Yoshikazu Nishi

Trace elements (copper, zinc, manganese, and selenium) in plasma and erythrocytes in relation to dietary intake during infancy.

All determinations of copper, zinc, manganese, and selenium were performed with a flameless atomic absorption spectrophotometer. Seventy-three full-term infants aged 1 to 52 weeks were divided into three age groups. Each age group contained two subgroups, breast-fed and formula-fed. No statistically significant differences between formula-fed and breast-fed subgroups were found in regard to the levels of copper and zinc in plasma and erythrocytes. At 1 to 5 weeks of age, the manganese concentration of erythrocytes was higher in formula-fed than in breast-fed infants (p < 0.001). This might be due to the high dietary intake of this element in the formula-fed subgroup. On the other hand, plasma selenium concentrations were significantly higher in breastfed than in formula-fed infants of all ages (p < 0.01 at 1 to 5 weeks and p < 0.05 at 6 to 52 weeks). This suggests that selenium compounds are biologically more available for infant nutrition in breast milk than in formula.

Changes in erythrocyte superoxide dismutase in a patient with copper deficiency

In a patient with typical copper deficiency, we found superoxide dismutase (SOD, 1.15.1.1) activity and copper in erythrocytes to be decreased to 52% and 46% of age-matched controls, respectively. However, these were not so markedly depleted as plasma copper (17%) or ceruloplasmin (20%). After copper replacement therapy, erythrocyte copper and SOD activity gradually returned to the control levels. Although certain abnormalities reported in copper deficiency in animals were expected, osmotic fragility of erythrocytes of the patient was normal and damage of the liver and heart were not a feature as far as could be determined by electrocardiography and routine laboratory examinations. Probably a decrease of SOD to this extent is not severe enough to lead to superoxide-induced damage.

Plasma Selenium Concentration in Healthy Japanese Children and Adults Determined by Flameless Atomic Absorption Spectrophotometry

This study showed a rapid and direct method for determining selenium concentration in plasma by flameless atomic absorption spectrophotometry, and differences in plasma selenium concentration in healthy children and adults. A direct method is possible, since selenium is heat stable in the presence of nickel. With this method, the recovery of selenium added to plasma was 100.3 +/- 5.7%, and the relative standard deviation in repeated determinations of pooled plasma selenium was 3.0% and 6.8%. The plasma selenium concentration in adults was 99.4 +/- 12.5 ng/ml, lower than reported concentrations from the United States and Canada, and higher than those from New Zealand. These variations may reflect dietary habits, bioavailability of selenium compounds in diet, racial difference, or different analytical methods. The mean concentration of plasma selenium at 1 to 6 months of age (51.0 +/- 13.1 ng/ml) was significantly lower than in adults (p less than 0.001); it increased gradually and steadily to the adult level with age. This age-related difference of plasma selenium level is similar to that reported previously.

Effect of long-term calcitonin therapy by injection and nasal spray on the incidence of fractures in osteogenesis imperfecta

The effect of calcitonin therapy by injection or nasal spray on the incidence of bone fractures was studied in patients with osteogenesis imperfecta. In contrast to injection of calcitonin, intranasal administration of calcitonin twice a week for 2 weeks, followed by 2 weeks of no therapy, was simple and seemed beneficial for decreasing bone fractures in patients with osteogenesis imperfecta.

Zinc, copper, manganese, and selenium metabolism in patients with human growth hormone deficiency or acromegaly

Summary This study was designed to evaluate trace metal metabolism in patients with known abnormalities of human growth hormone (hGH). The mean concentration of zinc in plasma and urine decreased in patients with hGH deficiency after hGH injection, whereas, after adenomectomy, in patients with acromegaly, zinc increased in plasma, remained the same in erythrocytes, and decreased in urine. There was a negative correlation between plasma zinc and serum hGH levels and a positive correlation between urinary zinc excretion and serum hGH levels in acromegaly. In hGH deficiency, the copper content remained unchanged in plasma and erythrocytes and rose in urine after treatment; however, in acromegaly, the copper content increased in plasma and remained unchanged in erythrocytes and urine after surgery. The mean concentration of erythrocyte manganese did not change significantly after treatment in patients with hGH deficiency or acromegaly, but the pre hGH treatment level of erythrocyte manganese in hGH deficiency was lower than in the controls. Plasma selenium concentrations were decreased in hGH deficiency and increased in acromegaly patients after therapy. These results suggest that hGH affects the metabolism of zinc, copper, manganese, and selenium. hGH treatment level of erythrocyte manganese in hGH deficiency was lower than in the controls. Plasma selenium concentrations were decreased in hGH deficiency and increased in acromegaly patients after therapy. These results suggest that hGH affects the metabolism of zinc, copper, manganese, and selenium.

