Effect of wheat-grain moxibustion on the expression of 5-HT and cortisol in the serum, and MR and GR in the hippocampus in rats with hypothyroidism complicated with depression / 中国针灸

OBJECTIVE@#To observe the effect of wheat-grain moxibustion on behavior, 5-hydroxytryptamine (5-HT) and cortisol in the serum, mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the hippocampus in rats with hypothyroidism complicated with depression, and to explore the possible mechanism of wheat-grain moxibustion on improving depression in rats with hypothyroidism.@*METHODS@#A total of 32 SPF SD rats were randomly divided into a blank group, a model group, a medication group and a wheat-grain moxibustion group, 8 rats in each group. Except for the blank group, the rats in the remaining groups were treated with intragastric administration of 0.1% propylthiouracil (PTU) suspension at 1 mL/100 g, once a day for 4 weeks to establish the rat model of hypothyroidism, and whether the rats were accompanied with depression-like behavior determined through behavioristics evaluation. The rats in the medication group were intervened with euthyrox at 0.9 mL/100 g, once a day, for 4 weeks; the rats in the wheat-grain moxibustion group were treated with wheat-grain moxibustion at "Dazhui" (GV 14), "Mingmen" (GV 4), "Shenshu" (BL 23) and "Pishu" (BL 20), 7 cones each acupoint, once a day, six times a week for 4 weeks. After the intervention, the depression status was observed by behavioristics test; the contents of thyroid stimulating hormone (TSH), total thyroxine (TT4), 5-HT and cortisol in the serum were detected by ELISA; the protein expressions of MR and GR in hippocampus were detected by Western blot; the expressions of MR mRNA and GR mRNA in the hippocampus were detected by real-time PCR.@*RESULTS@#Before the intervention, compared with the blank group, the scores of open field test (OFT) were decreased and the immobility time of tail suspension test (TST) was prolonged (P<0.05); the serum TSH contents were increased and TT4 contents were decreased (P<0.01) in the other three groups. After the intervention, compared with the model group, the vertical score of OFT was increased and the immobility time of forced swimming test (FST) was prolonged in the medication group (P<0.05), while the scores of three items of OFT were increased (P<0.05, P<0.01), and the immobility time of FST and TST was shortened in the wheat-grain moxibustion group (P<0.01, P<0.05). Compared with the medication group, the immobility time of TST and FST in the wheat-grain moxibustion group was shorter (P<0.05, P<0.01). Compared with the blank group, in the model group, the contents of serum TSH and cortisol were increased (P<0.01, P<0.001), while the contents of serum TT4 and 5-HT were decreased (P<0.01, P<0.001). Compared with the model group, the contents of serum TT4 and 5-HT were increased, while the contents of serum TSH and cortisol were decreased in the medication group and wheat-grain moxibustion group (P<0.01, P<0.05). Compared with the blank group, the protein and mRNA expression of MR, GR in the hippocampus in the model group was decreased (P<0.01, P<0.05, P<0.001); compared with the model group, the protein and mRNA expression of MR in the hippocampus in the medication group were increased (P<0.05), and the protein expression of MR, GR and mRNA expression of MR in the hippocampus in the wheat-grain moxibustion group were increased (P<0.05, P<0.01). Compared with the medication group, the expression of MR mRNA in the wheat-grain moxibustion group was increased (P<0.05).@*CONCLUSION@#Wheat-grain moxibustion could significantly improve thyroid function and depression in rats with hypothyroidism. Its mechanism may be related to up-regulating the protein and mRNA expression of MR and GR in the hippocampus, and then affecting the expression of serum cortisol and 5-HT.

Associations between thyroid-stimulating hormone and hypertension according to thyroid cyst status in the general population: a cross-sectional study

BACKGROUND@#The absence of thyroid cysts may indicate latent thyroid damage, as demonstrated in our previous study. However, the association between the absence of thyroid cysts and latent functional damage of the thyroid is unknown. At low thyroid hormone productivity, which may be associated with latent functional damage of the thyroid, the association between thyroid-stimulating hormone (TSH) and hypertension might be enhanced. Therefore, we evaluated the association between TSH level and hypertension stratified by thyroid cyst status.@*METHODS@#We conducted a cross-sectional study of 1724 euthyroid Japanese individuals aged 40-74 years who participated in an annual health checkup in 2014.@*RESULTS@#In the study population, 564 and 686 participants had thyroid cysts and hypertension, respectively. A significant positive association was observed between TSH and hypertension in subjects without a thyroid cyst but not in subjects with thyroid cysts. There was a significant positive association between hypertension and TSH in subjects without a thyroid cyst (odds ratio [OR] 1.27; 95% confidence intervals [CI] 1.01, 1.61) but not in subjects with thyroid cysts (OR 0.79; CI 0.57, 1.09) in the model fully adjusted for known confounding factors. The correlation between the TSH and free triiodothyronine (fee T3) levels (simple correlation coefficient [r] = - 0.13, p < 0.01) was stronger in the subjects without thyroid cysts than in those with thyroid cysts (r = - 0.03, p = 0.525).@*CONCLUSIONS@#TSH is positively associated with hypertension only in individuals without thyroid cysts. The correlation between the TSH and free T3 levels was stronger in the subjects without thyroid cysts than in those with thyroid cysts. Therefore, the absence of thyroid cysts could be related to the association between TSH level and hypertension, possibly by indicating that the subjects without thyroid cysts had limited thyroid hormone reserves. Therefore, the absence of thyroid cysts could indicate the latent functional damage of the thyroid.

