RESUMEN
OBJECTIVE: Thyrotoxicosis is established risk factor for osteoporosis due to increased bone turnover. Glucocorticoids often administered for Graves' orbitopathy (GO) have additional negative effect on bone mineral density (BMD). Our aim was to examine the influence of thyroid hormones, TSH, TSH-receptor antibodies (TRAb) and glucocorticoid treatment on bone in women with Graves' thyrotoxicosis and Graves' orbitopathy (GO). SUBJECTS AND METHODS: Forty seven women with Graves' disease, mean age 55.6 ± 12.8 (23 women with thyrotoxicosis and 24 hyperthyroid with concomitant GO and glucocorticoid therapy) and 40 age-matched healthy female controls were enrolled in the study. We analyzed clinical features, TSH, FT4, FT3, TRAb, TPO antibodies. BMD of lumbar spine and hip was measured by DEXA and 10-year fracture risk was calculated with FRAX tool. RESULTS: The study showed significantly lower spine and femoral BMD (g/cm2) in patients with and without GO compared to controls, as well as significantly higher fracture risk. Comparison between hyperthyroid patients without and with orbitopathy found out significantly lower spine BMD in the first group (p = 0.0049). Negative correlations between FT3 and femoral neck BMD (p = 0.0001), between FT4 and BMD (p = 0.049) and positive between TSH and BMD (p = 0.0001), TRAb and BMD (p = 0.026) were observed. Fracture risk for major fractures and TRAb were negatively associated (p = 0.05). We found negative correlation of BMD to duration of thyrotoxicosis and cumulative steroid dose. CONCLUSIONS: Our results confirm the negative effect of hyperthyroid status on BMD. TRAb, often in high titers in patients with GO, may have protective role for the bone, but further research is needed.
Asunto(s)
Glucocorticoides/efectos adversos , Enfermedad de Graves/complicaciones , Oftalmopatía de Graves/complicaciones , Inmunoglobulinas Estimulantes de la Tiroides/fisiología , Osteoporosis Posmenopáusica/fisiopatología , Hormonas Tiroideas/fisiología , Tirotropina/fisiología , Absorciometría de Fotón , Adulto , Anciano , Densidad Ósea/efectos de los fármacos , Densidad Ósea/fisiología , Estudios de Casos y Controles , Femenino , Fracturas Óseas/etiología , Fracturas Óseas/fisiopatología , Enfermedad de Graves/tratamiento farmacológico , Enfermedad de Graves/fisiopatología , Oftalmopatía de Graves/tratamiento farmacológico , Oftalmopatía de Graves/fisiopatología , Humanos , Persona de Mediana Edad , Osteoporosis Posmenopáusica/etiología , Osteoporosis Posmenopáusica/metabolismo , Valores de Referencia , Medición de Riesgo , Factores de Riesgo , Tirotoxicosis/complicaciones , Tirotoxicosis/tratamiento farmacológico , Tirotoxicosis/fisiopatologíaRESUMEN
ABSTRACT Objective Thyrotoxicosis is established risk factor for osteoporosis due to increased bone turnover. Glucocorticoids often administered for Graves' orbitopathy (GO) have additional negative effect on bone mineral density (BMD). Our aim was to examine the influence of thyroid hormones, TSH, TSH-receptor antibodies (TRAb) and glucocorticoid treatment on bone in women with Graves' thyrotoxicosis and Graves' orbitopathy (GO). Subjects and methods Forty seven women with Graves' disease, mean age 55.6 ± 12.8 (23 women with thyrotoxicosis and 24 hyperthyroid with concomitant GO and glucocorticoid therapy) and 40 age-matched healthy female controls were enrolled in the study. We analyzed clinical features, TSH, FT4, FT3, TRAb, TPO antibodies. BMD of lumbar spine and hip was measured by DEXA and 10-year fracture risk was calculated with FRAX tool. Results The study showed significantly lower spine and femoral BMD (g/cm2) in patients with and without GO compared to controls, as well as significantly higher fracture risk. Comparison between hyperthyroid patients without and with orbitopathy found out significantly lower spine BMD in the first group (p = 0.0049). Negative correlations between FT3 and femoral neck BMD (p = 0.0001), between FT4 and BMD (p = 0.049) and positive between TSH and BMD (p = 0.0001), TRAb and BMD (p = 0.026) were observed. Fracture risk for major fractures and TRAb were negatively associated (p = 0.05). We found negative correlation of BMD to duration of thyrotoxicosis and cumulative steroid dose. Conclusions Our results confirm the negative effect of hyperthyroid status on BMD. TRAb, often in high titers in patients with GO, may have protective role for the bone, but further research is needed.