Isolated growth hormone deficiency type 1A ina Japanese family

A Japanese family is described in which a 7-year-old child had isolated growth hormone deficiency type 1A, as described by Illig et al. He was shown to be homozygous for a deletion of the structural gene for hGH (hGH-N gene). Initially his growth rate responded well to hGH administration, but rapidly he developed high titers of hGH antibodies, and growth ceased. At that time, a somatomedin-C generation test gave negative results, suggesting that the growth arrest was related to the inability of hGH to generate somatomedin. Both parents were heterozygous for the hGH-N gene deletion and had a low hGH response to arginine and L-dopa tolerance tests, but had normal basal somatomedin-C levels and normal somatomedin-C generation tests. This family is the fourth to be reported with IGHD type 1A caused by deletion of the hGH-N gene. This cause of growth hormone deficiency can be distinguished from other severe autosomal recessive types of hGH deficiency by the demonstration of the deletion of hGH-N gene using restriction endonuclease analysis.

Primary hypothyroidism associated with pituitary enlargement, slipped capital femoral epiphysis and cystic ovaries

A case of primary hypothyroidism with pituitary enlargement, slipped capital femoral epiphysis and cystic ovaries is reported. The pituitary abnormality and cystic ovaries disappeared dramatically after thyroid hormone therapy. Hip pinning was performed. The recognition of these associations may eliminate unnecessary surgery and lead to the choice of hormone replacement therapy.

No Genetic Mutation in Type II 3β-Hydroxysteroid Dehydrogenase Gene in Patients with Biochemical Evidence of Enzyme Deficiency

Nonclassic or the mild form of 3 beta-hydroxysteroid dehydrogenase (NC3 beta-HSD) deficiency is an entity which is identified with typical features of premature pubarche, hirsutism, or oligomenorrhea. In this study, type II 3 beta-HSD gene from 4 girls who were diagnosed as NC3 beta-HSD deficient, base on the adrenal steroidogenic responses to ACTH, was analyzed to determine whether NC3 beta-HSD deficiency was an allelic variant of classical 3 beta-HSD deficiency by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). We could not detect any alterations of type II 3 beta-HSD gene from these patients. Our result strongly suggests that unlike classical 3 beta-HSD deficiency, NC3 beta-HSD deficiency may be secondary adrenal biosynthetic defects, rather than dual inherited deficiencies.

Pituitary enlargement, hypertrichosis and blunted growth hormone secretion in primary hypothyroidism.

ABSTRACT. Pituitary hyperplasia, hypertrichosis and blunted growth hormone (GH) secretion were observed in three children with untreated primary hypothyroidism. These abnormalities disappeared and improved after thyroid hormone therapy. The recognition of these associations may eliminate unnecessary surgery and GH therapy and lead to the choice of thyroid hormone replacement therapy.

Steroid-Dependent ACTH-Produced Thymic Carcinoid: Regulation of POMC Gene Expression by Cortisol via Methylation of Its Promoter Region

Aims: Metyrapone causes a decrease in the serum cortisol level without affecting ACTH production in ectopic tumors. We report a case who presented with Cushing’s syndrome due to an ectopic ACTH-producing thymic carcinoid. In the present case, it was demonstrated that metyrapone administration resulted in a significant decrease in the plasma ACTH and serum cortisol levels. We hypothesized that the steroid hormone may promote proopiomelanocortin (POMC) gene expression in the carcinoid cells. Methods: An 11-year-old boy presented with Cushing’s syndrome. Prior to the detection of a thymic tumor, metyrapone was administered to ameliorate the symptoms of Cushing’s syndrome. Interestingly, plasma ACTH as well as serum cortisol levels immediately decreased after metyrapone administration. The levels of cortisol and ACTH were observed to be normal after complete surgical resection of the tumor. Biological characterization of the tumor cells was by in vitro analysis. Results: Thein vitro culture of the tumor cells showed an increased expression of POMC in the presence of cortisol. A CpG methylation assay showed that the demethylation of the POMC promoter was induced by a steroid hormone. Conclusion: These findings suggest that the ectopic ACTH-producing tumor may partly be regulated by the elevated levels of cortisol.