Vitamin D metabolites in adolescents and young adults with cystic fibrosis: effects of sun and season.

To assess mineral metabolism in patients with cystic fibrosis and to study the effects of season and sunlight exposure on generation of vitamin D metabolites, we quantified serum levels of calcidiol and calcitriol, other measures of bone metabolism, and radiographic bone mass in 20 adolescents and young adults with CF and 20 age-matched normal volunteers. Levels of calcidiol were lower in patients with CF than in controls and lower in Massachusetts than in Arizona in both study groups. Controls in Arizona had higher (P less than 0.05) levels of calcitriol than in Massachusetts throughout the year. All control subjects in both states had higher levels of calcitriol than did patients with CF. Patients in Massachusetts had significantly lower levels of calcitriol in winter than in summer. Summer levels of calcitriol in CF were significantly higher in Massachusetts than in Arizona; during winter, lower levels were found in Massachusetts than in Arizona. Mean bone density in patients with CF was 88% and 89% of normal American standards in Massachusetts and Arizona, respectively. These data indicate a seasonal, sunlight-related influence on levels of vitamin D metabolites in patients with CF receiving approximately 1000 IU vitamin D per day. Older patients with CF with progressively diminishing sunlight exposure may be at increased risk for development of osteopenia. The detected radiographic abnormalities of bone mineralization may also be related to malabsorptive deficiencies of calcium and phosphorus.

The use of a commercially available somatomedin-C radioimmunoassay in patients with disorders of growth.

Somatomedin-C concentrations were measured by a newly available commercial radioimmunoassay in plasma samples from 41 children undergoing clinical evaluation of hypothalamic-pituitary function because of varied disorders of growth. Sequential Sm-C levels were stable; the coefficient of variation remained below 10% over a three-hour period. The Sm-C values of 27% of the children were discordant with the GH responses; of 25 patients with normal provoked-GH levels, seven had low Sm-C values, whereas four of 16 patients with inadequate GH responses had normal Sm-C concentrations. All of the discordant data occurred in 31 patients with diminished linear growth velocity. More patients with decreased growth velocity had diminished Sm-C levels than did short children with normal linear growth velocity. These data suggest that many variables, in addition to adequacy of GH production and plasma Sm-C levels, may affect net Sm-C activity. This possibly reduces the usefulness of the Sm-C radioimmunoassay as a single screening test for abnormalities of GH secretion.

Childhood thyromegaly: recent developments.

Evaluation of a child with goiter includes historical review, physical examination, and measurement of serum concentrations of PBI, T4 and T3RU, TSH, and titers of antithyroglobulin and antithyroid microsomal antibodies. If there are no indications for more intensive evaluation such as history of cervical irradiation, a palpable abnormality of the thyroid gland or unusual laboratory findings (e.g., a significant PBI-thyroxine iodine discrepancy in the absence of a positive antithyroid antibody titer), a trial of TSH-suppressive therapy with thyroxine is undertake, even if the cause of thyromegaly has not been identified. If thyroid size diminishes in the ensuing six to 12 months, treatment is maintained for approximately two years and then discontinued. If the goiter recurs, or if there is impaired thyroid function, treatment is resumed. Periodically, antithyroid antibody titers and indices of thyroid function are determined. If the goiter does not diminish after a reasonable trial of suppressive therapy with adequate amounts of thyroxine (i.e., those quantities which will inhibit TRH-induced secretion of TSH), subtotal thyroidectomy is recommended to be certain that an underlying neoplasm has not been overlooked. A biopsy of the thyroid is not performed routinely in such children prior to operative therapy. Almost invariably, examination of the surgical specimen reveals CLT. Postoperatively, suppressive doses of thyroxine are maintained indefinitely. Inasmuch as thyroxine suppression of TSH secretion is essential in the management of patients with thyroid neoplasms, a limited medical trial, as described, does not place the patient at undue risk.

Serum concentrations of 24,25(OH)2D in uremic children: a reflection of renal function.

The mean serum concentration of 24,25(OH)2D determined by competitive protein-binding radioassay was significantly lower in ten uremic children maintained on hemodialysis (0.82 +/- 0.43[SD] ng/ml) than in ten patients with impaired renal function not requiring hemodialysis (1.30 +/- 0.54 ng/ml, P less than 0.05), or in 12 normal children (2.98 +/- 1.57 ng/ml, P less than 0.01). The serum levels of 250HD were similar in all groups. There were significant (P less than 0.01) positive correlations between the serum concentration of 24,25(OH)2D or the ratio 24,25(OH)2D/25OHD and the creatinine clearance. The serum concentration of 24,25(OH)2D was significantly decreased also in six anephric adults relative to normal adult values. The data indicate that production of 24,25(OH)2D is impaired in subjects with compromised renal function. Inasmuch as the major active metabolite of Vitamin D, i.e., 1,25(OH)2D, is requried for renal synthesis of 24,25(OH)2D measurement of the latter metabolite may provide a convenient method for assessment of renal vitamin D metabolism. The role of this metabolite in the pathogenesis of renal osteodystrophy remains speculative.

Measurement of 24,25 dihydroxyvitamin D in sera of neonates and children.

Serum concentration of 25OHD and 24,25(OH)2D were measured in lipid extracts of serum by competitive radioassay following separation of the metabolits by Sephadex LH-20 column chromatography. The concentration of 24,25(OH)2D in children and adolescents (3.3 +/- 1.3 SD ng/ml) was significantly greater (P less than 0.01) than the levels recorded in neonates (1.8 +/- 0.6 ng/ml), and was approximately one-tenth the concentration of 25OHD in the two populations (children 35.2 +/- 9.2 ng/ml; neonates 14.4 +/- 3.4 ng/ml, P less than 0.01). Although 24,25(OH)2D is present in significant quantities in the sera of children and adolescents, its metabolic function remains unknown at present.

Secretion of the adrenal androgen, dehydroepiandrosterone sulfate, during normal infancy, childhood, and adolescence, in sick infants, and in children with endocrinologic abnormalities.

Serum concentrations of the adrenal androgen, dehydroepiandrosterone sulfate, were measured by radioimmunoassay in normal infants and children, in sick premature and full-term newborn infants, and in patients undergoing evaluation of the hypothalamic-pituitary-gonadal and -adrenal systems. Premature infants had significantly greater (p less than 0.001) levels of DHAS (263 +/- 40)[SE]migrong/dl) than did full-term infants (58.9 +/- 5.2) during the first ten days of life; further increments occurred in stressed "sick" infants. A gradual age- and maturity-related rise in serum concentrations of DHAS was observed during childhood with the earliest increase occurring prior to the onset of pubertal production of gonadal steroids. Serum levels of DHAS rose following administration of ACTH and were increased in patients with congenital adrenal hyperplasia, in whom rapid decrements followed treatment with dexamethasone. hCG or LH-RH treatment did not alter DHAS concentrations. These data suggest that direct secretion of DHAS by the adrenal gland and/or peripheral sulfation of DHA, rather than gonadal secretion, accounts for the majority of DHAS production. The involvement of adrenal androgens in the pubertal maturation of the reproductive endocrine system thus may be evaluated by quantitation of serum DHAS.