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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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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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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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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.

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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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K. W. Kastrup, J. Sandahl Christiansen, J. Koch Andersen, and H. Ørskov

Abstract. The effect of more frequent (daily) injections of human growth hormone (hGH) on growth rate was studied in 16 growth hormone deficient children (12 boys, 4 girls) during 2 years. All had previously been treated with im injection of hGH 2–3 times weekly and in the majority of the patients a waning growth response was observed.

For a total weekly dose of 12 IU hGH a daily dose of 2 IU was injected sc at night before sleep. This dosage has been shown by us to imitate the average nocturnal hGH profile in plasma.

Growth response on the im treatment was 5.2 ± 1.2 cm/year (sd) in boys and 5.4 ± 0.9 cm/year in girls. A significant increase was seen during the first year of sc treatment to 7.9 ± 2.7 cm in boys and 6.3 ± 2cm in girls. During the second year the growth response was still significantly increased in boys (7.2 ± 1.9 cm). Bone age was more advanced and the period of previous im treatment was longer in girls (6.7 vs 3.6 years) which may be the main cause of the waning second year response (4.7 ±1.3 cm/year). Pubertal development occurred in 9 children during treatment. However, the highest growth rates were not found in these children.

Absence of antibodies against hGH and local reactions at the injection site is evidence of the safety of the treatment, which was very well accepted by the children.

Daily sc injections thus represent an effective alternative to conventional im injections ensuring high acceptance in children with growth hormone deficiency.

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L. Kanaris, K. Ntalles, K. Alevizaki, P. Lapatsanis, Ch. Velentzas, P. Katsichtis, E. Georgiou, Ch. Drossos, and D.G. Ikkos

The aim of the present work was to obtain bone mass estimates of healthy Greek children aged 6–18 years. This work was considered worthwhile since similar data are very few in the world litterature (Bonnard 1968, Gryfe et al. 1971), while those for Greece (Livadas et al. 1975) refer to 902 children only (462 boys and 440 girls) aged 5–13 years.

The material of the present study consists of 2.406 schoolboys and 2.451 schoolgirls aged 6–18 years, of whom 864 boys and 1.189 girls were living in Attica, while the remaining 1.542 boys and 1.262 girls were living in communities outside Attica (i.e. Atalanti, Arnea, Elatia and Karpenisi). Standing body height and body weight was measured in all subjects. Furthermore, a plain x–ray of the left hand was taken in all children, using a focal distance of 80 cm.

By means of a micrometer apparatus (Taschenmessloupe TM4, C. Zeiss) the

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Gerhard Hintze, Dieter Emrich, Klaus Richter, Hanne Thal, Horst Thal, Thomas Wasielewski, and Johannes Köbberling

Abstract. The availability of iodinated salt containing 20 mg of iodine as iodate/kg salt consumed on a voluntary basis enabled us to investigate its effect on goitre prevalence and iodine excretion in urine in a longitudinal, prospective, randomized study over 4 years. With this salt, under the assumption of a consumption of 5 g salt per day and person, an additional intake of 100 μg of iodine can be achieved. The study was performed on initially 334 children (168 boys, 166 girls) at the age of 10 years living in an area of iodine deficiency. After 4 years, 286 children still participated in the study. Initially, goitre prevalence as assessed by palpation was found to be 30.5% (37.4% in girls and 23.8% in boys). Neck circumference was found to be significantly higher in children with goitre compared with those without (30.2 ± 1.4 vs 29.4 ± 1.4 cm; P < 0.001). Iodine excretion in the urine was significantly lower in children with goitre compared with those without (40.4 ± 16.7 μg/g creatinine vs 46.1 ± 24.9 μg/g creatinine; x ± sd; P < 0.05). The children were randomly assigned to two different groups: group A (N = 146) was asked to use iodinated salt, group B (N = 188) non-iodinated salt. Over the 4 years, a continuous increase in iodine excretion in urine could be demonstrated in group A. After 1 year, it was significantly higher than in the control group that used non-iodinated salt. After 4 years, the mean iodine excretion in children using iodinated salt was 60.1 ± 24.1 μg/g creatinine in contrast to 45.1 ± 18.6 μg/g in the control group (x ± sd; P< 0.0001). However, no decrease in goitre prevalence could be documented: after 4 years, 23.8% of the children belonging to the group using iodinated salt and 22.5% of those in the group taking non-iodinated salt had a goitre. From these observations we conclude: 1. The voluntary use of a commercially available iodinated salt containing 20 mg iodate/kg leads to a significant increase in iodine intake, measured by urinary iodine excretion. Even after 4 years, the value is far below the daily iodine intake recommended by the WHO. No decrease in goitre frequency could be assessed. 2. An increase in iodine ingestion can be achieved either by increasing the iodine content of the salt or by application of iodine by alternative measures. The safest way would be to use iodinated salt exclusively, i.e. also in the food industry and restaurants. An increase in the iodine content of the salt and its continuous voluntary use would lead to a large variation in iodine intake. A higher risk of adverse reaction, e.g. iodine-induced thyrotoxicosis, cannot be excluded in susceptible persons.

