[Formula: see text]Socioeconomic aspects are crucial to better intellectual outcome in early-treated adolescents with congenital hypothyroidism.

Congenital hypothyroidism (CH) is an important cause of preventable intellectual disability. Implementation of CH neonatal screening programs leading to early treatment has improved cognitive outcome. However, more subtle cognitive impairments are still reported, and there is lack of clarity regarding factors that impact long-term cognitive outcome. Research to better understand these factors can lead to further improvements in the cognitive prognosis for these patients. The current study aimed to evaluate the cognitive performance of adolescents who were early-treated for primary permanent CH and possible associated variables. Neurocognitive evaluation was carried out in 66 adolescents, 11 to 16 years old: 34 with CH and 29 paired controls. Intellectual quotient (IQ), verbal fluency, processing speed, executive functions, and memory were investigated. CH patients and control subjects were comparable regarding sex, age, schooling, family's socioeconomic status and caregiver's educational level. Both groups presented not only similar IQ scores but also equivalent performances regarding Perceptual Reasoning, Working Memory and Processing Speed index scores. Patients presenting different CH etiologies (dysgenesis and dyshormonogenesis) showed similar cognitive performance. Socioeconomic aspects along with the initial levothyroxine dose were the main variables to positively influence the cognitive performance, the family's socioeconomic status having the strongest association with patients' cognitive skills.

Identification of a novel mutation in DAX1/NR0B1A gene in two siblings with severe clinical presentation of adrenal hypoplasia congenita.

OBJECTIVE: To search for mutations in DAX1/NR0B1A gene in siblings to establish the molecular etiology of the adrenal hypoplasia congenita (AHC), a rare potentially life-threatening disorder. CASE REPORT: We describe two siblings who presented with salt-wasting syndrome in the newborn period and received hormonal replacement for primary adrenal insufficiency. A diagnostic hypothesis of AHC was suspected because the children maintained, during hormonal treatment, low plasma 17-OH progesterone (17-OHP) and androgens, despite high ACTH levels. RESULTS: DAX1 gene was studied by molecular analysis, which showed a mutation, confirming the diagnosis in the siblings and a heterozygous state in the mother. Direct sequencing of DAX1 revealed an insertion of an adenine base (c1382-1383 A ins), which lead to a pMet461Asp substitution. CONCLUSION: A novel frameshift mutation of DAX1 gene, which established the molecular etiology of the AHC in the siblings, was identified. Obtaining a precise genetic diagnosis of this adrenal disorder, which, sometimes, cannot be confirmed only by clinical aspects, may have important implications for the long-term management of the disease.

Identification of a novel mutation in DAX1/NR0B1A gene in two siblings with severe clinical presentation of adrenal hypoplasia congenita / Identificação de nova mutação no gene DAX1/NR0B1A em dois irmãos com forma clínica grave de hipoplasia adrenal congênita

OBJECTIVE: To search for mutations in DAX1/NR0B1A gene in siblings to establish the molecular etiology of the adrenal hypoplasia congenita (AHC), a rare potentially life-threatening disorder. CASE REPORT: We describe two siblings who presented with salt-wasting syndrome in the newborn period and received hormonal replacement for primary adrenal insufficiency. A diagnostic hypothesis of AHC was suspected because the children maintained, during hormonal treatment, low plasma 17-OH progesterone (17-OHP) and androgens, despite high ACTH levels. RESULTS: DAX1 gene was studied by molecular analysis, which showed a mutation, confirming the diagnosis in the siblings and a heterozygous state in the mother. Direct sequencing of DAX1 revealed an insertion of an adenine base (c1382-1383 A ins), which lead to a pMet461Asp substitution. CONCLUSION: A novel frameshift mutation of DAX1 gene, which established the molecular etiology of the AHC in the siblings, was identified. Obtaining a precise genetic diagnosis of this adrenal disorder, which, sometimes, cannot be confirmed only by clinical aspects, may have important implications for the long-term management of the disease.

OBJETIVO: Pesquisar mutações no gene DAX1/NR0B1A em dois irmãos com suspeita de hipoplasia adrenal congênita (HAC), rara doença potencialmente fatal, para estabelecer sua etiologia molecular. RELATO DOS CASOS: São apresentados os relatos de dois irmãos com síndrome perdedora de sal no período neonatal que receberam terapia de reposição hormonal para insuficiência adrenal primária. O diagnóstico de HAC foi suspeitado porque as crianças mantiveram, durante o tratamento hormonal, níveis plasmáticos reduzidos de 17-OH-progesterona e andrógenos ao lado de níveis elevados de ACTH. RESULTADOS: A análise molecular do gene DAX1 mostrou a mutação, confirmando o diagnóstico nos irmãos e o estado heterozigoto da mãe. No sequenciamento direto do DAX1 foi encontrada inserção de uma adenina (c1382-1383 A ins), levando à substituição pMet461Asp. CONCLUSÃO: Uma nova mutação da fase de leitura no gene DAX1 foi identificada, estabelecendo a etiologia molecular da HAC nos dois irmãos. Um diagnóstico genético preciso deste distúrbio adrenal, frequentemente não confirmado apenas pelos aspectos clínicos, pode ter importantes implicações para o manuseio em longo prazo da doença.