Effects of magnesium on cytomorphology and enzyme activities in thyroid of rats.

Till date knowledge regarding the effects of high dietary magnesium on thyroid gland is incomprehensive though certain epidemiological studies reported development of thyroid gland dysfunctions in people with chronic exposure to hard water (especially with high magnesium) despite sufficient iodine consumption. The present study is to explore the effects of chronic high dietary magnesium exposure on thyroid morphology and functional status. Male adult albino Wistar strain rats were treated with graded doses of magnesium sulphate (MgSO4; 0.5, 1.0 and 1.5 g %) for 60 days and changes in different thyroid parameters were investigated. Significantly stimulated thyroid peroxidase and Na+–K+-ATPase and altered idothyronine 5/- deiodinase type I activities, enhanced serum thyroxine (T4) (both total and free), total triiodothyronine (T3) and thyroid stimulating hormone with decreased free T3 levels and T3/T4 ratio (T3:T4) along with enlargement of thyroid with associated histopathological changes were observed in the treated groups. The results clearly confirm that chronic high dietary magnesium exposure causes potential thyroid disruption as reported in earlier epidemiological studies.

Endoscopic transnasal approach for removing pituitary tumors / Acesso transnasal endoscópico para remoção de tumores da hipófise

To describe a series of 129 consecutive patients submitted to the resection of pituitary tumors using the endoscopic transsphenoidal approach in a public medical center. Method: Retrospective analysis based on the records of patients submitted to the resection of a pituitary tumor through the endoscopic transsphenoidal approach between 2004 and 2009. Results: One hundred and twenty-nine records were analyzed. The tumor was non-secreting in 96 (74.42%) and secreting in 33 patients (22.58%). Out of the secretory tumors, the most prevalent was the growth hormone producer (7.65%), followed by the prolactinoma, (6.98%). Eleven patients developed cerebral spinal fluid (CSF) fistulas, and four of them developed meningitis. One patient died due to intracerebral hemorrhage in the postoperative period. Conclusion: The endoscopic transsphenoidal approach to sellar tumors proved to be safe when the majority of the tumors were non-secreting. The most frequent complication was CSF. This technique can be done even in a public hospital with financial limits, since the health professionals are integrated. .

Descrever uma série de 129 pacientes submetidos à ressecção de tumor de hipófise com acesso endoscópico transesfenoidal em um serviço de público referência em Belo Horizonte. Método: Análise retrospectiva realizada por análise dos prontuários de pacientes submetidos à ressecção de tumor de hipófise com acesso endoscópico transesfenoidal entre os anos 2004 e 2009. Resultados: Foram avaliados 129 prontuários. O tumor era não secretante em 96 (74,42%) e secretante em 33 pacientes (22,58%). Dos tumores secretores, o de maior prevalência foi o produtor de hormônio do crescimento: 15 pacientes (7,65%). Onze pacientes desenvolveram fístula liquórica. Um paciente faleceu devido hemorragia intracerebral no pós-operatório. Conclusão: O acesso endoscópico transfenoidal aos tumores selares mostrou-se seguro numa população em que a maioria dos tumores era não secretante. A principal complicação encontrada foi fístula liquórica. Esta técnica é passível de utilização em hospital público mesmo com limites financeiros desde que haja integração multiprofissional. .

L-Arginine attenuates oxidative stress condition during cardiomyopathy.