Asunto(s)
Humanos , Femenino , Adulto , Persona de Mediana Edad , Anciano , Hormonas Tiroideas/fisiología , Osteoporosis Posmenopáusica/fisiopatología , Enfermedad de Graves/complicaciones , Inmunoglobulinas Estimulantes de la Tiroides/fisiología , Oftalmopatía de Graves/complicaciones , Glucocorticoides/efectos adversos , Valores de Referencia , Tirotropina/fisiología , Absorciometría de Fotón , Densidad Ósea/efectos de los fármacos , Densidad Ósea/fisiología , Estudios de Casos y Controles , Enfermedad de Graves/fisiopatología , Enfermedad de Graves/tratamiento farmacológico , Fracturas Óseas/etiología , Fracturas Óseas/fisiopatologíaRESUMEN
BACKGROUND AND AIMS: The role of subtle thyroid alterations, such as subclinical thyroid disease and low/high serum thyrotropin (TSH) within the normal range, on cognitive decline is controversial. The aim of this study was to evaluate the association of serum TSH and subclinical thyroid dysfunction with performance on cognitive tests in a large sample of Brazilian middle-aged adults without overt thyroid disease. METHODS: In this cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health, we excluded individuals aged 65 years and older, with overt thyroid dysfunction, prevalent stroke, in use of medications that affect thyroid function or that indicate neurologic diseases, and from Asian or indigenous ethnicity. Thyroid status was assessed by serum TSH and free thyroxine (only when the TSH was altered). Individuals were divided according to TSH tertiles and classified according to thyroid function as euthyroidism, subclinical hypothyroidism, or subclinical hyperthyroidism. Cognition was evaluated using delayed word recall test, semantic verbal fluency test, and trail making test version B. The associations of cognitive tests performance with TSH tertiles (using the middle tertile as reference) and thyroid function were investigated using linear regression models, adjusted for an extensive set of possible confounders (sociodemographic characteristics, cardiovascular risk factors, and depression). RESULTS: The mean age of the 10,362 participants was 49.5±7.4years, 52.3% women. After adjustment for confounders, the first TSH tertile was associate with worse performance on the trail making test (ß=-0.05, 95% CI=-0.09; -0.01, p=0.017). When restricting the analysis to the 9769 individuals with TSH within the normal range, the association between TSH and performance on the trail making test remained significant (ß=-0.05, 95% CI=-0.09; -0.01, p=0.020) on multiple linear regression. Subclinical thyroid disease was not associated with performance on cognitive tests. CONCLUSION: Low TSH is associated with poorer performance on an executive function test in middle-aged adults without overt thyroid dysfunction.
Asunto(s)
Función Ejecutiva/fisiología , Tirotropina/análisis , Tirotropina/fisiología , Adulto , Brasil , Cognición/fisiología , Estudios Transversales , Femenino , Humanos , Hipertiroidismo , Hipotiroidismo , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Pruebas de Función de la Tiroides , Glándula Tiroides/fisiopatología , Tirotropina/sangre , Tiroxina/sangreRESUMEN
The hypothalamus-pituitary-thyroid (HPT) axis determines the set point of thyroid hormone (TH) production. Hypothalamic thyrotropin-releasing hormone (TRH) stimulates the synthesis and secretion of pituitary thyrotropin (thyroid-stimulating hormone, TSH), which acts at the thyroid to stimulate all steps of TH biosynthesis and secretion. The THs thyroxine (T4) and triiodothyronine (T3) control the secretion of TRH and TSH by negative feedback to maintain physiological levels of the main hormones of the HPT axis. Reduction of circulating TH levels due to primary thyroid failure results in increased TRH and TSH production, whereas the opposite occurs when circulating THs are in excess. Other neural, humoral, and local factors modulate the HPT axis and, in specific situations, determine alterations in the physiological function of the axis. The roles of THs are vital to nervous system development, linear growth, energetic metabolism, and thermogenesis. THs also regulate the hepatic metabolism of nutrients, fluid balance and the cardiovascular system. In cells, TH actions are mediated mainly by nuclear TH receptors (210), which modify gene expression. T3 is the preferred ligand of THR, whereas T4, the serum concentration of which is 100-fold higher than that of T3, undergoes extra-thyroidal conversion to T3. This conversion is catalyzed by 5'-deiodinases (D1 and D2), which are TH-activating enzymes. T4 can also be inactivated by conversion to reverse T3, which has very low affinity for THR, by 5-deiodinase (D3). The regulation of deiodinases, particularly D2, and TH transporters at the cell membrane control T3 availability, which is fundamental for TH action. © 2016 American Physiological Society. Compr Physiol 6:1387-1428, 2016.
