O hipertireoidismo da doença de Graves é a forma mais comum de hipertireoidismo em pacientes entre 20-50 anos. Três abordagens terapêuticas são atualmente utilizadas, drogas antitireoidiana, cirurgia e iodo radioativo (131I). O iodo radioativo tem sido cada vez mais aceito como primeira escolha terapêutica, porque é um tratamento seguro, definitivo e de fácil administração. O risco de piora do quadro de tireotoxicose após administração do 131I, os fatores prognósticos de falência e o cálculo da dose administrada têm sido alguns dos aspectos discutidos na literatura recentemente, e constituem o foco desta artigo. Em pacientes com bócios pequenos (<30g), crianças e adolescentes, e em situações especiais como na gravidez, as drogas antitireoidianas ainda é a primeira escolha no tratamento para a maioria dos autores. O tratamento cirúrgico é, atualmente, quase um tratamento de exceção, com indicação restrita para os casos em que as terapias anteriores não possam ser utilizadas. / Graves’ disease is the most frequent cause of hyperthyroidism and current treatment options are antithyroid drugs, radioiodine (131I) and surgery. Radioactive iodine is increasingly being used as definitive therapy, because it long has proven to be a safe, cheap and effective treatment. The risk of exacerbation of hyperthyroidism after 131I administration, factors that may predict the response to radioiodine and the dose to be administrated have been discussed in the literature and we comment the controversies in this review. In patients with mild disease, small goiters, children, adolescents and in special situations, as pregnancy, antityhyroid drugs are still the first choice of treatment for most authors. Surgery is rarely employed, and it is indicated only in cases where antithyroid drugs have not been effective and radioiodine is contraindicated or not acceptable by the patients.

O hipertireoidismo da doença de Graves é a forma mais comum de hipertireoidismo em pacientes entre 20-50 anos. Três abordagens terapêuticas são atualmente utilizadas, drogas antitireoidiana, cirurgia e iodo radioativo (131I). O iodo radioativo tem sido cada vez mais aceito como primeira escolha terapêutica, porque é um tratamento seguro, definitivo e de fácil administração. O risco de piora do quadro de tireotoxicose após administração do 131I, os fatores prognósticos de falência e o cálculo da dose administrada têm sido alguns dos aspectos discutidos na literatura recentemente, e constituem o foco desta artigo. Em pacientes com bócios pequenos (<30g), crianças e adolescentes, e em situações especiais como na gravidez, as drogas antitireoidianas ainda é a primeira escolha no tratamento para a maioria dos autores. O tratamento cirúrgico é, atualmente, quase um tratamento de exceção, com indicação restrita para os casos em que as terapias anteriores não possam ser utilizadas. / Graves’ disease is the most frequent cause of hyperthyroidism and current treatment options are antithyroid drugs, radioiodine (131I) and surgery. Radioactive iodine is increasingly being used as definitive therapy, because it long has proven to be a safe, cheap and effective treatment. The risk of exacerbation of hyperthyroidism after 131I administration, factors that may predict the response to radioiodine and the dose to be administrated have been discussed in the literature and we comment the controversies in this review. In patients with mild disease, small goiters, children, adolescents and in special situations, as pregnancy, antityhyroid drugs are still the first choice of treatment for most authors. Surgery is rarely employed, and it is indicated only in cases where antithyroid drugs have not been effective and radioiodine is contraindicated or not acceptable by the patients.

