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Gerhard Ulrich Exner, Andrea Prader, Urs Elsasser, and Max Anliker


125I Computed Tomography (CT) allows for the selective determination of trabecular and compact bone mineral parameters in the radius. Using this technique the effects of high dose oestrogen treatment in 11 tall girls, and of high dose testosterone treatment in 5 tall boys were monitored. In both groups trabecular bone density (TBD) increased steadily during treatment at a rate of about 1% per month. Also in both groups the compact bone mineral increased steadily. These results are compared with those from a cross sectional study on 49 normal children and 36 normal adults, in whom TBD was found to be independent of age and sex, so that the increases in TBD in both treatment groups can be attributed directly to the influence of the sex hormones. Since the compact bone mineral is higher in adults than in children it cannot yet be decided whether the increases seen in the treated patients are related to the sex hormone treatment, or reflect only the normal development of the bone during adolescence.

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Bjarne Lund, Niels Clausen, Birger Lund, Else Andersen, and Ole H. Sørensen


Circulating 1,25-dihydroxyvitamin D (1,25-(OH)2D) was measured in 87 children aged 3 months to 15 years, and in 11 adolescents 16–19 years of age. A positive correlation to growth velocity was observed, indicating that the biologically active vitamin D metabolite is an important physiological factor in the regulation of growth and development of the skeleton.

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Seppo Leisti and Jaakko Perheentupa


An im vasopressin test was given to 141 children and adolescents, 52 with normal HPA axis and 89 with evident or suspected defect of the axis, and repeated in 36 cases, to establish criteria of a normal response, and to examine the accuracy and precision of the responses. Comparisons were made with the responses to the 2-h ACTH, insulin and 3-h metyrapone test.

The distributions of plasma cortisol levels and increments were positively skew, and a log transformation was made for appropriate statistical analysis. Maximal plasma cortisol level was positively and maximal increment negatively correlated with the basal level. In precision, the maximal level was superior to the maximal increment. Hence, a normal result was best defined by an area around the regression of maximal level on basal level in the normal series. The best single index of the response was the maximal level. A useful new method was introduced for quantitative comparison of plasma cortisol responses to different tests.

The vasopressin test result was frequently normal in patients who, according to repeated insulin tests were ACTH-deficient. Furthermore, the 10 patients with organic expansive hypothalamic lesions had a mean vasopressin response, that was greater relative to the insulin response than that of the reference series. However, 3 of 21 patients with organic non-expansive hypothalamic disease gave a subnormal vasopressin response but a normal insulin response. Moreover, in isolated GH deficiency and after prednisone medication the mean vasopressin response was lower relative to the insulin response than in the reference series. Thus, this test is not reliable in screening for, or in anatomical diagnoses of ACTH deficiency.

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Jerzy Kosowicz

An early diagnosis of Turner's syndrome is usually difficult, especially in cases with female-type chromatin. Hence the frequent occurrence of changes of the medial tibial condyle, resembling Blount's disease, deserves special attention.

Blount's disease belongs to the group of aseptic necrosis of the bone and cartilage (osteochondritis). The causes of the aseptic necrosis remain, however, still unknown. Some authors believe that trauma may be responsible for an arterial occlusion and impairment of blood supply with subsequent necrosis. The fact that the changes are bilateral and early in onset in infancy or childhood may also suggest that osteochondritis is some form of local disturbance of growth. According to its location, osteochondritis is called Legg-Perthes' disease, Scheuermann's disease, Köhler's disease, Osgood-Schlatter's disease – according to the names of the authors who first described the condition. The above mentioned diseases occur rather frequently in children and adolescents. The aseptic necrosis of the medial

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J. Ludvigsson and L. G. Heding


Fasting serum C-peptide and total immunoreactive insulin (IRI) were determined in 38 non-diabetic children and adolescents 6–22 years old. C-peptide varied between 0.22–0.73 pmol/ml (mean ± sd, 0.45 ± 0.11). There was a tendency to higher values during puberty. No difference was found between subjects with or without a family history for diabetes. IRI varied between 0–31 μU/ml (mean ± sd, 11.3 ± 6.5).

The C-peptide response to glucagon was studied in 10 insulin dependent juvenile diabetics 11–19 years old, who had had measurable amounts of fasting C-peptide on some occasions during the previous years. Duration of diabetes varied between 4–12 years. A slight but significant rise in C-peptide level occurred in 3 patients. Their metabolic control estimated on the basis of daily urinalysis was "excellent" or "good". The results support the hypothesis that even trace remnants of the beta cell function may be of importance for the metabolic control in juvenile diabetes.

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D. C. L. Savage, Constance C. Forsyth, Eileen McCafferty, and Jenny Cameron


The excretion of 7 individual 17-oxosteroids and 7 individual corticosteroids in 24 h urine samples from 62 normal infants, children and adolescents, based on an accurate and specific paper chromatographic method for their separation and quantitation, is reported. The excretion of the 11-deoxy-17-oxosteroids gradually increases from 7 years of age and the increase becomes more rapid 2 or 3 years before the clinical signs of puberty appear. The rise continues throughout puberty and beyond it until the adult level is reached. The increase far exceeds that which would be accounted for by the growth of the individual. The increase in the excretion of the 11-oxy-17-oxosteroids with age is much more gradual. Androgens favour the formation of 5α metabolites and the 5α:5β ratio of the total 5α 17-oxosteroids and the total 5β 17-oxosteroids shows a statistically significant increase with age. In addition, a relatively high 5α:5β ratio is noted in male infants, which is likely to be related to their relatively high plasma testosterone levels. The excretion of the 17-hydroxycorticosteroids and the α-ketolic metabolites of cortisol gradually rises with age and correlates with body weight. The α-ketolic metabolites of corticosterone are relatively high in infancy, but after the age of 4 years their excretion also correlates with body weight. An increase in the 5α:5β ratio of allo-THF to THF is noted at puberty similar to that found with the 5α:5β ratios of the 17-oxosteroids.

