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Association of the UGT1A1-53(TA)(n) polymorphism with L-thyroxine doses required for thyrotropin suppression in patients with differentiated thyroid cancer

VARGENS, Daniela D.; NEVES, Ronaldo R. S.; BULZICO, Daniel A.; OJOPI, Elida B.; MEIRELLES, Ricardo M. R.; PESSOA, Cencita N.; PRADO, Carolina M.; GONCALVES, Pedro A.; LEAL, Vera L. G.; SUAREZ-KURTZ, Guilherme
Fonte: LIPPINCOTT WILLIAMS & WILKINS Publicador: LIPPINCOTT WILLIAMS & WILKINS
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
77.4405%
There is a considerable interindividual variation in L-thyroxine [ 3,5,3`,5`-tetraiodo-l-thyronine (T(4))] dose required for thyrotropin (thyroid-stimulating hormone) suppression in patients with differentiated thyroid cancer. To investigate whether uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)-mediated T(4) glucuronidation in liver affects T(4) dose, we genotyped 101 patients for the common UGT1A1-53(TA)(n) polymorphism and compared T(4) doses among patients having zero (5/6 and 6/6 genotypes), one (6/7 genotype), or two (7/7 and 7/8 genotypes) copies of the low-expression (TA) 7 and (TA) 8 alleles. A significant trend for decreasing T(4) dose with increasing number of copies of (TA)(7) and (TA)(8) (P = 0.037) and significant difference in T(4) dose across the UGT1A1-53(TA)(n) genotypes (P = 0.048) were observed, despite considerable overlap of T(4) doses among different genotypes. These results are consistent with reduced T(4) glucuronidation in patients with low-expression (TA) 7 and (TA) 8 alleles and provide the first evidence for association between UGT1A1-53(TA)(n) and T(4)-dose requirement for thyroid-stimulating hormone suppression in a natural clinical setting. Pharmacogenetics and Genomics 21: 341-343 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. Pharmacogenetics and Genomics 2011...

Lack of clastogenic effects of L-thyroxine in whole-blood cultured human lymphocytes

Djelic,Ninoslav; Djelic,Dijana; Spremo-Potparevic,Biljana; Zivkovic,Lada; Markovic,Biljana; Lozance,Olivera; Blagojevic,Milos
Fonte: Sociedade Brasileira de Genética Publicador: Sociedade Brasileira de Genética
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2007 Português
Relevância na Pesquisa
57.45246%
Thyroid hormones stimulate aerobic metabolism which may lead to oxidative stress accompanied by damage to various cellular macromolecules, including DNA. Previous comet assay studies have shown that thyroid hormones cause DNA damage due to the creation of reactive oxygen species (ROS). However, cytogenetic studies have been equivocal because although an increase in the sister-chromatid exchange frequency per cell has been reported increased micronuclei frequency has not. We used cytogenetic examination of chromosome breakage and aberrations in whole-blood cultures of human peripheral blood lymphocytes to investigate possible clastogenic effects when lymphocytes were exposed to 0.002 µM to 50 µM of L-thyroxine for 24 h and 48 h, these concentrations being chosen because they had been used in previous studies of sister-chromatid exchange and micronuclei frequency. Under our experimental conditions thyroxine did not induced any statistically significant increase in chromosome breakage or aberrations. This lack of clastogenic effects is in contrast to the reported comet assay results obtained using purified lymphocytes, possibly because whole-blood cultures contain catalase and glutathione peroxidase capable of reducing the effects of reactive oxygen species.

Propylthiouracil inhibits the conversion of l-thyroxine to l-triiodothyronine: An explanation of the antithyroxine effect of propylthiouracil and evidence supporting the concept that triiodothyronine is the active thyroid hormone

Oppenheimer, Jack H.; Schwartz, Harold L.; Surks, Martin I.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /09/1972 Português
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57.4599%
6-n-propylthiouracil (PTU) administered to male Sprague-Dawley rats maintained on 2 and 5 μg L-thyroxine (T4)/100 g body weight resulted in a marked reduction in the rate of conversion of L-thyroxine to L-triiodothyronine (T3). These effects could not be ascribed to induced hypothyroidism since the group maintained on 5 μg T4/day had normal levels of liver mitochondrial alpha glycerophosphate dehydrogenase. In confirmation of previous studies, PTU also reduced the fractional rate of deiodination of T3. These observations provide a possible explanation of the many published observations indicating that PTU antagonizes the tissue effects of T4 but not of T3. The data suggest that monodeiodination of T4 but not of T3 is essential before hormonal effects can be manifested at the cellular level.