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Lene Lavard, Ida Ranløv, Hans Perrild, Ole Andersen, and Bendt Brock Jacobsen

Lavard L, Ranlov I, Perrild H, Andersen O, Jacobsen BB. Incidence of juvenile thyrotoxicosis in Denmark, 1982-1988. A nationwide study. Eur J Endocrinol 1994;130:565–8. ISSN 0804–4643

The objective of this study was to ascertain the annual incidence density of thyrotoxicosis in children under the age of 15 years in Denmark in 1982–1988. The design was based on computerized hospital registration of patient admittances in all departments of paediatrics and internal medicine of Denmark (Faroe Islands and Greenland excluded). Fifty-six children (48 girls and 8 boys) had a confirmed diagnosis of thyrotoxicosis, giving a national incidence density of 0.79/100 000 person-years. In children aged 0–4 years the incidence was very low (0.1/100 000), with no sex difference. In boys aged 5–9 years a similar low incidence was found, while in boys aged 10–14 years the incidence increased to 0.48/100 000. In girls aged 5–9 years the incidence increased to 0.96/100 000, reaching a maximum of 3.01 in the 10–14-year-old girls. In children of > 4 years of age a female preponderance of 6.7:1 was significant. It is concluded that thyrotoxicosis is a rare disorder in Danish children under the age of 15 years, and the incidence increases with age. Female preponderance is significant from early childhood.

Lene Lavard, Department of Paediatrics, Hvidovre University Hospital, DK-2650 Hvidovre, Denmark

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Maria N Moreira-Andrés, Karen Papapietro, Francisco J Cañizo, Javier Rejas, Luisa Larrodera, and Federico G Hawkins

Moreira-Andrés MN, Papapietro K, Cañizo FJ, Rejas J, Larrodera L, Hawkins FG. Correlations between bone mineral density, insulin-like growth factor I and auxological variables. Eur J Endocrinol 1995; 132:573–9. ISSN 0804–4643

Recent studies have shown growth-related changes in spinal bone mineral density (BMD) in children; however, there is less information available on the relationship between BMD and insulin-like growth factor I (IGF-I). The aim of this study was to relate the BMD of the spine and radius with serum IGF-I levels and auxological variables in normally growing children. We used dual X-ray absorptiometry to measure the BMD in the lumbar spine (L1–L4) and distal radius of 121 children (69 boys, 52 girls) aged 3–18 years whose growth velocity was normal. Lumbar and radial BMD increased with age (p < 0.001) and puberty (p < 0.001) and was highly correlated to age, weight, height, body surface and bone age (r = 0.70–0.89 and p < 0.001 for all variables). Partial correlation, with age held constant, was weaker but still significant for most auxological variables. Serum IGF-I concentrations increased slowly during childhood and markedly during early stages of puberty, and correlated with lumbar and radial BMD (r = 0.55 and 0.45, respectively; p < 0.001) and with the auxological variables (p < 0.001). When age was held constant, IGF-I levels still correlated significantly with the auxological variables and with BMD, except in the case of radial BMD in boys. By multiple regression analysis IGF-I, unlike auxological variables, did not reach significance in the ability to predict BMD. Therefore, in healthy children, serum IGF-I levels show a weaker relationship to BMD than do auxological variables.

MN Moreira-Andrés, Servicio de Endocrinología, Hospital 12 de Octubre, Carretera de Andalucia km. 5,4, 28041 Madrid, Spain