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Objective: We aimed to investigate the role of DIO2 polymorphisms rs225014 and rs12885300 in Graves’ disease patients, mainly for controlling body weight following treatment. Subjects and methods: We genotyped 280 GD patients by the time of diagnosis and 297 healthy control individuals using a TaqMan SNP Genotyping technique. We followed up 141 patients for 18.94 ± 6.59 months after treatment. Results: There was no relationship between the investigated polymorphisms with susceptibility to GD and gain or loss of weight after GD treatment. However, the polymorphic inheritance (CC+CT genotype) of DIO2 rs225014 was associated with a lower body weight variation after GD treatment (4.26 ± 6.25 kg) when compared to wild type TT genotype (6.34 ± 7.26 kg; p = 0.0456 adjusted for the follow-up time). This data was confirmed by a multivariate analysis (p = 0.0138) along with a longer follow-up period (p = 0.0228), older age (p = 0.0306), treatment with radioiodine (p-value = 0.0080) and polymorphic inheritance of DIO2 rs12885300 (p = 0.0306). Conclusion: We suggest that DIO2 rs225014 genotyping may have an auxiliary role in predicting the post-treatment weight behavior of GD patients.

A tireotoxicose é uma rara síndrome clínica decorrente da exacerbação do hipertireoidismo, de etiologia e fatores desencadeantes diversos. A abordagem terapêutica pode ser realizada por meio de medicamentos para bloqueio da síntese, secreção e/ou inibição da ação periférica hormonal, além de terapia dirigida aos fatores desencadeantes. Entretanto, em casos refratários, a plasmaférese surge como importante opção de tratamento. Relatamos o caso de um paciente com doença de Graves, internado com quadro de hepatotoxicidade grave por propiltiouracil, que evoluiu com tireotoxicose, sendo indicada plasmaférese para rápida redução dos hormônios tireoidianos, em preparo para a tireoidectomia total.

Orientadores: Laura Sterian Ward, Danilo Glauco Pereira Villagelin Neto Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas Resumo: A Doença de Graves (DG) se caracteriza pela perda de tolerância imunológica à antígenos comuns à tireoide e outros órgãos afetados, desencadeando a produção de anticorpos que irão competir com o TSH e mimetizar suas ações, sustentando uma reação autoimune caracterizada por bócio e hipertireoidismo de elevada relação triiodotironina/tiroxina (T3/T4). Frente à doença ativa, a resposta adaptativa ao aumento da taxa metabólica basal é a perda ponderal, sendo o ganho de peso via de regra à medida que a função tireoidiana se restabelece. Contudo, há grande variabilidade na magnitude deste ganho e os fatores preditores ainda são pouco estudados. A deiodinase tipo 2 (D2) é uma enzima que contribui prioritariamente para a sinalização intracelular do hormônio tireoidiano e, por consequência, para as ações genômicas mediadas por T3. O AMP cíclico e o T3 são reguladores transcricionais do gene DIO2. O RNA mensageiro deste gene encontra se super expresso na tireoide afetada por DG e também expresso no pré adipócito humano, no tecido adiposo branco e marrom, no hipotálamo, na hipófise e no músculo esquelético; que são tecidos envolvidos na regulação do peso corporal e na patogênese da orbitopatia de Graves (OG). O T3 é capaz de modular a reposta imunológica. Os polimorfismos do gene DIO2 rs225014, rs12885300 e rs225015 podem alterar funcionalmente esta enzima. Neste estudo foram genotipados 280 casos de DG e 297 indivíduos controle pela técnica de Taqman SNP Genotyping para investigar a relação entre os polimorfismos do DIO2 rs225014, rs12885300 e rs225015 com as características clínicas exibidas pelos pacientes com DG (suscetibilidade, variação do peso corporal pós-tratamento, atividade da OG ao diagnóstico e anticorpos tireoidianos). Observamos que a herança polimórfica do DIO2 rs225014 associou se com a menor variação do peso corporal após o tratamento da DG, sugerindo seu papel auxiliar para predizer o comportamento ponderal pós-tratamento Abstract: Graves' disease (GD) is characterized by the loss of immune tolerance to antigens common to the thyroid and other affected organs, triggering the production of antibodies that will compete with TSH and mimic their actions, supporting an autoimmune reaction characterized by goiter and hyperthyroidism of high triiodothyronine to thyroxine ratio (T3/T4). In the face of active disease, the adaptive response to the increase in basal metabolic rate is weight loss, with weight gain being the rule as thyroid function reestablishes. However, there is great variability in the magnitude of this gain and the predictive factors are still poorly studied. Deiodinase type 2 (D2) is an enzyme that contributes primarily to the intracellular signaling of the thyroid hormone and, consequently, to the T3-mediated genomic actions. Cyclic AMP and T3 are transcriptional regulators of the DIO2 gene. The mRNA of DIO2 gene is overexpressed in the thyroid affected by GD and expressed in the human adipocyte, white and brown adipose tissue, hypothalamus, pituitary and skeletal muscle, which are tissues involved in the regulation of body weight and in the pathogenesis of Graves' orbitopathy (GO). T3 can modulate the immune response. The polymorphisms of the DIO2 gene 225014, rs12885300 and rs225015 can functionally modify this enzyme. In this study 280 cases of DG and 297 control individuals were genotyped by the Taqman SNP Genotyping technique to investigate the relationship between DIO2 polymorphisms rs225014, rs12885300 and rs225015 with the clinical characteristics exhibited by the patients with GD (susceptibility, post-treatment body weight variation, GO activity at diagnosis, and thyroid antibodies). We observed that the polymorphic inheritance of DIO2 rs225014 was associated with the lower body weight variation after GD treatment, suggesting its auxiliary role in predicting post-treatment weight behavior Mestrado Clínica Médica Mestra em Ciências CAPES

