Effect of UGT1A1, UGT1A3, DIO1 and DIO2 polymorphisms on L-thyroxine doses required for TSH suppression in patients with differentiated thyroid cancer.

AIM: To evaluate the impact of genetic polymorphisms in uridine 5'-glucuronosylytansferases UGT1A1 and UGT1A3 and iodothyronine-deiodinases types 1 and 2 on levothyroxine (T4 ; 3,5,3',5'-triiodo-L-thyronine) dose requirement for suppression of thyrotropin (TSH) secretion in patients with differentiated thyroid cancer (DTC). METHODS: Patients (n = 268) submitted to total thyroidectomy and ablation by (131) I, under T4 therapy for at least 6 months were recruited in three public institutions in Brazil. Multivariate regression modelling was applied to assess the association of T4 dosing with polymorphisms in UGT1A1 (rs8175347), UGT1A3 (rs3806596 and rs1983023), DIO1 (rs11206244 and rs2235544) and DIO2 (rs225014 and rs12885300), demographic and clinical variables. RESULTS: A regression model including UGT1A haplotypes, age, gender, body weight and serum TSH concentration accounted for 39% of the inter-individual variation in the T4 dosage. The association of T4 dose with UGT1A haplotype is attributed to reduced UGT1A1 expression and T4 glucuronidation in liver of carriers of low expression UGT1A1 rs8175347 alleles. The DIO1 and DIO2 genotypes had no influence of T4 dosage. CONCLUSION: UGT1A haplotypes associate with T4 dosage in DTC patients, but the effect accounts for only 2% of the total variability and recommendation of pre-emptive UGT1A genotyping is not warranted.

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

There is a considerable interindividual variation in L-thyroxine [3,5,3',5'-tetraiodo-l-thyronine (T4)] dose required for thyrotropin (thyroid-stimulating hormone) suppression in patients with differentiated thyroid cancer. To investigate whether uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)-mediated T4 glucuronidation in liver affects T4 dose, we genotyped 101 patients for the common UGT1A1-53(TA)n polymorphism and compared T4 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 T4 dose with increasing number of copies of (TA)7 and (TA)8 (P=0.037) and significant difference in T4 dose across the UGT1A1-53(TA)n genotypes (P=0.048) were observed, despite considerable overlap of T4 doses among different genotypes. These results are consistent with reduced T4 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 T4-dose requirement for thyroid-stimulating hormone suppression in a natural clinical setting.

Relation between insulin resistance and hematological parameters in a Brazilian sample.

It has already been demonstrated that insulin resistance (IR) is associated with the stimulation of erythroid progenitors and with increased levels of inflammation markers. Therefore, IR should also be associated with increased red blood cell (RBC) and white blood cell (WBC) count. The aim of this study is to demonstrate that IR is independently associated with altered hematological parameters in a Brazilian sample. We analyzed laboratorial exams from 925 subjects. All data on hematological parameters, insulin resistance (Homeostasis Model Assessment [HOMA]) and lipid levels were included in the analysis. Demographic information included age and gender. HOMA correlated positively with RBC (r= 0.17, p< 0.001), plasma hemoglobin concentrations (r= 0.14, p< 0.001), hematocrit value (r= 0.15, p< 0.001) and WBC (r= 0.17, p< 0.01). Subjects in the upper quartile of IR had higher levels of plasma glucose, fasting insulin, triglycerides, hematocrit, hemoglobin, RBC and WBC count than those in the lower quartile. In conclusion, IR seems to be associated with alterations in several hematological parameters. These hematological alterations may be considered an indirect feature of the IR syndrome.

[Hormonal therapy of menopause: 2004 position of the Department of Female Endocrinology and Andrology of the Brazilian Society of Endocrinology and Metabolism]. / Terapia hormonal da menopausa: posicionamento do Departamento de Endocrinologia Feminina e Andrologia da SBEM em 2004.

