Acrodysostosis and pseudohypoparathyroidism (PHP): adaptation of Japanese patients with a newly proposed classification and expanding the phenotypic spectrum of variants.

Objective: This study aimed to report on 15 Japanese patients with acrodysostosis and pseudohypoparathyroidism (PHP) and analyze them using the newly proposed classification of the EuroPHP network to determine whether this classification system is suitable for Japanese patients. Design: We divided the patients into three groups based on hormone resistance, the number of fingers with short metacarpals, the existence of cone-shaped epiphyses and gene defects. Methods: We carried out clinical, radiological and genetic evaluations of two patients in group A (iPPSD5), six patients in group B (iPPDS4) and seven patients in group C (iPPSD2). Results: Group A consisted of two siblings without hormone resistance who had the most severe bone and physical developmental delays. PDE4D gene defects were detected in both cases. Group B consisted of six patients who showed hormone resistance without hypocalcemia. Short metacarpal bones with corn-shaped epiphyses were observed in all patients. In two cases, PRKAR1A gene defects were detected; however, their clinical and radiological features were not identical. The facial dysmorphism and developmental delay were less severe and PRKAR1A gene defects were detected in case B-3. Severe facial dysmorphism and deformity of metacarpal bones were observed, but no gene defect was detected in case B-1. Group C consisted of seven patients with PHP1a, four of whom had maternally inherited heterozygous inactivating mutations in one of the GNAS genes. The clinical and radiological features of the patients in group C were not identical either. Conclusions: The newly proposed classification is suitable for Japanese patients; however, heterogeneities still existed within groups B and C.

Rescue from dwarfism by thyroid function compensation in rdw rats.

The rdw rat was initially reported as having hereditary dwarfism caused by pituitary dysfunction. Subsequent studies on the rdw rat, however, have demonstrated that the primary cause of rdw dwarfism is present in the thyroid gland but not in the pituitary gland. The primary cause of rdw rat disorders is a missense mutation of the thyroglobulin (Tg) gene by a one-point mutation. In the present study, we attempted to rescue the dwarfism of the rdw rats using a diet supplemented with thyroid powder (T-powder) and a thyroid graft (T-graft). The infants of the rdw rat were successfully raised to a mature stage body weight, accompanied by elevation of serum growth hormone (GH) and prolactin (PRL), by the T-powder. Furthermore, the T-graft successfully increased the body weight with fertility. The serum GH and PRL levels in the T-graft rdw rat significantly increased. The serum thyroid-stimulating hormone (TSH) levels in the T-graft rdw rat were significantly decreased but were significantly higher than those in the control rat. The GH and PRL mRNA expression in the rdw rat with the T-graft was virtually the same as that of the control, but the TSH beta mRNA differed from that of the control rats. Thus, the dwarfism in the rdw rat is rescued by thyroid function compensation, such as that afforded by T-powder and T-graft.

Assays for thyroid-stimulating antibodies and thyrotropin-binding inhibitory immunoglobulins in children with Graves' disease.

Studies on thyrotropin receptor autoantibodies (TRAb) by measurement of both thyroid-stimulating antibodies (TSAb) and thyrotropin-binding inhibitory immunoglobulins (TBII) in serum from children with Graves' disease are limited in number of studies. The aim of this study was to investigate the levels of serum TSAb and TBII in children with Graves' disease, and to evaluate the clinical significance of these antibodies. We measured the serum TSAb and TBII at diagnosis and during management in 65 children with Graves' disease. Patients were divided into four groups according to their metabolic state: those with untreated active Graves' disease, those receiving treatment with antithyroid drugs, those in remission, and those in relapse. At diagnosis, both TSAb and TBII assays had high sensitivities and high specificities. In follow-up, the levels of both TSAb and TBII paralleled the course of the disease. There was a strong positive correlation between TSAb and TBII. TBII levels were significantly higher in the patients with ophthalmopathy than those without ophthalmopathy in untreated Graves' children. It was concluded that TSAb and TBII measurements are valuable in the diagnosis and management of children with Graves' disease.