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J. W. Honour, C. J. H. Kelnar, and C. G. D. Brook

Abstract.

Normal ranges for daily urine steroid excretion rates in childhood are reported for the first time by gas chromatographic analysis using capillary columns and flame ionisation detector. Longitudinal data came from a study over 3 years of 127 normal boys (aged 7.5-15.6 years) studied on 5 occasions and 14 pubertal girls studied over 2 years. Cross-sectional data were collected from 115 hospitalized patients (58 males, 57 females) aged 2.9 to 14 years with normal adrenal function. The excretion rate of cortisol metabolites was constant for body size, whereas androgen metabolite excretion rates rose sharply in childhood to approach adult levels at the end of puberty. The new data will enable better interpretation of pediatric patient data.

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Ian R. Lee, Linda E. Lawder, David C. Townend, John D. Wetherall, and Roland Hähnel

Abstract. The steroid binding capacity and concentration of plasma sex hormone binding globulin have been compared in 116 children aged between 2 and 14 years. Concentration was measured by electroimmunodiffusion standardised with reference to the mass of the pure protein and binding capacity by quantitating the binding of radiolabelled 5α-dihydrotestosterone. Binding capacity correlated highly with concentration in all subjects and neither differed significantly between the sexes before or during puberty. However, both were significantly lower in pubertal than in pre-pubertal children. These findings suggest the metabolism of the protein is similar in boys and girls and that the fall in its steroid binding capacity at puberty in fact is due to a fall in its concentration rather than to changes in its physicochemical properties.

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J. L. C. Ch'ng, A. Kaiser, J. Lynn, and G. F. Joplin

Abstract. Total parathyroidectomy is required to cure neonatal primary hyperparathyroidism (NPH) as any parathyroid remnant quickly becomes hyperplastic, causing recurrent hypercalcaemia. We present a patient with NPH who had total removal of his eutopic parathyroid glands but continued to have parathyroid hormone secretion from presumed ectopic parathyroid tissue. Hypercalcaemia initially recurred but normal calcium homeostasis was established as the child grew older. We postulate that the underlying defect in NPH is decreased sensitivity to the serum ionic calcium feedback inhibition at the parathyroid receptor level and that this sensitivity can improve with age.

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Peter Christiansen

ABSTRACT

The influence of ovine follicle stimulating hormone (NIH-FSH-S-3) on ovine luteinizing hormone (NIH-LH-S-8) in the Ventral Prostate Weight method (VPW) was studied. Adding of NIH-FSH-S-3 to NIH-LH-S-8 at ratios of 1:1, 4:1 and 10:1 gave no significantly higher responses than did NIH-LH-S-8 alone.

Urinary extracts from 2 women, hypophysectomized for metastasizing mammary carcinoma and from 3 children between 2 and 5 years old (1 boy, 2 girls) gave no positive response with the doses employed (1/4 of a 24 hours urine sample total per rat). It is concluded that the Ventral Prostate Weight method in hypophysectomized rats is specific for the assay of luteinizing hormone.

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E. M. de Wijn and R. Steendijk

Abstract.

In 4 girls and 1 boy with pseudo-hypoparathyroidism growth and physical maturation were followed longitudinally for 7 – 13 years until adult height had been reached. As a result of early puberty and cessation of growth all patients were relatively shorter as adults than in their childhood years. The difference between average height at the age of 8.0 years and average adult height was 2.25 sd. This observation offers an explanation for the finding in the literature that short stature is more common in adults with this disease than in children. Skeletal age was advanced in all cases and the development of the tubular bones of the hand was more advanced than the development of the round bones. It is possible that this difference resulted from inappropriately early closure of the epiphyseal discs of disproportionally short metacarpals and phalanges. On the other hand it may be an aspecific phenomenon of advanced skeletal maturation.

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Susan M. Scott, Carmela Guardian, Cathy Rogers, Pam Angelus, and Sher Werner

Abstract.

We have previously demonstrated that changes in urinary epidermal growth factor/creatinine ratios relate to gestational age and gender. It is unclear what controls this developmental pattern although chronic renal disease and thyroid aberrations have significant effects on epidermal growth factor and creatinine excretion in childhood and in adults. Therefore, we chose to explore the effects of these disease states on epidermal growth factor excretion during the perinatal time period. We collected urine samples from 8 infants with congenital renal disease and 45 infants with low T4 and normal TSH values who 'failed' the newborn screen. In addition, 2 infants with hypothyroidism and 2 infants with neonatal Grave's disease had urine samples examined. Values were compared with the epidermal growth factor and creatinine excretion from 190 infants. We demonstrated that epidermal growth factor excretion increased earlier in gestation than does creatinine excretion. In infants with renal disease or hypothyroidism, epidermal growth factor excretion was decreased while hyperthyroidism enhanced excretion. Epidermal growth factor excretion increased with relief of an obstruction but still remained low and creatinine excretion was unchanged. We confirm that in preterm infants as in childhood there are similar effects of thyroid and renal diseases on epidermal growth factor excretion.