Asunto(s)
Sistema Hipotálamo-Hipofisario/fisiología , Glándula Tiroides/fisiología , Humanos , Sistema Hipotálamo-Hipofisario/metabolismo , Yoduro Peroxidasa/metabolismo , Receptores de Hormona Tiroidea/metabolismo , Hormonas Tiroideas/fisiología , Tirotropina/fisiología , Hormona Liberadora de Tirotropina/fisiologíaRESUMEN
BACKGROUND: Glucose is transported into cells by specific glucose transporter proteins (GLUTs) that are widely expressed in a tissue-specific manner. The mechanisms that regulate glucose uptake and metabolism in thyroid cells are poorly defined. Recently, our group showed that AMP-activated protein kinase (AMPK) plays a pivotal role in the rat thyroid gland, downregulating iodide uptake by thyroid cells even in the presence of its main stimulator thyrotropin (TSH). Since AMPK increases glucose uptake in different tissues, and taken into consideration that in pathophysiological conditions such as thyroid cancer a negative correlation between iodide and glucose uptake occurs, we hypothesized that AMPK might modulate glucose uptake in thyroid cells. METHODS: Rat follicular thyroid PCCL3 cells cultivated in Ham's F-12 supplemented with 5% calf serum and hormones were exposed to the AMPK pharmacological activator 5-aminoimidazole-4 carboxamide ribonucleoside (AICAR) or AMPK antagonist compound C for 24 hours either in the presence or absence of TSH. Glucose uptake was assessed in vitro using 2-deoxy-D-[(3)H]glucose. RESULTS: AMPK activation by AICAR induced a significant increase in glucose uptake by PCCL3 cells, an effect that was completely reversed by the AMPK inhibitor compound C. Also, the AICAR mediated increase in glucose uptake was detected either in the presence or absence of TSH. The mechanism by which AICAR increases glucose uptake is related to higher levels of GLUT 1 protein content and hexokinase (HK) activity in thyroid cells. CONCLUSION: Our results show that AMPK activation significantly upregulates GLUT 1 content and glucose uptake, and it also stimulates hexokinase activity, the first step of glycolysis.
Asunto(s)
Proteínas Quinasas Activadas por AMP/fisiología , Glucosa/metabolismo , Glándula Tiroides/metabolismo , Tirotropina/fisiología , Proteínas Quinasas Activadas por AMP/antagonistas & inhibidores , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacología , Animales , Células Cultivadas , Transportador de Glucosa de Tipo 1/biosíntesis , Pirazoles/farmacología , Pirimidinas/farmacología , Ratas , Ribonucleótidos/farmacología , Glándula Tiroides/efectos de los fármacos , Regulación hacia ArribaRESUMEN
OBJECTIVE: The aim of this study was to evaluate the accuracy of the measurement of thyroglobulin in washout needle aspiration biopsy (FNAB-Tg) to detect papillary thyroid cancer (PTC) metastases. SUBJECTS AND METHODS: Forty-three patients (51.4 ± 14.6 years) with PTC diagnosis and evidence of enlarged cervical lymph nodes (LN) were included. An ultrasound-guided fine-needle aspiration of suspicious LN was performed, for both cytological examination and measurement of FNAB-Tg. RESULTS: The median values of FNAB-Tg in patients with metastatic LN (n = 5) was 3,419 ng/mL (11.1-25,538), while patients without LN metastasis (n = 38) showed levels of 3.7 ng/mL (0.8-7.4). Considering a 10 ng/mL cutoff value for FNAB-Tg, the sensitivity and specificity was 100%. There were no differences on the median of FNAB-Tg measurements between those on (TSH 0.07 mUI/mL) or off levothyroxine (TSH 97.4 mUI/mL) therapy (3.3 vs. 3.8 ng/mL, respectively; P = 0.2). CONCLUSION: The results show that evaluation of FNAB-Tg in cervical LN is a valuable diagnostic tool for PTC metastases that can be used independent of the thyroid status.
Asunto(s)
Biomarcadores de Tumor/análisis , Biopsia con Aguja Fina/métodos , Carcinoma Papilar/diagnóstico , Ganglios Linfáticos/química , Tiroglobulina/análisis , Neoplasias de la Tiroides/diagnóstico , Adulto , Anciano , Carcinoma , Carcinoma Papilar/secundario , Femenino , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática/diagnóstico , Masculino , Persona de Mediana Edad , Cuello , Sensibilidad y Especificidad , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/secundario , Tirotropina/fisiologíaRESUMEN
OBJECTIVE: The aim of this study was to evaluate the accuracy of the measurement of thyroglobulin in washout needle aspiration biopsy (FNAB-Tg) to detect papillary thyroid cancer (PTC) metastases. SUBJECTS AND METHODS: Forty-three patients (51.4 ± 14.6 years) with PTC diagnosis and evidence of enlarged cervical lymph nodes (LN) were included. An ultrasound-guided fine-needle aspiration of suspicious LN was performed, for both cytological examination and measurement of FNAB-Tg. RESULTS: The median values of FNAB-Tg in patients with metastatic LN (n = 5) was 3,419 ng/mL (11.1-25,538), while patients without LN metastasis (n = 38) showed levels of 3.7 ng/mL (0.8-7.4). Considering a 10 ng/mL cutoff value for FNAB-Tg, the sensitivity and specificity was 100 percent. There were no differences on the median of FNAB-Tg measurements between those on (TSH 0.07 mUI/mL) or off levothyroxine (TSH 97.4 mUI/mL) therapy (3.3 vs. 3.8 ng/mL, respectively; P = 0.2). CONCLUSION: The results show that evaluation of FNAB-Tg in cervical LN is a valuable diagnostic tool for PTC metastases that can be used independent of the thyroid status.
