Can renal handling of phosphate predict response to growth hormone therapy in normal variant short children by short-term treatment?

We investigated if renal handling of phosphate could predict height velocity in 28 normal variant short children (16 boys and 12 girls). Before and after human growth hormone was given for four consecutive days, the ratio of maximum tubular reabsorption rate for phosphorus to glomerular filtration rate (TmP/GFR) was calculated. Based on increments in TmP/GFR (delta TmP/GFR) with growth hormone administration, the patients were divided into two groups; children in whom the levels of delta TmP/GFR were 0.8 mg/dl GF or more (group A, n = 7) and those with levels less than 0.8 mg/dl GF (group B, n = 21). All children in group A and some in group B (n = 9) were injected with 0.5 IU/kg/week of recombinant human growth hormone for over one year. Height velocity during therapy was significantly greater in treated children in group A than in group B and was similar among treated (n = 9) and untreated (n = 12) children in group B. The present study suggests that change in renal handling of phosphate during short-term growth hormone administration can serve to select normal variant short children who will respond well to growth hormone therapy.

Zinc kinetics in patients with bone demineralization due to physical immobilization.

To examine the relationship between zinc (Zn) status and bone demineralization, a body Zn kinetics study was performed with 74 (37 male, 37 female) disabled persons ranging in age from 16 to 45 years. Three groups were classified according to degree of limited mobility: group 1 (n = 23), capable of walking; group 2 (n = 20), capable of crawling; group 3 (n = 31), bed-ridden, Serum Zn levels were similar in the three groups, whereas body Zn clearance and the distribution of Zn showed a pattern [group 1 < group 2 < group 3 (p < 0.01, p < 0.05)], with the reverse in cases of bone mineral density (BMD) [group 1 > group 2 > group 3 (p < 0.01)]. Renal handling of Zn did not different among the three groups. There was a negative correlation between Zn distribution volume and values of BMD (p < 0.005, gamma = 0.387). Thus, various organs, as well as the skeleton, are Zn deficient in immobilized patients.

Renal handling of phosphate can predict height velocity during growth hormone therapy for short children.

Renal tubular reabsorption of phosphate in response to GH administration was studied in 28 short Japanese children, aged 5-11 yr (height SD score, less than -2.0 SD). Three groups included a classical GH deficiency (group 1; n = 12), a partial GH deficiency (group 2; n = 7), and children with non-GH deficiency (group 3; n = 9), depending on the peak response of serum GH in four provocative tests. Serum phosphorus, alkaline phosphatase, insulin-like growth factor-I (IGF-I), osteocalcin, and ratio of the maximum tubular reabsorption rate for phosphorus to the glomerular filtration rate (Tmp/GFR) were all significantly lower in group 1 compared with findings in groups 2 and 3 (P less than 0.05, P less than 0.01, and P less than 0.001). After the administration of GH (0.1 U/kg.day) for 4 consecutive days, increments in serum phosphorus and Tmp/GFR were significantly higher in group 1 than in group 2 (P less than 0.01 and P less than 0.01) or group 3 (P less than 0.01 and P less than 0.01), whereas the increment in IGF-I was similar in all 3 groups, and the levels of serum alkaline phosphatase and osteocalcin remained unchanged in all 3 groups. The calculated ratio of the increment in Tmp/GFR to the increment in IGF-I (delta Tmp/GFR/delta IGF-I) was highest in group 1, intermediate in group 2, and lowest in group 3 (P less than 0.001). One year after the GH treatment (0.5 U/kg.week), height velocity was 7.9 +/- 2.2 cm/yr in group 1 and 5.9 +/- 1.2 cm/yr in group 2; no child in group 3 was treated. When the above calculated parameters, delta Tmp/GFR/delta IGF-I and increment in height velocity (difference between pre- and posttherapy values), were taken into account, there was a significant positive correlation (n = 19; r = 0.78; P less than 0.001). This parameter can be used for purposes of predicting the outcome after 1 yr of GH therapy.

Self-limited neonatal familial hyperparathyroidism associated with hypercalciuria and renal tubular acidosis in three siblings.

Three siblings with neonatal familial hyperparathyroidism diagnosed at age 4 months, 2 months, and 5 days, respectively, were treated. Hypercalciuria, nephrocalcinosis, and renal tubular acidosis were present in each child. In all three, there were higher responses of serum parathyroid hormone to serum calcium and higher elevation of serum calcium with oral calcium loading. The metabolism of vitamin D and calcitonin seemed to be intact. Hypercalcemia associated with the abnormal response of parathyroid hormone secretion disappeared when the children passed the age of approximately 2 years, although renal tubular acidosis and nephrocalcinosis remained. An autosomal recessive inheritance seems likely.

Differences in basal and postexercise osteocalcin levels in athletic and nonathletic humans.

The levels of serum osteocalcin, in addition to other parameters, were monitored in athletic (N = 9) and nonathletic (N = 10) university male students before, immediately after, and 60 min after 30 min of exercise on a running ergometer and at a constant workload of approximately 50% of their maximum capacity; there was adequate replenishment of drinking water. In both groups, the increase in serum parathyroid hormone levels observed immediately after exercise correlated well with a decrease in ionized calcium as well as the total calcium, and also with an increase in serum phosphorus, whereas the concentration of serum albumin remained stable. The response of serum osteocalcin differed between the two groups, in that (1) the concentration before exercise was significantly higher in athletic than in nonathletic students (P less than 0.001), and (2) the maximum level was evident in the former group 60 min after exercise, whereas it was present in the latter group immediately after exercise. We speculate that athletic subjects have a higher turnover of bone status compared with nonathletic subjects.