crónico/fisiopatología , Fallo Renal Crónico/prevención & control , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/fisiopatología , Factores de Riesgo , Método Simple Ciego , Bicarbonato de Sodio/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
ABSTRACT Objective The current study was aimed at analyzing sarcoplasmic reticulum Ca2+ ATPase (Serca2) and ryanodine receptor type 2 (Ryr2) gene expression in rats subjected to surgery that induced HF and were subsequently treated with T4 using physiological doses. Materials and methods HF was induced in 18 male Wistar rats by clipping the ascending thoracic aorta to generate aortic stenosis (HFS group), while the control group (9-sham) underwent thoracotomy. After 21 weeks, the HFS group was subdivided into two subgroups. One group (9 Wistar rats) with HF received 1.0 µg of T4/100 g of body weight for five consecutive days (HFS/T4); the other group (9 Wistar rats) received isotonic saline solution (HFS/S). The animals were sacrificed after this treatment and examined for signs of HF. Samples from the left ventricles of these animals were analyzed by RT-qPCR for the expression of Serca2 and Ryr2 genes. Results Rats with HF developed euthyroid sick syndrome (ESS) and treatment with T4 restored the T3 values to the Sham level and increased Serca2 and Ryr2 gene expression, thereby demonstrating a possible benefit of T4 treatment for heart function in ESS associated with HF. Conclusion The T4 treatment can potentially normalize the levels of T3 as well elevated Serca2 and Ryr2 gene expression in the myocardium in heart failure rats with euthyroid sick syndrome.
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Animales , Masculino , Tiroxina/administración & dosificación , Síndromes del Eutiroideo Enfermo/tratamiento farmacológico , Canal Liberador de Calcio Receptor de Rianodina/efectos de los fármacos , Estenosis de la Válvula Aórtica/complicaciones , Tiroxina/uso terapéutico , Triyodotironina/efectos de los fármacos , Síndromes del Eutiroideo Enfermo/complicaciones , Síndromes del Eutiroideo Enfermo/genética , ARN Mensajero/metabolismo , Expresión Génica/efectos de los fármacos , Ratas Wistar , Canal Liberador de Calcio Receptor de Rianodina/genética , Modelos Animales , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/efectos de los fármacos , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/genética , Insuficiencia Cardíaca/complicacionesRESUMEN
BACKGROUND: Neuromyelitis optica (NMO) sometimes coexists with serological marker-positive, non-organ-specific autoimmune disorders. We evaluated the prevalence of thyroid dysfunction and anti-thyroid antibodies in patients with NMO spectrum disorder (NMOSD) and investigated the associations between thyroid dysfunction/autoimmunity and clinical features of NMOSD. METHODS: Forty-nine NMOSD patients with anti-aquaporin-4 antibody and 392 age- and sex-matched healthy controls were included. We measured the levels of thyroid hormones and anti-thyroid antibodies. RESULTS: The prevalence of clinical hypothyroidism, subclinical hyperthyroidism, and low T3 syndrome were higher in patients with NMOSD (4.1%, 12.2%, and 20.4%, respectively) compared with healthy controls (0.3%, 2.8%, and 0.5%, respectively; p=0.034, p=0.001, and p<0.001, respectively). However, anti-thyroperoxidase antibody (anti-TPO)-positivity did not significantly differ between NMOSD patients (20.4%) and controls (11.5%). Low T3 syndrome was more prevalent among patients during an attack (N=10/19, 52.6%) than those in remission (N=1/30, 3.3%). In addition, patients with low T 3 syndrome had significantly higher EDSS scores at the last visits as well as at sampling compared to those without low T3 syndrome. T3 levels were inversely correlated with EDSS score at the last visit after adjustment for age, sex, disease duration, clinical status (attack vs. remission), oral prednisolone use, iv methylprednisolone use, other immunosuppressive agents use, and the location of lesion (ρ=-0.416, p=0.010). CONCLUSIONS: Our study suggests that thyroid dysfunction is frequent in patients with NMOSD; particularly, serum T3 levels may be a useful indicator of disease activity and disability in NMOSD.