OBJETIVO: O objetivo deste estudo foi avaliar a acurácia da dosagem de tireoglobulina no lavado da agulha da punção aspirativa (PAAF-Tg) de linfonodos (LN) cervicais para detecção de metástases do câncer papilar de tireoide (CPT). SUJEITOS E MÉTODOS: Foram incluídos 43 pacientes (51,4 ± 14,6 anos) com diagnóstico de CPT e evidência de LN cervicais aumentados. Os LN suspeitos foram submetidos à punção aspiração com agulha fina guiada por ecografia para análise citológica e dosagem de tireoglobulina (PAAF-Tg). RESULTADOS: A mediana dos valores de PAAF-Tg nos LN metastáticos (n = 5) foi 3.419,0 ng/mL (11,1-25.538), enquanto nos LN não metastáticos (n= 38) a mediana foi de 3,7 ng/mL (0,8-7,4). Utilizando-se o nível de 10 ng/mL como ponto de corte, observaram-se sensibilidade e especificidade de 100 por cento. Os níveis de TSH sérico não interferiram na dosagem de PAAF-Tg (3,3 e 3,8 ng/mL nos grupos com TSH supresso (TSH 0,07 mUI/mL) e hipotireoidismo (TSH 97,4 mUI/mL), respectivamente, P = 0,2). CONCLUSÃO: Os resultados demonstram que a dosagem de PAAF-Tg é uma ferramenta importante no diagnóstico de metástases do CPT, podendo ser utilizada independente do "status" tireoidiano.
Asunto(s)
Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biopsia con Aguja Fina/métodos , Carcinoma Papilar/diagnóstico , Ganglios Linfáticos/química , Tiroglobulina/análisis , Neoplasias de la Tiroides/diagnóstico , Biomarcadores de Tumor/análisis , Carcinoma Papilar/secundario , Ganglios Linfáticos/patología , Metástasis Linfática/diagnóstico , Cuello , Sensibilidad y Especificidad , Neoplasias de la Tiroides/secundario , Tirotropina/fisiologíaRESUMEN
Data collected from medical literature indicate that dopaminergic agonists alleviate Restless Legs Syndrome symptoms while dopaminergic agonists antagonists aggravate them. Dopaminergic agonists is a physiological regulator of thyroid-stimulating hormone. Dopaminergic agonists infusion diminishes the levels of thyroid hormones, which have the ability to provoke restlessness, hyperkinetic states, tremors, and insomnia. Conditions associated with higher levels of thyroid hormones, such as pregnancy or hyperthyroidism, have a higher prevalence of Restless Legs Syndrome symptoms. Low iron levels can cause secondary Restless Legs Syndrome or aggravate symptoms of primary disease as well as diminish enzymatic activities that are involved in dopaminergic agonists production and the degradation of thyroid hormones. Moreover, as a result of low iron levels, dopaminergic agonists diminishes and thyroid hormones increase. Iron therapy improves Restless Legs Syndrome symptoms in iron deprived patients. Medical hypothesis. To discuss the theory that thyroid hormones, when not counterbalanced by dopaminergic agonists, may precipitate the signs and symptoms underpinning Restless Legs Syndrome. The main cause of Restless Legs Syndrome might be an imbalance between the dopaminergic agonists system and thyroid hormones.
Asunto(s)
Agonistas de Dopamina/metabolismo , Síndrome de las Piernas Inquietas/fisiopatología , Hormonas Tiroideas/fisiología , Nivel de Alerta/fisiología , Ritmo Circadiano , Sistema Enzimático del Citocromo P-450 , Femenino , Humanos , Hipertiroidismo/metabolismo , Hipertiroidismo/fisiopatología , Hierro/metabolismo , Embarazo , Complicaciones del Embarazo/fisiopatología , Síndrome de las Piernas Inquietas/tratamiento farmacológico , Síndrome de las Piernas Inquietas/etiología , Trastornos del Sueño-Vigilia/metabolismo , Trastornos del Sueño-Vigilia/fisiopatología , Tirotropina/fisiología , Tirosina 3-Monooxigenasa/fisiologíaRESUMEN
Data collected from medical literature indicate that dopaminergic agonists alleviate Restless Legs Syndrome symptoms while dopaminergic agonists antagonists aggravate them. Dopaminergic agonists is a physiological regulator of thyroid-stimulating hormone. Dopaminergic agonists infusion diminishes the levels of thyroid hormones, which have the ability to provoke restlessness, hyperkinetic states, tremors, and insomnia. Conditions associated with higher levels of thyroid hormones, such as pregnancy or hyperthyroidism, have a higher prevalence of Restless Legs Syndrome symptoms. Low iron levels can cause secondary Restless Legs Syndrome or aggravate symptoms of primary disease as well as diminish enzymatic activities that are involved in dopaminergic agonists production and the degradation of thyroid hormones. Moreover, as a result of low iron levels, dopaminergic agonists diminishes and thyroid hormones increase. Iron therapy improves Restless Legs Syndrome symptoms in iron deprived patients. Medical hypothesis. To discuss the theory that thyroid hormones, when not counterbalanced by dopaminergic agonists, may precipitate the signs and symptoms underpinning Restless Legs Syndrome. The main cause of Restless Legs Syndrome might be an imbalance between the dopaminergic agonists system and thyroid hormones.
