Paul Malvaux

Linear Growth in Patients With Turner Syndrome - Influence of Spontaneous Puberty and Parental Height

Growth data on 100 patients with Turner syndrome are reported. Seventeen had spontaneous puberty. Between the ages 11 and 13 years, height and height velocity were higher in these girls than in those with induced puberty. Final adult height, however, was not different. Patients disomic for Xp chromosome were taller than the monosomic ones, and the majority of them had spontaneous puberty. Significant positive correlations were found between height of Turner syndrome patients and corrected mid parental height, mothers height and fathers height from the age of 6 years. It is concluded that in patients with Turner syndrome spontaneous puberty and parental height should be accounted for in the evaluation of linear growth.

NEUROPSYCHOLOGICAL STUDY IN TREATED THYROID DYSGENESIS

Abstract. Wolter, R., Noël, P., De Cock, P., Craen, M., Ernould, Ch., Malvaux, P., Verstraeten, F., Simons, J., Mertens, S., Van Broeck, N. and Vanderschueren‐Lodeweyckx, M. (Departments of Paediatrics, Universities of Brussels, Leuven, Ghent, Liège and Louvain, Belgium). Neuropsychological study in treated thyroid dysgenesis. Acta Paediatr Scand, Suppl. 277: 41, 1979.—Neuropsychological assessment was carried out in 57 patients aged 3.0 to 17.5 years (mean 8.5) with thyroid dysgenesis under adequate long‐term therapy. Starting age of hypothyroidism as estimated by bone age at diagnosis was prenatal in 32 cases, close to birth in 13 cases and postnatal of 1–12 months in 12 cases. Hypothyroidism of prenatal onset results in severe neuropsychological disorders and mental retardation if not treated early. Only some signs of “minimal brain dysfunction” which compensate with advancing age and normal IQ are found in these children if therapy is started before one month of age. Hypothyroidism starting at birth does not result in mental retardation but neuropsychological disorders are found. They are more frequent if treatment is started after 6 months of age. Children who become hypothyroid between 1 and 12 months of age are usually not mentally retarded and show minor neuropsychological disorders.

Longitudinal study of behavioral and affective patterns in girls with central precocious puberty during long-acting triptorelin therapy

Abstract The aim of the present study was to evaluate the behavioral and affective characteristics and the changes in psychosocial functioning resulting from precocious puberty in 15 girls with central precocious puberty treated for 2 y using the GnRH agonist long‐acting triptorelin, and in 5 untreated girls. After diagnosis of precocious puberty at 6.6–10.4 y of age, height, weight and pubertal development were evaluated at 3‐month intervals over 2 y. Semi‐structured interviews were carried out with the patient, the parents and the pediatric endocrinologists at 1, 8, 16 and 24 months after diagnosis. Standardized questionnaires (Child Behavior Checklist, Self‐esteem Inventory) were administered at 1 and 24 months or 16 and 24 months, respectively. There was a mean 1.5‐y delay between the observation of signs of puberty as reported by the parents and the diagnosis of precocious puberty at the first consultation of a pediatric endocrinologist. Before follow‐up, all 20 girls were very concerned about physical differences from peers, particularly breast development. During therapy, breast regression to minimal or absent development occurred in 5/15 treated patients, who then no longer felt embarrassed about pubertal development in contrast to the other patients. Fear of sexuality remained obvious throughout the study in most patients. Feelings of loneliness and exemplary behavior were observed and tended to decrease in the treated patients and to increase in the untreated patients. Elevated scores of withdrawal, anxiety/depression and somatic complaints at Child Behavior Checklist were still observed after 2 y. These changes in behavioral and affective characteristics appeared to be related neither to height and weight, nor to development of pubic hair, which progressed in most patients. After 2 y, the physical differences remained a concern for 13 girls and the risk of short adult stature for 6. In summary, some behavioral and affective characteristics and particularities in psychosocial functioning are observed in girls with precocious puberty. During treatment with long acting triptorelin, problematic behavior and functioning decrease slightly, particularly in the few girls showing breast regression to minimal or absent development.

Subcutaneous adipose tissue and lipids in blood in growth hormone deficiency before and after treatment with human growth hormone.

