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Jan Åman, Sten Rosberg, and Kerstin Albertsson-Wikland

Aman J. Rosberg S, Albertsson-Wikland K. Effect of growth hormone treatment on insulin secretion and glucose metabolism in prepubertal boys with short stature. Eur Endocrinol 1994;131:246–50. ISSN 0804–4643

The purpose of this study was to evaluate the effect on insulin secretion and glucose metabolism of daily growth hormone (GH) treatment, 0.1 U/kg. for up to 3 years in 42 short prepubertal boys without GH deficiency. Their median height standard deviation (sd) score increased from −2.7 to −1.7, whereas their weight for height sd score was unchanged after 3 years of treatment. Fasting plasma glucose concentrations were unchanged, but median fasting insulin concentrations increased from 6.0 mU/l before treatment to 7.8 mU/l (p < 0.05) after the first year. No further increase was seen during the second or third years. The median insulin area under the curve 10–60 min after an intravenous glucose tolerance test increased from 480 mU·1−1·min−1 before treatment to 799 mU·1−1 · min−1 (p < 0.05) after 1 year. The median glucose disposal rate (K value) before GH treatment, 2.2%/min, was unchanged after 1 year of treatment. A significant positive correlation was found between the change in the height sd score and the change in fasting insulin concentration during the first (r = 0.45; p < 0.01) and second (r = 0.56; p < 0.05) years of GH treatment. It was concluded that GH treatment in prepubertal children without GH deficiency caused a moderate increase in fasting and stimulated insulin concentrations during the first year of treatment. There was no further change during the following years of treatment, and there were no negative effects on fasting plasma glucose concentrations or glucose disposal rates. The increase in insulin concentration was related positively to the growth response.

Jan Åman, Department of Pediatrics, Örebro Medical Centre Hospital, S-701 85 Örebro, Sweden

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CL Boguszewski, C Jansson, MC Boguszewski, S Rosberg, KA Wikland, B Carlsson, and LM Carlsson

The proportion of non-22 kDa GH isoforms was evaluated in 93 healthy children (48 boys aged 6.8-18.4 years and 45 girls aged 3.9-18.4 years) of normal stature (height +/- 2 s.d. score) at different stages of puberty. In addition, correlations among the proportion of non-22 kDa GH isoforms, auxology, spontaneous GH secretion and biochemical measurements were investigated. Serum non-22 kDa GH levels, expressed as percentage of total GH concentration in the samples, were determined by the 22 kDa GH exclusion assay, in which monomeric and dimeric 22 kDa GH are removed from serum and the non-22 kDa GH isoforms are quantitated using a polyclonal antibody GH assay. Samples were selected from spontaneous GH peaks in 24-h GH profiles. For boys, the median proportion of non-22 kDa GH isoforms was 8.5% (range 3.2-26.6%) and for girls it was 9.6% (1.8-17.4%), with no influence of age and no sex-related difference in prepubertal (boys, 7.2%; girls, 8.8%) or pubertal children (boys, 9.1%; girls, 9.9%). However, the median proportion of non-22 kDa GH isoforms was significantly higher in pubertal boys (9.1%) than in prepubertal boys (7.2%; P = 0.03). In pubertal boys, height S.D. scores (SDS) were inversely correlated to the proportion of non-22 kDa GH isoforms (r = -0.38; P = 0.02), especially at mid-puberty (r = -0.7; P = 0.01), indicating that the presence of increased amounts of circulating non-22 kDa GH isoforms was associated with less growth. In prepubertal children, positive correlations between non-22 kDa GH and weight SDS (r = 0.46; P = 0.03), weight-for-height SDS (r = 0.51; P = 0.01) and body mass index (r = 0.42; P = 0.04) were observed. No significant correlations were seen with spontaneous GH secretion or measurements of IGF-1, IGF-binding protein-3, insulin and leptin. These findings in normal children indicate that the proportion of circulating non-22 kDa GH isoforms may have physiologic significance for growth and metabolism in different stages of development, and emphasize the importance of evaluating the circulating ratio of 22 kDa and non-22 kDa GH in children with growth disorders.

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M Boguszewski, J Dahlgren, R Bjarnason, S Rosberg, LM Carlsson, B Carlsson, and K Albertsson-Wikland