Slow fractional removal of nonextractable iodine from rat tissue after injection of labeled l-thyroxine and 3,5,3′-triiodo-l-thyronine: A possible clue to the mechanism of initiation and persistence of hormonal action

Oppenheimer, Jack H.; Surks, Martin I.; Schwartz, Harold L.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /11/1972 Português
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57.208203%
Previous studies have shown that a small but significant proportion of radioiodine from labeled L-thyroxine (T4) and 3,5,3′-triiodo-L-thyronine (T3) is incorporated into plasma and tissue proteins and is not, therefore, extractable with ethanol or other organic solvents. Other studies have shown that the complex consists, at least in part, of the iodothyronine in apparent covalent linkage with protein. In the present series of experiments the disappearance rate of nonextractable iodine (NEI) was determined in plasma, liver, and kidney after the injection of rats with a single dose of T4 and T3 labeled with radioiodine in the phenolic ring. The t½ of NEI decay was substantially longer than the t½ of the initial metabolic removal of T4 (16 hr) and T3 (4-6 hr). Thus, between days 3 and 11 the average t½ of plasma NEI derived from T4 was 2.2 days, from T3, 1.9 days; kidney NEI from T4, 7.4 days, from T3, 6.1 days; hepatic NEI from T4, 4.3 days, from T3, 5.2 days.

Effects of Replacement Doses of Sodium-L-Thyroxine on the Peripheral Metabolism of Thyroxine and Triiodothyronine in Man

Braverman, Lewis E.; Vagenakis, Apostolos; Downs, Patricia; Foster, Angela E.; Sterling, Kenneth; Ingbar, Sidney H.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /05/1973 Português
Relevância na Pesquisa
47.947334%
Studies of the effect of L-thyroxine administration (0.3 mg daily for 7-9 wk) on the peripheral metabolism of 131I-labeled triiodothyronine (T3) and 125I-labeled thyroxine (T4) and on the concentration and binding of T4 and T3 in serum were carried out in 11 euthyroid female subjects. Administration of L-thyroxine led to consistent increases in serum T3 concentration (137 vs. 197 ng/100 ml), T3 distribution space (39.3 vs. 51.7 liters), T3 clearance rate (22.9 vs. 30.6 liters/day) and absolute T3 disposal rate (30 vs. 58 μg/day), but no change in apparent fractional turnover rate (60.3 vs. 60.6%/day). The proportion and absolute concentration of free T3 also increased during L-thyroxine administration. Increases in serum total T4 concentration (7.3 vs. 12.8 μg/100 ml) and in both the proportion and absolute concentration of free thyroxine also occurred. In five of the subjects, the kinetics of peripheral T4 turnover were simultaneously determined and a consistent increase in fractional turnover rate (9.7 vs. 14.2%/day), clearance rate (0.84 vs. 1.37 liters/day), and absolute disposal rate (64.2 vs. 185.0 μg/day) occurred during L-thyroxine administration. Despite these increases in the serum concentration and daily disposal rate of both T4 and T3...

Differences in primary cellular factors influencing the metabolism and distribution of 3,5,3′-L-triiodothyronine and L-thyroxine