After randomized clinical trials produced impact and questions at the medical community on menopause hormonal therapy (MHT), the Department of Female Endocrinology and Andrology of the Brazilian Society of Endocrinology convened a group of specialists to produce an informative, critical and position paper, offering guidelines for those who practice or are called to express their opinion on menopause therapy. MHT is indicated for relief of vasomotor symptoms, maintenance of vaginal tropism, bone mass and collagen preservation, sexual and general well-being. Studies on primary cardiovascular prevention are not conclusive, and thus insufficient to indicate or not MHT for this purpose. Schemes and forms of association should de individualized. Whenever possible, one should use 17-beta estradiol, associated to natural progesterone or its derivatives in women with an intact uterus, at the lowest effective doses. Duration of therapy depends on its aims, and should be periodically re-evaluated through an individual indication/contra-indication balance. Orientation toward a healthier lifestyle, with smoking cessation, adequate calcium intake and a low fat diet, together with regular physical activity is fundamental during menopause.

[Evaluation of the sibutramine effect on satiety with a visual analogue scale in obese adolescents]. / Avaliação do efeito da sibutramina sobre a saciedade por escala visual analógica em adolescentes obesos.

Initially used to measure algic symptoms, visual analogue scales (VAS) can also be useful for the evaluation of satiety. The antiobesity agent sibutramine, unlike anorectic agents, decreases food intake mainly by stimulating satiety. To evaluate the effect of sibutramine on satiety, we used a VAS in obese adolescents participating in a double-blind, randomized trial comparing 10 mg of sibutramine to placebo. Each patient received 13 scales to be checked at hourly intervals, in a single day, from 9 am to 9 pm. A 500 kcal deficit diet was divided into 3 meals, with previously fixed times: 9:30 h, 12:30 h, 18:30 h. Using the scores obtained from each scale, a line graph was designed to represent the average satiety score throughout the day. Comparing the area under the curve for the 2 groups, we found 4.609 +/- 1.309 for the group treated with sibutramine and 4.141 +/- 1.432 for the placebo group, not reaching statistical significance (p= NS). Therefore, sibutramine does not seem do have an effect on satiety of obese adolescents, at least when satiety is evaluated by a VAS.

[Menopause and metabolic syndrome]. / Menopausa e síndrome metabólica.

The incidence of cardiovascular disease increases considerably after the menopause. One reason for the increased cardiovascular risk seems to be determined by metabolic syndrome, in which all components (visceral obesity, dyslipidemia, hypertension, and glucose metabolism disorder) are associated with higher incidence of coronary artery disease. After menopause, metabolic syndrome is more prevalent than in premenopausal women, and may plays an important role in the occurrence of myocardial infarction and other atherosclerotic and cardiovascular morbidities. Obesity, an essential component of the metabolic syndrome, is also associated with increased incidence of breast, endometrial, bowel, esophagus, and kidney cancer. The treatment of metabolic syndrome is based on the change in lifestyle and, when necessary, the use of medication directed to its components. In the presence of symptoms of the climacteric syndrome, hormonal therapy, when indicated, will also contribute to the improvement of the metabolic syndrome.

[Evaluation of TSH cutoff value in blood-spot samples in neonatal screening for the diagnosis of congenital hypothyroidism in the Programa "Primeiros Passos" - IEDE/RJ]. / Avaliação do valor de corte de TSH em amostras de filtro na triagem neonatal para diagnóstico de hipotireoidismo congênito no Programa "Primeiros Passos" - IEDE/RJ.

OBJECTIVE: To analyze the confirmed or not-confirmed cases of neonatal screening (CH) screened in the Programa "Primeiros Passos", stratifying them into TSH blood-spot (TSH-BS) ranges. MATERIALS AND METHODS: To stratify, in ranges of TSH-BS as a function of TSH serum (TSH-S), the cases called for a confirmatory test from January, 2006 to July, 2009. RESULTS: Around 37% of the confirmed cases (475) showed TSH-F > 9.5 mUi/L, but most of the confirmed cases were in lower TSH-F ranges. Among the unconfirmed cases (4,613), most were found in the lower ranges. There was no TSH-F range exclusive to unconfirmed cases. CONCLUSION: TSH-BS cutoff value used is crucial in the diagnosis of CH and should be low, even if more confirmatory tests are performed. More studies are needed to determine the best cutoff value of TSH-BS for neonatal screening.