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Síndromes del Eutiroideo Enfermo/complicaciones , Síndromes del Eutiroideo Enfermo/fisiopatología , Neuromielitis Óptica/complicaciones , Neuromielitis Óptica/fisiopatología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Acuaporina 4/inmunología , Autoanticuerpos/sangre , Biomarcadores/sangre , Complejo CD3/sangre , Evaluación de la Discapacidad , Síndromes del Eutiroideo Enfermo/diagnóstico , Síndromes del Eutiroideo Enfermo/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuromielitis Óptica/diagnóstico , Neuromielitis Óptica/tratamiento farmacológico , Prevalencia , Estudios Retrospectivos , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/fisiopatología , Hormonas Tiroideas/sangre , Adulto JovenRESUMEN
OBJECTIVE: The current study was aimed at analyzing sarcoplasmic reticulum Ca2+ ATPase (Serca2) and ryanodine receptor type 2 (Ryr2) gene expression in rats subjected to surgery that induced HF and were subsequently treated with T4 using physiological doses. MATERIALS AND METHODS: HF was induced in 18 male Wistar rats by clipping the ascending thoracic aorta to generate aortic stenosis (HFS group), while the control group (9-sham) underwent thoracotomy. After 21 weeks, the HFS group was subdivided into two subgroups. One group (9 Wistar rats) with HF received 1.0 µg of T4/100 g of body weight for five consecutive days (HFS/T4); the other group (9 Wistar rats) received isotonic saline solution (HFS/S). The animals were sacrificed after this treatment and examined for signs of HF. Samples from the left ventricles of these animals were analyzed by RT-qPCR for the expression of Serca2 and Ryr2 genes. RESULTS: Rats with HF developed euthyroid sick syndrome (ESS) and treatment with T4 restored the T3 values to the Sham level and increased Serca2 and Ryr2 gene expression, thereby demonstrating a possible benefit of T4 treatment for heart function in ESS associated with HF. CONCLUSION: The T4 treatment can potentially normalize the levels of T3 as well elevated Serca2 and Ryr2 gene expression in the myocardium in heart failure rats with euthyroid sick syndrome.
Asunto(s)
Síndromes del Eutiroideo Enfermo/tratamiento farmacológico , Canal Liberador de Calcio Receptor de Rianodina/efectos de los fármacos , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/efectos de los fármacos , Tiroxina/administración & dosificación , Animales , Estenosis de la Válvula Aórtica/complicaciones , Síndromes del Eutiroideo Enfermo/complicaciones , Síndromes del Eutiroideo Enfermo/genética , Expresión Génica/efectos de los fármacos , Insuficiencia Cardíaca/complicaciones , Masculino , Modelos Animales , ARN Mensajero/metabolismo , Ratas Wistar , Canal Liberador de Calcio Receptor de Rianodina/genética , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/genética , Tiroxina/uso terapéutico , Triyodotironina/efectos de los fármacosRESUMEN
In this review, we discuss the characteristics, pathophysiology, and therapeutic implications of the euthyroid sick syndrome. Multiple mechanisms have been identified to contribute to the development of euthyroid sick syndrome, including alterations in the iodothyronine deiodinases, thyroid-stimulating hormone secretion, thyroid hormone binding to plasma protein, transport of thyroid hormone in peripheral tissues, and thyroid hormone receptor activity. The euthyroid sick syndrome appears to be a complex mix of physiologic adaptation and pathologic response to acute illness. The underlying cause for these alterations has not yet been elucidated. Treatment of the euthyroid sick syndrome with thyroid hormone to restore normal serum thyroid hormone levels in an effort to improve disease prognosis and outcomes continues to be a focus of many clinical studies, although currently available data do not provide evidence of a clear benefit of treatment.
