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Peter M. Messer, Berthold P. Hauffa, Thomas Olbricht, Georg Benker, Peter Kotulla, and Dankwart Reinwein


With regard to their thyroid function, somatic and intellectual development, we compared 17 children of 13 hyperthyroid mothers (group I) receiving antithyroid drug treatment during their pregnancies with 25 children of 15 mothers who were euthyroid without any antithyroid treatment during their pregnancy (group II). Mean duration of maternal treatment was 3.5 months in group I, using carbimazole or thiamazole (N=12) and propylthiouracil (N=1). Age at examination in group I was 7.2±6.2 years, in group II 8.7±7.1 years (mean±sd). Both groups showed no significant differences in the results of the clinical examination and in the degree of their mental and psychomotoric development at the time of study. We found the mean birth weight of the infants in group I significantly lower than in group II(3165±339 vs 3666±670 g, p<0.03). The individual birth weights, however, were normal for gestational age. The body weight difference between groups disappeared during the further somatic development of the children. The serum concentration of free thyroxine in group I was significantly higher than in group II (17.2 ± 2.4 vs 14.9±1.9 pmol/l, p<0.003), but fell in both groups within the normal range. The evaluation of the psychomotoric and intellectual capacity of the children at different developmental stages showed no abnormalities detectable by our tests. Thus, in the children of the two groups we found no adverse effects of a maternal antithyroid drug treatment during pregnancy or of inactive maternal Graves' disease alone, neither on thyroid gland size and function nor on the physical or intellectual development, after the neonatal period.

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Michel Polak, Jo Blair, Primoz Kotnik, Effie Pournara, Birgitte Tønnes Pedersen, and Tilman R Rohrer


To investigate the effect of age at growth hormone (GH) treatment start on near adult height (NAH) in children with isolated GH deficiency (GHD).


NordiNet® International Outcome Study (IOS) (Nbib960128), a non-interventional, multicentre study, evaluates the long-term effectiveness and safety of Norditropin® (somatropin) (Novo Nordisk A/S) in the real-life clinical setting.


Patients (n = 172) treated to NAH (height at ≥18 years, or height velocity <2 cm/year at ≥16 (boys) or ≥15 (girls) years) were grouped by age (years) at treatment start (early (girls, <8; boys, <9), intermediate (girls, 8–10; boys, 9–11) or late (girls, >10; boys, >11)) and GHD severity (<3 ng/mL or 3 to ≤10 ng/mL). Multiple regression analysis was used to evaluate the effect of age at treatment start (as a categorical and continuous variable) on NAH standard deviation score (SDS).


Age at treatment start had a marked effect on NAH SDS; NAH SDS achieved by patients starting treatment early (n = 40 (boys, 70.0%); least squares mean (standard error) −0.76 (0.14)) exceeded that achieved by those starting later (intermediate, n = 42 (boys, 57.1%); −1.14 (0.15); late, n = 90 (boys, 68.9%); −1.21 (0.10)). Multiple regression analysis showed a significant association between NAH SDS and age at treatment start (P < 0.0242), baseline height SDS (HSDS) (P < 0.0001), target HSDS (P < 0.0001), and GHD severity (P = 0.0012). Most (78.5%) patients achieved a normal NAH irrespective of age at treatment start.


Early initiation of GH treatment in children with isolated GHD improves their chance of achieving their genetic height potential.

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Kerstin Hall, Gösta Enberg, Martin Ritzén, Håkan Svan, Linda Fryklund, and Kazue Takano


Serum somatomedin A (SMA) has been determined in healthy children (n = 188) in relation to age using both a radioimmunoassay and a radioreceptor assay. The SMA levels, only 50% of adult values at birth, rise gradually with age and reach adult levels at 10 years of age. There is a significant correlation (r = 0.46, P < 0.001) between SMA determined by the two methods throughout childhood except during puberty. Immunoreactive SMA shows a marked pubertal rise in values with a peak 2 years earlier for girls than boys, which is not observed by the radioreceptor assay technique. In boys with delayed puberty the increase in immunoreactive SMA is seen first when the testes reach a size of 5 ml. Children with growth hormone deficiency (n = 30) had significantly lower levels of SMA than healthy age-matched controls. Immunoreactive SMA gives a better separation of these groups than the values obtained by radioreceptor assay.