Determination of insulin-like growth factor-I reference values using an immunoradiometric assay in a Brazilian adult population.

BACKGROUND: Serum levels of total insulin-like growth factor I (IGF-I) reflect endogenous growth hormone (GH) secretion in healthy adults, which makes it a good diagnostic marker for screening of GH-related disorders. Studies also have supported a possible relation between IGF-I levels and the risk and prognostic for some malignancies, besides a relation between IGF-I levels and mortality. OBJECTIVE: As the determination of the IGF-I normal values for local populations is strongly desired, the aim of this investigation was to determine reference values for IGF-I using an immunoradiometric assay (IRMA) in an adult Brazilian population of Rio de Janeiro city, since there is no other study using this methodology in Brazilian population, and that this method is widely used in Brazil and worldwide. MATERIALS AND METHODS: The study included samples of blood taken from 484 healthy subjects (251 men and 233 women) aged 18-70. The subjects agreed with this study, approved by the Ethical Committee of the Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti, Rio de Janeiro, Brazil. The samples were analyzed using a Diagnostic System Laboratories kit. For data analysis, age- and sex-specific figures were fitted after transformation of IGF-I values. RESULTS: In adulthood, a slow age-dependent decrease was found. There was no significant difference in IGF-I values between men and women. CONCLUSION: This study established age-specific IGF-I reference values, for a healthy Brazilian adult population, determined by a widely IGF-I, IRMA used currently in Brazil.

Menopausa e síndrome metabólica / Menopause and metabolic syndrome

A incidência de doença cardiovascular aumenta consideravelmente após a menopausa. Um dos motivos para o crescente risco cardiovascular parece ser determinado pela síndrome metabólica, da qual todos os componentes (obesidade visceral, dislipidemia, hipertensão arterial e distúrbio do metabolismo glicídico) se associam à maior incidência de coronariopatia. Após a menopausa, a síndrome metabólica é mais prevalente do que na pré-menopausa, podendo ter importante papel na ocorrência de infarto do miocárdio e outras morbidades ateroscleróticas e cardiovasculares. A obesidade, componente primordial da síndrome metabólica, se associa ainda ao aumento da incidência de câncer de mama, endométrio, intestino, esôfago e rim. O tratamento da síndrome metabólica se baseia na mudança de hábitos de vida e, quando necessário, no emprego de medicação dirigida aos seus componentes. Na presença de sintomas de síndrome do climatério, a terapia hormonal, quando indicada, concorrerá também para a melhora da síndrome metabólica.

The incidence of cardiovascular disease increases considerably after the menopause. One reason for the increased cardiovascular risk seems to be determined by metabolic syndrome, in which all components (visceral obesity, dyslipidemia, hypertension, and glucose metabolism disorder) are associated with higher incidence of coronary artery disease. After menopause, metabolic syndrome is more prevalent than in premenopausal women, and may plays an important role in the occurrence of myocardial infarction and other atherosclerotic and cardiovascular morbidities. Obesity, an essential component of the metabolic syndrome, is also associated with increased incidence of breast, endometrial, bowel, esophagus, and kidney cancer. The treatment of metabolic syndrome is based on the change in lifestyle and, when necessary, the use of medication directed to its components. In the presence of symptoms of the climacteric syndrome, hormonal therapy, when indicated, will also contribute to the improvement of the metabolic syndrome.

[Diabetes and autoimmune diseases: prevalence of celiac disease in children and adolescents with type 1 diabetes]. / Diabetes e doenças auto-imunes: prevalência de doença celíaca em crianças e adolescentes portadores de diabetes melito tipo 1.

OBJECTIVE: Determine the prevalence of celiac disease in children and adolescents with type 1 diabetes mellitus (DM1) in attendance in Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione (IEDE). METHODS: Blood samples were analyzed in 120 children and adolescents with DM1 from IEDE Diabetes Clinic for the IgA antitissue-transglutaminase antibody and dosage of the seric IgA. Those with positive serology were guided for upper endoscopy with small-bowel biopsy to confirm the celiac disease. RESULTS: The antibody was positive in 3 of the 120 patients. The small-bowel biopsy was confirmatory in all of the positive patients, leading to a prevalence of celiac disease of 2.5% in the studied group. CONCLUSIONS: The prevalence of celiac disease is increased in children and adolescents with DM1 when compared with normality. As most are asymptomatic, it is recommended periodical screening of celiac disease in children with DM1.