Asunto(s)
Femenino , Humanos , Embarazo , Agonistas de Dopamina/metabolismo , Síndrome de las Piernas Inquietas/fisiopatología , Hormonas Tiroideas/fisiología , Nivel de Alerta/fisiología , Ritmo Circadiano , Hipertiroidismo/metabolismo , Hipertiroidismo/fisiopatología , Hierro/metabolismo , Complicaciones del Embarazo/fisiopatología , Síndrome de las Piernas Inquietas/tratamiento farmacológico , Síndrome de las Piernas Inquietas/etiología , Trastornos del Sueño-Vigilia/metabolismo , Trastornos del Sueño-Vigilia/fisiopatología , Tirotropina/fisiología , /fisiologíaRESUMEN
RNA splicing is an essential, precisely regulated process that occurs after gene transcription and before mRNA translation, in which introns may be removed and exons, retained. Variability in splicing patterns is a major source of protein diversity from the genome and function to generate a tremendously diverse proteome from a relatively small number of genes. Changes in splice site choice can determine different effects on the encoded protein. Small changes in peptide sequence can alter ligand binding, enzymatic activity, allosteric regulation, or protein localization. Errors in splicing regulation have been implicated in a number of different disease states. This study reviewed the mechanisms of splicing and their repercussion in endocrinology, emphasizing its importance in some thyroid physiological and pathological conditions.
Asunto(s)
Empalme del ARN/genética , Glándula Tiroides , Hormonas Tiroideas/genética , Neoplasias de la Tiroides/genética , Empalme Alternativo/genética , Humanos , Receptores de Hormona Tiroidea/fisiología , Glándula Tiroides/fisiología , Hormonas Tiroideas/metabolismo , Neoplasias de la Tiroides/metabolismo , Tirotropina/fisiologíaRESUMEN
RNA splicing is an essential, precisely regulated process that occurs after gene transcription and before mRNA translation, in which introns may be removed and exons, retained. Variability in splicing patterns is a major source of protein diversity from the genome and function to generate a tremendously diverse proteome from a relatively small number of genes. Changes in splice site choice can determine different effects on the encoded protein. Small changes in peptide sequence can alter ligand binding, enzymatic activity, allosteric regulation, or protein localization. Errors in splicing regulation have been implicated in a number of different disease states. This study reviewed the mechanisms of splicing and their repercussion in endocrinology, emphasizing its importance in some thyroid physiological and pathological conditions.
Após a transcrição genética e antes da tradução do mRNA, ocorre o splicing do RNA, que consiste em um processo essencial, precisamente regulado, por meio do qual podem ocorrer excisões de íntrons e retenções de éxons. A variabilidade dos padrões de splicing é a principal fonte de diversidade de proteínas geradas por um pequeno número de genes. Alterações na escolha do sítio de splicing podem determinar efeitos diferentes nas proteínas codificadas. Pequenas alterações na sequência peptídica podem alterar o seu sítio de ligação de substratos, sua atividade enzimática, a regulação alostérica ou a localização proteica. Erros na regulação do splicing têm sido implicados em grande número de doenças. Nessa revisão, foram descritos os mecanismos de splicing enfatizando sua importância em algumas condições fisiológicas e patológicas envolvendo a tireoide.
Asunto(s)
Humanos , Empalme del ARN/genética , Glándula Tiroides , Hormonas Tiroideas/genética , Neoplasias de la Tiroides/genética , Empalme Alternativo/genética , Receptores de Hormona Tiroidea/fisiología , Glándula Tiroides/fisiología , Hormonas Tiroideas/metabolismo , Neoplasias de la Tiroides/metabolismo , Tirotropina/fisiologíaRESUMEN
A utilização de esteróides anabolizantes por indivíduos que desejam aumentar sua performance física, ou simplesmente para fins estéticos, tem atingido índices alarmantes nas últimas três décadas. Além dos efeitos desejados, uma infinidade de efeitos colaterais já foi bem descrita na literatura, como vários tipos de câncer, ginecomastia, peliosis hepatis, insuficiência renal, virilização, dentre outros. Sobre a função tireóidea, o efeito mais pronunciado em seres humanos é a diminuição da TBG, com conseqüente diminuição sérica de T3 e T4 totais, dependendo, porém, da susceptibilidade da molécula à aromatização e conseqüente transformação em estrógeno. Em ratos, o tratamento com esteróides anabolizantes altera a metabolização periférica dos hormônios tireóideos e também parece causar importante efeito proliferativo sobre as células tireóideas. Assim, o presente artigo visa rever os dados publicados acerca dos efeitos de doses suprafisiológicas de esteróides anabolizantes sobre a função tireóidea, reforçando o perigo que a utilização indiscriminada dessas drogas pode causar à saúde.
