Mutação E449X no receptor β do hormônio tireoidiano associada com doença tireoidiana auto-imune e retardo neuropscicomotor grave

OBJECTIVE: To report the clinical and molecular aspects of a patient with a diagnosis of Resistance to Thyroid Hormone (RTH) harboring the E449X mutation associated with autoimmune thyroid disease and severe neuropsychomotor retardation. METHODS: We present a case report including clinical and laboratory findings, and molecular analysis of a Brazilian patient with RTH. RESULTS: A 23-year old male presented hyperactivity disorder, attention deficit, delayed neuropsychomotor development, and goiter. Since the age of 1 year and 8 months, his mother had sought medical care for her son for the investigation of delayed neuropsychomotor development associated with irritability, aggressiveness, recurrent headache, profuse sudoresis, intermittent diarrhea, polyphagia, goiter, and low weight. Laboratory tests revealed normal TSH, increased T3, T4, antithyroglobulin and antimicrosomal antibody titers. Increasing doses of levothyroxine were prescribed, reaching 200 µg/day, without significant changes in his clinical-laboratory picture. Increasing doses of tiratricol were introduced, with a clear clinical improvement of aggressiveness, hyperactivity, tremor of the extremities, and greater weight gain. Molecular study revealed a nonsense mutation in exon 10, in which a substitution of a guanine to tyrosine in nucleotide 1345 (codon 449) generates the stop codon TAA, confirming the diagnosis of RTH. CONCLUSION: This patient has severe neuropsychomotor retardation not observed in a single previous report with the same mutation. This may reflect the lack of a genotype-phenotype correlation in affected cases with this syndrome, suggesting that genetic variability of factors other than β receptor of thyroid hormone (TRβ) might modulate the phenotype of RTH.OBJETIVOS: Descrever aspectos clínicos e moleculares de um paciente com resistência ao hormônio tireoidiano (RHT) portador da mutação E449X associada a doença tireoideana auto-imune e retardo neuropscicomotor grave. MÉTODOS: Relatamos um caso incluindo achados clínicos, laboratoriais e análise molecular de um paciente brasileiro com RHT. RESULTADOS: Paciente masculino, 23 anos de idade, apresentou-se com distúrbio de hiperatividade, déficit de atenção, retardo no desenvolvimento neuropsicomotor e bócio. Desde 1 ano e 8 meses de idade, sua mãe procurou assistência médica para investigação do retardo do desenvolvimento neuropsicomotor associado com irritabilidade, agressividade, cefaléia recorrente, sudorese profusa, diarréia intermitente, polifagia, bócio e perda de peso. Avaliação laboratorial evidenciou TSH normal e aumento do T3, T4 e anticorpos antimicrossomal e antitireoglobulina. Doses crescentes de levotiroxina foram prescritas, máximo de 200 µg/dia, sem significativas alterações em seu quadro clínico-laboratorial. Doses crescentes de tiratricol foram introduzidas com melhora clínica evidente da agressividade, da hiperatividade, do tremor de extremidades e maior ganho de peso. O estudo molecular revelou uma mutação nonsense no éxon 10, no qual a substituição da guanina pela tirosina no nucleotídeo 1345 (códon 449) gerou um stop códon TAA, confirmando o diagnóstico da RHT. CONCLUSÃO: Este paciente tem um grave retardo neuropiscomotor não observado em um relato único anterior com a mesma mutação. Isto pode refletir a falta de relação genotipo-fenótipo nos casos afetados com esta síndrome sugerindo que a variabilidade genética de outros fatores, além do receptor do hormônio tireoidiano (HT), possa modular o fenótipo da RHT

Cardiovascular risk factors in patients with premature myocardial infarction and in their first-degree relatives[