Avaliação do valor de corte de TSH em amostras de filtro na triagem neonatal para diagnóstico de hipotireoidismo congênito no Programa "Primeiros Passos" - IEDE/RJ / Evaluation of TSH cutoff value in blood-spot samples in neonatal screening for the diagnosis of congenital hypothyroidism in the Programa "Primeiros Passos" - IEDE/RJ

OBJETIVO: Analisar casos de hipotireoidismo congênito (HC) confirmados ou não, triados pelo Programa "Primeiros Passos", estratificando-os em faixas de TSH em filtro (TSH-F). MATERIAIS E MÉTODOS: Estratificar, em faixas de TSH-F em função do TSH em soro (TSH-S), os casos convocados para teste confirmatório de janeiro/2006 a julho/2009. RESULTADOS: Cerca de 37% dos casos confirmados (475) apresentaram TSH-F > 9,5 mUi/L, mas a maioria dos casos confirmados estava nas faixas de TSH-F mais baixas. Entre os casos não confirmados (4.613), a maior parte se encontrava nas faixas mais baixas. Não houve faixa de TSH-F exclusiva dos casos não confirmados. CONCLUSÃO: O valor de corte do TSH-F utilizado é fundamental no diagnóstico do HC e deve ser baixo, mesmo que sejam realizados mais testes confirmatórios. Mais estudos são necessários para determinar o melhor valor de corte de TSH-F para triagem neonatal.

OBJECTIVE: To analyze the confirmed or not-confirmed cases of neonatal screening (CH) screened in the Programa "Primeiros Passos", stratifying them into TSH blood-spot (TSH-BS) ranges. MATERIALS AND METHODS: To stratify, in ranges of TSH-BS as a function of TSH serum (TSH-S), the cases called for a confirmatory test from January, 2006 to July, 2009. RESULTS: Around 37% of the confirmed cases (475) showed TSH-F > 9.5 mUi/L, but most of the confirmed cases were in lower TSH-F ranges. Among the unconfirmed cases (4,613), most were found in the lower ranges. There was no TSH-F range exclusive to unconfirmed cases. CONCLUSION: TSH-BS cutoff value used is crucial in the diagnosis of CH and should be low, even if more confirmatory tests are performed. More studies are needed to determine the best cutoff value of TSH-BS for neonatal screening.

Determination of insulin-like growth factor-I reference values using an immunoradiometric assay in a Brazilian adult population.

Background: Serum levels of total insulin-like growth factor I (IGF-I) reflect endogenous growth hormone (GH) secretion in healthy adults, which makes it a good diagnostic marker for screening of GH-related disorders. Studies also have supported a possible relation between IGF-I levels and the risk and prognostic for some malignancies, besides a relation between IGF-I levels and mortality. Objective: As the determination of the IGF-I normal values for local populations is strongly desired, the aim of this investigation was to determine reference values for IGF-I using an immunoradiometric assay (IRMA) in an adult Brazilian population of Rio de Janeiro city, since there is no other study using this methodology in Brazilian population, and that this method is widely used in Brazil and worldwide. Materials and Methods: The study included samples of blood taken from 484 healthy subjects (251 men and 233 women) aged 18-70. The subjects agreed with this study, approved by the Ethical Committee of the Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti, Rio de Janeiro, Brazil. The samples were analyzed using a Diagnostic System Laboratories kit. For data analysis, age- and sex-specific figures were fitted after transformation of IGF-I values. Results: In adulthood, a slow age-dependent decrease was found. There was no significant difference in IGF-I values between men and women. Conclusion: This study established age-specific IGF-I reference values, for a healthy Brazilian adult population, determined by a widely IGF-I, IRMA used currently in Brazil.