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C Evans, NJ Jordan, G Owens, D Bradley, M Ludgate, and R John

OBJECTIVE: We describe an infant with surprisingly severe neonatal hypothyroidism due to transplacental passage of thyrotrophin receptor (TSH-R)-blocking antibodies (TBAb). DESIGN AND METHODS: TBAb were detected using a cell line which stably expresses the human TSH-R and a cAMP-responsive luciferase reporter by their ability to inhibit TSH-stimulated luciferase expression. Potent TBAb were detected in maternal serum and initially in the infant's serum but, in the latter, TBAb decreased over time to within the reference range by 3-4 months of age, illustrating the transient nature of this condition. RESULTS: The thyroid function of this child did not return to normal on withdrawal of thyroxine therapy at 16 months of age when he developed transient compensated hypothyroidism. CONCLUSIONS: We propose that the presence of potent TBAb in utero and in the first weeks of life may have implications for the development of a normally sized thyroid gland. We have demonstrated the presence of TBAb in the mother's milk and, as far as we are aware, this is the first such report. However, the TBAb in the milk probably did not contribute significantly to hypothyroidism in the child, given the reducing antibody titre in his circulation.

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S. Wirth, W. Schönberger, A. Roth, and W. Grimm

Abstract.

Serum somatomedin B levels were determined by radioimmunoassay in 209 healthy boys and girls from one month to 16 years of age.

Low values were found up to the second year life. In the first year the mean level was 13.8 mg/l in girls and 11.5 mg/l in boys. In older children the values increased to levels between 13 and 22 mg/l in boys and between 13 and 18.5 mg/l in girls. They were independent of the stage of pubertal development.

Somatomedin B levels were normal in 71 children with constitutional growth delay, primordial dwarfism, familial dwarfism and other forms of growth disturbance. The mean levels were between 12.1 and 14.4 mg/l.

Values below 6 mg/l were present only in children with hGH deficiency. In these patients we could find an increase of the mean level from 4.3 mg/l without therapy to 9.4 mg/l under treatment.

Thus the determination of somatomedin B seems to be useful for the diagnosis of hGH deficiency.

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M. H. Gons, J. H. Kok, W. H. H. Tegelaers, and J. J. M. de Vijlder

Abstract. In this paper we describe methods for the early aetiological diagnosis of congenital hypothyroidism, using beside the classical T4, T3 and TSH plasma concentrations, four additional parameters in plasma and urine. The first one is thyroglobulin (Tg). In normal children of more than one year of age and in adults, 5–35 ng/ml plasma is found, in neonates 2–3 weeks old, this level is 10–250 ng/ml. In patients with a stimulated thyroid gland, as in primary congenital hypothyroidism, plasma Tg levels increase. High Tg values are found in iodine deficiency and in organification defects. In the absence of the thyroid gland plasma Tg is undetectable. Low to normal levels are found in cases with hypoplasia of the gland. In patients with a disturbed synthesis of Tg, resulting in Tg deficiency of the gland, plasma Tg levels vary from undetectable to normal. The PBI-T4 plasma difference, which is caused by circulating abnormal iodoproteins is the second parameter. The products of thyroidal breakdown processes of the abnormal iodoproteins are excreted in the urine and used as the third parameter. We found that the excretion of this low molecular weight iodinated material (LOMWIOM) was increased only in Tg-deficient patients.

If the neonate is found to be hypothyroid, thyroid hormone substitution must be given immediately. Blood and urine sampling can be done just before or even directly after starting the therapy. The measurements extended with the determination of the total iodine excretion (fourth parameter) can be carried out within 1 week. With these additional methods it appeared to be possible to distinguish between several types of congenital hypothyroidism in neonates found by screening.

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T. Torresani, E. Schuster, and R. Illig

Abstract. Luteinizing hormone (LH) bioactivity was determined by an in vitro microbioassay in 65 plasma samples from 26 infants and young children between 10 days and 6.5 years of age. In addition LH was measured by radioimmunoassay. For both, LH preparation LER-907 was used as standard.

Biologically measured LH values (bio-LH) were always higher than radioimmunologically determined LH values (RIA-LH) as reflected by bio/RIA ratios greater then 1.0.

In male infants bio-LH was elevated up to 7 months of age. Thereafter, it decreased and remained low over the age range of our study. In female infants bio-LH was also elevated, but decreased after 1 month and showed a slight tendency to rise in the age group 3–6.5 years.

The results of RIA-LH showed approximately the same pattern, but at a lower level. In boys RIA-LH levels were highest around 1 month of age, decreased steadily between 2 and 7 months and remained constant thereafter. Girls had rather constant RIA-LH values between 2 months and 3 years of age. In contrast to bio-LH, there is a clear-cut drop of RIA-LH in the age group 3–6.5 years, resulting in a statistically significant increase of the bio/RIA ratio.

In boys the time course of the bio-LH changes coincides with the known elevation of testosterone during the first months of life.

In girls the elevated bio-LH levels observed during the first month are not so far associated with a known steroid correlate.

Our study shows an increased biological activity of circulating LH and a marked dissociation of biologically and radioimmunologically active LH during early infancy, analogous to observations during puberty.