Twenty-two hypopituitary boys treated with human GH were studied longitudinally before and during puberty. Eight patients entered spontaneous puberty at a mean bone age of 12.4 +/- 1.0 (+/- SD) yr. Height velocity reached a mean peak of 6.8 cm/yr during the second year of spontaneous puberty. In these patients, the mean total height gain throughout puberty was 22.8 +/- 5.2 cm, and the mean final height was 158.6 +/- 7.2 cm. Fourteen patients received testosterone enanthate (100 mg/month, im) starting at a mean bone age of 13.6 +/- 1.1 yr. Height velocity was maximal (7.5 cm/yr) during the first year of therapy. The mean final height was 162.9 +/- 5.0 cm, with a mean pubertal gain of 15.9 +/- 3.8 cm. Genital development, peak height velocity, and increase in plasma testosterone levels occurred earlier during testosterone therapy than during spontaneous puberty. In both groups of patients, there was a positive correlation between the bone age at onset of puberty and the height at onset of puberty (r = 0.65). There was also a negative correlation between bone age and total pubertal height gain (r = -0.73). This reduction in pubertal height increase was less than expected for bone age at onset of puberty, which can be explained by a decrease in bone age velocity in relation to bone age at onset of puberty (r = -0.81). Therefore, advancement in bone age at the onset of testosterone therapy did not impair final height, whereas it may increase height at onset of puberty, which is the major factor in final height. We conclude that in GH- and gonadotropin-deficient boys 1) a reduced dosage of testosterone enanthate (25 mg twice a month, im) should be used to induce pubertal development, and 2) the major criterion to decide when to give testosterone is height reached at that time regardless of bone age.

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Wolter, R., Noel, 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, Liege 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 ofprenatal 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 I and 12 months of age are usually not mentally retarded and show minor neuropsychological disorders.

Three sibs, a boy and two girls, born to Moroccan consanguineous parents, were affected with a syndrome characterized by brittle hair, mental retardation, short stature, ataxia, and gonadal dysfunction. The hair in these three patients displayed the morphological and biochemical hallmarks of trichothiodystrophy (TTD). Gonadal function tests showed abnormal gonadotropic responses to LHRH, consistent with delayed puberty in the male and ovarian failure in both females. Comparison with previously reported cases of TTD associated with mental retardation suggests genetic heterogeneity, although specific biochemical markers are needed in order to answer this question.

We studied the effect of a single intravenous bolus of 0.5 µg/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 < 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 < 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 < 0.005); GH peaks within the normal range were seen in 5 out of 8 GHD children with a bone age < 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 µU/ml, p < 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 µg/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 < 5 years and

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Vanderschueren-Lodeweyckx, M., Van den Broeck,

The mechnisms whereby growth hormone (GH) secretion is decreased in human obsity remain obscure. We studied the response of plasma GH and prolactin (PRL) to an I.V. dose of 0.5 mcg/kg of growth hormone releasing factor (GRF) in three groups of children: lean (N=12), obese (N=15) and GRF-deficient, i.e. children with complete GH deficiency on the basis of conventional provocative testing and evidence of hypothalamic dyfunction on the basis of thyrotropin-releasing hormone testing (N=7). Mean (±SEM) peak plasma GH after GRF was blunted to the same extent in obese and in GRF deficient children (11.1 ± 2.2 and 8.3 ± 2.8 mg/ml) as compared to lean control children (34.7 ± 4.7 mg/ml). The pattern of PRL response to GRF was however different in GRF after GRF injection, and in obese and lean children, who had no acute change in PRL levels after GRF. Baseline plasma somatomedin C concentrations were low for age in GRF deficient children and tended to be high for age in obese children. On the basisi of these discrepant patterns of response of PRL to GRF and plasma somatomedin C concentration, we conculde that GRF defeciency does not account for the decreased GH secreation observed in obese children.