Diabetes e doenças auto-imunes: prevalência de doença celíaca em crianças e adolescentes portadores de diabetes melito tipo 1 / Diabetes and autoimmune diseases: prevalence of celiac disease in children and adolescents with type 1 diabetes

OBJETIVO: Determinar a prevalência de doença celíaca em crianças e adolescentes portadores de diabetes melito tipo1 (DM1) no Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione (IEDE). MÉTODOS: Foram analisadas amostras de sangue de 120 crianças e adolescentes portadores de DM1 do Ambulatório de Diabetes do IEDE para a pesquisa do anticorpo antitransglutaminase tecidual humana IgA e dosagem da IgA sérica. Aqueles com sorologia positiva foram encaminhados para endoscopia digestiva alta com biópsia de intestino delgado para a confirmação da doença celíaca. RESULTADOS: O anticorpo foi positivo em três dos 120 pacientes analisados. Todos os positivos apresentaram biópsia de intestino delgado confirmatória para doença celíaca, gerando prevalência desta doença no grupo estudado de 2,5 por cento. CONCLUSÃO: A prevalência de doença celíaca encontra-se aumentada entre crianças e adolescentes com DM1 acompanhadas no IEDE quando comparadas à normalidade. Como a maioria é assintomática, recomenda-se o rastreamento periódico desta doença em todas as crianças com DM1.

OBJECTIVE: Determinate the prevalence of celiac disease in children and adolescents with type 1 diabetes mellitus (DM1) in attendance in Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione (IEDE). METHODS: Blood samples were analyzed in 120 children and adolescents with DM1 from IEDE Diabetes Clinic for the IgA antitissue-transglutaminase antibody and dosage of the seric IgA. Those with positive serology were guided for upper endoscopy with small-bowel biopsy to confirm the celiac disease. RESULTS: The antibody was positive in 3 of the 120 patients. The small-bowel biopsy was confirmatory in all of the positive patients, leading to a prevalence of celiac disease of 2.5 percent in the studied group. CONCLUSIONS: The prevalence of celiac disease is increased in children and adolescents with DM1 when compared with normality. As most are asymptomatic, it is recommended periodical screening of celiac disease in children with DM1.

Relation between insulin resistance and hematological parameters in a Brazilian sample

Já foi demonstrado que a resistência à insulina (RI) está associada com a estimulação de progenitores eritrocitários e com níveis aumentados de marcadores inflamatórios. Desta maneira, a RI pode também estar associada o aumento de hemácias e leucócitos. Esse estudo objetivou demonstrar que a RI está independentemente associada com a alteração de parâmetros hematológicos em uma amostra da população brasileira. Nós analisamos exames laboratoriais de 925 indivíduos, incluindo todos os dados de parâmetros hematológicos, resistência insulínica (homeostasis model assessment - HOMA) e níveis lipídicos. Informação demográfica incluiu idade e gênero. HOMA correlacionou-se positivamente com a contagem de eritrócitos (r= 0,17; p<0,001), a concentração de hemoglobina (r= 0,14; p<0,001), o hematócrito (r= 0,15; p<0,001) e a contagem de leucócitos (r= 0,17; p<0,01). Indivíduos no quartil superior de RI tinham níveis mais elevados de glicemia, insulina de jejum, triglicérides, hematócrito, hemoglobina e contagem de leucócitos e eritrócitos do que aqueles no quartil inferior. Em conclusão: a RI parece estar associada com alterações em diversos parâmetros hematológicos. Essa alterações hematológicas podem ser consideradas um achado indireto da síndrome de resistência insulínica.