Extract: This study was undertaken to evaluate adipose cell size and number and subcutaneous fat and blood lipids composition in hypopituitary patients before and daring treatment with human growth hormone (HGH). The investigations were performed in 14 prepubertal children 6–17 11/12 years of age, with idiopathic hypopituitarism. Human growth hormone was administered successfully to 6 of these 14 patients for at least 1 year.Before HGH treatment there was a significant reduction of adipose tissue cell number according to chronologic age and to skeletal age. The average adipose cell size was significantly larger than normal. A significant correlation between subcutaneous adipose cell mean weight and tricipital and subscapular skin fold thickness, similar to that observed in normal children, was observed. The distribution of fatty acids in the subcutaneous fat and in the blood lipid composition was normal.During the 1st and 2nd year of HGH treatment, the total number of adipose cells increased rapidly. There was also a highly significant reduction of the average adipose cell size after the 1st year. A significant reduction of the fatty acids unsaturated fraction was observed after the 1st year without further changes after the 2nd year of treatment. The blood lipid composition did not change significantly after either 1 or 2 years of HGH treatment.Speculation: The striking increase in total number of adipose cells observed during HGH administration in hypopituitary patients tends to prove that the adipose tissue organogenesis is not limited to a finite period ending after the 1st year of life.The modifications in composition of adipose tissue triglycerides induced by long term treatment with HGH would mean that the several components of the fatty acid pool are differentially liberated.

Plasma Androgens in Children and Adolescents

In this cross-sectional study, plasma levels of dehydroepiandrosterone sulfate (DHEA-S), dehydroepiandrosterone (DHEA), Δ4-androstenedione (Δ4) and testosterone (T) were measured by RIA in 2

Final Height in Children with Idiopathic Growth Hormone Deficiency Treated with Recombinant Human Growth Hormone: The Belgian Experience

Background: The growth response to recombinant hGH (rhGH) treatment and final height of 61 Belgian children (32 boys) with idiopathic growth hormone deficiency (GHD) were studied. Patients/Methods: Two patient groups were compared: Group 1 with spontaneous puberty (n = 49), Group 2 with induced puberty (n = 12). The patients were treated with daily subcutaneous injections of rhGH in a dose of 0.5–0.7 IU/kg/week (0.17–0.23 mg/kg/week) from the mean ± SD age of 11.9 ± 3.1 years during 5.1 ± 2.1 years. Results: rhGH treatment induced a doubling of the height velocity during the first year and resulted in a normalisation of height in 53 (87%) patients. Final height was –0.7 ± 1.1 SDS, being 170.4 ± 7.2 cm in boys and 158.0 ± 6.4 cm in girls. Corrected for mid-parental height, final height was 0.0 ± 1.1 SDS. Ninety-two percent of the patients attained an adult height within the genetically determined target height range. Although height gain during puberty was smaller in the patients with induced puberty (boys: 17.1 ± 7.0 cm vs. 27.5 ± 6.6 cm (p < 0.005); girls: 9.6 ± 7.4 cm vs. 22.2 ± 6.1 cm (p < 0.005)), no differences in final height after adjustment for mid-parental height were found between patients with spontaneous or induced puberty. Conclusions: We conclude that patients with idiopathic GHD treated with rhGH administered as daily subcutaneous injections in a dose of 0.5–0.7 IU/kg/week reach their genetic growth potential, resulting in a normalisation of height in the majority of them, irrespective of spontaneous or induced puberty.

Effect of Growth Hormone-Releasing Factor on Plasma Growth Hormone, Prolactin and Somatomedin C in Hypopituitary and Short Normal Children