Increased production of oxygen free radicals and decreased oxidant capacity occur in coronary artery diseases (CAD). This pro-oxidant shift in intracellular redox state may induce cell death by either direct cell membrane damage by lipid peroxidation or apoptosis through activation of transcription factors. These changes occur not only in cardiomyocytes, but also in cardiac sympathetic nerves, which are very sensitive to oxidative damage. Patients with heart failure encounter reduced peripheral blood flow at rest, during exercise and in response to endothelium-dependent vasodilators. Current treatments of cardiomyopathy, a degenerative condition of the myocardium frequently associated with heart failure have done little to enhance patient survival. Decreased myocardial contractility and altered regulation of peripheral circulation along with oxidative conditions are important contributors to the symptoms and prognosis of the disease process. Nitric oxide formed from L-arginine (2-amino-5 guanidinovaleric acid) metabolism in endothelial cells contributes to regulation of blood flow under these conditions. L-Arginine is the precursor of nitric oxide, an endogenous messenger molecule involved in a variety of endothelium-mediated physiological effects in the vascular system. In the present study, we investigated the effect of oral administration of L-arginine (3 g/day) on the intracellular redox status of the patients of ischemic cardiomyopathy aged 45-60 yrs. The enzymatic and non-enzymatic antioxidant parameters like superoxide dismutase, catalase, total thiols (TSH) and ascorbic acid along with pro-oxidant parameters, such as xanthine oxidase, as well as index of oxidative stress as protein carbonyl content and malondialdehyde (a marker of lipid peroxidation) were investigated in the plasma and RBC lysate. L-Arginine (3 g/day) administration was found to improve the levels of these parameters in the patients and regulate the blood flow, as evident by the improved blood pressure of the patients. Thus, it is inferred that L-arginine attenuates the oxidative stress conditions along with maintaining the blood pressure rate of patients suffering from cardiomyopathy.

Tirotrofina serica en secreening neonatal: intervalos poblacionales de referencia y su correlación clínica / Secreening serum thyrotropin in neonatal population reference intervals and clinical correlation

ANTECEDENTES: La detección del hipotiroidismo congénito (HC) por el screening neonatal evita la morbilidad física con retardo mental. El screening del Hospital Privado deCórdoba (HPCba) utiliza como marcador bioquímico TSH sérica= 10 μU/ml y T4 como complemento. HIPÓTESIS: Es un método eficaz en el screening neonatal el uso de TSHsérica con un nivel de corte apropiado y rangos de referencia acorde a la edad. OBJETIVOS: Evaluar la capacidad de TSH sérica para detectar HC y obtener la frecuencia de HC. Definir el valor óptimo de corte y valores de referencia para TSH sérica. Identificar factores de riesgoque inciden sobre la elevación de TSH. MATERIALES Y MÉTODOS: Todos los recién nacidos (RN) entre años 2001 y 2007. Se excluyeron TSH procesadas en otro laboratorio,menores de 0.5 mUI/ml, y las obtenidas después de 20 días de vida. Fueron excluidos los RN fallecidos antes del mes y con menos de 1.500 grs. La población en estudio se dividió en 3 grupos: total, grupo problema (TSH >10) y grupo control. Las herramientas estadísticas: pruebas t de Student, análisis de regresión logarítmica, curvas ROC, media, desvío estándar y logaritmo natural y antinatural. RESULTADOS: Total de RN 7.869, fallecidos 43, excluidos980. De los 6.846 estudiados 6.546 (87,47%) presentaron TSH <10 μU/ml y 300 (3,83%) TSH >10 μU/ml. Del total de RN se confirmó HC en 6 (0,07%) ubicando la incidencia en1:1.304 con igual relación femenino-masculino. La media de TSH sérica fue de 4,42 (± 4,17) μU/ml. El 75% fueron testeados a los 5,85 (± 2,58 días). Con el valor de corte utilizado (TSH=10 μU/ml) 4,38% fueron falsos positivos, reducidos a 1,28% con el uso complementario de T4; este elevado porcentaje obligó a un exhaustivo análisis que permitió sugerir un nuevo valor de TSH sérica= 20 μU/ml. Se observó relación inversa entre edad del RN y la posibilidad de tener TSH >10 μU/ml, por lo que se definieron rangos de referencia para TSH sérica según edad del RN...

Lactantes menores alimentados con fórmula de soya: evaluación de hormonas tiroideas / Infants fed with soy formula: evaluation of thyroid hormones

La alimentación a base de soya, se ha relacionado con alteración de la función tiroidea, debido a la presencia de fitoestrógenos en su composición. Es por ello, que el presente estudio tiene como objetivo determinar la función tiroidea en lactantes menores de 6 meses alimentados con fórmula infantil a base de soya. Es un estudio descriptivo, transversal. Se evaluaron 28 lactantes que recibieron fórmula infantil de soya, como única alimentación. Variables utilizadas: edad, sexo, Graffar-Méndez Castellano, motivo de indicación de la fórmula, dilución, onzas diarias ingeridas, determinación de T3-libre y T4-libre y TSH sérico. Para el análisis estadístico se aplicó t de Student para un nivel de significación estadística de p<0,05. Los valores séricos de T3 y T4 libres se mantuvieron dentro de rangos normales. 7% de la muestra mostró valores elevados de TSH, no siendo estadísticamente significativo. No existió relación estadística entre el consumo de fórmula de soya y función tiroidea. Sin embargo, en la muestra estudiadados de los pacientes presentaron aumento de los niveles de TSH, por lo que no se puede descartar la posibilidad de una asociación dado lo limitado de la muestra.