Objectives Evaluate the management of hypothyroidism in fertile-aged and pregnant women and compare these practices to the recommendations of the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Latin American Thyroid Society, published in 2013. Materials and methods In the first trimester of 2014, SBEM made available to all members an electronic questionnaire based on clinical scenarios in the management of gestational hypothyroidism. The responses of 406 physicians, most of them endocrinologists, were analyzed. Results Eighty-one per cent of the endocrinologists screen all their pregnant patients for thyroid dysfunction, mostly during the pregestational period or after the first prenatal visit. Following screening, 82% of the respondents initiate treatment when TSH levels are > 2.5 mIU/L while 67% monitor their pregnant patients even if TSH was normal on first trimester screening. For hypothyroid women who are planning pregnancy, 96% of the clinicians are aware of the importance of adjusting the levothyroxine (LT4) dose as soon as pregnancy is confirmed. However, opinions diverge with respect to adjusting the LT4 dose before or after reassessing thyroid function. The most widely used tests for monitoring pregnant women in use of LT4 are TSH and free T4 (62%) or TSH alone (21%). Unanimously, the treatment goal is to achieve the target TSH level for each trimester of gestation. Conclusion The recommendations of the consensus statements are incorporated into the respondents’ clinical practice. It is noteworthy that the great majority of the clinicians favor universal screening.

Thyrotoxicosis is a rare clinical syndrome resulting from an exacerbation of hyperthyroidism, with various etiology and triggering factors. Its approach may be accomplished by blocking the synthesis of hormones, their secretion and/or inhibition of their peripheral action, besides treating the triggering factors. However, in refractory cases, plasmapheresis appears as an important option for treatment. We report a patient with Graves' disease who was admitted with thyrotoxicosis and signs of severe hepatotoxicity induced by propylthiouracil. Plasmapheresis was indicated, with the aim of rapidly reducing thyroid hormones in the preparation for total thyroidectomy.