Association between X-linked hypophosphatemic rickets and Klinefelter's syndrome: effects on growth and body proportion.

Growth failure with disproportionate short stature is the major clinical feature of patients with X-linked hypophosphatemic rickets (HYP). We studied the pattern of linear growth and body proportion in an untreated normally growing HYP child also affected by Klinefelter's syndrome. Auxologic data were compared with those of a HYP half-brother who showed growth failure despite long-term treatment either with vitamin D or with vitamin-D-analog plus phosphate salt supplementation. The degree of body disproportion changed from negative values to positive values in the proband, whereas it was reduced in the half-brother. We conclude that, in the proband, the normal pattern of growth and the lack of the typical body disproportion as seen in HYP patients are attributable to the concomitant presence of Klinefelter's syndrome.

Effects of growth hormone on phosphocalcium homeostasis and bone metabolism.

In this review the effects of growth hormone (GH) on phosphocalcium homeostasis and bone metabolism are reported. Some in vitro effects of GH on chondrocytes and osteoblasts are discussed too. The main GH effects on phosphocalcium homeostasis are the permissive action on renal 1 alpha-hydroxylase activity by the hypophosphatemic stimulus and the antiphosphaturic effect by the stimulation of the maximum rate of renal tubular reabsorption of phosphate. On bone, GH is able to stimulate bone turnover and to increase bone mass. In addition, GH stimulates type I and type III collagen metabolism. In vitro, GH increases the proliferation of chondrocytes from the human growing cartilage together with the levels of interleukin-6 in the supernatant. The hormone increases also the proliferation of the human osteosarcoma-derived osteoblast-like cells and augments the osteocalcin levels in the supernatant. Thus, GH markedly influences phosphocalcium homeostasis and bone metabolism in childhood and adolescence. In addition, it is possible that GH continues to play a role in bone physiology during adulthood when final height is reached.

Ketoconazole decreases the serum ionized calcium and 1,25-dihydroxyvitamin D levels in tuberculosis-associated hypercalcemia.

OBJECTIVE: To evaluate whether tuberculosis-associated hypercalcemia is related to abnormal synthesis of 1,25-dihydroxyvitamin D (1,25[OH]2D) and whether ketoconazole administration may be useful in treating tuberculosis-associated hypercalcemia. DESIGN: Case study. SETTING: Endocrine Unit, Pediatric Clinic, University of Pisa (Italy). PARTICIPANTS: Two boys (aged 10.5 years and 14.7 years) with active tuberculosis and hypercalcemia. MEASUREMENTS/MAIN RESULTS: At admission, serum 1,25-dihydroxyvitamin D levels were elevated. Oral ketoconazole administration (3.0 mg/kg every 8 hours) decreased 1,25-dihydroxyvitamin D levels within the first week of therapy (from 208.8 to 57.6 pmol/L [-72.4%] in one boy and from 321.6 to 115.2 pmol/L [-64.2%] in the other). We also found a coincident normalization of serum ionized calcium concentration (from 1.45 to 1.24 mmol/L [-13.0%] in one boy and from 1.55 to 1.26 mmol/L [-17.0%] in the other). CONCLUSIONS: Abnormal elevated levels of 1,25-dihydroxyvitamin D caused hypercalcemia in our patients; ketoconazole administration may be effective in the treatment of hypercalcemia in patients with tuberculosis, which decreases 1,25-dihydroxyvitamin D synthesis.

[Vitamin D prophylaxis in childhood]. / Profilassi con vitamina D in età pediatrica.

The past 10 years have seen a return of rickets. Clinical and/or biochemical signs of vitamin D deficiency are still found in some children and adolescents, mainly during the winter. Sunlight exposure is able to prevent vitamin D deficiency and rickets but the dramatic influence of changes in solar ultraviolet-B radiation on cutaneous vitamin D3 synthesis, related to latitude and season effects, suggest that a vitamin D supplementation may be advisable. Moreover, human milk and common foods contain low quantities of vitamin D. So, we recommend routinely 400 IU of supplementary vitamin D per day in all infants. The vitamin D requirements in low-birth-weight infants are higher than at term infants; it is recommended the use of 1000-1600 IU per day in the first months of life. Intermittent high-dose of vitamin D and vitamin D metabolites are not advisable for prophylaxis of rickets.

Intact parathyroid hormone levels during pregnancy, in healthy term neonates and in hypocalcemic preterm infants.

We measured parathyroid hormone levels in pregnant and nonpregnant women and at 1, 2 and 5 days of life in healthy term neonates and in hypocalcemic preterm infants using a new immunoradiometric assay which measures only biologically active intact parathyroid hormone and by a mid-molecule parathyroid hormone radioimmunoassay. During pregnancy intact and mid-molecule parathyroid hormone levels did not show any modification and were not different from parathyroid hormone levels of nonpregnant age-matched controls. Serum calcium and phosphorus levels did not vary during each trimester of pregnancy. In cord serum intact and mid-molecule parathyroid hormone values were low in both term and preterm infants. In term neonates intact and mid-molecule parathyroid hormone levels peaked on day 1; in preterm infants intact parathyroid hormone levels peaked on day 1 while mid-molecule parathyroid hormone values peaked on day 2. Intact parathyroid hormone levels showed a more marked increase in preterm (19-fold) than in term neonates (7.5-fold) on day 1. Our data do not confirm the previously reported "physiologic" hyperparathyroidism in pregnancy. Moreover we found a normal parathyroid gland responsiveness to decreasing serum calcium levels in the first days of life in term and preterm infants. Our results suggest that measurement of intact parathyroid hormone 1-84 by immunoradiometric assay in the first days of life is a more sensitive index of parathyroid gland secretory function than the measurement of middle or carboxyl-terminal parathyroid hormone fragments allowing the detection of the dynamic changes of parathyroid hormone which occur in hypocalcemic preterm infants.