The product of the obese (ob) gene, leptin, is an adipocyte-derived hormone that is involved in the regulation of appetite and body weight. This study was undertaken in order to describe the basal serum levels of leptin in prepubertal short children born small for gestational age (SGA) and their relationship with growth parameters, before and during growth hormone (GH) treatment. Eighty-nine prepubertal short children (66 boys, 23 girls; height standard deviation score (SDS), -5.4 to -2.0; age, 2.0 to 12.8 years) born SGA, 12 of whom (9 boys, 3 girls) had signs of Silver-Russell syndrome, were included in the study. Serum leptin concentrations were measured by radioimmunoassay. Leptin levels in the children born SGA were compared with those in a reference group of 109 prepubertal healthy children born at an appropriate size for gestational age (AGA). The mean (S.D.) change in height SDS was 0.11 (0.22) during the year before the start of GH therapy (0.1 IU/kg/day) and increased to 0.82 (0.44) during the first year (P < 0.001) and to 1.28 (0.59) during the 2-year period of GH therapy (P < 0.001). The children born SGA were significantly leaner than the reference group. An inverse correlation was found between leptin and chronological age in the SGA group (r = -0.31, P < 0.01). The mean serum level of leptin in the children born SGA who were older than 5.5 years of age was 2.8 micrograms/l which was significantly lower than the mean value of 3.7 micrograms/l found in the children born AGA of the same age range. The difference remained after adjustment of leptin levels for sex, age, body mass index (BMI) and weight-for-height SDS (WHSDSSDS). Leptin correlated with WHSDSSDS (r = 0.32, P < 0.001) and BMI (r = 0.36, P < 0.01) in the reference population, but not in the SGA group. No correlation was found between leptin and spontaneous 24-h GH secretion, insulin-like growth factor (IGF)-I or IGF-binding protein-3 levels, or with fasting insulin or cortisol levels. Leptin levels at the start of GH treatment were correlated with the growth response over both 1 year (r = 0.46, P < 0.001) and 2 years (r = 0.51, P < 0.001) of GH therapy. Using multiple regression analysis, models including leptin levels at the start of GH therapy could explain 51% of the variance in the growth response after 1 year and 44% after 2 years of GH treatment. In conclusion, serum leptin levels are reduced in short children born SGA and are inversely correlated with chronological age. Leptin concentrations correlate with the growth response to GH treatment and might be used as a marker for predicting the growth response to GH treatment.

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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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Selma F Siegel, Mamdouha Ahdab-Barmada, Silva Arslanian, and Thomas P Foley Jr

Siegel SF, Ahdab-Barmada M, Arslanian S, Foley Jr TP. Ectopic posterior pituitary tissue and paracentric inversion of the short arm of chromosome 1 in twins. Eur J Endocrinol 1995;133:87–92. ISSN 0804–4643

Twin boys with hypopituitarism, hypoplasia of the anterior pituitary gland, ectopic posterior pituitary tissue and paracentric inversion of the short arm of chromosome 1 are described. The smooth appearance at the base of the median eminence and the absence of a pituitary stalk at autopsy in these boys implies that the hypopituitarism resulted from a developmental aberration. It remains to be determined if there is a causal relationship between the chromosome 1 anomaly and hypopituitarism.

Selma F Siegel, Division of Endocrinology, Children's Hospital of Pittsburgh, 3705 Fifth Avenue, Pittsburgh, PA, 15213, USA

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C. C. Jensen and S.-I. Björklund

With the discovery of cortisone the adrenogenital syndrome with or without clinical signs of adrenocortical dysfunction, but always showing increased urinary 17-ketosteroids (17-KS) and genital symptoms, became capable of treatment (Wilkins et al., 1950). Although the etiology of the disease is still obscure, cumulative evidence suggests the occurrence of a hereditary factor. The underlying pathogenic mechanism is not clearly understood, but the modern trend is to ascribe the syndrome to a disturbance of the steroid metabolism rather than to an increased production of a single hormone.

This paper is concerned with (a) the excretion of 17-KS before, during and after cortisone therapy, by a boy in whom the adrenogenital syndrome was diagnosed at 14 days of age, and (b) the steroid pattern of the parents, an aspect that has apparently never before received attention.

CASE RECORD

The patient was an only child (birthweight 4250 gm.). The mother was 26 and

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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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ANKE A. EHRHARDT and HEINO F.L. MEYER-BAHLBURG

ABSTRACT

Precocious puberty in girls has endocrinological as well as behavioral implications. We present data from a first systematic controlled follow-up study of 16 adolescent girls with a history of idiopathic precocious puberty (IPP) compared to closely pairmatched adolescent control subjects of comparable pubertal status and normal pubertal history. Findings in four areas of behavior are reported: (1) Psychiatric sequelae: the IPP sample showed an increase in minor psychopathological symptoms. (2) Psychosexual development: The IPP sample was advanced in sociosexual milestones, albeit mostly within the normal range for adolescents. (3) Intelligence: IQ was not different from controls. However, school achievement was accelerated during childhood. (4) Cognitive pattern: The IPP sample had lower spatial perception scores than controls.

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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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Kerstin Hall, Gunnel Lundin, and Guilherme Póvoa

Abstract. The low molecular weight form of insulin-like growth factor binding protein (35 kD IGFBP), determined in serum by radioimmunoassay during non-fasting conditions, was high at birth and declined with increasing age during childhood and adolescence (N = 149). Inverse correlation was found between chronological age and 35 kD IGFBP values (r = −0.61, P < 0.001) during childhood and adolescence, but no age dependency was found in adult subjects aged 20–66 years (N = 73). The mean and 95% confidence limits of immunoreactive 35 kD IGFBP were 34 μg/l and 15–79 μg/l, respectively, in healthy adults (N = 73) in whom the blood samples were drawn after a one-night fast. The mean level of the 35 kD IGFBP in patients with acromegaly (19 μg/l, N = 23) was decreased by 50% in comparison with healthy adults, whereas a 2-fold elevation of the mean levels was found in both anorexia nervosa patients (70 μg/l, N = 13) and adult patients with GH deficiency (69 μg/l, N = 22). In patients with anorexia nervosa, the 35 kD IGFBP levels were inversely related to the body mass index (r = −0.65, P < 0.02).