INTRODUÇÃO: O Infarto agudo do miocárdio (IAM) é infrequente em indivíduos jovens (<45 anos) e está associado à história familiar precoce de doença cardiovascular.OBJETIVO: O presente estudo descreveu o perfil sócio-demográfico e os fatores de risco cardiovascular de indivíduos com diagnóstico de IAM < 45 anos de idade e seus familiares de primeiro grau. Avaliou-se também a relação de parâmetros clínico-laboratoriais de acordo com a extensão angiográfica da doença arterial coronária (DAC) dos casos índices (doença uniarterial vs. multiarterial) e dos seus respectivos familiares.MÉTODOS: Estudo transversal realizado de novembro de 2010 a janeiro de 2015 em hospital terciário em Fortaleza, Ceará. Foram incluídos 103 casos índices e 166 familiares de primeiro grau que não apresentavam suspeita de hipercolesterolemia familiar. Estes foram comparados com 111 indivíduos assintomáticos e sem história familiar de DAC pareados para sexo e idade. Foram avaliados os parâmetros clínicos e laboratoriais dos 3 grupos. Os dados foram estudados por análises uni e multivariadas. RESULTADOS:O grupo casos apresentou maior prevalência de tabagismo (57,3 vs. 28,6%, p < 0,001), diabete melito tipo 2 - DM2 (43,4 vs. 19,5%, p < 0,001) e hipertensão arterial sistêmica - HAS (42,7 vs. 19%, p < 0,001) quando comparado aos familiares pareados para sexo e idade. Da mesma forma, os casos, quando comparados ao grupo controle, apresentaram, além destes fatores, concentrações mais elevadas de triglicerídeos (192 ± 75 vs. 140±74mg/dL, p < 0,001), menores concentrações de HDL-c (36 ± 12 vs. 48 ± 14mg/dL, p < 0,001) e uma maior prevalência de síndrome metabólica -SM (82,2 vs. 36%, p<0,001). Observou-se que 50,5% dos casos tinham acometimento multiarterial. Após análise multivariada, a HAS (p=0,030) e o DM2 (p=0,028) associaram-se de forma independente à DAC multiarterial. Quando comparados ao grupo controle, os familiares apresentaram maior prevalência de tabagismo (29,5 vs. 6,3%, p < 0,001), DM2 (19,9 vs. 1,8%, p < 0,001), pré-diabetes (40,4 vs. 27%, p < 0,024) e SM (64,7 vs. 36% p < 0,001). Foram observadas aindaconcentrações mais baixas de HDL-c (39±10 vs. 48 ± 14mg/dL, p < 0,001), valores mais elevados de triglicerídeos (179 ± 71 vs. 140 ± 74mg/dL, p = 0,002), LDL-c (122±37 vs. 113±36mg/dL, p = 0,031) e colesterol não-HDL (157 ± 43 vs. 141 ± 41mg/dL, p = 0,004) nos familiares. Não houve diferenças entre familiares e controles quanto ao IMC (p=0,051). Os familiares também apresentaram maior prevalência do risco calculado como alto/intermediário de acordo com o escore de Framingham (82,7 vs. 2,6%, p < 0,001) em relação aos controles. Os valores de TSH foram maiores, mesmo dentro do valor de referência do método, no grupo de casos (2,6 ± 1,6 vs. 1,9 ± 1,0 mUI/L, p < 0,001) e familiare (2,4±1,6 vs. 1,9 ± 1,0 mUI/L, p=0,002) em relação aos controles. CONCLUSÃO: Evidenciou-seelevada prevalência de fatores de risco cardiovascular, principalmente a SM, dislipidemia aterogênica, DM2, HAS e tabagismo em casos e familiares de primeiro grau de