Antonio José das Chagas

Hipotiroidismo congênito transitório: perfil das crianças identificadas no programa estadual de triagem neonatal de Minas Gerais, Brasil

Early diagnosis and treatment of congenital hypothyroidism are the main goals of the neonatal screening programs. A retrospective analysis was carried out to assess the characteristics and etiologies of congenital transient hypothyroidism (CTH) in the Newborn Screening Program of the State of Minas Gerais, Brazil. To reach a diagnosis of CTH, altered screening and serum confirmatory T4 and TSH tests and normal serum free T4 and TSH at 4 and 8 weeks after the withdrawal of levothyroxine were used. We studied 21 children with CTH who represented 4.23% of the whole group with detected hypothyroidism and followed them up in the Screening Program. These patients received LT4 therapy for a variable period of one month to three years. Serum confirmatory TSH levels varied from 10.4 to 583.4 microUI/mL. Maternal antibodies, TRAB and anti-TPO, were associated to CTH in two children and iodine overload in one of them. We concluded that CTH is an important component in neonatal screening and hormonal treatment during the first months of the life is essential. The TSH initial levels are not relevant to determine whether the thyroid dysfunction is transient or permanent.

Final height in congenital adrenal hyperplasia: the dilemma of hypercortisolism versus hyperandrogenism

OBJECTIVE The purpose of this study was to identify factors that might interfere with reaching the final height in patients with 21-hydroxylase deficiency (21-OHD). SUBJECTS AND METHODS Thirty-one patients with classical 21-OHD who reached their FH in our Institution were evaluated in order to compare the Z score for final height (FHZ) with: (1) the target height, (2) the standard height for the population, and (3) the hydrocortisone treatment schedule. RESULTS The FHZ of -2.13 ± 1.11 had a significant negative correlation with the hydrocortisone doses used throughout the period of study. Patients who reached FH within the normal population range were those who received lower doses of hydrocortisone, as compared to those whose FH remained below -2 SDS. CONCLUSION We conclude that careful treatment adjustments have a major influence on growth of children with CAH, and that the dose range for hydrocortisone replacement that does not lead to side effects is relatively narrow. The better height outcome was achieved in 21-OHD patients who received lower doses of hydrocortisone.

Monoallelic thyroid peroxidase gene mutation in a patient with congenital hypothyroidism with total iodide organification defect

The aim of this study was to identify the genetic defect of a patient with dyshormonogenetic congenital hypothyroidisms (CH) with total iodide organification defect (TIOD). A male child diagnosed with CH during neonatal screening. Laboratory tests confirmed the permanent and severe CH with TIOD (99% perchlorate release). The coding sequence of TPO, DUOX2, and DUOXA2 genes and 2957 base pairs (bp) of the TPO promoter were sequenced. Molecular analysis of patients DNA identified the heterozygous duplication GGCC (c.1186_1187insGGCC) in exon 8 of the TPO gene. No additional mutation was detected either in the TPO gene, TPO promoter, DUOX2 or DUOXA2 genes. We have described a patient with a clear TIOD causing severe goitrous CH due to a monoallelic TPO mutation. A plausible explanation for the association between an autosomal recessive disorder with a single TPO-mutated allele is the presence of monoallelic TPO expression.

Morning steroid profile in children with congenital adrenal hyperplasia under different hydrocortisone schedules

We studied 13 children with 21-hydroxyalse deficiency to explore the immediate potential suppressive effect of hydrocortisone dose schedule on the adrenal cortex. They were given 20 mg/m2 daily in a controlled trial. After random administration of a greater dose in the morning (7 patients) or at night (6 patients), we measured plasma levels of 17-hydroxyprogesterone, testosterone, and androstenedione at times-24, 0, 2, 4, and 6h. Considerable fluctuation of the steroid levels, unrelated to the drug intake, was observed. There was no statistically significant differences between the “morning dose” and “night dose” groups for any steroid. We conclude that; (i) the greater night dose did not avoid the 17-hydroxyprogesterone morning peaks, and (ii) the variation in plasma steroid levels is so marked that a single morning sample is unreliable to reflect the degree of adrenal suppression.

Avaliaçäo antropométrica e bioquímica de crianças e adolescentes com diabetes do tipo 1 comparados a um grupo de näo diabéticos de mesmo nível sócio-econômico

O objetivo deste trabalho foi verificar possiveis diferencas entre parâmetros nutricionais, antropometricos e bioquimicos, de criancas e adolescentes diabeticos, atendidos por equipe multidisciplinar, no Setor de Endocrinologia Pediatrica do Hospital das Clinicas da UFMG, quando comparados a um grupo de nao diabeticos proveniente do mesmo hospital. Foram estudados 100 diabeticos e 100 nao diabeticos equivalentes quanto a idade, sexo e indicadores sociais: indice de aglomeracao, renda familiar mensal e escolaridade dos pais. Nestes, foram verificamos peso, altura, IMC e os indices antropometricos altura/idade, peso/idade e peso/altura. Foram dosados o colesterol total e fracoes, triglicerideos e a hemoglobina glicosilada. Os grupos nao diferiram quanto a media de peso e estatura, IMC e os indices peso/idade, peso/altura e altura/idade. Quando o indice altura/idade foi analisado no percentil 10 os diabeticos estavam mais baixos. Metade dos pacientes diabeticos apresentou um controle metabolico considerado ruim. O colesterol e as fracoes estavam mais elevados nos diabeticos (p<0,0001) e triglicerideos e VLDL estavam proximos ao limiar de significância. No grupo diabetico, nao houve correlacao entre o tempo de doenca e a altura. Em conclusao, o colesterol total e as fracoes HDL e LDL estavam elevadas nos diabeticos quando comparados aos nao diabeticos. Todavia, os indices antropometricos mostraram-se equivalentes nos dois grupos, quando a comparacao foi com ponto de corte no percentil 2,3 e mais baixos nos diabeticos quando no percentil 10. Embora o atendimento ao grupo de diabeticos tenha sido feito por meio de uma equipe multidisciplinar, o controle metabolico foi ruim em cerca da metade dos pacientes.

Analysis of the PAX8 gene in 32 children with thyroid dysgenesis and functional characterization of a promoter variant.

Abstract Background: The molecular basis underlying the development of thyroid dysgenesis remains largely unknown. The objective of this study was to analyze the PAX8 gene in 32 children with congenital hypothyroidism due to thyroid dysgenesis for mutations, and to characterize the functional consequences of the mutations. Methods: The 5′-untranslated region and the entire coding region of the PAX8 gene were analyzed in 32 children. Functional analyses with a reporter gene assay were performed in transfected PCCL3 and TSA cells. Results: Thirty children did not have any sequence alterations. Two individuals had a previously identified monoallelic cytosine to thymine transition at position -983 in the promoter (-983C>T; mutant P. A of the ATG of the initiator codon is designated as +1), and a novel guanine to cytosine transversion in the non-coding exon 1 (-465G>C; mutant E). Functional analysis revealed that the basal transcriptional activity of the mutants is decreased compared to the wild type. Gel mobility shift assays indicated that mutant P does not interact with a transacting factor whose nature remains to be elucidated. The DNA binding property of mutant E were similar compared to the wild type. Conclusions: These results suggest that mutations in PAX8 are most likely a very rare cause of thyroid dysgenesis. The observed sequence alterations result in diminished transcriptional activity and, in conjunction with other genetic and non-genetic modifiers, they may contribute to the pathogenesis of thyroid hypoplasia and hypothyroidism.