Feeding with soy has been related to alteration of thyroid function. The objective of this study was to determine thyroid functionalism in babies under 6 months of age fed with infantile soy based formula. Descriptive, cross-sectional, non experimental study. Twenty eight babies who received exclusively infantile soy based formula were evaluated. Variables studied were: age, gender, socio-economical level, reason for the prescription of soy formula, dilution, daily ounces, determination of free T3, T4 and TSH. For the statistic analysis, Student’s t test was applied for a statistical significance level of p<0.05. Serum free T3 and T4 were within normal ranges. 7% of the sample showed elevated levels of TSH, with no statistic significance. there was no statistical relationship between consumption of soy formula and thyroid function. However, two patients had increased levels of TSH and therefore, the possibility of an association cannot be ruled out given the small size of the sample.

Associação do TSH, do gasto energético de repouso e do zincona composição corporal de mulheres com sobrepeso/obesas / Association of TSH, resting energy expenditure and zinc to body compositionof overweight/obese women

Introdução: Alterações nas concentrações plasmáticas de tirotropina (TSH) e do zinco (Zn) podem afetar o gasto energético de repouso (GER, kcal/dia) e o desenvolvimento da obesidade. O objetivo deste estudo foi avaliar as correlações entre o GER, os níveis plasmáticos do TSH (μU/ml) e do Zn (mg/dL), a composição corporal e variáveis antropométricas de mulheres com sobrepeso ou obesas. Materiais e Metodologia: Foram selecionadas 35 mulheres sedentárias (31±7, anos; M±DP), índice de massa corporal >25 a 57 (31±6)kg/m2, a composição corporal avaliada por antropometria e bioimpedância, dosados o TSH e o Zn e medido o GER. Resultados: O TSH e Zn não foram correlacionados a variável alguma; o GER correlacionou-se positivamente à maioria das medidas antropométricas e à composição corporal, sendo a maior correlação com a massa corporal total (kg) (p<0,05). A gordura corporal foi mais bem correlacionada ao GER do que a massa magra. Vários perímetros foram positivamente correlacionados ao GER e o melhor foi o pescoço (p<0,05). Discussão e conclusão: Nessas mulheres o TSH e o Zn não foram associados a fatores relacionados ao desenvolvimento da obesidade. O aumento de peso nesse grupo de mulheres parece não estar associado às alterações do TSH e do Zn. Simples medidas antropométricas, como o perímetro do pescoço, podem dar informações importantes sobre a composição corporal e foram associadas ao GER.

Objectives: Alterations in plasmatic thyroid-stimulating hormone(TSH) and zinc (Zn) could affect the resting energy expenditure (REE, kcal/day) and obesity development. The objective of the present study was to evaluate the correlations between of the REE, the plasmatic TSH (μU/ml), and Zn (mg/dL) to body composition and anthropometric variables of overweight or obese women. Methods: Thirty five sedentary women (31±7years old; mean±SD) had been selected, with body mass index >25 to 57 (31±6) kg/m2, the body composition was evaluated by anthropometry and bioimpedance, TSH and Zn were dosed, and REE was measured. Results: TSH and Zn were not correlated to any one of the variables; REE was positively correlated with the majority of measurements of the anthropometrics components and body composition, the total body mass (kg) had the major correlation (p<0.05). The body fat had a greater correlation to REE than the lean mass. The perimeters had been correlated in general to REE and the neck had the best correspondence of all (p<0.05). Discussion and conclusion: In these women, the TSH and Zn were not associated to factors related to the development of obesity. The gain of weight in these women does not appear to have association with TSH and Zn alterations. Simply anthropometric measurements, like the neck perimeter, could lead to relevant information related to body composition and it was associated to REE.