Oppenheimer, Jack H.; Schwartz, Harold L.; Shapiro, Harvey C.; Bernstein, Gerald; Surks, Martin I.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /05/1970 Português
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Administration of phenobarbital, which acts exclusively on cellular sites, results in an augmentation of the liver/plasma concentration ratio of L-thyroxine (T4) in rats but no change in the liver/plasma concentration ratio of L-triiodothyronine (T3). Whereas phenobarbital stimulates the fecal clearance rate both of T3 and T4, it increases the deiodinative clearance rate of T4 only. These findings suggest basic differences in the cellular metabolism of T3 and T4. Further evidence pointing to cellular differences was obtained from a comparison of the distribution and metabolism of these hormones with appropriate corrections for the effect of differential plasma binding. The percentage of total exchangeable cellular T4 within the liver (28.5) is significantly greater than the corresponding percentage of exchangeable cellular T3 within this organ (12.3). Extrahepatic tissues bind T3 twice as firmly as T4. The cellular metabolic clearance rate (= free hormone clearance rate) of T3 exceeds that of T4 by a factor 1.8 in the rat. The corresponding ratio in man, 2.4, was determined by noncompartmental analysis of turnover studies in four individuals after the simultaneous injection of T4-125I and T3-131I. The greater cellular metabolic clearance rate of T3 both in rat and man may be related to the higher specific hormonal potency of this iodothyronine.

Maintenance Requirements of L-Thyroxine in the Treatment of Hypothyroidism

Kehoe, William A.; Dong, Betty J.; Greenspan, Francis S.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /06/1984 Português
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47.680283%
By analyzing data from 68 hypothyroid patients ranging in age from 15 to 75 years who had been maintained in a euthyroid state for at least a year with oral levothyroxine sodium therapy, we attempted to determine whether there was a correlation between L-thyroxine dose and body weight or patient age. The mean replacement dose of L-thyroxine was 186 μg a day ±69.6 or 2.76 μg per kg of body weight a day ±0.82. There was a significant correlation between L-thyroxine dose and body weight (P<.001), but due to the small number of patients studied who were older than 65 years of age, no correlation was noted between L-thyroxine dose and age.

Differential effect of L-thyroxine on phospholipid biosynthesis in mitochondria and microsomal fraction.

Pasquini, J M; Faryna de Raveglia, I; Capitman, N; Soto, E F
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/01/1980 Português
Relevância na Pesquisa
47.769624%
1. The action of L-thyroxine on the incorporation of radioactive choline or CDP-choline into phosphatidylcholine in vitro was explored in liver and brain microsomal fraction and mitochondria obtained from young adult rats. 2. In liver mitochondria isolated from animals treated with L-thyroxine (40 mg/kg body wt. during 6 days), the incorporation of both radioactive precursors into phosphatidylcholine was significantly decreased compared with normal controls, whereas in the total homogenate and in the microsomal fraction the incorporation was similar in the experimental and control groups. In subcellular fractions isolated from brain, the incorporation of precursors was similar in L-thyroxine-treated and normal animals. 3. Liver mitochondria isolated from normal animals incubated in vitro with CDP-choline, in the presence of different concentrations of L-thyroxine, showed also a marked decrease in the incorporation of label into phosphatidylcholine, whereas no significant changes were found in the total homogenate and in the microsomal fraction compared with control experiments. 4. The differential effect of L-thyroxine on the incorporation of radioactive precursors into phosphatidylcholine of isolated liver subcellular fractions gives further support to the hypothesis that liver mitochondria can independently synthesize part of their own phospholipids. 5. Possible mechanisms of the action of the hormone at the mitochondrial level are discussed.

Deiodination of l-thyroxine and its activity on the oxidation in vitro of reduced nicotinamide–adenine dinucleotide by peroxidase plus hydrogen peroxide

Jolin, Trinidad; De Escobar, Gabriella Morreale
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /12/1971 Português
Relevância na Pesquisa
47.77409%
When l-thyroxine activates the oxidation of NADH by peroxidase+H2O2, little removal of phenolic-ring iodine atoms becomes apparent until most of the NADH has been oxidized, after which it increases markedly. This extensive deiodination is accompanied by loss of the ability of thyroxine to catalyse the oxidation of NADH by peroxidase+H2O2. The slight deiodination observed before the appearance of extensive deiodination is somewhat higher when the effect of thyroxine on NADH oxidation is greater, and lower when thyroxine has exerted a slighter effect. ICN (but not I2 or thyronine) catalyses NADH oxidation, in both the presence and the absence of peroxidase+H2O2: thyroxine+peroxidase+H2O2 are thus comparable with ICN alone in their effects on NADH oxidation. The obvious conclusion from the above observation, namely that the active moiety is the halogen liberated from thyroxine (or ICN) is, however, not directly supported by some of the results obtained by measuring the degree of deiodination of thyroxine in the system. In an attempt to reconcile some apparently contradictory conclusions, it is suggested that, when thyroxine activates oxidation of NADH by peroxidase+H2O2, the diphenyl ether structure is undergoing cyclic deiodination and iodination. This would be accompanied by the maintenance in the reaction medium of an oxidized form of iodine...