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O hipertireoidismo da doença de Graves é a forma mais comum de hipertireoidismo em pacientes entre 20-50 anos. Três abordagens terapêuticas são atualmente utilizadas, drogas antitireoidiana, cirurgia e iodo radioativo (131I). O iodo radioativo tem sido cada vez mais aceito como primeira escolha terapêutica, porque é um tratamento seguro, definitivo e de fácil administração. O risco de piora do quadro de tireotoxicose após administração do 131I, os fatores prognósticos de falência e o cálculo da dose administrada têm sido alguns dos aspectos discutidos na literatura recentemente, e constituem o foco desta artigo. Em pacientes com bócios pequenos (<30g), crianças e adolescentes, e em situações especiais como na gravidez, as drogas antitireoidianas ainda é a primeira escolha no tratamento para a maioria dos autores. O tratamento cirúrgico é, atualmente, quase um tratamento de exceção, com indicação restrita para os casos em que as terapias anteriores não possam ser utilizadas. / Graves’ disease is the most frequent cause of hyperthyroidism and current treatment options are antithyroid drugs, radioiodine (131I) and surgery. Radioactive iodine is increasingly being used as definitive therapy, because it long has proven to be a safe, cheap and effective treatment. The risk of exacerbation of hyperthyroidism after 131I administration, factors that may predict the response to radioiodine and the dose to be administrated have been discussed in the literature and we comment the controversies in this review. In patients with mild disease, small goiters, children, adolescents and in special situations, as pregnancy, antityhyroid drugs are still the first choice of treatment for most authors. Surgery is rarely employed, and it is indicated only in cases where antithyroid drugs have not been effective and radioiodine is contraindicated or not acceptable by the patients.

Made available in DSpace on 2014-10-09T12:23:56Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:06:47Z (GMT). No. of bitstreams: 1 01284.pdf: 4352198 bytes, checksum: f153ada9e8c083a925fdcac3eedb0d46 (MD5) / Tese (Docencia) / IEA/T / Faculdade de Medicina, Universidade de Sao Paulo - FM/USP

Reactive oxygen species (ROS) such as superoxide radical anion (O2•¯), hydroxylradical (OH•), hydrogen peroxide (H2O2) and peroxynitrite (ONOO-) that are produced during the metabolism of oxygen under oxidative stress in aerobic organisms destroy several key biomolecules and lead to a number of disease states. Mammalian systems possess several effective defense mechanisms including antioxidant enzymes to detoxify these ROS. The selenocysteine-containing Glutathione peroxidase (GPx) is particularly an efficient enzyme in the detoxification of H2O2 and other hydroperoxides by using glutathione (GSH) as cofactor. The chemistry at the active siteof GPx has been extensively investigated with the help of synthetic selenium compounds. Although the anti-inflammatory compound ebselen(2-phenyl-1,2-benzoisoselenazol-3(2H)-one) is undergoing phase III clinical trial as antioxidant, the chemistry of ebselen is still not understood. The present study on a number of ebselen derivatives with various N-substitutions reveals that the substitution at the N atom is important for the antioxidant activity. This study also suggests that the nature for thiol cofactor has a dramatic effect on the GPx activity of ebselen derivatives. It has been shown that ebselen exhibits very poor catalytic activity in the presence of aromatic thiols mainly due to strong Se….O nonbonded interactions that lead to extensive thiol exchange reactions in the selenenyl sulfide intermediate. To prevent the se….O interactions, a series of tertiary amide-based diselenides have been synthesized along with their secondary amide counterparts. Detailed structure-activity correlation studies reveal that the GPx-like activity of the sec-amide-based compounds can be significantly enhanced by the substitution at the free-NH group of sec-amide functionality. The N,N-dialkylbenzylamine-based diselenides exhibit their catalytic activities via the generation of selenols which was confirmed by the reaction with anti-arthritic gold(I) compounds. Interestingly, the replacement of the hydrogen atom at the 6th position of the benzene ring of N,N-dialkylbenzylamine-based diselenides by a methoxy group prevents the thiol exchange reactions mainly be weakening the Se…N interactions and thus enhances the GPx activity. On the other hand, the catalytic activity of the tert-amine-based diselenides can also be increased by replacing the tert-amino groups with the corresponding sec-amine moieties. It has been observed that the basic amino group in the amine-based diselenides deprotonates the selenol and also the thiol cofactor, which is crucial for the higher catalytic activities of the amine-based compounds. Peroxynitrite (PN, ONOO), a strong nitrating agent, is known to inactivate a number of proteins, enzymes and other biomolecules by nitration of tyrosine residues. In this study, we have shown that the commonly used antithyroid drugs and their analogues inhibit protein tyrosine nitration. This study reveals that antithyroid agents having PN scavenging activity may be beneficial of hyperthyroidism as these compounds may protect the thyroid gland from nitrative or nitrosative stress.