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A. Parra, S. Villalpando, E. Junco, B. Urquieta, S. Alatorre, and G. García-Bulnes


Serum thyrotrophin (TSH), thyroxine (T4), triiodothyronine (T3), thyroxine-binding globulin (TBG) and reverse T3 (rT3) were measured by radioimmunoassay in 175 girls and 187 boys aged 6.0 to 16.9 years, who were clinically healthy, and had negative serum antithyroglobulin and antimicrosomal antibodies. All the children had normal weight and height and were grouped at 12 months' intervals. In girls, TSH levels ranged between 5.3 ± 0.4 and 6.9 ± 0.5 μU/ml without significant changes with age; serum T4 decreased up to 13.9 years and rose afterwards; serum TBG was constant up to 13.9 years, decreased subsequently and rose after 15.9 years; serum T3 levels were lower after 13.0 years than previously; serum rT3 decreased between 11.0 and 11.9 years and rose thereafter; the calculated serum free T4 (FT4) and free T3 (FT3) concentrations had a significant rise from 14.0 to 15.9 years followed by a sharp decline; T3:T4, rT3:T3 and rT3:T4 ratios were constant up to 11.9 years, then a rise was seen in T3:T4 and a fall in the later ratios, followed by a drop in T3:T4 ratio and a sustained rise in rT3:T3 and rT3:T4 ratios. In boys, TSH levels were constant between 5.2 ± 0.4 and 6.6 ± 0.4 μU/ml; serum T4 decreased with increasing age; serum TBG was constant up to 13.9 years, and had a sustained fall thereafter; serum T3 was constant over the age range studied; serum rT3 levels decreased up to 13.9 years and rose thereafter; FT4 had no changes with increasing age while FT3, although constant up to 13.9 years, had a sustained rise afterwards; T3:T4 ratio did not change with age, while rT3:T3 and rT3:T4 ratios, although constant up to 13.9 years, showed a tendency toward a sustained rise thereafter. These sex-different variations in serum thyroid hormone concentrations might be related to the fact that girls mature at an earlier chronological age than boys and may represent a partial response of the body to the qualitatively and quantitatively different energy needs in girls as compared with boys, consecutive to the differences in body composition first appearing at puberty.

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A. Parra, C. Cervantes, M. Sánchez, L. Fletes, G. García-Bulnes, R. M. Argote, I. Sojo, A. Carranco, R. Arias, and V. Cortés-Gallegos


Plasma concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17 alpha-hydroxyprogesterone (17α-OHP), 17β-oestradiol (Oe2) and progesterone (P) were measured in 352 healthy girls aged 6.0 to 15.9 years, as a function of age (CA), weight, height and calculated lean body mass (LBM) and total body fat (TBF). The earliest hormonal changes were a fall in mean plasma FSH concentrations together with a small but significant rise in plasma Oe2 well in advance of any sign of pubertal development. The next changes were a progressive rise in plasma FSH and 17α-OHP concentrations without further increments in plasma Oe2; these changes corresponded to a mean body weight of 29.8 kg, a mean height of 132.0 cm (initiation of the adolescent growth spurt), a mean LBM of 24.7 kg and a mean TBF of 5.1 kg. The last events were a progressive rise in plasma LH and Oe2 and less marked in P, which occurred in association with a mean body weight of 40.0 kg, a mean height of 142.0 cm (time of peak velocity of weight and height gain), a mean LBM of 31.8 kg and a mean TBF of 9.1 kg. Significant quadratic equations were disclosed between plasma FSH and LH versus CA, weight, height and LBM, and a significant linear correlation was observed between each gonadotrophin and TBF. These results show an association, not necessarily causal, between a 'critical level' of body composition and hormonal changes at the start of the adolescent growth spurt, as well as with late hormonal events at the time of peak velocity in weight and height gain. On the other hand, LBM rather than TBF seems more closely associated with the initiation and progression of puberty.

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Salvador Villalpando, Ignacia Cisneros, Guadalupe García-Bulnes, Bárbara Urquieta, Lourdes Mondragón, Elisa Junco, and Adalberto Parra