The use of anabolic steroids to increase physical performance and for aesthetic ends has reached alarming indices in the last three decades. Besides the desired actions, several collateral effects have been described in the literature, such as the development of some types of cancer, ginecomasty, peliosis hepatis, renal insufficiency, virilization, amongst others. The most proeminent effect on human thyroid function is the reduction of thyroxine binding globulin (TBG), with consequent reductions of total serum T3 and T4, depending however on the susceptibility of the drug to aromatization and subsequent transformation into estrogen. In rats, anabolic steroids also act in the peripheral metabolism of thyroid hormones and seem to exert an important proliferative effect on thyroid cells. Thus, the aim of the present paper is to review data on the effect of supraphysiological doses of anabolic steroids on thyroid function, showing the danger that indiscriminate use of these drugs can cause to health.
Asunto(s)
Animales , Humanos , Ratas , Anabolizantes/efectos adversos , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/fisiología , Tirotropina/fisiología , Anabolizantes/administración & dosificación , Doping en los Deportes , Relación Dosis-Respuesta a Droga , Yoduro Peroxidasa/sangre , Pruebas de Función de la Tiroides , Hormonas Tiroideas/fisiologíaRESUMEN
The thyroid gland has the ability to uptake and concentrate iodide, which is a fundamental step in thyroid hormone biosynthesis. Radioiodine has been used as a diagnostic and therapeutic tool for several years. However, the studies related to the mechanisms of iodide transport were only possible after the cloning of the gene that encodes the sodium/iodide symporter (NIS). The studies about the regulation of NIS expression and the possibility of gene therapy with the aim of transferring NIS gene to cells that normally do not express the symporter have also become possible. In the majority of hypofunctioning thyroid nodules, both benign and malignant, NIS gene expression is maintained, but NIS protein is retained in the intracellular compartment. The expression of NIS in non-thyroid tumoral cells in vivo has been possible through the transfer of NIS gene under the control of tissue-specific promoters. Apart from its therapeutic use, NIS has also been used for the localization of metastases by scintigraphy or PET-scan with 124I. In conclusion, NIS gene cloning led to an important development in the field of thyroid pathophysiology, and has also been fundamental to extend the use of radioiodine for the management of non-thyroid tumors.
Asunto(s)
Adenocarcinoma Folicular/metabolismo , Carcinoma Papilar/metabolismo , Yodo/metabolismo , Simportadores/metabolismo , Neoplasias de la Tiroides/metabolismo , Adenocarcinoma Folicular/terapia , Transporte Biológico , Carcinoma Papilar/terapia , Clonación Molecular , Regulación hacia Abajo , Expresión Génica , Técnicas de Transferencia de Gen , Terapia Genética , Humanos , Yoduros/metabolismo , Radioisótopos de Yodo/uso terapéutico , Simportadores/genética , Neoplasias de la Tiroides/terapia , Tirotropina/fisiologíaRESUMEN
The thyroid gland has the ability to uptake and concentrate iodide, which is a fundamental step in thyroid hormone biosynthesis. Radioiodine has been used as a diagnostic and therapeutic tool for several years. However, the studies related to the mechanisms of iodide transport were only possible after the cloning of the gene that encodes the sodium/iodide symporter (NIS). The studies about the regulation of NIS expression and the possibility of gene therapy with the aim of transferring NIS gene to cells that normally do not express the symporter have also become possible. In the majority of hypofunctioning thyroid nodules, both benign and malignant, NIS gene expression is maintained, but NIS protein is retained in the intracellular compartment. The expression of NIS in non-thyroid tumoral cells in vivo has been possible through the transfer of NIS gene under the control of tissue-specific promoters. Apart from its therapeutic use, NIS has also been used for the localization of metastases by scintigraphy or PET-scan with 124I. In conclusion, NIS gene cloning led to an important development in the field of thyroid pathophysiology, and has also been fundamental to extend the use of radioiodine for the management of non-thyroid tumors.
A glândula tireóide tem capacidade de captar e concentrar iodeto, etapa fundamental na biossíntese dos hormônios tireóideos. O uso de iodo radioativo para fins de diagnóstico e terapia das doenças da tireóide vem sendo feito há muitos anos. Entretanto, somente após a clonagem do gene que codifica o co-transportador de sódio/iodeto (NIS) houve aumento significativo dos estudos relacionados ao mecanismo de transporte de iodeto. Os estudos sobre a regulação da expressão do NIS e a possibilidade de terapia gênica visando à transferência do gene NIS para células que normalmente não expressam esse transportador, foram também viabilizados. Na maior parte dos nódulos tireóideos hipofuncionantes, tanto benignos quanto malignos, a expressão do gene do NIS está presente, mas a proteína NIS fica retida no compartimento intracelular. A transferência do gene usando-se promotores tecido-específicos possibilitou a expressão do NIS em células tumorais não-tireóideas in vivo. Além do seu uso terapêutico, o NIS também vem sendo usado para a localização de metástases tumorais através da cintilografia ou do PET-scan usando-se 124I. Em conclusão, a clonagem do NIS possibilitou enorme avanço na área de fisiopatologia tireóidea e foi também fundamental para estender o uso do radioiodo para tumores não tireóideos.