Regulation of Inhibitors of Differentiation Family Proteins by Thyroid-Stimulating Hormone in FRTL-5 Thyroid Cells

Members of the inhibitors of differentiation (Id) family of helix-loop-helix (HLH) proteins are known to play important roles in the proliferation and differentiation of many cell types. Thyroid-stimulating hormone (TSH) regulates proliferation and differentiation by activating TSH receptor (TSHR) in thyrocytes. In this study, we found that Id2, one of the Id family proteins, is a major target for regulation by TSH in FRTL-5 thyroid cells. TSH rapidly increases the Id2 mRNA level in FRTL-5 thyroid cells but the Id2 protein showed biphasic regulatory patterns, being transiently reduced and subsequently induced by TSH treatment. Transient reduction of Id2 protein was noted within 2 hr of TSH treatment and was mediated by proteasomal degradation. Moreover, reduced Id2 expression correlated with the activity of the phosphatidylinositol 3 kinase pathway, which is activated by TSH. Although TSH increases the activity of the Id2 promoter, TSH-induced activation of this promoter was independent of c-Myc. Id2 did not alter TTF-1- and Pax-8-mediated effects on the regulation of the Tg promoter. Thus, in summary, we found that TSH regulates Id2 expression, but that Id2 does not alter the expression of thyroid-specific genes, such as Tg, in FRTL-5 thyroid cells.

Relevance of iodine intake as a reputed predisposing factor for thyroid cancer

Iodine is a trace element that is essential for the synthesis of thyroid hormone. Both chronic iodine deficiency and iodine excess have been associated with hypertrophy and hyperplasia of follicular cells, attributed to excessive secretion of TSH. This may be associated to thyroid cancer risk, particularly in women. Experimental studies have documented thyroid cancer induction by elevation of endogenous TSH, although in a small number of animals. Iodine deficiency associated with carcinogenic agents and chemical mutagens will result in a higher incidence of thyroid malignancy. Inadequate low iodine intake will result in increased TSH stimulation, increased thyroid cell responsiveness to TSH, increased thyroid cell EGF-induced proliferation, decreased TGFbeta 1 production and increased angiogenesis, all phenomena related to promotion of tumor growth. Epidemiological studies associating iodine intake and thyroid cancer led to controversial and conflicting results. There is no doubt that introduction of universal iodine prophylaxis in population previously in chronic iodine-deficiency leads to a changing pattern of more prevalent papillary thyroid cancer and declining of follicular thyroid cancer. Also anaplastic thyroid cancer is practically not seen after years of iodine supplementation. Iodine excess has also been indicated as a possible nutritional factor in the prevalence of differentiated thyroid cancer in Iceland, Hawaii and, more recently, in China. In conclusion: available evidence from animal experiments, epidemiological studies and iodine prophylaxis has demonstrated a shift towards a rise in papillary carcinoma, but no clear relationship between overall thyroid cancer incidence and iodine intake.

O iodo é essencial para a síntese de hormônios tireóideos e tanto a deficiência crônica deste halogeno como o excesso nutricional de iodo levam a hiperplasia e hipertrofia dos elementos foliculares (por excesso de TSH). Esse fenômeno pode se associar a maior risco de câncer de tireóide, especialmente no sexo feminino. Estudos experimentais documentam indução de câncer de tireóide após prolongado excesso circulante de TSH, o qual induz aumento da proliferação celular medida por fator de crescimento epidermal (EGF), decréscimo de síntese de fator de transformação do crescimento (TGFbeta 1) e aumento da angiogenese. Estudos epidemiológicos entre nutrição de iodo e câncer de tireóide são conflitantes. É, todavia, aceito que a correção de prévia deficiência de iodo com aporte nutricional adequado deste halogeno leva à maior prevalência de carcinoma papilífero (e decréscimo de carcinoma folicular). Em alguns países, o excesso de iodo foi apontado como causa aparente de maior prevalência de câncer de tireóide. Em conclusão: não existe uma relação causa-efeito entre iodo nutricional e prevalência de câncer de tireóide, e outros fatores intervenientes ambientais devem ser considerados.

TSH signalling and cancer

Thyroid cancers are the most frequent endocrine neoplasms and mutations in the thyrotropin receptor (TSHR) are unusually frequent. Here we present the state-of-the-art concerning the role of TSHR in thyroid cancer and discuss it in light of the cancer stem cell theory or the classical view. We briefly review the gene and protein structure updating the cancer related TSHR mutations database. Intriguingly, hyperfunctioning TSHR mutants characterise differentiated cancers in contrast to undifferentiated thyroid cancers which very often bear silenced TSHR. It remains unclear whether TSHR alterations in thyroid cancers play a role in the onset or they appear as a consequence of genetic instability during evolution, but the presence of functional TSHR is exploited in therapy. We outline the signalling network build up in the thyrocyte between TSHR/PKA and other proliferative pathways such as Wnt, PI3K and MAPK. This networks integrity surely plays a role in the onset/evolution of thyroid cancer and needs further research. Lastly, future investigation of epigenetic events occurring at the TSHR and other loci may give better clues for molecular based therapy of undifferentiated thyroid carcinomas. Targeted demethylating agents, histone deacetylase inhibitors combined with retinoids and specific RNAis may help treatment in the future.