Effects of thyroidectomy and L-thyroxine on adrenaline and noradrenaline concentrations in the adrenal glands and plasma of rats during the pro-oestrous phase of the oestrous cycle and pregnancy.

Ismahan, G; Parvez, H; Parvez, S
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1977 Português
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47.680283%
1 The influence of thyroidectomy upon the adrenaline and noraddrenaline content of adrenal glands and plasma in mature female rats in pro-oestrus and in pregnant rats was studied. 2 Adrenal adrenaline and noradrenaline declined significantly after thyroidectomy in pro-oestrous and pregnant females but the effects were more marked in pregnant females. 3 Plasma adrenaline increased by 160% after thyroidectomy in pro-oestrous females but similar treatment resulted in 85% decrease in plasma adrenaline of pregnant rats. The loss of thyroid increased plasma noradrenaline significaantly in both groups of females. 4 The administration of L-thyroxine of thyroidectomized females increased adrenal noradrenaline stores of both the groups. The effects of L-thyroxine in pro-oestrous females resulted in decreased adrenaline stores of the adrenals but the pregnant group showed an increase. Plasma noradrenaline increased after treatment of pro-oestrous and pregnant-thyroidectomized females with L-thyroxine. 5 The thyroidectomized females in pro-oestrous phase receiving L-thyroxine showed a return to the control values for plasma adrenaline but in pregnant females whose plasma adrenaline had declined after thyroidectomy no such change occurred. 6 Considering the variations in total catecholamines in plasma and adrenals...

D-propranolol and DL-propranolol both decrease conversion of L-thyroxine to L-triiodothyronine.

Heyma, P; Larkins, R G; Higginbotham, L; Ng, K W
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 05/07/1980 Português
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57.208203%
The effects of propranolol (DL-propranolol) and D-propranolol on thyroid hormone metabolism were studied in six euthyroid volunteers receiving L-thyroxine (T4) and six hypothyroid patients receiving T4 replacement. D-propranolol as well as propranolol decreased L-triiodothyronine (T3) concentrations and the ratio of T3 to T4 in the euthyroid subjects, and D-propranolol decreased these variables in the subjects with hypothyroidism (propranolol was not given to this group). It is concluded from this study and from parallel invitro investigations that the effect of propranolol on the conversion of T4 to T3 is unrelated to its beta-adrenergic blocking activity, and that at low therapeutic doses propranolol may exert appreciable "membrane-stabilising" effects in vivo.

The Swelling of Rat Liver Mitochondria by Thyroxine and its Reversal

Lehninger, Albert L.; Ray, Betty Lou; Schneider, Marion
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 25/01/1959 Português
Relevância na Pesquisa
47.796943%
The in vitro swelling action of L-thyroxine on rat liver mitochondria as examined photometrically represents an acceleration of a process which the mitochondria are already inherently capable of undergoing spontaneously, as indicated by the identical kinetic characteristics and the extent of thyroxine-induced and spontaneous swelling, the nearly identical pH dependence, and the fact that sucrose has a specific inhibitory action on both types of swelling. However, thyroxine does not appear to be a "catalyst" or coenzyme since it does not decrease the temperature coefficient of spontaneous swelling. The temperature coefficient is very high, approximately 6.0 near 20°. Aging of mitochondria at 0° causes loss of thyroxine sensitivity which correlates closely with the loss of bound DPN from the mitochondria, but not with loss of activity of the respiratory chain or with the efficiency of oxidative phosphorylation. Tests with various respiratory chain inhibitors showed that the oxidation state of bound DPN may be a major determinant of thyroxine sensitivity; the oxidation state of the other respiratory carriers does not appear to influence sensitivity to thyroxine. These facts and other considerations suggest that a bound form of mitochondrial DPN is the "target" of the action of thyroxine. The thyroxine-induced swelling is not reversed by increasing the osmolar concentration of external sucrose...