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Humanos , Adenocarcinoma Folicular/metabolismo , Carcinoma Papilar/metabolismo , Yodo/metabolismo , Simportadores/metabolismo , Neoplasias de la Tiroides/metabolismo , Adenocarcinoma Folicular/terapia , Transporte Biológico , Clonación Molecular , Carcinoma Papilar/terapia , Regulación hacia Abajo , Expresión Génica , Técnicas de Transferencia de Gen , Terapia Genética , Yoduros/metabolismo , Radioisótopos de Yodo , Radioisótopos de Yodo/uso terapéutico , Simportadores/genética , Neoplasias de la Tiroides/terapia , Tirotropina/fisiologíaRESUMEN
The use of anabolic steroids to increase physical performance and for aesthetic ends has reached alarming indices in the last three decades. Besides the desired actions, several collateral effects have been described in the literature, such as the development of some types of cancer, ginecomasty, peliosis hepatis, renal insufficiency, virilization, amongst others. The most proeminent effect on human thyroid function is the reduction of thyroxine binding globulin (TBG), with consequent reductions of total serum T3 and T4, depending however on the susceptibility of the drug to aromatization and subsequent transformation into estrogen. In rats, anabolic steroids also act in the peripheral metabolism of thyroid hormones and seem to exert an important proliferative effect on thyroid cells. Thus, the aim of the present paper is to review data on the effect of supraphysiological doses of anabolic steroids on thyroid function, showing the danger that indiscriminate use of these drugs can cause to health.
Asunto(s)
Anabolizantes/efectos adversos , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/fisiología , Tirotropina/fisiología , Anabolizantes/administración & dosificación , Animales , Doping en los Deportes , Relación Dosis-Respuesta a Droga , Humanos , Yoduro Peroxidasa/sangre , Ratas , Pruebas de Función de la Tiroides , Hormonas Tiroideas/fisiologíaRESUMEN
The pituitary gonadotropins--luteinizing hormone and follicle-stimulating hormone--as well as the placental choriogonadotropin belong to the family of glycoprotein hormones. These structurally related hormones, which regulate several major reproductive functions of the body, are heterodimers consisting of a common alpha-subunit noncovalently bound to a beta-subunit. The N- and O-linked oligosaccharide chains of these gonadotropins play an important role in intracellular folding, assembly, secretion, metabolic clearance, and biological activity of the hormone. Gonadotropin glycosylation is a highly complex process; within the gonadotropes it is modulated by a variety of extrapituitary factors of hypothalamic and gonadal origin. In particular, estrogens and androgens appear to regulate terminal sialylation and/or sulfation of the oligosaccharide attachments and hence some functional properties of the gonadotropin molecule determined by these residues, i.e., metabolic clearance and in vivo biopotency. Through these extrapituitary inputs, the anterior pituitary may not only regulate the quantity but also the quality of the gonadotropin signal delivered to the gonads in a given physiologic or pathologic condition.
Asunto(s)
Hormonas Esteroides Gonadales/fisiología , Gonadotropinas Hipofisarias/metabolismo , Procesamiento Proteico-Postraduccional/fisiología , Secuencias de Aminoácidos , Andrógenos/farmacología , Andrógenos/fisiología , Animales , Secuencia de Carbohidratos , Castración , Gonadotropina Coriónica/química , Gonadotropina Coriónica/metabolismo , Enfermedades del Sistema Endocrino/metabolismo , Retículo Endoplásmico Rugoso/metabolismo , Estrógenos/farmacología , Estrógenos/fisiología , Femenino , Hormona Folículo Estimulante/química , Hormona Folículo Estimulante/metabolismo , Glicosilación , Hormonas Esteroides Gonadales/farmacología , Hormona Liberadora de Gonadotropina/fisiología , Gonadotropinas Hipofisarias/química , Humanos , Sistema Hipotálamo-Hipofisario/fisiología , Hormona Luteinizante/química , Hormona Luteinizante/metabolismo , Masculino , Mamíferos/fisiología , Tasa de Depuración Metabólica , Datos de Secuencia Molecular , Ácido N-Acetilneuramínico/metabolismo , Oligosacáridos/metabolismo , Adenohipófisis/metabolismo , Placenta/metabolismo , Embarazo , Pliegue de Proteína , Ratas , Relación Estructura-Actividad , Tirotropina/fisiología , Hormona Liberadora de Tirotropina/fisiologíaRESUMEN