indivíduos com IAM < 45 anos. A HAS e o DM2 associaram-se à maior extensão angiográfica da DACBACKGROUND: The acute myocardial infarction (AMI) is uncommon in young individuals ( < 45 years), and is associated with premature family history of cardiovascular disease. OBJECTIVE: This study described the socio-demographic and cardiovascular risk factors of both subjects with AMI < 45 years of age and their first-degree relatives. The association of clinical and laboratory parameters with the angiographic extension of coronary artery disease (CAD) of index cases (single-vessel vs. multivessel disease) and in their respective relatives was also evaluated. METHODS: Cross-sectional study conducted from November 2010 to January 2015 in a tertiary hospital in Fortaleza, Ceara. One hundred and three index cases and 166 first-degree relatives without suspicion of familial hypercholesterolemia were included. These were compared with 111 asymptomatic individuals without family history of CAD matched for sex and age. Clinical and laboratory parameters of the 3 groups were evaluated. Associations were tested by univariate and multivariate analysis. RESULTS: AMI cases presented a higher prevalence of smoking (57.3% vs. 28.6%, p < 0.001), type 2 diabetes mellitus -DM2 (43.4 vs. 19.5%, p < 0.001), and hypertension (42.7 vs. 19%, p < 0.001) when compared to relatives matched for sex and age. Likewise cases, when compared to controls showed in addition higher triglycerides (192 ± 75mg/dL vs. 140 ± 74mg/dL, p < 0.001), lower HDL-C (36 ± 12mg/dL vs. 48±14mg/dL, p < 0.001), and a greater prevalence of the metabolic syndrome-MS (82.2% vs. 36%, p < 0.001). Multivessel disease was found in 50.5% of cases. After multivariate analysis, hypertension (p=0.030), and DM2 (p=0.028) were independently associated with multivessel disease. First-degree relatives showed a greater prevalence of smoking (29.5% vs. 6.3%, p < 0.001), DM2 (19.9% vs. 1.8%, p < 0.001), pre-diabetes (40.4 % vs. 27%, p < 0.024) and MS (64.7% vs. 36%, p < 0.001), when compared to controls. Lower HDL-c (39±10mg/dL vs. 48 ± 14mg/dL, p < 0.001), higher triglycerides (179±71mg/dL vs. 140±74mg/dL, p=0.002), higher LDL-C (122 ± 37mg/dL vs. 113 ± 36mg/dL, p=0.031) and non-HDL cholesterol (157 ± 43 vs. 141±41mg/dL, p=0.004) were found in relatives than controls. There was no difference in BMI (p=0.051) between the groups. Relatives also showed a higher prevalence of high/intermediate calculated coronary heart disease risk according to the Framingham risk score (82.7% vs. 2.6%, p < 0.001). TSH levels even within the reference value method were higher in AMI patients (2.6 ± 1.6mUI/mL, p < 0.001) and relatives (2.4 ± 1.6mUI/mL, p=0.002) in comparison with controls 1.9±1.0mUI/mL). CONCLUSION: A high prevalence of risk factors mainly MS, atherogenic dyslipidemia, type 2 DM, hypertension and smoking were encountered in cases and first-degree relatives of individuals with AMI < 45 years. Hypertension and DM2 were associated with greater angiographic extent of coronary artery diseas