Normal thyrotrophin response to intravenous thyrotrophin releasing hormone administration: the best index of optimal L-thyroxine therapy in primary hypothyroidism.

Kabadi, U. M.
Fonte: BMJ Group Publicador: BMJ Group
Tipo: Artigo de Revista Científica
Publicado em /08/1985 Português
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47.629004%
Normalization of basal thyrotrophin (TSH) level is used as the endpoint in L-thyroxine (L-T4) therapy of primary hypothyroidism. However, several reports have questioned the reliability of this index because of seasonal variation of TSH. Therefore, we studied 85 consecutive patients with primary hypothyroidism over a period of 3.5 y. In these patients, TSH response (delta TSH) to intravenous thyrotrophin releasing hormone (TRH) administration was examined when basal TSH was normalized with L-T4 therapy. Eight patients showed a blunted response (delta TSH less than 5 microU), whereas 27 patients demonstrated an exaggerated response (delta TSH greater than 25 microU). Thus, 42% of patients were apparently on inappropriate L-T4 dosage. These abnormal TSH responses normalized on adjusting the L-T4 dosage alone; prolonged therapy with the same dose failed to normalize TSH responses. Minor seasonal variations of basal TSH were observed in 30% of patients. However, TSH response to TRH remained normal. Hence, no adjustment of L-thyroxine dose was required. This study, therefore, demonstrates that normalization of TSH response to TRH administration rather than basal TSH may be the best index of adequate L-thyroxine therapy in primary hypothyroidism.

Life-threatening hyponatremia due to cessation of L-thyroxine.

Sari, Ramazan; Sevinc, Alper
Fonte: National Medical Association Publicador: National Medical Association
Tipo: Artigo de Revista Científica
Publicado em /10/2003 Português
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47.784297%
Electrolyte disorders in hypothyroidism are frequently subtle and rarely observed in clinical practice. A 50-year-old woman was admitted to the emergency room with complaints of nausea, weakness, and lethargy. Her medical history revealed total thyroidectomy two years earlier. She was commenced on L-thyroxine after the surgery. However, the patient stopped the treatment for three months. Thyroid function tests showed free T3 0.80 pg/ml (n: 1.8-4.2), free T4 <0.20 ng/dl (n: 0.8-1.9), TSH 56.84 microU/ml (n: 0.4-4.0). Her biochemical and laboratory investigations were normal, except for a plasma sodium value of 114 mmol/L (n: 135-145). Hypertonic saline treatment with L-thyroxine was immediately started. Symptomatic hyponatremia caused by hypothyroidism was the direct consequence of cessation of L-thyroxine treatment. The patient was followed up for a year and still using L-thyroxine (0.1 mg). In conclusion, it should be kept in mind that life-threatening hyponatremia may occur in patients with total thyroidectomy-induced hypothyroidism; L-thyroxine should be immediately started if stopped for any reason.

The Effects of L-thyroxine Treatment on QT Dispersion in Primary Hypothyroidism

Kweon, Kyoung Hee; Park, Byoung Hyun; Cho, Chung Gu
Fonte: The Korean Academy of Medical Sciences Publicador: The Korean Academy of Medical Sciences
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
47.769624%
Hypothyroidism has various cardiovascular manifestation and exhibits electrocardiographic change. The QT dispersion on surface ECG reflects regional variations in myocardial repolarization. The effect of L-thyroxine treatment on ECG parameters, such as QT dispersion, in patients with primary hypothyroidism were investigated. This study involved 18 patients (3 men, 15 women, ages: 48±18 yr) with primary hypothyroidism. All patients were checked with a standard 12-lead ECG before and after L-thyroxine treatment. Various ECG parameters were then measured twice. The mean L-thyroxine treatment duration was 22±2.7 months. The mean thyroid-stimulating hormone levels of patients before and after therapy were 40.2±29.8 µU/mL, 3.6±4.6 µU/mL (p<0.001) and free-T4 levels were 0.44±0.38 ng/dL, 1.51±0.39 ng/dL (p<0.001). After L-thyroxine treatment, QT interval (395±42 vs. 380±24 msec, p<0.05), QTc interval (434±32 vs. 417±23 msec, p<0.05), QT dispersion (45±23 vs. 30±13 msec, p=0.008), QTc dispersion (49±23 vs. 32±14 msec, p=0.005) significantly decreased. There were no significant changes in the PR and RR intervals, as well as the QRS duration. Our findings suggest that the thyroid hormone affects ventricular inhomogenicity, and that L-thyroxine replacement therapy may reduce malignant ventricular arrhythmia and sudden cardiac death in primary hypothyroidism.

