Tsuneyasu Ishii

Serum calcium regulating hormones in the perinatal period.

SummaryTo clarify perinatal vitamin D metabolism, we measured 25-hydroxyvitamin D (25OHD), 24,25-dihydroxyvitamin D [24,25(OH)2D], 1,25-dihydroxyvitamin D [1,25(OH)2D], calcium (Ca), phosphorus (P), parathyroid hormone (PTH), and human calcitonin (CT) in paired maternal, cord, and infant serum. Cord serum 25OHD was significantly lower than the maternal level, and cord serum 24,25(OH)2D was also significantly below the maternal concentrations. Maternal, cord, and infant serum 1,25(OH)2D, on the other hand, was significantly higher than the normal adult level. The serum PTH was low, but the CT concentration was high in the cord. Cord serum Ca and P levels were significantly higher than maternal. The reason for the elevated circulating 1,25(OH)2D level in the perinatal period is uncertain, and we speculate that the possible factors are gonadal steroids, placental lactogen, prolactin, and CT. In addition, serum 24,25(OH)2D and 1,25(OH)2D concentrations are under some control by the fetus.

Plasma 1,25-dihydroxyvitamin D concentrations in cords, newborns, infants, and children

SummaryPlasma 1,25-dihydroxyvitamin D [1,25-(OH)2-D] was measured in cord serum, newborns, infants, and children. The mean for the values obtained from the six cords was significantly higher than the mean for the older children (6–15 years). The mean for the six newborns (0–1 week) was significantly higher than that for the older children. The mean for the nine infants (1 week-6 months) and the 14 younger children (6 months-6 years) was significantly higher than that for older children. The present study suggests that the perinatal period is associated with a marked increase in 1,25-(OH)2-D.

A specific competitive protein binding assay for serum 24,25-dihydroxyvitamin d in normal children and patients with nephrotic syndrome

A specific competitive protein binding assay for 24,25-dihydroxyvitamin D by Sephadex LH-20 column chromatography, followed by high pressure liquid chromatography with normal rat kidney cytosol as the binding protein, was developed. The mean concentrations of serum 24,25-dihydroxyvitamin D of the cord, in newborn infants and in infants under 12 months of age were 0.90 +/- 0.40 (S.D.) ng/ml, 0.52 +/- 0.21 (S.D.) ng/ml and 1.20 +/- 0.38 (S.D.) ng/ml, respectively. These concentrations were significantly lower than those in children aged 1-15 years (1.96 +/- 0.83 (S.D.) ng/ml). The serum levels in the acute stage of the nephrotic syndrome were significantly reduced, and they increased in remission. These results show that patients wioth nephrotic syndrome have low levels of serum 24,25-dihydroxyvitamin D. This is probably due to its loss in the urine.

Vitamin D Metabolism in Hypophosphatemic Vitamin D-Resistant Rickets

Plasma levels of 1,25-(OH)2-D were low in children with hypophosphatemic vitamin D-resistant rickets (HVDRR), but increased after very large doses of 1 alpha-OH-D3. These results suggest that the metabolism of 1,25-(OH)2-D is accelerated in HVDRR. In addition, the lower level of plasma 1,25-(OH)2-D in untreated HVDRR was correlated with the lower level of serum phosphate and renal threshold phosphate concentration (TmP/GFR). The administration of 1 alpha-OH-D3 to the patients with HVDRR could enhance the renal threshold phosphate concentration.

Differential diagnosis of hypoparathyroid disorders during childhood.

SummaryChanges in the plasma and urinary adenosine 3′,5′ monophosphate (cyclic AMP) levels on infusion of parathyroid hormone were studied in 10 normal children, 5 children with idiopathic hypoparathyroidism, and 3 children with pseudohypoparathyroidism.In normal children the plasma concentration of cyclic AMP ranges from 18.0 to 68.0 pmoles/ml under basal conditions, and increases to a peak of about 10-fold the basal level 5 min after infusion of parathyroid hormone.Infusion of parathyroid hormone caused no increase in plasma cyclic AMP in patients with pseudohypoparathyroidism but about 18-fold increase in those with idiopathic hypoparathyroidism.The measurement of plasma cyclic AMP before and 5 min after infusion of parathyroid hormone is concluded to be a simple and effective method for differential diagnosis of hypoparathyroid disorders.

Secondary hyperparathyroidism with 1,25-dihydroxyvitamin D deficiency and pseudohypoparathyroidism in childhood: Relationship between plasma 1,25-dihydroxyvitamin D and parathyroid hormone levels and urinary cyclic AMP response to exogenous PTH

In order to clarify the complex interrelationship between serum calcium, 1,25-dihydroxyvitamin D (1,25(OH)2D), and parathyroid hormone (PTH), and the urinary excretion of cyclic AMP (cAMP) in response to exogenous PTH in pseudohypoparathyroidism (PHP) and related diseases, we investigated 3 patients with parathyroid disorders before and after treatment with 1α-hydroxyvitamin D3 (1α-OH-D3).Low plasma 1,25(OH)2D before treatment increased after giving 1α-OH-D3 (0.1 μg/kg/day), where-as high plasma PTH measured by the C-terminal assay (C-PTH) decreased in all 3. No response in urinary cAMP was found before or after treatment in 2 patients with PHP type I, despite the fall of plasma C-PTH. However, in one patient with extremely high plasma C-PTH but normal N-PTH (measured by a homologous radioimmunoassay using 1–34 human PTH), urinary cAMP response to exogenous PTH was increased after treatment with 1α-OH-D3. We suggest that he had pseudopseudohypoparathyroidism (PPHP) with Albrights hereditary osteodystrophy and a partial deficiency of renal 1α-hydroxylase. In this patient secondary hyperparathyroidism is thought to be due to 1,25(OH)2D deficiency, and the decreased responsiveness to exogenous PTH before treatment due to excess PTH occupying renal receptors.

Studies on the Regulation of Calcium Metabolism in Neonatal: Period: Plasma 25‐Hydroxyvitamin D and Calcium

The plasma levels of 25-hydroxyvitamin D (25-OH-D), calcium, magnesium and inorganic phosphorus were measured in the perinatal period and in early infants. The mean concentrations of 25-OH-D in the mothers’ plasma, the cord plasma and the plasma of full-term infants within two days after birth were 16.328.2 (SD) ng/ml (n=27), 12.8k8.2 (SD) ng/ml (n=25) and 11.4&8.6 (SD) ng/ml (n=27), respectively, and there were all significantly lower than that in the plasma of healthy infants and children, 21.6k10.1 (SD) ng/ml (n=17, P<O.Ol). The mean concentration of calcium in the perinatal period was significantly high in the cord plasma, compared with that in the maternal and neonatal plasma. A highly significant correlation was observed in the 25-OH-D concentration not only between the matermal plasma and the cords plasma of their respective infants, but also between the maternal and the neonatal plasma. The mean concentration of neonatal plasma 25-OH-D decreased gradually after birth and did not return to the plasma level of the newborn infants immediately after birth until one month of age. The concentrations of plasma 25-OH-D correlated significantly, but weakly with those of plasma calcium in the newborn infants and did not correlate with the plasma magnesium and inorganic phosphorus. The present data suggest that a placental passive or sometimes active transfer of calcium and 25-OH-D take place, but a latent vitamin D deficiency appears to be present for several weeks after birth. Vitamin D deficiency, however, does not play a significant role by itself in the neonatal hypocalcemia.