Terapia hormonal da menopausa: posicionamento do Departamento de Endocrinologia Feminina e Andrologia da SBEM em 2004 / Hormonal therapy of menopause: 2004 position of the Department of Female Endocrinology and Andrology of the Brazilian Society of Endocrinology and Metabolism

Após os estudos clínicos randomizados produzirem impacto e questionamentos sobre terapia hormonal da menopausa (THM) na comunidade médica, o Departamento de Endocrinologia Feminina e Andrologia da SBEM reuniu um grupo de especialistas para formular um documento informativo, crítico e de posicionamento que pudesse servir de orientação aos que praticam ou opinam sobre tratamento da menopausa. THM está indicada para alívio dos sintomas motores, conservação do trofismo vaginal, preservação de massa óssea e colágeno, melhora do bem estar e sexualidade. Os estudos sobre prevenção cardiovascular primária não são conclusivos, portanto insuficientes para indicar ou deixar de indicar THM com este objetivo. Esquemas e tipos de associação devem ser individualizados. Sempre que possível deve-se optar pelas menores doses eficazes de 17-beta estradiol, associado a progesterona natural ou seus derivados nas mulheres com útero. A duração do tratamento é vinculada a seus objetivos, devendo ser reavaliada periodicamente através de um balanço individual entre indicação e contra-indicação. Orientação quanto a um estilo de vida mais saudável, com eliminação de tabagismo, alimentação adequada em cálcio e pobre em gorduras e atividade física regular são fundamentais como cuidados associados durante a menopausa.

Avaliacão do efeito da sibutramina sobre a saciedade por escala visual analógica em adolescentes obesos / Evaluation of the sibutramine effect on satiety with a visual analogue scale in obese adolescents

Inicialmente empregadas para mensuracão de sintomas álgicos, as escalas visuais analógicas (EVAs) podem ser também um instrumento útil para avaliacão da saciedade. O agente antiobesidade sibutramina, ao contrário dos anorexígenos, parece exercer seu efeito de reducão de ingestão alimentar principalmente por estímulo da saciedade. Com o objetivo de avaliar o efeito da sibutramina sobre a saciedade, utilizamos uma EVA em adolescentes obesos que participaram de um estudo duplo-cego randomizado, comparando sibutramina 10mg com placebo. Cada paciente recebeu 13 escalas para serem preenchidas em intervalos de uma hora, num único dia, das 9 às 21h. Uma dieta com déficit de 500kcal diárias foi dividida em 3 refeicões, com horários previamente estipulados: 9:30h, 12:30h, 18:30h. A partir da pontuacão obtida em cada uma das escalas, construiu-se um gráfico de linha representativo da pontuacão média de saciedade ao longo do dia. Comparando-se a área sob a curva dos 2 grupos, encontramos 4.609 n 1.309 para o grupo tratado com sibutramina e 4.141 n 1.432 para o grupo placebo (p= NS). Desta forma, a sibutramina não parece apresentar efeito sobre a saciedade de adolescentes obesos, pelo menos quando avaliado através de uma EVA.

Associaçäo entre traços de personalidade e sintomas depressivos em mulheres com síndrome do climatério / Association between personality traits and depressive symptoms in woman with climacteric syndrome

O climatério é reconhecido como um período da vida da mulher associado a um aumento de sintomas psiquiátricos. O objetivo deste estudo foi o de investigar as possíveis relaçöes entre alguns traços de personalidade hipocondríacos no aparecimento de determinados sintomas depressivos nessa populaçäo. Cento e dezoito (118) mulheres que procuraram atendimento para os sintomas associados ao climatério foram avaliadas; 43 mulheres entre 45 e 55 anos, todas na pós-menopausa e com sintomas somáticos e psicológicos da síndrome do climatério, foram selecionadas para o estudo. Os sintomas somáticos da síndrome foram avaliados pelo índice menopáusico (MI). Os sintomas psicológicos foram avaliados pelas escalas de Hamilton Depressäo (HAM-D) e pelo inventário multifásico Minnesota de personalidade (MMPI). As paciente foram divididas em 2 grupos, de acordo com o critério de gravidade dos sintomas depressivos encontrados. O grupo I era constituído por 22 pacientes com pontuaçöes >/= 15 na escala HAM-D e o grupo II por 21 pacientes com pontuaçöes < 15 na HAM-D. Näo observamos aumento significativo dos traços de personalidade da "tríade neurótica" do MMPI, considerados característicos de um comportamento hipocondríaco no grupo I, comparado ao grupo II. Pudemos concluir que o surgimento de sintomatologia depressiva na síndrome do climatério nessa populaçäo näo parece estar relacionado com a presença de traços hipocondríacos prévios.