Normal values of urinary-free cortisol in children and adolescents.
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Biomedical subjects
Publications and source records attributed to Z Hochberg.
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Cranial irradiation has been shown to impair growth hormone secretion in children. In this study a cell culture of dispersed rat anterior pituitary cells was exposed to single doses of radiation in the range of 100-1500 rad: Survival curves were obtained for the different anterior pituitary cell lines, and growth hormone secretion was measured in the tissue culture medium. Both survival and growth hormone secretion curves showed an initial shoulder in the range of 0-300 rad, followed by a decline between 300-750 rad. It is concluded that growth hormone secreting acidophilic pituicytes are sensitive to radiation at single doses greater than 300 rad.
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Seven subjects with Kallmann's syndrome were studied to determine whether they had disturbances of fluid homeostasis. Simultaneous measurements of urine and plasma osmolality (Uosm and Posm, respectively) were made during free access to fluids. The Uosm-Posm relationship was abnormal in five patients on at least one occasion. Patient 2 was frequently overhydrated (Posm less than or equal to 280 mosmol/kg) and patient 5 excreted a dilute urine when his Posm was 290 mosmol/kg. The three subjects (1, 5, and 7) tending to have an increased Psom (greater than or equal to 300 mosmol/kg) were able to concentrate their urine (Uosm greater than 800 mosmol/kg) and denied polyuria and polydipsia. Their elevated Posms could be explained by impairment of thirst, rather than increased excretion of water, because the patients concentrated their urines at normal Posms during fluid deprivation. The osmotic threshold for vasopressin release was decreased (Posm = 270.6 mosmol/kg) in one patient and increased (Posm greater than or equal to 295 mosmol/kg) in two others of the seven patients. The elevated osmotic threshold was not due to chronic hyperosmolality or a generalized defect in vasopressin secretion. In the patient with the highest osmotic threshold (Posm = 296 mosmol/kg) and Posms between 289--301 mosmol/kg during free access to fluid, the osmotic threshold decreased to only 293 mosmol/kg after 6 weeks of adequate hydration and desmopressin acetate. However, in response to hypotension induced by trimethaphan, he increased his plasma vasopressin from 1--26 microU/ml. In conclusion, some patients with Kallmann's syndrome may have osmoreceptor dysfunction and abnormal thirst regulation, indicating more extensive hypothalamic involvement than previously appreciated.
A new case of vitamin D dependent rickets (Type II) with alopecia in a 5 yr old child is reported. Skin fibroblasts were propagated in culture and analyzed for cytoplasmic 1,25(OH)2D3 receptors. The rachitic cells failed to exhibit specific, high-affinity binding sites by either Scatchard analysis or sucrose density gradient. Furthermore, a rise in 24-hydroxylase activity could not be elicited following incubation of the rachitig cells with 1,25(OH)2D3. Fibroblasts from a non-rachitic child examined in parallel experiments demonstrated high affinity binding sites (Kd = 0.1 nM, Nmax = 33 fmol/100 micrograms DNA) and the induction of 24-hydroxylase activity. The molecular basis of the unresponsiveness of the cells from the rachitic child appears to be due to defective or absent 1,25(OH)2D3 receptors.
We simplified the procedures for identifying children with diabetes insipidus by using the relationship between urine and plasma osmolality (Uosm and Posm). We defined the normal Uosm-Posm relationship as the area within the 95% confidence regions for pairs of osmolality measurements obtained from normal children during periods of free access to fluids and after oral hydration. In 13 patients with diabetes insipidus, Uosm-Posm coordinates were outside these regions in 50 of 64 pairs (one to ten per patient) during periods of free access to fluids. After three hours of fluid deprivation, the Uosm-Posm relationship was abnormal in 12 patients; the 13th was unable to void. For those with a normal Posm, and Uosm less than Posm, another pair of osmolality measurements after three hours of fluid restriction should determine the diagnosis.