Anti-thyroid antibodies are frequently found in otherwise normal populations (4.5–25.8%); however, there is scanty information about thyroid function status in affected individuals. In this report, the serum concentrations of TSH, T3, T4, rT3 and TBG and the titre of anti-thyroglobulin and anti-microsomal antibodies (haemagglutination technique) were studied in 520 healthy school children (260 boys and 260 girls) aged 6.0–17.9 years. Titres equal or greater than 1:16 of one or both antibodies were detected in 58 boys and in 77 girls (in 33 boys and in 24 girls with, and in 25 boys and 43 girls without, associated abnormalities in the serum concentrations of one or several hormones). The age distribution of thyroid antibodies followed a trimodal pattern with peaks at 7, 11 and 16–17 years in both sexes. The most striking finding was an abnormally elevated T3 concentration in 22 boys and 5 girls with positive antibodies, with no symptoms of thyroid dysfunction and with no clear relationship with simultaneous abnormalities in TSH, T4 or rT3; however, in 5 boys the TBG serum levels were increased. Serum from these patients was incubated with [125I]T3 before free radioactivity was precipitated with dextran-coated charcoal and the aliquots were analyzed by paper electrophoresis. Serum samples with high T3 levels bound significantly more radioactivity than normal or T3-free serum (P < 0.001) and an abnormal peak of radioactivity was present in the gamma globulin fraction, in the former but not in the latter two types of sera. The presence of high serum T3 levels in the absence of clinical symptoms of hyperthyroidism was probably due to sequestration of T3 by the anti-thyroglobulin antibody, which may have cross-reactivity with T3 and T4, as has previously been demonstrated both in animals and humans.

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Georg Dhom


Report about two cases of gonadal dysgenesis with negative sex chromatin pattern in early childhood.

  1. 38-day old girl with unsuspected female external genitals, myelomeningocele, one-sided renal aplasia and uterus unicornis. The only present gonad is an ovary developed according to the age and full of ripening follicles.

  2. A two-hours old premature birth with various deformities. Completely female external genitals, vagina and uterus duplex. On both sides serial sections show very small dysgenetical ovaries with a strongly reduced number of primordial follicles.

The observations show, that ovaries may be developed in cases of negativ sex chromatin pattern. It will be necessary to pay attention to the sex chromatin and the gonadal dysgenesis in female cases of various deformities.

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Sigrun Korth-Schutz, Lenore S. Levine, Maria I. New, and Diane M. Chow


In order to determine the source of androgens in precocious adrenarche, serum androgens were determined in 8 girls with precocious adrenarche and 5 agonadal children in adrenarche under conditions of adrenal and gonadal stimulation and suppression. All androgens increased with ACTH stimulation in both groups. Stimulability of serum androgens in girls with precocious adrenarche with ACTH was more consistent than in 13 prepubertal children. Human chorionic gonadotrophin administration increased serum Δ4-androstenedione, testosterone and dihydrotestosterone in the girls with precocious adrenarche but not in the agonadal children, demonstrating the failure of HCG to stimulate adrenals.

Dexamethasone suppression decreased levels of all androgens in both groups, whereas Norlutin® or Ovral® produced variable changes.

These studies support the adrenal origin of androgens in precocious adrenarche and the lack of ovarian contributions in this condition.

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Olav Trygstad


This study was carried out in order to determine whether children with a transitory type of growth hormone deficiency showed an accelerated growth in height velocity on treatment with human growth hormone (HGH).

Following careful diagnostic routine procedures 13 extremely short children were diagnosed as having isolated growth hormone deficiency, and were successfully treated with HGH. A true isolated growth hormone deficiency was present in 5 of the children, whereas 8 showed a normal increase in serum growth hormone on repeated growth hormone stimulation tests after their development of puberty and termination of HGH treatment. Three boys with bone ages of 5.5, 8.0 and 9.5 years showed an undisputable effect following HGH administration. They showed an initial growth at the start of treatment, and a second growth spurt during development of puberty. Two of the boys reached final statures of 14 cm taller than the predicted heights. The other patients, including the children with true isolated growth hormone deficiency showed an initial spurt of growth at the start of the HGH treatment immediately followed by a pubertal growth spurt. The mean acceleration of height velocity for the children with true isolated growth hormone deficiency was from 3.4 cm during the year before treatment to 7.0 cm during the first year on treatment, as compared to 2.8 and 7.4 cm, respectively, for the children with transitory growth hormone deficiency. A girl with severe anorexia nervosa who had a transitory growth hormone deficiency, showed an accelerated high velocity from 1.1 cm to 7.6 cm during the first year following treatment with HGH.

The question whether HGH treatment should be made available to all short children with no known syndrome, and presenting a height less than −3.5 sds, a bone age/chronological age ratio of less than ⅔, and a height velocity less than −2 sds is discussed. The only way to know if a child will respond to HGH treatment is to give it for a trial period of at least six months. At least a physiological stimulus to growth hormone secretion should be decisive in the selection of growth retarded children for HGH treatment. Different mechanisms seem to be responsible for physiological growth hormone secretion to sleep or exercise, and the secretion obtained with pharmacological stimuli.

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


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.