Dry Olive Leaf Extract Counteracts L-Thyroxine-Induced Genotoxicity in Human Peripheral Blood Leukocytes In Vitro

Žukovec Topalović, Dijana; Živković, Lada; Čabarkapa, Andrea; Djelić, Ninoslav; Bajić, Vladan; Dekanski, Dragana; Spremo-Potparević, Biljana
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
47.769624%
The thyroid hormones change the rate of basal metabolism, modulating the consumption of oxygen and causing production of reactive oxygen species, which leads to the development of oxidative stress and DNA strand breaks. Olive (Olea europaea L.) leaf contains many potentially bioactive compounds, making it one of the most potent natural antioxidants. The objective of this study was to evaluate the genotoxicity of L-thyroxine and to investigate antioxidative and antigenotoxic potential of the standardized oleuropein-rich dry olive leaf extract (DOLE) against hydrogen peroxide and L-thyroxine-induced DNA damage in human peripheral blood leukocytes by using the comet assay. Various concentrations of the extract were tested with both DNA damage inducers, under two different experimental conditions, pretreatment and posttreatment. Results indicate that L-thyroxine exhibited genotoxic effect and that DOLE displayed protective effect against thyroxine-induced genotoxicity. The number of cells with DNA damage, was significantly reduced, in both pretreated and posttreated samples (P < 0.05). Comparing the beneficial effect of all tested concentrations of DOLE, in both experimental protocols, it appears that extract was more effective in reducing DNA damage in the pretreatment...

Análise de biomarcadores salivares e plasmáticos após realização de um esforço submáximo em mulheres com hipotireoidismo subclínico tratadas com L-tiroxina sódica

Lamounier, Romeu Paulo Martins Silva
Fonte: Universidade Federal de Uberlândia Publicador: Universidade Federal de Uberlândia
Tipo: Dissertação
Português
Relevância na Pesquisa
57.89522%
CAPÍTULO I: Vários estudos associam o hipotireoidismo subclínico a fatores de risco para doença aterosclerótica, mas poucos correlacionam este distúrbio à diminuição da tolerância ao esforço físico e sua relação com os biomarcadores salivares. Neste contexto, a reposição hormonal com o emprego da L-tiroxina no tratamento destes pacientes permanece controvertida. O exercício induz o aumento no recrutamento de unidades motoras e alterações bioquímicas nos sistemas corporais que modificam a composição de alguns componentes do sangue e saliva, entre outros fluidos corporais. Essas alterações podem ser usadas como indicadores da resposta fisiológica dos vários sistemas. A análise de componentes salivares, tais como, eletrólitos, proteína total e atividade da a-amilase para detectar o limiar salivar (LAsa), e atividade elétrica do músculo para detectar o limiar eletromiográfico (EMGlan) podem representar uma alternativa não invasiva na determinação da intensidade de exercício correspondente ao limiar anaeróbio (LAN). CAPÍTULO II: Pacientes com hipotireoidismo subclínico tratados com L-tiroxina sódica realizaram teste de esforço físico em ciclo ergômetro. Selecionou-se oito voluntários do sexo feminino com idade 51...

Avaliação terapêutica e posológica da levotiroxina sódica em cães com hipotiroidismo primário adquirido; L-levothyroxine therapeutic dosage evaluation in dogs with primary hypothyroidism

