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Philippe E. Gamier, Jean-Louis Chaussain, Elisabeth Binet, Ariane Schlumberger, and Jean-Claude Job

ABSTRACT

Plasma gonadotrophins (LH and FSH) were radio-immunoassayed before and after injection of 0.1 mg/m2 of synthetic luteinizing hormone-releasing hormone (LH-RH) in infants 1 to 12 months old, prepubertal children aged more than 12 months, and pubertal subjects of both sexes. The pubertal changes of gonadotrophins include a highly significant increase of LH pituitary mobilizable reserve in both sexes, while the FSH reserve shows a significant decrease in females and no significant variation in males. From the first year of life up to childhood, the basal blood levels of FSH and LH decrease significantly in girls but do not vary in boys, while the FSH reserve decreases significantly in girls and increases significantly in boys, the LH reserve showing a non-significant decrease in both sexes. In the first year of life, girls show a very significantly higher FSH secretion and reserve than boys, while boys have a significantly higher LH reserve than girls. After the end of the first year up to the onset of puberty, the FSH reserve remains significantly higher in girls than in boys. The interpretation of these facts is discussed.

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D. Knorr, F. Bidlingmaier, O. Butenandt, H. Fendel, and R. Ehrt-Wehle

ABSTRACT

Plasma testosterone was investigated by gas-liquid chromatography with an electron capture detector in a cross-sectional study in childhood and during puberty in 214 boys. The testosterone values were correlated with sexual characteristics such as axillary hair, pubic hair, testicular size and bone age.

In 22 individuals during puberty a longitudinal study was started, indicating a very steep increase of plasma testosterone between 40 and 240 ng/100 ml. This stage is mostly passed through very rapidly within 10 months.

Plasma testosterone, growth velocity and weight gain were correlated in two boys during puberty. The peak of growth spurt occurs between 50 and 170 ng of plasma testosterone.

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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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Pierre Ferrier and Thérèse Lemarchand-Beraud

Very little is known yet about thyroid hormone transport capacity of the serum and thyroid hormone protein binding in children. Except for the studies by Haddad (1) and by Dreyer and Man (2), all observations so far published are concerned with hormone transport mechanisms in the adult. In order to establish reference values, thyroid function tests were performed in 35 eumetabolic children (20 boys and 15 girls) aged from 6 weeks to 11 years. In vitro erythrocyte uptake of T3 was measured according to the procedure of Hamolsky et al. (3). Protein binding of T4 was studied at progressive degrees of saturation by paper electrophoresis in tris-maleate buffer at pH 8.6 according to Ingbar et al. (4). Values were compared with those from a group of 21 euthyroid adults, tested in the same laboratory. PBI was found to be higher in children than in adults. This tendency has been noted

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L. A. Nilsson

Cytologic aspiration biopsy of the thyroid was used in 48 of 63 children being the material of juvenile atoxic goitre (aged 10–15 years) from the last 31/2 years in Gothenburg. Cytologic signs of lymphoid thyroiditis were found in 23 girls and 3 boys.

Clinical signs and symptoms in 35 children with auto-immune thyroiditis are reported. One third had no complaints apart from the goitre, 12 were more or less hypothyroid and the rest had chiefly mild and diffuse symptoms. Increased firmness of the goitre was found in 27 of 32 cases, the surface was nodular or bosselated in 15.

Thyroid function: PBI was low only in 3 cases with myxedema, was above the upper normal limit in several cases. The difference between the PBI- and the BEI-levels was disproportionately great in most cases examined. The thyroid uptake of I131 showed abnormal discharge of iodide in every fourth patient.

Thyroid antibodies:

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Naphtali Brand, Ruwen A. Kathein, and Gideon Hasis

ABSTRACT

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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Svend G. Johnsen

The fat, feminine boy has been a clinical problem and a subject of much discussion for the past 50 years. The problem has been whether these boys (i. e. boys manifesting pronounced obesity, feminine distribution of the fat, small external genitals and absence of signs of intracranial lesion) actually suffer from an endocrine disease, a functional parallelism to the true Fröhlich' syndrome, or whether they should be merely classified as variants of simple obesity.

It has been claimed by some authors that simple obesity in children always tends to be distributed in a feminine manner and that the apparent hypogenitalism in fat boys is nothing but normal genitals buried in fat. Other investigators regard the hypogenitalism in certain fat boys as a true maldevelopment and recommend hormonal treatment for its correction.

It is clear that in the problem of the classification of fat boys, knowledge of the later sexual development

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G. Birke, E. Diczfalusy, L.-O. Plantin, H. Robbe, and A. Westman

Congenital hyperplasia of the adrenal cortex is manifested in boys as macrogenitosomia praecox and in girls as female pseudohermaphroditism, with or without concomitant adrenocortical insufficiency.

Some tendency to familial occurrence of congenital adrenocortical hyperplasia has previously been observed. According to a survey by Bentinck et al. (1952) a total of 97 cases of familial somatosexual aberrations affecting 42 families were reported between 1852 and 1952. Eighty of these children were either definitely or probably female pseudohermaphrodites and 17 had either demonstrable or probable macrogenitosomia praecox. In no family, however. was it possible to demonstrate virilizing adrenocortical hyperplasia in more than one generation. Wilkins et al. (1950, 1955) have accordingly assumed that congenital hyperplasia of the adrenal cortex is due to a recessive hereditary genital defect, clinically manifest only in homozygotes.

In this paper a description will be given of the clinical findings in a family with six children, including three

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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.

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H.-J. Quabbe, H. Helge, and S. Kubicki

ABSTRACT

Half-hourly blood samples and continuous EEG recordings were obtained during nocturnal sleep in ten adults in whom a special sampling system working from the adjacent room was used in order not to disturb the sleep. In nine of the ten adults the first D/E-stage during sleep was accompanied by a significant increase in plasma growth hormone (HGH) (2.5 to 31.8 ng/ml). Of 16 subsequent D/E-stages only three were accompanied by HGH peaks.

Similar studies but without EEG recordings were done in 25 children and adolescents. HGH peaks comparable to those seen in adults occurred in normal children, children with constitutional or primordial dwarfism, with retarded growth associated with renal or with miscellaneous diseases and in children with overgrowth. These peaks frequently seemed to coincide with periods of deeper sleep as judged from observation of the children. There was no evidence that HGH peaks occurred less often or were smaller in dwarfed children or that children with overgrowth had higher or more frequent HGH peaks. However, fewer and smaller HGH peaks were seen in obese children, whether or not obesity was associated with overgrowth.

There was no correlation between nocturnal HGH peaks and variations in the concentration of blood sugar (BS), free fatty acids (FFA) or immunoreactive insulin (IRI).

No apparent correlation could be seen between the height of the nocturnal HGH peaks and the response of plasma HGH concentration to provocative stimuli.

It is concluded that nocturnal HGH peaks are related to, but not exclusively determined by phases of slow-wave sleep. They are not due to disturbance of sleep by the sampling procedure. Their pattern is the same in adults, normal children and in children with non-pituitary dwarfism or overgrowth. Obese subjects often have fewer and smaller nocturnal HGH peaks even when obesity is associated with overgrowth.