Projeto sala de espera: uma proposta para a educação em diabetes - doi:10.5020/18061230.2006.p197

Education is an essential aspect of diabetic care. For this, many strategies have been searched. The objectives of the present study were to describe “The Waiting Room Project”, a proposal based on using the time in which the patient waits for individual attendance, to promote Diabetes Education; and to evaluate the clinical and epidemiological profile of diabetic participants of this project. Twenty meetings were conducted from March to October 2006, with 350 patients followed-up at the Diabetes Clinics of Walter Cantídio University Hospital-UFC, and their companions. Of these, 76 randomly assigned patients were interviewed. The meetings occurred on each Friday, in 2 sessions of approximately half hour, which were coordinated by a multidisciplinary team, and took into account 25 patients each. At the end, a breakfast was served and used for nutritional education. Among the interviewed participants, women prevailed (85.5%), with mean age of 60.4±9.1 years, and average time of diagnosis of 10.6±5.9 years. In relation to treatment, 40.7% used insulin, 63.1% used oral anti-diabetics and 9.2% only adopted life style changes. Drugs compliance was present in only 47.8% of the participants and the majority (67.1%) did not practice physical activities. Regarding to the diet, only 31.5% fully adhered to it. More than 75% of the participants could read and write, and earned a minimum wage or less. From the observations derived from practice, one may perceive: a greater motivation of the patients after each meeting, a more active participation in doctor’s appointments and an increasing interest on their disease and care. To provide the participation of diabetic patients in their treatments, stimulating self-care, is a challenge to be reached by all health units, and that can be favored by strategies like this described.A educação é um aspecto fundamental do cuidado do diabético. Para tal, várias estratégias têm sido buscadas. Os objetivos do presente estudo foram descrever o “Projeto Sala de Espera”, uma proposta que se baseia na utilização do período em que o paciente aguarda o atendimento individual para promover educação em diabetes; e avaliar o perfil clínico-epidemiológico dos diabéticos participantes deste projeto. Foram realizadas 20 reuniões, de março a outubro de 2006, com 350 pacientes seguidos no Ambulatório de Diabetes, do Hospital Universitário Walter Cantídio - UFC e seus acompanhantes. Desses, 76 pacientes, selecionados aleatoriamente, foram entrevistados. As reuniões ocorriam a cada sexta-feira, em 2 sessões de aproximadamente meia-hora, que eram dirigidas por equipe uma multidisciplinar, e contavam com 25 participantes em cada. Ao término, era servido um café da manhã, o qual era utilizado para a educação nutricional. Entre os entrevistados, predominaram mulheres (85,5%), com média de idade 60,4±9,1 anos e tempo médio de diagnóstico de 10,6±5,9anos. Em relação ao tratamento, dos participantes, 40,7% usavam insulina; 63,1% antidiabéticos orais e 9,2% adotavam apenas mudanças no estilo de vida. A adesão às drogas era contínua em apenas 47,8% e a maioria (67,1%) não praticava atividades físicas. Quanto a dietoterapia, somente 31,5% aderiam plenamente. Mais de 75% dos avaliados eram alfabetizados e recebiam um salário mínimo ou menos. A partir das observações oriundas da prática, pode-se perceber: maior motivação dos pacientes após cada reunião, participação mais ativa nas consultas médicas e um crescente interesse sobre a sua enfermidade e o seu cuidado. Proporcionar a participação do diabético no seu tratamento, estimulando o autocuidado, é um desafio a ser alcançado por todos os serviços de saúde e que pode ser facilitada com a utilização de propostas como a descrita

Early commitment of cardiovascular autonomic modulation in Brazilian patients with congenital generalized lipodystrophy

Abstract Background Metabolic abnormalities in congenital generalized lipodystrophy (CGL) are associated with microvascular complications. However, the evaluation of different types of neuropathy in these patients, including the commitment of cardiovascular autonomic modulation, is scarce. The objective of the present study was to determine the prevalence of cardiovascular autonomic neuropathy (CAN) in patients with CGL compared with individuals with type 1 diabetes and healthy subjects. Methods Ten patients with CGL, 20 patients with type 1 diabetes and 20 healthy subjects were included in the study. Controls were paired 1:2 for age, gender, BMI and pubertal stage. Heart rate variability (HRV) was analyzed using cardiovascular autonomic reflex tests, including postural hypotension test, Valsalva (VAL), respiratory (E/I) and orthostatic (30/15) coefficients, and spectral analysis of the HRV, determining very low (VLF), low (LF) and high (HF) frequencies components. The diagnosis of CAN was defined as the presence of at least two altered tests. Results CAN was detected in 40% of the CGL patients, 5% in type 1 diabetes patients and was absent in healthy individuals (p < 0.05). We observed a significant reduction in the E/I, VLF, LF and HF in CGL cases vs. type 1 diabetes and healthy individuals and lower levels of 30/15 and VAL in CGL vs. healthy individuals. A significant positive correlation was observed between leptin and 30/15 coefficient (r = 0.396; p = 0.036) after adjusting for insulin resistance and triglycerides. Autonomic cardiovascular tests were associated with HbA1c, HOMA-IR, triglycerides and albumin/creatinine ratio in CGL cases. Conclusions We observed a high prevalence of CAN in young patients with CGL, suggesting that insulin resistance, hypertriglyceridemia and hypoleptinemia, may have been involved in early CAN development. Additional studies are needed to evaluate the role of leptinemia in the physiopathogenesis of the condition