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Síndromes del Eutiroideo Enfermo/metabolismo , Animales , Síndromes del Eutiroideo Enfermo/tratamiento farmacológico , Síndromes del Eutiroideo Enfermo/fisiopatología , Humanos , Hormonas Tiroideas/metabolismo , Hormonas Tiroideas/uso terapéutico , Tirotropina/metabolismoRESUMEN
BACKGROUND: The roles of antioxidant therapy on non-thyroidal illness syndrome (NTIS) in uremic rats is still unclear. MATERIALS AND METHODS: Twenty-four Sprague-Dawley (SD) rats were randomly divided into blank, 5/6 nephrectomy (Nx), pyrrolidine dithiocarbamate (PDTC, 10 mg/100 g), sodium bicarbonate (SB, 0.1 g/100 g), N-acetylcysteine (NAC, 80 mg/100 g) and thyroid hormones (TH, levothyroxine 2 µg/100 g) groups. The serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), advanced oxidation protein products (AOPP), interleukin (IL)-1ß, free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) were detected in the sixth week. The expressions of IL-1ß and deiodinase type 1 (DIO1) were assessed by western blotting. The nuclear factor kappa B (NF-κB) inflammatory signal pathway was confirmed by electrophoretic mobility shift assay (EMSA). RESULTS: Compared with 5/6 Nx group, PDTC and NAC significantly reduced the levels (p < 0.01, respectively) of serum MDA, AOPP, TSH, and elevated levels of serum SOD (p < 0.01, respectively) and FT3 (p = 0.016 and p < 0.01). Neither had significant effects on serum IL-1ß content (p = 0.612 and p = 0.582). PDTC and NAC markedly decreased the protein expression of IL-1ß (p < 0.01) and increased the protein expression of DIO1 (p < 0.01), respectively. Both had been considerably blunted NF-κB activity (p < 0.01). CONCLUSIONS: In uremic rat model, PDTC and NAC can effectively improve oxidative stress level and NTIS. In terms of improving oxidative stress level, NAC is probably superior to PDTC.
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Acetilcisteína/uso terapéutico , Antioxidantes/uso terapéutico , Síndromes del Eutiroideo Enfermo/tratamiento farmacológico , Depuradores de Radicales Libres/uso terapéutico , Pirrolidinas/uso terapéutico , Tiocarbamatos/uso terapéutico , Animales , Síndromes del Eutiroideo Enfermo/etiología , Femenino , Masculino , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Uremia/complicacionesRESUMEN
UNLABELLED: Nonthyroidal illness syndrome (NTIS) is marked by low T3 and high reverse T3 levels. The physiopathology is poorly understood but involves oxidative stress-induced disruption of the iodothyronine deiodinases, which activate or inactivate thyroid hormones. Selenium, an essential trace element, exerts antioxidant function mainly through the thioredoxin reductase (TRx) and glutathione peroxidase (GPx) redox-regulating systems. We evaluated the effect of sodium selenite on IL6-induced disruption on deiodinase function. Cell lines expressing endogenous deiodinases type 1(D1), 2(D2) or 3(D3) (HepG2, MSTO, and MCF-7 cells, respectively) were used in an intact cell model that mimics the deiodination process under physiological conditions of substrate and cofactor, in the presence or not of IL6, with or without selenite. Deiodinase activity was quantified by the amount of iodine-125 in the medium (D1 and D2) or by ion-exchange chromatography (D3). Oxidative stress was evaluated by measuring reactive species (RS), carbonyl content as well as enzymatic and non-enzymatic antioxidant defenses. RESULTS: IL6 induced ROS and carbonyl content in all 3 cell lines (all P<0.001). Increased ROS was paralleled by D1 and D2-decreased T3-production (P<0.01) and increased D3-catalyzed T3-inactivation (P<0.001). Selenite decreases the IL6-induced ROS and carbonyl content, while enhances Gpx and Trx activities. Nevertheless, it failed on restoring D1 or D2 function and only attenuates D3 activation (P<0.05). In conclusion, although sodium selenite reduces IL6-induced redox imbalance it does not fully repair deiodinase function. These results shed light on NTIS physiopathology and might explain why low T3 levels are unaffected by selenium supplementation in sick patients.
