[Management of Graves' disease and hypothyroidism in pregnancy].

In the treatment of pregnant patients with Graves' disease, propylthiouracil is preferred over methimazole in early pregnancy because of a possible teratogenicity of methimazole. Methimazole is preferable to propylthiouracil in other time of pregnancy on the basis of severe liver dysfunction occasionally caused by propylthiouracil. Fetal hypothyroidism can be avoided when maternal free T4 levels are maintained at or above the upper normal limit for non-pregnant subjects.

Neurodevelopment in children born to hypothyroid mothers restored to normal thyroxine (T₄) concentration by late pregnancy in Japan: no apparent influence of maternal T₄ deficiency.

Context: The importance of maternal T₄ for brain development prior to the onset of fetal thyroid function has been suggested in basic studies, and a correlation between mild maternal T₄ deficiency in early gestation and disturbance of neurodevelopment in progenies has been shown in large case-control studies. These findings suggest that maternal T₄ deficiency in early pregnancy potentially affects neurointellectual development. On the other hand, no apparent adverse effect in children born to mothers with overt hypothyroidism in Japan has been reported where maternal T₄ had been restored to normal by late pregnancy.

Genetic factors and clinical significance of acanthosis nigricans in obese Japanese children and adolescents.

Aim: To clarify the clinical significance of acanthosis nigricans (AN) and the association of gene polymorphisms in the ss2- and ss3-adrenergic receptors (B2ADR and B3ADR) in Japanese obese children and adolescents.

Methods: Seventy obese subjects (56 boys, 14 girls) from 5 to 19 y of age were examined as to clinical features. Genetic analyses were performed in 83 obese subjects (61 boys, 22 girls), 2 to 17 y of age.

Short-term secretory regulation of ghrelin during growth hormone provocative tests in prepubertal children with various growth hormone secretory capacities.

Background And Objective: Ghrelin is a novel gastric peptide which stimulates GH secretion and has been demonstrated to have orexigenic and adipogenic properties. Insulin is a physiological and dynamic modulator of plasma ghrelin, and insulinemia possibly mediates the effect of the nutritional state on the plasma concentrations of ghrelin in adults. No data on the regulation of GH secretion by ghrelin have so far been reported, nor has the possible influence of hypoglycemia on the plasma ghrelin levels in children been reported.

Association of HLA-DR, -DQ genotype and CTLA-4 gene polymorphism with Graves' disease in Japanese children.

Objective: Childhood onset Graves' disease (GD) has been documented to be clinically distinct from adult onset GD, and an association with the genes encoding HLA and CTLA-4 (cytotoxic T lymphocyte antigen-4) has been reported in both Caucasian and Japanese adult GD patients. The aim of this study was to determine whether HLA-DR, -DQ and CTLA-4 are associated with childhood onset GD in Japanese individuals.

Methods: We investigated the genotype of HLA class II (DRB1, DQB1) and the A/G transition polymorphism of CTLA-4 exon 1 position 49 in 43 GD patients and in healthy controls for comparison.

Absence of Heterozygous K83E and R257X Mutations of the AIRE-1 Gene in 46 Children with Type 1 Diabetes and 44 Children with Graves' Disease.

Type 1 diabetes mellitus (DM) and Graves' disease are autoimmune diseases, and a number of genetic factors, including HLA and CTLA-4 genes, have been reported to contribute to their etiology. The gene responsible for autoimmune polyendocrinopathy- candidiasis-ectodermal dystrophy (APECED) has been cloned and named the autoimmune regulator-1 (AIRE-1) gene. AIRE-1 protein is thought to be a transcription regulatory protein and to have a role in the maintenance of immunological tolerance.

Fasting plasma ghrelin levels are negatively correlated with insulin resistance and PAI-1, but not with leptin, in obese children and adolescents.

Ghrelin is a novel growth hormone-releasing peptide isolated from human and rat stomach that induces weight gain by increasing food intake and reducing fat utilization. Although recent data indicate that ghrelin is downregulated in human adult obesity, the characteristics of human obesity are heterogeneous, especially in children and adolescents, and depend on the distribution of subcutaneous and visceral fat tissue. We measured fasting plasma ghrelin concentrations by radioimmunoassay in 49 obese Japanese children and adolescents (38 boys and 11 girls; mean age 10.

Impact of polymorphisms of human beta-adrenergic receptor gene on changes in height during growth hormone treatment.

The aim of this study was to investigate the occurrence of polymorphisms of the beta-adrenergic receptor gene in short children and to evaluate the possible influence of the polymorphisms on changes in height and obesity index in response to GH treatment. Of the 75 children enrolled in the study, 40 completed at least 5 years of GH treatment. The genotype distribution of the beta2 and 3-adrenergic receptor polymorphisms in the study population did not differ significantly from those reported in non-obese subjects.