A minority of children born small for gestational age (SGA) fail to achieve sufficient catch-up growth during infancy and remain short throughout childhood. apparently without being growth hormone (GH) deficient. The effect of GH administration was evaluated over 2 years in short prepubertal children born SGA. The children (n = 244). who were taking part in four independent multicentre studies, had been randomly allocated to groups receiving either no treatment or GH treatment at a daily dose of 0.1.0.2 or 0.3 IU/kg (0.033.0.067 or 0.1 mg/kg) S.C. At birth, their mean length SD score (SDS) was -3.6 and their mean weight SDS -2.6; at the start of the study. mean age was 5.2 years, bone age 3.8 years, height SDS -3.3. height SDS adjusted for parental height -2.4, weight SDS -4.7 and body mass index (BMI) SDS -I .4. The untreated children had a low-normal growth velocity and poor weight gain. Although bone maturation progressed more slowly than chronological age. final height prognosis tended to decrease, according to height SDS for bone age. GH treatment induced a dose-dependent effect on growth, up to a near doubling of height velocity and weight gain; BMI SDS was not altered. Bone maturation was also

Although specific GH receptors have been demonstrated in various tissues of a number of species, the presence of GH receptors on human peripheral mononuclear cells (PMC) is controversial. Binding of human GH (hGH) to its receptor as the hypothesized initial step of hormone action was consequently studied using mononuclear cells from peripheral venous blood of normal subjects. Specific binding of [125I]hGH was rapid, reversible, and time and temperature dependent. Specific GH binding to PMC was maximal after 8-24 h of preincubation. Binding of hormone was maximal at 37 C after incubation of cells for 2 h. Dissociation of GH was maximal at 37 C after the addition of 6 M NaCl. A linear relationship between specific GH binding and cell number was found. Saturation of GH binding to 10(6) PMC was obtained with 25 ng iodinated hormones. Half-maximal inhibition of GH binding occurred at 12-25 ng unlabeled hGH/tube. Hypothalamic and pituitary hormones as well as insulin did not interfere with specific hGH binding to PMC. Scatchard analysis of [125I]hGH binding to PMC revealed a receptor with a mean affinity constant of 1.5 +/- 0.2 (+/- SD) X 10(9)/M-1 (n = 72) and a maximal binding capacity of 7.1 +/- 2.0 X 10(-11) M/10(6) cells. The concentrations of calcium, sodium, and magnesium ions in the incubation medium strongly influenced GH binding, whereas pH or potassium concentration did not. As interassay variation of the binding assay was low (14% for total binding; 6% for specific hGH binding), this direct approach to study tissue receptors for hGH in a human in vitro test was reproducible and should encourage the investigation of receptor regulation as well as the study of binding in human disease.

Plasma concentrations of estrone and estradiol were determined by radioimmunoassay of cord blood from 17 neonates and of venous blood of 15 neonates, 61 boys and 69 girls of all developmental stages, 27 healthy women, 20 healthy men, and 89 male and female adolescents with different disorders of sexual development. In cord blood both estrone and estradiol averaged 15,000 pg/ml. Blood drawn from neonates shortly after birth showed levels between 300 and 500 pg/ml. These levels fell to 5-15 pg/ml within a few days after birth, which is the normal range for both sexes up to 7 years. Before puberty, estrone rises earlier in girls than in boys. The increase of estradiol follows the onset of puberty. Boys reach adult levels in stage IV, whereas girls in stage V still have lower estrogen levels than mature women. We did not find higher levels in 29 adolescents with gynecomastia than in normal adolescents at the same stage of puberty. We observed abnormally high estrogens in children with congenital adrenal hyperplasia, but, in spite of some very high levels, we did not observe premature thelarche or gynecomastia in children with this disease. Six females and 10 males with panhypopituitarism, aged from 10 to 19 years, revealed low values within the infantile range. Six boys between 5 and 14 years who suffered from anorchia had very low levels of estrogen, especially estradiol (which was nearly undetectable). In contrast to patients with functioning testicle tissue, the patients with anorchia did not show any increase of estrogens after stimulation with human chorionic gonadotropin. Abnormally low levels were found in females with Turner's syndrome, but only in those with 45, XO karyotype. Patients with 45, XO/46, XX, or 46, XXp~ karyotype had high levels of estrogen which corresponded to clinical signs of advanced puberty. Speculation As demonstrated by our results, the radioimmunologic method enables us to measure the low estrogen levels which are found in children. This will permit a more intensive examination of the pituitary-gonadal and pituitary-adrenal interrelation in the future.

We report on 49 boys with constitutional growth delay (CGD) who were initially seen in our clinic at a mean chronological age of 13.3 years (range, 7.3-16.4) and a bone age of 11.1 years (range, 6.0-13.5). All were below the 5th height percentile for chronological age. A positive family history with delayed growth and puberty in one or both parents could be elicited in 75%. All 49 patients were re-examined at a mean age of 22.9 years (range, 20.4-31.2). Measured final height was 171.3 cm (range, 161.2-181.7), which was slightly, but significantly lower than mean target height of 173.0 cm. Final height expressed as standard deviation score (SDS) of a male adult population standard was -1.0 (range, -2.4 to 5), also significantly lower than initial height SDS related to bone age (SDSBA) of -0.5 (range, -1.6 to 2). If related to target height (Tanner), final height was found to correlate positively with the initial bone age deficit and the initial height SDSBA. Observed final height was also compared with the predicted adult height by the methods of Bayley-Pinneau (BP), Tanner-Whitehouse Mark II (TW II) and Roche-Wainer-Thissen. Regression equations between all three prediction methods and final height showed an excellent correlation (P < 0.0001). However, only by the BP method was predicted height very close to and no different from measured final height (paired t-test). Despite this, final height in 16 of 49 patients (32.6%) differed by more than 5.0 cm from BP predicted height.(ABSTRACT TRUNCATED AT 250 WORDS)

Documenting the spontaneous growth pattern of children with idiopathic short stature (ISS) should be helpful in evaluating the effects of growth promoting treatments. Growth curves for children with ISS were constructed, based on 229 untreated children (145 boys and 84 girls) from nine European countries. The children were subdivided according to target range and onset of puberty, and the growth of these subgroups was evaluated from standard deviation scores (SDS). At birth, children with ISS were already shorter than normal (means; boys -0.8 SDS, girls -1.3 SDS). Height slowly decreased from -1.7 SDS at the age of 2 years to -2.7 SDS at the age of 16 years in boys and 13 years in girls. Final height was -1.5 SDS in boys and -1.6 SDS in girls (mean (SD): boys 164.8 (6.1) cm, girls 152.7 (5.3) cm)), which was 5-6 cm below their target height. The onset of puberty was delayed (boys 13.8 (1.3) years, girls 12.9 (1.1) years). Subclassification resulted in similar growth curves. These specific growth data may be more suitable for evaluating the effects of growth promoting treatments than population based references.