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Síndromes del Eutiroideo Enfermo/tratamiento farmacológico , Yoduro Peroxidasa/metabolismo , Estrés Oxidativo , Selenito de Sodio/farmacología , Acetilcisteína/farmacología , Antioxidantes/farmacología , Síndromes del Eutiroideo Enfermo/enzimología , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Células HEK293 , Células Hep G2 , Humanos , Interleucina-6/metabolismo , Carbonilación Proteica , Especies Reactivas de Oxígeno/metabolismo , Reductasa de Tiorredoxina-Disulfuro/metabolismoRESUMEN
INTRODUCTION: Traumatic brain injury (TBI) is a common cause of morbidity and mortality in the developed world. In particular, TBI is an important cause of death and disability in young adults with consequences ranging from physical disabilities to long-term cognitive, behavioural, psychological and social defects. AREAS COVERED: There is a large body of evidence that suggest that TBI conditions may adversely affect pituitary function in both the acute and chronic phases of recovery. Prevalence of hypopituitarism, from total to isolated pituitary deficiency, ranges from 5 to 90%. The time interval between TBI and pituitary function evaluation is one of the major factors responsible for variations in the prevalence of hypopituitarism reported. Diagnosis of hypopituitarism and accurate treatment of pituitary disorders offers the opportunity to improve mortality and outcome in TBI conditions. EXPERT OPINION: The aim of this paper is to review the history and pathophysiology of TBI and to summarize the best evidence of TBI as a cause of pituitary deficiency. Moreover, in this article we will describe the multiple changes which occur within the hypothalamic-pituitary-thyroid axis in critical illness, giving rise to 'sick euthyroid syndrome', focus our attention on thyroid hormones circulating levels from the initial insult to critical illness.
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Lesiones Encefálicas/tratamiento farmacológico , Hipopituitarismo/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Animales , Lesiones Encefálicas/complicaciones , Lesiones Encefálicas/fisiopatología , Enfermedad Crítica , Diseño de Fármacos , Síndromes del Eutiroideo Enfermo/tratamiento farmacológico , Síndromes del Eutiroideo Enfermo/etiología , Humanos , Hipopituitarismo/epidemiología , Hipopituitarismo/etiología , Sistema Hipotálamo-Hipofisario/metabolismo , Inflamación/etiología , Sistema Hipófiso-Suprarrenal/metabolismo , Prevalencia , Adulto JovenRESUMEN
OBJECTIVE: To assess the efficacy of thyroid hormone replacement therapy for nephrotic syndrome (NS) patients associated with euthyroid sick syndrome (ESS). MATERIALS AND METHODS: The Cochrane library, ISI, Ovid, PubMed, Chinese Biomedicine Database were searched, and reference list of relevant articles were selected. Randomized controlled trials (RCTs) or quasi-RCTs with thyroid hormone replacement on NS patients associated with ESS were included in this analysis. RESULTS: Six trials (329 participants) were included. Meta-analysis showed that thyroid hormone replacement therapy can significantly increase the completely remission rate [OR = 3.04, 95% confidence interval (CI): 3.04-1.88, p < 0.00001] and total response rate (OR = 4.63, 95% CI: 2.46-8.71, p < 0.00001) of NS patients associated with ESS. No side effect was observed during the follow-up period. There was no obvious publication bias in the mete-analysis studies. CONCLUSIONS: Thyroid hormone replacement therapy significantly increases the remission of ESS in patients with NS.