Sporadic congenital hypothyroidism is most commonly caused by developmental abnormalities of the thyroid gland. More rarely, it is due to defects in gene products involved in the regulation of the hypothalamic-pituitary-thyroid axis or thyroid hormone synthesis. Loss of function mutations in the thyrotropin (TSH) receptor have been shown to result in resistance to biologically active TSH. In complete resistance to TSH, the thyroid gland is hypoplastic and unable to synthesize and secrete sufficient amounts of thyroid hormones. In partial resistance, referred to as euthyroid hyperthyrotropinemia, the size of the gland and the thyroid hormone levels are normal at the expense of an elevated TSH. Four patients with sporadic congenital hypothyroidism and properly located hypoplastic thyroid glands were included in this study. Serum TSH concentrations were 150 mU/L or higher, serum thyroglobulin levels were within normal limits (6.1 to 8.2 ng/mL; normal range: 2.1 to 32 ng/mL), and thyroid autoantibodies were absent. The coding region of the TSHbeta subunit gene, the TSH receptor gene, and exons 8 and 9 of Gsalpha were analyzed by direct sequencing and found to be normal in all patients. One patient was heterozygous for a G to A transition in the TSHbeta gene resulting in a substitution of alanine by threonine at position -7 of the signal peptide. This substitution was also found in her euthyroid father. In addition, Southern analysis of the TSH receptor gene excluded major structural alterations. These findings support previous reports that indicate that TSH resistance is genetically heterogeneous. In addition to mutations in the TSH receptor or the Gsalpha genes, other genetic defects can lead to an identical phenotype. These observations also suggest that TSH receptor mutations might be a relatively rare cause of congenital thyroid hypoplasia.
Asunto(s)
Hipotiroidismo Congénito , Hipotiroidismo/metabolismo , Receptores de Tirotropina/metabolismo , Southern Blotting , Femenino , Haplotipos , Humanos , Hipotiroidismo/etiología , Recién Nacido , Mutación/fisiología , Tamizaje Neonatal , Linaje , Cintigrafía , Tiroglobulina/metabolismo , Glándula Tiroides/diagnóstico por imagen , Glándula Tiroides/crecimiento & desarrollo , Tirotropina/fisiología , UltrasonografíaRESUMEN
INTRODUÇÄO: Diversos autores têm chamado a atençäo para as dificuldades no diagnóstico de disfunçäo tireóidea no idoso. Manifestaçöes características dessas afecçöes, como fadiga, pele seca, obstipaçäo, diminuiçäo da memória, humor depressivo, podem ser interpretadas como próprias do envelhecimento. OBJETIVOS: determinar a prevalência das disfunçöes tireóideas em idosos residentes em três abrigos da cidade do Salvador, avaliando as manifestaçöes clínicas no diagnóstico de disfunçöes tireóideas, a necessidade do teste de estímulo do TSH com TRH na avaliaçäo das disfunçöes tireóideas, a prevalência de anti-TPO e a associaçäo entre disfunçäo tireóidea e perfil lipídico. DESENHO DE ESTUDO: seccional. MATERIAL E MÉTODOS: foram estudados 170 idosos, voluntários, residentes em três abrigos da cidade do Salvador, com idade média de 78,4 ñ 6,8 anos, mediana de 78 anos, variando de 65 a 96 anos, sendo 27 idosos (15, 9 porcento) do sexo masculino e 143 (84,1 porcento) do sexo feminino. Nenhum deles apresentava antecedentes de doença tireoideana. Todos os idosos foram submetidos a exame clínico, as determinaçöes de T3, T4 total, T4 livre e TSH, por imunoensaios, pesquisa de anticorpos séricos anti-TPO e determinação do perfil lipídico (colesterol total e fraçöes HDL e LDL, triglicérides). Cento e vinte e dois idosos (71,8) que apresentaram TSH basal <5µUI/ml foram submetidos ao teste de estímulo com TRH (200µg), venoso, avaliado através de determinaçöes séricas de TSH nos tempos 0, 30, 60 e 90 minutos. Considerou-se hipotireoidismo franco quando o TSH (maior igual que) 5µUI/ml, com T3, T4 total e T4 livre baixos; hipotireoidismo subclínico quando o TSH (maior igual que) 5µUI/ml, com T3, T4 total e T4 livre normais ou quando o TSH após estímulo com TRH foi (maior igual que) 20µUI/ml em um dos tempos. RESULTADOS: disfunçäo tireóidea foi encontrada em 41 idosos (24, 1 porcento), sendo todos os casos representados por hipotireoidismo. Trinta idosos (17,6 porcento) apresentaram títulos significativos de anticorpos séricos anti-TPO. As manifestaçöes clínicas, nos idosos, foram atípicas, e a presença seis ou mais manifestaçöes indicou disfunçäo tireóidea. Quando se analisou as médias de CT, TG, HDL-c e LDL-c entre os idosos com e sem disfunçäo tireóidea näo houve diferença estatisticamente significante (p=0,06). Observou-se correlaçäo negativa entre níveis séricos de TSH e T3 (r = - 0,57 e p < 0,0001), T4 total (r = - 0,53 e p < 0,0001), T4 livre ...