Os cânceres de tiróide são as neoplasias endócrinas mais frequentes e as mutações no receptor de tirotrofina (TSHR) são incomumente frequentes. Nesta revisão nós apresentamos o "estado da arte" com relação ao papel do TSHR no câncer de tiróide e o discutimos à luz da teoria da célula matriz do câncer ou a visão clássica. Revisamos brevemente a estrutura do gene e da proteína, atualizando a base de dados das mutações do TSHR relacionadas ao câncer. Curiosamente, mutações do TSHR com hiperfunção caracterizam cânceres diferenciados, em contraste com os cânceres de tiróide indiferenciados, os quais muito comumente mostram TSHR silenciados. Permanece obscuro se as alterações do TSHR em cânceres de tiróide têm algum papel no surgimento ou se elas aparecem como conseqüência da instabilidade genética durante seu desenvolvimento, mas a presença de TSHR funcional é explorada na terapia. Nós delineamos a rede de sinalizacão desenvolvida no tirócito entre TSHR/PKA e outras vias proliferativas como a Wnt, PI3k e MAPK. A integridade desta rede certamente tem um papel no surgimento/evolução do câncer de tiróide e necessita de novas pesquisas. Finalmente, novas investigacões sobre os eventos epigenéticos que ocorrem no TSHR e outros locais poderão trazer novas informações para uma terapia de base molecular nos carcinomas indiferenciados de tiróide. Agentes demetilantes direcionados, inibidores da histona-deacetilase, combinados com retinóides e RNAs específicos poderão auxiliar no tratamento futuro.

Biphasic modulation of insulin receptor substrate-1 during goitrogenesis

Insulin receptor substrate-1 (IRS-1) is the main intracellular substrate for both insulin and insulin-like growth factor I (IGF-I) receptors and is critical for cell mitogenesis. Thyrotropin is able to induce thyroid cell proliferation through the cyclic AMP intracellular cascade; however, the presence of either insulin or IGF-I is required for the mitogenic effect of thyroid-stimulating hormone (TSH) to occur. The aim of the present study was to determine whether thyroid IRS-1 content is modulated by TSH in vivo. Strikingly, hypothyroid goitrous rats, which have chronically high serum TSH levels (control, C = 2.31 ± 0.28; methimazole (MMI) 21d = 51.02 ± 6.02 ng/mL, N = 12 rats), when treated with 0.03 percent MMI in drinking water for 21 days, showed significantly reduced thyroid IRS-1 mRNA content. Since goiter was already established in these animals by MMI for 21 days, we also evaluated IRS-1 expression during goitrogenesis. Animals treated with MMI for different periods of time showed a progressive increase in thyroid weight (C = 22.18 ± 1.21; MMI 5d = 32.83 ± 1.48; MMI 7d = 31.1 ± 3.25; MMI 10d = 33.8 ± 1.25; MMI 14d = 45.5 ± 2.56; MMI 18d = 53.0 ± 3.01; MMI 21d = 61.9 ± 3.92 mg, N = 9-15 animals per group) and serum TSH levels (C = 1.57 ± 0.2; MMI 5d = 9.95 ± 0.74; MMI 7d = 10.38 ± 0.84; MMI 10d = 17.72 ± 1.47; MMI 14d = 25.65 ± 1.23; MMI 18d = 35.38 ± 3.69; MMI 21d = 31.3 ± 2.7 ng/mL, N = 9-15 animals per group). Thyroid IRS-1 mRNA expression increased progressively during goitrogenesis, being significantly higher by the 14th day of MMI treatment, and then started to decline, reaching the lowest values by the 21st day, when a significant reduction was detected. In the liver of these animals, however, a significant decrease of IRS-1 mRNA was detected after 14 days of MMI treatment, a mechanism probably involved in the insulin resistance that occurs in hypothyroidism. The increase in IRS-1 expression during goitrogenesis may represent...

Eixos hormonais na obesidade: causa ou efeito? / Hormonal axes in obesity: cause or effect?

Diversas alterações endócrinas são descritas na obesidade. O eixo corticotrófico encontra-se hiper-responsivo, com maior depuração dos hormônios e nível de cortisol normal. A caracterização do pseudo-Cushing é importante. A leptina parece ser um hormônio permissivo para o desencadeamento da puberdade. Em adultos, as gonadotrofinas são normais, hiperandrogenismo e hiperestrogenismo são encontrados. Nas mulheres, a resistência insulínica é central no desenvolvimento da síndrome dos ovários policísticos (SOP), associada a hiperandrogenemia ovariana. Nos obesos, GH geralmente é baixo e IGF1 normal. A função tireoidiana é habitualmente normal nos obesos.