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Síndromes del Eutiroideo Enfermo/tratamiento farmacológico , Terapia de Reemplazo de Hormonas/métodos , Síndrome Nefrótico/tratamiento farmacológico , Hormonas Tiroideas/uso terapéutico , Síndromes del Eutiroideo Enfermo/complicaciones , Humanos , Síndrome Nefrótico/complicaciones , Resultado del TratamientoRESUMEN
Acute critically ill patients experience a rapid decline in plasma free thyroid hormone levels (free triiodothyronine (FT3) and free levothyroxine (FT4)), with a marked elevation of reverse T3, recognized as the euthyroid sick syndrome (ESS) or low-T3 syndrome. The ESS is also often associated with depressed myocardial function, sometimes referred to as the 'stunned myocardium'. Its clinical effects may vary from minimal hemodynamic impairment to cardiogenic shock. Medical management may range from aspirin alone to placement of a left ventricular assist device. With adequate supportive therapy, recovery usually occurs within days or weeks. The effect of T3/T4 therapy has been studied in three conditions in which the ESS and myocardial functional depression have been documented - i) transient regional myocardial ischemia and reperfusion, ii) transient global myocardial ischemia in patients undergoing cardiac surgery on cardiopulmonary bypass, and iii) transient inadequate global myocardial perfusion in brain-dead potential organ donors. Under all three conditions, myocardial ischemia leads to rapid loss of high-energy phosphates, accumulation of myocardial tissue lactate, and probably loss of homeostasis of cytosolic calcium, which may further increase cell injury. There is an inability to generate ATP through the Krebs cycle, which reduces the high-energy phosphate pool essential for all cell ATPases. Under all three conditions, following administration of T3/T4, the myocardial dysfunction was rapidly reversed. We, therefore, cautiously advocate the use of thyroid hormonal therapy to any patient with the ESS and/or a stunned myocardium.
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Síndromes del Eutiroideo Enfermo/tratamiento farmacológico , Aturdimiento Miocárdico/tratamiento farmacológico , Hormonas Tiroideas/uso terapéutico , Animales , Síndromes del Eutiroideo Enfermo/sangre , Síndromes del Eutiroideo Enfermo/fisiopatología , Hemodinámica/efectos de los fármacos , Terapia de Reemplazo de Hormonas , Humanos , Aturdimiento Miocárdico/sangre , Aturdimiento Miocárdico/fisiopatología , Hormonas Tiroideas/sangre , Tiroxina/sangre , Tiroxina/uso terapéutico , Resultado del Tratamiento , Triyodotironina/sangre , Triyodotironina/uso terapéuticoRESUMEN
UNLABELLED: The clinical significance of subclinical hypothyroidism (SH) has not been determined. There are different opinions with regard to symptoms and clinical consequences of SH as well as effectiveness of treatment. Aim of study was the analysis of incidence of hypothyroidism symptoms and selected cardiovascular risk factors in patients with SH in comparison to euthyroid individuals and the evaluation of the effect of treatment of SH on the above parameters. MATERIALS AND METHODS: Fifty patients were included in the study: 25 with SH, 25 in euthyreosis (C). The incidence of hypothyroidism symptoms and metabolic syndrome (MS), as well as total cholesterol (TCH), LDL, HDL triglycerides (TGL), glucose levels, values of systolic (SBP) and diastolic (DBP) blood pressure and the relationship between these factors and laboratory indexes of SH intensity were analyzed. Moreover, the risk of cardiovascular mortality (RCM) with the application of the HeartSCORE Risk Chart was evaluated. After a period of six months a similar analysis in the SH group was conducted; all the patients were administered L-thyroxin (mean dose +/- SD: 67.5 +/- 32.1 microg). RESULTS: The mean number of hypothyroidism symptoms was higher in SH than in C group (SH: 8.4 +/- 3.2 vs. C: 1.7 +/- 1.5, p < 0.0005). Normalization of TSH observed in 17 patients resulted in a decrease in the mean number of symptoms (9.1 +/- 2.8 vs. 5.9 +/- 2.9, p < 0.0001). There were not differences between groups in the incidence of the MS and MS components and also the RCM. However only in SH group a positive correlations between TSH and BMI, TSH and age, age and TCH and LDL levels and SBP DBP values and also between TSH and the RCM were noted. Normalization of TSH level resulted in a decrease in the RCM (p = 0.055). CONCLUSIONS: Treatment of SH might bring potential benefits; it might lessen symptoms and reduce the risk of cardiovascular mortality.