Thyroid autoimmunity in children and adolescents with type 1 diabetes mellitus: prevalence and risk factors.

UNLABELLED: Studies show great variation in prevalence of anti-thyroid antibodies in children with type 1 diabetes mellitus (DM1). There still is no consensus regarding screening of autoimmune thyroiditis in patients with DM1, especially in asymptomatic patients. AIM: To investigate the natural history and prevalence of autoimmune thyroiditis in pediatric patients with DM1 and relate it to potential risk factors. PATIENTS AND METHODS: This study is a historical cohort, through research of the records of 474 patients with DM1 from 9 months to 25 years of age, between 1980 and 2005 - 222 boys (46.8%) and 252 girls (53.2%), with an average duration of DM1 of 9.3 +/- 5.8 years. The sample was selected by having at least one measurement of TSH and anti-thyroid autoantibodies (antithyroperoxidase or anti-microssomal and/or anti-thyroglobulin) at any time from diagnosis of DM1. A questionnaire was answered in order to study the variables of interest for the study. Thyroid function disorder was defined as altered levels of TSH, with or without altered free T4 levels. RESULTS: A total of 383 patients (9 months to 25 years of age) were studied, 199 girls (52%) and 184 boys (48%). Sixty-four (16.7%) had positive anti-thyroid antibodies, predominantly girls (p = 0.064). Average duration of DM1 was 9.3 +/- 5.8 years and those above this age had a higher incidence of thyroiditis (p = 0.01). The prevalence of thyroid function disorder in patients with DM1 was 7.3% (n = 28), mostly with thyroiditis (32.8% vs 2.2% with negative antibodies, p < 0.001). There was a positive association between thyroiditis, as well as thyroid function disorders, and other autoimmune disorders (p < 0.001 and p < 0.02, respectively). CONCLUSIONS: Prevalence of thyroiditis in the diabetic population is considerably higher than in the general population. Annual laboratory determinations of anti-TPO antibodies and dosage of TSH should be part of routine tests in the diabetic population, especially in girls, children with DM1 for > 9 years, patients above 12 years of age, and those in whom DM1 is associated with another autoimmune disease. Anti-thyroid antibody positivity may indicate the necessity for thyroid function testing at shorter intervals.

A sindrome do T3 baixo e o crescimento da crianca com Diabetes Mellitus Insulino-Dependente / Syndrome of the T3 low and the growth of the child with Diabetes Mellitus Insulin-Dependent

Os hormonios tiroidianos sao de importancia fundamental para o crescimento somatico. Realizou-se um estudo de 35 criancas diabeticas com o objetivo de analisar se os niveis diminuidos do hormonio metabolicamente ativo, T3, pelo Diabetes Mellitus Insulino - Dependente teria uma possivel repercussao no crescimento estatural destas criancas. Os pacientes foram divididos em 2 grupos, conforme o grau de controle metabolico, medindo pelos niveis de hemoglobina glicosilada (HbAl). O grupo DI com 19 pacientes, apresentando controle metabolico bom e regular, HbAl < 12%, e o grupo DII com 16 pacientes de mau controle metabolico, HbAl < 12%. Os niveis medios de T3 dos diabeticos sem divisao em grupos (108 +- 25 ng/dl) foram significativamente menores que dos controle 132 +- 3l ng/dl,128 +- 24 ng/dl e 135 +- 34 ng/dl, respectivamente). Nao foram verificadasdiferencas nos outros parametros de funcao tiroidiana estudados (T4; T3/T4; rT3;rT3/rT3 e TSH) dos pacientes e das criancas nao diabeticas. No grupo de controlemetabolico bom e regular as concentracoes baixas de T3 relacionaram-se com os menores percentis de altura, mas nao houve correlacao entre essas variaveis no grupo do mau controle metabolico nem nos 35 pacientes sem divisao em grupos. O estudo sugeriu que o DMID alterou o metabolismo dos HT ao diminuir os niveis de T3, mas nao se pode afirmar que essas alteracoes interfiram no crescimento da crianca diabetica .

Tireoidite linfocitica cronica (TLC) / Thyroiditis lymphocitics cronics (TLC)

Foram estudadas 13 criancas com diagnostico comprovado deTLC, acompanhadas no servico de Endocrinologia infantil da UFMG no periodo de 1975 a 1984. Todas as pacientes sao do sexo feminino, com idade media de 11,2 anosA maioria mostrou alteracoes clinicas e laboratoriais de hipotireodismo (62%) ealtos titulos de anticorpos antireodianos, especialmente antimicrossomal (73%). Os aspectos clinico-laboratoriais sao discutidos em relacao aos dados da litera-tura .