De Marco, Viviani; Silva, Roberta M. T.; Karamm, Mariana A.; Florio, Jorge Camilo; Lorigrados, Carla A. B.
Fonte: REVISTA PESQUISA VETERINARIA BRASILEIRA; RIO JANEIRO Publicador: REVISTA PESQUISA VETERINARIA BRASILEIRA; RIO JANEIRO
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
57.93916%
O hipotireoidismo primário adquirido é uma endocrinopatia frequentemente diagnosticada na espécie canina. A terapia consiste na suplementação oral com levotiroxina sódica (L-tiroxina), no entanto vários protocolos terapêuticos têm sido propostos pela literatura, com doses variando 11 a 44µg/kg uma a duas vezes ao dia, visto à grande variabilidade de absorção e meia-vida plasmática do fármaco. Foram estudados 30 cães com hipotiroidismo primário adquirido (13 machos e 17 fêmeas, idade média de 7,9±1,9 anos e peso médio de 19,1±12,6 kg) atendidos no Hospital Veterinário da Universidade Guarulhos (UnG) e no Serviço de Endocrinologia de duas clínicas particulares da cidade de São Paulo (2009-2011), com o objetivo de avaliar a posologia e a frequência de administração da L-tiroxina, mais frequentemente utilizada, capaz de garantir um controle terapêutico satisfatório, avaliado através dos sinais clínicos e do teste pós-tiroxina, além de correlacionar a dose de tiroxina empregada com o peso dos animais. A dose média de tiroxina utilizada em nossa casuística foi de 16,9±3,1µg/kg, sendo a frequência de administração a cada 12 horas em 50% dos casos. Para se investigar uma possível correlação entre o peso e a dosagem de tiroxina utilizada...

Serum thyroxine and thyroid stimulating hormone concentrations after treatment of congenital hypothyroidism.

Abusrewil, S S; Tyfield, L; Savage, D C
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /11/1988 Português
Relevância na Pesquisa
47.72335%
Serum thyroid stimulating hormone and thyroxine concentrations were monitored in 42 infants who had been treated for congenital hypothyroidism. Serum thyroid stimulating hormone concentrations were raised in 22 of the infants (52%) at 2 to 4 months, in 16 (38%) at 5 to 11 months, in 14 (33%) at 12 to 18 months, and in eight (19%) at 2 to 4 years. Serum thyroxine and the dose of L-thyroxine/kg/body weight were significantly lower in those infants with raised thyroid stimulating hormone concentrations. Thyroid stimulating hormone was appropriately suppressed when the dose of L-thyroxine was increased, and only one child had delayed maturation of the hypothalamic/pituitary/thyroid axis. We believe it is the infant's rapid gain in weight in the first two years of life that necessitates this decrease in the dose of L-thyroxine/kg body weight and recommend that the treatment of this age group is reviewed every two to three months.

Role of L-thyroxine in nuclear thyroid hormone receptor occupancy and growth hormone production in cultured GC cells.

Halperin, Y; Shapiro, L E; Surks, M I
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/1991 Português
Relevância na Pesquisa
57.18134%
The contribution of L-thyroxine (T4) to nuclear thyroid receptor occupancy was studied in GC cells incubated with concentrations of 3,5,3'-triiodo-L-thyronine (T3) and T4 that resulted in free iodothyronine levels similar to those in serum of euthyroid rats. T4 accounted for 5.4-10% of the occupied receptors: T3 derived from T4 [T3(T4)] and T3 added to medium accounted for the remainder of receptor occupancy. Incubation with increasing medium free T4 resulted in a progressive increase in the contribution of T4 and T3(T4) to receptor occupancy. In incubations with 3.6-fold increased medium free T4, T4 accounted for 20.4%, and T3(T4) for 40.3% of receptor occupancy. These occupancy data and the experimentally determined Ka of thyroid receptor for T3 and T4 allowed calculation of nuclear free iodothyronine concentrations. Nuclear free T3 was 3-6-fold greater than medium free T3 and nuclear [corrected] free T4 was 12-19-fold greater than medium free T4. When GC cells were incubated with decreased medium free T3 and physiological medium free T4, both nuclear receptor occupancy and growth hormone production decreased as well. However, a twofold increase in medium free T4, in the presence of decreased medium free T3, restored receptor occupancy and growth hormone production to or near control values. These findings establish a role for T4 in addition to T3(T4) in nuclear receptor occupancy and biological activity in rat anterior pituitary tissue both in physiologic conditions and when medium free T4 is raised. The findings may have relevance to the sick euthyroid thyroid syndrome in which free T4 may be increased in some patients who have decreased serum free T3.