Several endocrine changes have been described in the obesity state. The corticotropic axis is hyperresponsive and there is enhancement of hormonal clearance, but cortisol levels are within the normal range. It is important to characterize a pseudo-Cushing in obesity. Leptin seems to be a permissive hormone for the beginning of puberty. In adults, gonadotropines are normal, and hyperandrogenism and hyperestrogenism are found. In women, insulin resistance has a central role in polycystic ovarian syndrome (POS), which is associated to ovarian hyperandrogenemia. In obese subjects, growth hormone (GH) is generally low and IGF1 is normal. Thyroid function is commonly normal in obese subjects.

Vitamin E prevents deleterious effects of di (2-ethyl hexyl) phthalate, a plasticizer used in PVC blood storage bags.

Vitamin E administration prevented DEHP induced deleterious effects like (i) degenerative changes in the brain and thyroid, (ii) decrease in the activity of neuronal membrane Na+ - K+ ATPase, (iii) decrease in the concentration of insulin, cortisol and TSH, and (iv) the increase in T3 and T4 in female Albino rats. The results suggest use of vitamin E to prevent harmful effects of repeated transfusion of DEHP containing blood as in thalassemia patient. The possibility of using vitamin E to prevent the harmful effects of repeated transfusion of DEHP containing blood, as in thalassemia patients, is discussed.

A relação entre a função tireoidiana e a depressão: uma revisão / The relation between thyroid function and depression: a review

OBJETIVO: O papel da função tireoidiana nas doenças depressivas é pouco claro. Embora existam algumas evidências de que discretas alterações tireoidianas predisponham a casos de depressão, as anormalidades específicas envolvendo a tireóide e os quadros depressivos permanecem pouco conhecidas. Serão destacados nesta revisão os principais achados envolvendo os quadros depressivos e a função tireoidiana, com especial atenção na participação das monoaminas cerebrais nesta relação. MÉTODO: Foram realizados levantamento no sistema Medline e na literatura. RESULTADOS: Existem evidências de atividade alterada do eixo hipotálamo-hipófise-tireóide (HHT) em alguns casos de depressão, que incluem: aumento dos níveis de T4, resposta alterada do TSH pós-estímulo com TRH, presença de anticorpos antitireoidianos e concentração elevada de TRH no LCR. A relação entre estas anormalidades, as principais monoaminas cerebrais e os subtipos de quadros depressivos é complexa e ainda não permite o estabelecimento de hipóteses diretas de compreensão. CONCLUSÕES: Após anos de pesquisas, permanece pouco esclarecida a importância da relação entre o eixo HHT e as depressões, assim como os mecanismos subjacentes às alterações tireoidianas encontradas nos pacientes deprimidos. Portanto, mais pesquisas serão necessárias para uma melhor compreensão do papel do eixo HHT na patogênese e no tratamento dos quadros depressivos.

A case of thyrotropin-secreting pituitary macroadenoma.

We present a 49 year old male patient with thyroid stimulating hormone (TSH) producing pituitary macroadenoma. He had been mistakenly diagnosed and treated as Graves' disease for 1 year. Serum TSH level was inappropriately elevated in the presence of high serum total and free thyroid hormone concentrations. Thyrotropin releasing hormone stimulation showed blunt response of TSH but good response for prolactin. The alpha-subunit level and alpha-subunit to TSH molar ratio were measured and found to be high before surgery. The sex hormone-binding globulin level was also high. MRI demonstrated a pituitary macroadenoma. Insulin tolerance test and GnRH revealed normal response. The patient was given a high dose of PTU combined with lugol's solution for controlling hyperthyroidism preoperatively. Transfrontal surgery was performed and the tumor was partially removed. The diagnosis was confirmed by tissue pathology and immunohistochemistry staining of the tumor. The immunohistochemistry staining was performed and found that tumor cells were strongly reactive to TSH with a relatively mild degree for follicular stimulating hormone and leutinizing hormone. The tumor cells were not stained for prolactin, growth hormone and ACTH. Supervoltage irradiation by 60Co was delivered to the pituitary area because of persistence of hyperthyroidism. While waiting for the remote effect of radiotherapy, the patient was given an antithyroid drug to control hyperthyroidism.

