Acta paediatrica Scandinavica. Supplement最新文献

A total of 42 patients (22 previously untreated and 20 previously treated) with GH deficiency were included in a Spanish multicentre trial of recombinant somatropin, 0.5 IU/kg/week. In previously untreated patients typical catch-up growth was observed and the height velocity increased from 3.3 +/- 0.6 cm/year to 9.8 +/- 2.4 cm/year during 1 year of therapy. In previously treated children, the height velocity was maintained (7.2 +/- 2.0 cm/year at the start and 7.9 +/- 1.6 cm/year after 1 year). No anti-GH antibodies were detected in previously untreated patients, and they disappeared from previously treated ones. No adverse reactions were reported.

Twenty-five hypopituitary patients were treated with recombinant somatropin for 1 year at a dosage of 0.5 IU/kg/week. In previously untreated patients (n = 16), heights increased by between 4.5 and 10.2 cm, with a mean height velocity of 7.7 +/- 1.8 cm/year (mean +/- SD). In previously treated patients (n = 9), heights increased by between 3.9 and 7.6 cm, with a mean height velocity of 5.8 +/- 1.0 cm/year, similar to that observed during previous treatment with pituitary GH. Anti-GH antibodies were observed in two patients at a low titre. The antibodies disappeared in one patient during the treatment. These data indicate that recombinant somatropin has a growth promoting effect and low immunogenicity.

A total of 23 previously untreated and 28 previously treated GH deficient children were included for at least 12 months in a trial of recombinant somatropin, 0.1 IU/kg/day given by subcutaneous injection. All the children increased their height velocity over the pretreatment values, to nearly 11 cm/year, corresponding to a significant increase in height of 1 SD score for chronological age. The increase in height SD score for bone age was also statistically significant. No adverse effects were recorded, though one child experienced local itching and redness at the injection site which did not recur after a short cessation of therapy. One child developed detectable antibodies to recombinant somatropin, but the binding capacity was low and no clinical symptoms or growth attenuation occurred. Recombinant somatropin was shown to be safe and effective during the first year of therapy in children with GH deficiency.

It is unclear how important age at onset of puberty is for adult stature. The growth effects of differences in timing of puberty have been studied on a bone age basis in 22 hypopituitary boys and on a chronological age basis in male subjects with early, normal or delayed onset of puberty. Very early onset of puberty results in short adult stature. This is because a marked reduction of prepubertal height gain is only partially compensated for by an increase in pubertal height gain. In contrast, very late onset of puberty determines no increase or a minor increase in adult stature. This results from a reduction in pubertal height gain, counterbalancing the increased prepubertal height gain. Differences in duration of growth are the major factor accounting for the different height gains observed in relation to timing of puberty, while mean growth rate shows only minor changes. The differences in duration of pubertal growth are paralleled by differences in the rate of bone maturation, which therefore do not account for differences in duration of puberty. It is concluded that, except in severely precocious puberty, manipulation of the timing of puberty is unlikely to affect final height to any great extent.

Many hormones are secreted in pulses or oscillations. If deductions about amplitude or frequency of these oscillations are to be made, then the oscillatory attributes must be analysed. The method of doing this is known as time series analysis. Samples for such analysis need to be properly spaced, taken for a sufficient period of time and de-trended. The techniques of pulse counting, autocorrelation or Fourier transformation may then be applied to demonstrate dominant features in groups of subjects. The advantages and disadvantages of these methods are discussed.

Using primary culture of steroidogenic cells in vitro, in serum-free chemically defined medium, strong evidence has been provided for actions of IGF-I on the differentiation of immature Leydig cells and on the maintenance of a differentiated function of mature adrenocortical cells. These data point to the steroidogenic cells as a target for IGF-I action. They also add further evidence for a role of IGF-I in the differentiation process. These actions can be of importance in normal physiological situations as well as in abnormal conditions where IGF-I is decreased, such as hypopituitarism and malnutrition.

The timing of the growth spurt of normal children does not affect their final height attainment. Growth rate during the growth acceleration of puberty correlates with changes in GH, and not sex steroid, secretion. GH secretion during puberty is pulse amplitude, and not frequency, modulated. In both central precocious puberty and normal puberty suppressed with a GnRH analogue, the rate of epiphyseal maturation is decreased as are GH pulse amplitude and growth, but with no influence on final height.

According to the original somatomedin hypothesis, GH promotes growth by generating 'somatomedins' or insulin-like growth factors (IGFs) in the liver. The advent of large amounts of IGF-I produced by recombinant DNA technology has now allowed testing of this hypothesis, by comparing the growth promoting activity of IGF-I and GH in three animal models of growth deficiency. When injected or infused subcutaneously, or infused intravenously, IGF-I is a weak growth promoter in the hypophysectomized rat compared with GH, even when infused in combination with small amounts of GH. Growth arrest in the diabetic rat was corrected by insulin infusion which also restored GH secretion. Insulin or IGF-I caused a large initial weight gain in diabetic rats, accompanied by a partial correction of food and water balance, even in the presence of persistent hyperglycaemia. A new mutant GH deficient dwarf rat grows in response to both GH and IGF-I infusions, but these agents elicit different patterns of organ growth. For the same overall body growth, GH was more effective in stimulating bone growth, whereas IGF-I stimulated renal and splenic growth. This new dwarf rat may prove useful for the study of the relative growth promoting effects of IGF-I and GH in more detail in future.