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An 8-year-old girl with hypothalamic hypopituitarism is described. The clinical course was characterized by fluctuation between diabetes insipidus and water intoxication. In an attempt to find a physiological explanation she underwent two sets of dehydration and osmotic threshold tests. The presence of endogenous vasopressin, and the normally functioning volume receptors, was demonstrated by the normal urine osmolality during dehydration. The osmotic threshold was 263 mosm/kg on one test and 300 mosm/kg on the other. More extreme values might be suspected based on simultaneous urine and plasma osmolality obtained during acute episodes of water intoxication and severe dehydration. With plasma osmolality as high as 307 mosm/kg, the child denied thirst. The data appear to indicate an instability of the osmoreceptor mechanism and a deficiency of the thirst mechanism with intact volume receptors.
To determine if the anterior pituitary gland is the site of negative feedback inhibition of GH release, we studied the effect of GH and multiplication-stimulating activity (MSA), a member of the somatomedin family, on isolated rat anterior pituitary cells in primary culture. The effect of GH was examined in two ways: 1) by adding to the cultures human GH (10 ng/ml to 20 microgram/ml) which was biologically active in the rat but not cross-reactive in the rat GH (rGH) RIA, and 2) by comparing rGH secretion in cultures of different cell densities. No suppression of either basal or prostaglandin E1-stimulated rGH release was found. An enhancement observed in serum-free conditions at high human GH concentrations was interpreted as a nonspecific response to protein, because bovine serum albumin produced the same effect. When added in the presence of serum, MSA (1--500 ng/ml) had no effect on rGH secretion. In the absence of serum, there were 71% and 30% increases in the basal and prostaglandin E1-stimulated rates of hormone release, respectively, possibly attributable to a trophic effect of MSA. Six other hormones having structural or functional similarity to either GH or somatomedin also failed to inhibit rGH secretion. Our results do not support the hypothesis that GH or somatomedin exerts a negative feedback effect on GH release directly on the anterior pituitary gland. Most likely, the hypothalamus or a higher brain center is the site for such regulation.
The effect of hypo- and hyperglycemia on the renin-aldosterone system was studied in 10 endocrinologically normal children. Insulin-induced hypoglycemia caused an elevation of plasma renin activity (PRA) up to 371 +/- 23% (mean +/- SEM) over the basal level (p less than 0.001) and of the plasma aldosterone level up to 243 +/- 7% (mean +/- SEM) over the basal values (p less than 0.001). Hyperglycemia caused an elevation of PRA up to 135 +/- 40% (mean +/- SEM) over the basal values (p less than 0.05) and a reduction in the plasma aldosterone level to 53 +/- 12% (mean +/- SEM, p less than 0.01). It is suggested that the widely used diagnostic procedures, the insulin tolerance and oral glucose tolerance tests, be also applied for the investigation of the renin-aldosterone system.
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Two patients with gonadal dysgenesis are described. One had X-isochromosome and the other had a 45,X karyotype. They both had Hashimoto's thyroiditis with extremely low levels of thyroid hormones, but no clinical signs or symptoms of hypothyroidism, and no goiter. Even with replacement therapy and restoration of normal thyroid hormone levels, there was no increase in their growth rates. The need for routine thyroid hormone determinations in patients with gonadal dysgenesis is emphasized. The absence of clinical signs and symptoms of hypothyroidism in a patient with gonadal dysgenesis does not exclude the presence of Hashimoto's thyroiditis.
Sydenham's chorea can be successfully treated with haloperidol, an agent that is known to interfere with the binding of dopamine to its receptors. This suggests that dopamine and its metabolic end product, homovanillic acid (HVA), might be elevated in Sydenham's chorea. To test this hypothesis, the urine of three patients with the clinical diagnosis of Sydenham's chorea was analyzed for HVA and vanillylmandelic acid (VMA). Urinary HVA and the HVA:VMA ratio were significantly higher in these three patients compared with seven control children. Urinary VMA was not different in these two groups. It is suggested that increased dopamine metabolism is involved in the pathogenesis of Sydenham's chorea and that the determination of urinary HVA and the HVA:VMA ratio may be helpful in establishing this diagnosis. We report a case that demonstrates the use of urinary HVA determination in the diagnosis of Sydenham's chorea.
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