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W. Andler, G. Biro, S. Bernasconi, and G. Giovanelli


Insulin and propranolol-glucagon stimulation tests were carried out on 28 children and 5 adolescents and the results of their growth hormone and plasma cortisol estimations were compared.

Twenty-nine subjects with normal growth hormone reserves showed a mean maximum rise of 17.4 μU/ml of serum growth hormone in the insulin test whereas the intramuscular injection of glucagon after oral premedication with propranolol produced a rise of 38.5 μU/ml. Five subjects with normal growth hormone reserves showed a reduced hormone output in the insulin stimulation tests but normal response in the propranolol-glucagon stimulation tests. Only one subject showed a poor response in the propranolol-glucagon but normal response in the insulin stimulation test.

In 30 subjects with normal adrenocortical function the mean maximum increase of plasma cortisol was 15.6 μU/ml in the insulin – and 14.9 μU/ml in the propranolol-glucagon stimulation tests, respectively. Both methods are suitable for studying the pituitary-adrenocortical interrelationships. The mechanism of the release of glucagon-induced growth hormone is not clear but the fall in blood glucose does not seem to play a major role in the process. A stress-like mechanism is equally unlikely because vegetative symptoms occurred only i a small number of subjects after intramuscular glucagon administration. It is possible that glucagon possesses a releasing-like mechanism which operates in the pituitary itself.

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W. Croughs, H. K. A. Visser, M. G. Woldring, and A. Bakker

The kinetics of thyroxin metabolism in adult man has been studied extensively (1, 2). In children only the data of Haddad (3) on 17 euthyroid children between 3 and 9 years of age are available.

Thyroxin turnover studies were carried out in 19 children between 3 and 15 years of age: euthyroid control 5; pituitary insufficiency 4; hypothyroidism during treatment 2; off treatment for 2 months 1; adolescent goiter 3; obesity 3 and one 3 years old eumetabolic child who had an iodine goiter at birth. Fractional rate of turnover K, thyroxin degradation rate D and other data were calculated according to Sterling cs. (2). In part of the children the thyroid gland was blocked with propylthiouracil; in the others also the thyroxin secretion rate S was calculated according to Ingbar cs. (1).

Results: Values for D and S were in good agreement. Mean value for K in 5 normal

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Naphtali Brand, Ruwen A. Kathein, and Gideon Hasis


A parallelism in the incidence of human and bovine goitre in the northern part of Israel is described.

Among 1475 children and adolescents from 8–18 years of age of both sexes and examined from Upper Galilee an average incidence of goitre of more than 10% was found.

A three years follow up study showed an increase in percentage of goitre to 30% among girls. No cretins or deaf or dumb subjects were found.

Thyroid weights of 385 heads of cattle slaughtered at the slaughter-houses or on the farms were determined. While the mean weight of thyroids of cattle from a non-endemic control area was 17.7 g the mean weight for the goitrous area attained 23.4 g. The mean relative thyroid weights for the control and goitrous areas were 3.75 and 6.98 g/100 kg respectively. The histopathological examination of several excised non selected thyroids from Upper Galilee showed pathological findings: hyperplasia, fibrosis, nodular goitre.

These data are the first evidence of the incidence of endemic goitre of cattle in Israel and suggest most strongly that here the unfavourable environment plays a decisive role among the factors which influence the weight of bovine thyroids.

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Eva Al Taji, Heike Biebermann, Zdeňka Límanová, Olga Hníková, Jaroslav Zikmund, Christof Dame, Annette Grüters, Jan Lebl, and Heiko Krude

Objective: Mutations in NKX2.1, NKX2.5, FOXE1 and PAX8 genes, encoding for transcription factors involved in the development of the thyroid gland, have been identified in a minority of patients with syndromic and non-syndromic congenital hypothyroidism (CH).

Design: In a phenotype-selected cohort of 170 Czech paediatric and adolescent patients with non-goitre CH, including thyroid dysgenesis, or non-goitre early-onset hypothyroidism, PAX8, NKX2.1, NKX2.5, FOXE1 and HHEX genes were analysed for mutations.

Methods: NKX2.1, NKX2.5, FOXE1 and HHEX genes were directly sequenced in patients with syndromic CH. PAX8 mutational screening was performed in all 170 patients by single-stranded conformation polymorphism, followed by direct sequencing of samples with abnormal findings. The R52P PAX8 mutation was functionally characterized by DNA binding studies.

Results: We identified a novel PAX8 mutation R52P, dominantly inherited in a three-generation pedigree and leading to non-congenital, early-onset, non-goitre, non-autoimmune hypothyroidism with gradual postnatal regression of the thyroid size and function. The R52P PAX8 mutation results in the substitution of a highly conserved residue of the DNA-binding domain with a loss-of-function effect. Conclusions: The very low frequency of genetic defects in a population-based cohort of children affected by non-goitre congenital and early-onset hypothyroidism, even in a phenotype-focussed screening study, suggests the pathogenetic role of either non-classic genetic mechanisms or the involvement of genes unknown so far. Identification of a novel PAX8 mutation in a particular variant of non-congenital early-onset hypothyroidism indicates a key function of PAX8 in the postnatal growth and functional maintenance of the thyroid gland.