We studied the effect of a single intravenous bolus of 0.5 microgram/kg of growth hormone-releasing factor (GRF) on plasma GH, prolactin (PRL) and somatomedin C (SMC) in 12 short normal children and 24 patients with severe GH deficiency (GHD), i.e. GH less than 5 ng/ml after insulin and glucagon tolerance tests. GRF elicited an increase in plasma GH in both short normal and GHD children. The mean GH peak was lower in the GHD than in the short normal children (8.2 +/- 2.5 vs. 39.2 +/- 5.1 ng/ml, p less than 0.001). In the GHD patients (but not in the short normals) there was a negative correlation between bone age and peak GH after GRF (r = -0.58, p less than 0.005); GH peaks within the normal range were seen in 5 out of 8 GHD children with a bone age less than 5 years. In the short normal children, GRF had no effect on plasma PRL, which decreased continuously between 8.30 and 11 a.m. (from 206 +/- 22 to 86 +/- 10 microU/ml, p less than 0.005), a reflection of its circadian rhythm. In the majority of the GHD patients, PRL levels were higher than in the short normal children but had the same circadian rhythm, except that a slight increase in PRL was observed 15 min after GRF; this increase in PRL was seen both in children with isolated GHD and in those with multiple hormone deficiencies; it did occur in some GHD patients who had no GH response to GRF. Serum SMC did not change 24 h after GRF in the short normal children. We conclude that: (1) in short normal children: (a) the mean GH response to a single intravenous bolus of 0.5 microgram/kg of GRF is similar to that reported in young adults and (b) GRF has no effect on PRL secretion; (2) in GHD patients: (a) normal GH responses to GRF are seen in patients with a bone age less than 5 years and establish the integrity of the somatotrophs in those cases; (b) the GH responsiveness to GRF decreases with age, which probably reflects the duration of endogenous GRF deficiency, and (c) although the PRL response to GRF is heterogeneous, it does in some patients provide additional evidence of responsive pituitary tissue.

THYROID DYSHORMONOGENESIS - SEVERE HYPOTHYROIDISM AFTER NORMAL NEONATAL THYROID STIMULATING HORMONE SCREENING

We report four children who presented no evidence of primary hypothyroidism in the neonatal period, either clinically (normal growth velocity) or biochemically (normal plasma levels of thyroid stimulating hormone and/or thyroid hormone). However, in early childhood, these children developed severe hypothyroidism due to dyshormonogenesis. We conclude that apparently normal thyroid function in the neonatal period does not preclude the development of severe hypothyroidism due to thyroid dyshormonogenesis later in childhood.

Variations in pituitary-gonadal suppression during intranasal buserelin and intramuscular depot-triptorelin therapy for central precocious puberty

Heinrichs C, Craen M, Vanderschueren‐Lodeweyckx M, Malvaux P, Fawe L, Bourguignon JP. Variations in pituitary‐gonadal suppression during intranasal buserelin and intramuscular depot‐triptorelin therapy for central precocious puberty. Acta Pædiatr 1994;83:627–33. Stockholm. ISSN 0803–5253

Treatment of central precocious puberty with an intranasal analogue of GnRH (Buserelin)

One boy and 13 girls with central precocious puberty were treated for 1 year using Buserelin, a GnRH analogue, given intranasally (0.3 mg, four times a day). After 1, 3 and 12 months of therapy, the gonadotropin responses to GnRH were abolished in all the patients whereas mean basal serum concentrations of luteinizing hormone (LH) remained similar to those of pubertal controls. During Buserelin treatment, genital development in the boy and breast development in the girls showed no further progress or some regression. In the boy, serum testosterone levels returned to prepubertal values. In the girls, serum oestradiol levels were variable and, in four of them, vaginal smears showed the persistence of a slight oestrogenic effect during therapy. Pelvic ultrasonography did not show any significant variation in ovarian and uterine lengths. Among the 14 patients, 3 had some progression of pubic hair development, irrespective of serum dehydroepiandrosterone sulphate (DHEAS) levels. In eight patients previously treated with cyproterone, elevated prolactin levels were observed before and during the first month of Buserelin administration. During treatment, mean height velocity was markedly reduced from 11.6 to 6.1 cm/year and mean bone age velocity (±1 SD) was 0.85±0.38 year/year. After 1 year of treatment, the differences in predicted adult height ranged between −0.74 and +1.04 SDS (standard deviation score). These differences were inversely related (r=−0.72) to the prognosis of adult height calculated before treatment. We conclude that, in central precocious puberty, intranasal administration of Buserelin, 1.2 mg/day, may arrest sexual development and reduce height velocity and bone maturation. Improvement of adult height prognosis may occur, especially when it was markedly impaired before treatment.