Tratamento medicamentoso dos tumores hipofisários. Parte II: adenomas secretores de ACTH, TSH e adenomas clinicamente näo funcionantes / Drug therapy of hypophyseal tumors. Part II: ACTH and TSH secreting adenomas and functionless clinically adenomas

Este artigo revisa o potencial papel do tratamento medicamentoso para os adenomas hipofisários secretores de ACTH, TSH e aqueles clinicamente näo-funcionantes (ACNF). Metirapona, mitotano e cetoconazol (preferível por causar menos efeitos colaterais) säo as drogas mais eficazes no controle do hipercortisolismo, mas nenhuma delas supera a eficácia da cirurgia transesfeinodal (TSA). O tratamento medicamentoso da doença de Cushing está, portanto, melhor indicado para pacientes aguardando o efeito pleno da radioterapia ou, como alternativa para esta última, em casos de hipercortisolismo persistente após TSA, e para pacientes com rejeiçäo ou limitaçöes clínicaspara a cirurgia. Outra indicaçäo potencial seria em idosos com microadenomas ou pequenos macroadenomas, ou em casos associados a sela vazia. No que se refere aos adenomas secretores de TSH, os análogos somatostatínicos (SRIFa) proporcionam normalizaçäo dos hormônios tireoidianos em até 95 por cento dos casos. Assim, eles podem se mostrar úteis em casos de insucesso da cirurgia ou como terapia primária de casos selecionados. Ocasonalmente, agonistas dopaminérgicos (DA), sobretudo a cabergolina, também podem ser eficazes. Em contraste, DA e SRIFa raramente induzem uma significante reduçäo das dimensöes dos ACNFs. Por isso, em pacientes com tais tumores, essas drogas devem ser principlamente consideradas diante de contra-indicaçöes ou limitaçöes clínicas para a cirurgia ou quando a cirurgia e a radioterapia tenham sido mal-sucedidas.

Effect of medroxyprogesterone acetate on thyrotropin secretion in adult and old female rats

Steroid hormones have been implicated in the modulation of TSH secretion; however, there are few and controversial data regarding the effect of progesterone (Pg) on TSH secretion. Medroxyprogesterone acetate (MPA) is a synthetic alpha-hydroxyprogesterone analog that has been extensively employed in therapeutics for its Pg-like actions, but that also has some glucocorticoid and androgen activity. Both hormones have been shown to interfere with TSH secretion. The objective of the present study was to investigate the effects of MPA or Pg administration to ovariectomized (OVX) rats on in vivo and in vitro TSH release and pituitary TSH content. The treatment of adult OVX rats with MPA (0.25 mg/100 g body weight, sc, daily for 9 days) induced a significant (P<0.05) increase in the pituitary TSH content, which was not observed when the same treatment was used with a 10 times higher MPA dose or with Pg doses similar to those of MPA. Serum TSH was similar for all groups. MPA administered to OVX rats at the lower dose also had a stimulatory effect on the in vitro basal and TRH-induced TSH release. The in vitro basal and TRH-stimulated TSH release was not significantly affected by Pg treatment. Conversely, MPA had no effect on old OVX rats. However, in these old rats, ovariectomy alone significantly reduced (P<0.05) basal and TRH-stimulated TSH release in vitro, as well as pituitary TSH content. The results suggest that in adult, but not in old OVX rats, MPA but not Pg has a stimulatory effect on TSH stores and on the response to TRH in vitro

Peptídeos bombesina-símiles: novos reguladores da secreçäo adeno-hipofisária / Bombesin-similes peptides: news regulatory of adenohypophyseal secretion

A neuromedina B (NB) e o peptídeo liberador de gastrina são peptídeos bombesina-símiles encontrados em mamíferos, inclusive em seres humanos. Ambos inibem a secreção hipofisária de tireotrofina (TSH); entretanto, somente a NB tem importância fisiológica demonstrada. A NB é produzida em abundância em tireotrofos e parece inibir a secreção de TSH por via autócrina, uma vez que o bloqueio do peptídeo endógeno causa aumento na liberação do TSH, tanto in vivo quanto in vitro. A NB é positivamente regulada pelos hormônios tireóideos (HT). Os HT aumentam o conteúdo de neuromedina B e do seu RNAm em adeno-hipófises de ratos hipotireóideos, poucas horas após sua administração, o que coincide com diminuição do TSH sérico. Isto nos levou a sugerir que a NB possa ser um intermediário protéico envolvido na inibição aguda da liberação de TSH induzida pelos HT. O TRH também altera rapidamente a expressão da NB. Quinze e 30 minutos após a administração do TRH em ratos normais já há diminuição do conteúdo hipofisário de NB e dos níveis do seu RNAm. No jejum e diabetes experimental, que se caracterizam por diminuição de HT séricos com níveis inadequadamente normais ou diminuídos de TSH, ocorre aumento do conteúdo de NB e de seu RNAm. O análogo de somatostatina, octreotide, também é capaz de aumentar o conteúdo de NB. Assim, a neuromedina B é um importante inibidor local da secreção de TSH, podendo ser uma via final comum de hormônios e neuro-hormônios que determinam variações na secreção de TSH.