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Enfermedades Cardiovasculares/mortalidad , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/epidemiología , Tiroxina/uso terapéutico , Adulto , Glucemia/metabolismo , Determinación de la Presión Sanguínea , Índice de Masa Corporal , Enfermedades Cardiovasculares/prevención & control , Colesterol/sangre , Comorbilidad , Síndromes del Eutiroideo Enfermo/tratamiento farmacológico , Síndromes del Eutiroideo Enfermo/epidemiología , Femenino , Humanos , Hipotiroidismo/metabolismo , Incidencia , Síndrome Metabólico/epidemiología , Persona de Mediana Edad , Factores de Riesgo , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Nonthyroidal illness syndrome (NTIS) is widely found in the patients with chronic kidney disease (CKD) or critical illness. However, the exact pathogenesis and reasonable treatment remain unclear. To identify suitable studies for inclusion in present review, a search for articles using PubMed search engine with combined terms: (thyroid OR hypothyroidism OR hyperthyroidism OR triiodothyronine) AND (glomerulonephritis OR chronic kidney disease OR chronic renal failure OR end stage renal disease OR hemodialysis OR peritoneal dialysis OR kidney transplantation OR renal transplantation) was performed. The bibliographies of relevant articles were also hand searched. The search was updated on November 8, 2013. Mechanisms for the alternations of thyroid hormone concentrations in NTIS are complicated. Inflammatory cytokines and oxidative stress may play pivotal roles in the pathogenesis of NTIS in patients with CKD. It was controversial whether CKD patients with NTIS should be treated with thyroid hormone replacement. N-Acetyl cysteine or sodium bicarbonate may negatively regulate the progress of micro-inflammation in CKD. Large-scale, multi-centered randomized controlled trials should be conducted to verify the NTIS hypothesis in CKD patients.
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Citocinas/fisiología , Síndromes del Eutiroideo Enfermo/fisiopatología , Estrés Oxidativo/fisiología , Insuficiencia Renal Crónica/fisiopatología , Hormonas Tiroideas/fisiología , Acetilcisteína/uso terapéutico , Comorbilidad , Progresión de la Enfermedad , Síndromes del Eutiroideo Enfermo/tratamiento farmacológico , Síndromes del Eutiroideo Enfermo/epidemiología , Terapia de Reemplazo de Hormonas , Humanos , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/epidemiología , Bicarbonato de Sodio/uso terapéuticoRESUMEN
PURPOSE OF REVIEW: The current state of the pathophysiology, diagnosis, and therapeutic implications of the nonthyroidal illness syndrome is reviewed. RECENT FINDINGS: Previous studies attributed the development of the nonthyroidal illness syndrome to alterations in three main areas of thyroid hormone metabolism: deiodinase activity, thyroid-stimulating hormone secretion, and hormone binding to serum proteins. New studies suggest that alterations in thyroid hormone transport into tissues and alterations of the nuclear thyroid hormone receptors may also play a role. Therapy of the nonthyroidal illness syndrome remains a controversial topic. SUMMARY: Multiple factors lead to the development of the nonthyroidal illness syndrome, including alterations in type 1 and 3 deiodinase activity, thyrotropin-releasing hormone and thyroid-stimulating hormone secretion, hormone binding to plasma proteins, thyroid hormone transporter expression and activity, and the thyroid hormone nuclear receptor complex. These data show that acute and chronic illness affect all aspects of thyroid hormone metabolism and action. Some of these changes are physiologic and some are pharmacologic. The mediators of these alterations are still largely unclear. There continues to be no indication for thyroid hormone therapy in the vast majority of patients with the nonthyroidal illness syndrome, although interesting data suggest a possible role for treating a small subset of patients.