SERUM GROWTH HORMONE BINDING PROTEIN ACTIVITY IN HEALTHY NEONATES, CHILDREN AND YOUNG ADULTS: CORRELATION WITH AGE, HEIGHT AND WEIGHT

Serum growth hormone binding protein (GHBP) activity was estimated in healthy neonates (n = 6), children and adolescents (n = 97) and young adults (n = 19). GHBP activity was measured by incubating 125I-hGH (human growth hormone) (approximately 25,000 c.p.m.) with serum (100 microliters) in the presence and in the absence of excess unlabelled hGH, followed by separation of specifically bound 125I-hGHBP complexes from free 125I-hGH by gel filtration on Ultrogel AcA44 minicolumns. The results are expressed as the percentage specific binding relative to an adult reference serum (%RSB), after correction for endogenous hGH of the unknown serum. The between-assay coefficients of variation for two sera of %RSB activity of 51.2 and 115.4% were 6.0 and 7.0% respectively. In neonates, low values of serum GHBP were found (%RSB = 27.1 +/- 5.0 SEM) followed by a major rise during the first 6 years of life to a mean value (%RSB = 68.3 +/- 4.1 SEM) which more than doubled that of neonates. Thereafter, values rose progressively throughout childhood and puberty to reach maximum values in young adults (%RSB = 95.0 +/- 3.1 SEM). A novel observation was that serum GHBP activity correlated significantly with height standard deviation score (SDS) (males: r = 0.77, P less than 0.001; females: r = 0.56, P = 0.01) and weight SDS (P less than 0.001) for both sexes before puberty. During puberty GHBP correlated only with weight SDS in males (r = 0.60, P less than 0.01). In all age groups studied, no correlation could be found between serum GHBP and height velocity.     

RISE IN PLASMA GROWTH HORMONE IN RESPONSE TO EXOGENOUS LRH IN KLINEFELTER'S SYNDROME

In a group of sixteen patients with Klinefelter's syndrome (KS) aged from 2 years 8 months to 31 years, a study was made of the plasma growth hormone (hGH) response to LRH (50 μg/m² i.v.; n= 16), TRH (200 μg i.v.; n= 14) and insulin-induced hypoglycaemia (0·1 u R.I,/kg i.v.; n= 6). There was a rise in hGH following LRH from a level below 5 ng/ml during fasting to a level above 8 ng/ml (P < 0·001) in nine (56·3%) of the sixteen patients tested; a similar response was found in only one of a control group of fifteen boys matched for age. TRH stimulation led to a rise in hGH in one of the fourteen KS patients tested, with none in the control group. Insulin-induced hypoglycaemia elicited a normal response of hGH in the six KS patients tested, from 1·8 ± 0·7 to 16·5 ± 3·7 ng/ml, (M ± SD, P < 0·001). Basal prolactin (PRL) levels were normal in the KS patients (9·4 ± 4·1 ng/ml, M ± SD) but the response to TRH stimulation was significantly higher (63·3 ± 40 ng/ml; P < 0·01) than that of the control group (30 ± 15 ng/ml). Plasma gonadotrophin levels and the response to LRH stimulation were increased in all of the KS patients except those below the age of 13. Plasma TSH levels and the response to TRH stimulation as well as the levels of serum thyroxine were found to be normal in all the KS patients tested. The abnormal rise of hGH following LRH stimulation and of PRL following TRH stimulation suggests a disturbance in the neuroendocrine regulation mechanisms of these hormones in KS.     

EFFECT OF HUMAN GROWTH HORMONE THERAPY ON HEAD CIRCUMFERENCE IN CHILDREN WITH HYPOPITUITARISM

Head circumference was measured before and during hGH therapy in fourteen children with isolated growth hormone deficiency (IGHD) and in twenty-one children with multiple pituitary hormone deficiencies (MPHD). In both groups there was a retardation in growth of the neurocranium, more marked in the children with IGHD, which was less than the retardation in linear height. In the group with IGHD, initiation of hGH therapy before a chronological age of 5 and a bone age of 3 had been reached led to a rapid catch-up in cranial growth with normalization of the head size. In older children the induction of head growth was similar to that achieved by the long bones but without a true catch-up phenomenon. In three adults with hereditary IGHD without therapy or with irregular treatment during late puberty, the head circumference was below normal range. In view of the possible role played by development of brain tissue upon cranial size, the importance of early diagnosis and initiation of therapy in infants and young children with a deficiency of hGH is stressed.     

TREATMENT OF PRECOCIOUS PUBERTY WITH LHRH ANALOGUE IN COMBINATION WITH CYPROTERONE ACETATE—FURTHER EXPERIENCE

Six girls and one boy with precocious puberty were treated with a superactive LHRH analogue (D-TRP6-LHRH) for periods ranging from 1 year to 2 years and 3 months. In the first phase of the treatment it was administered in combination with cyproterone acetate (CyA) to counteract an early stimulatory effect until inhibition of gonadotrophin secretion was achieved. The gonadotrophin-dependent signs i.e. gonadarche, showed sustained arrest and even regression. Gonadal sex steroids decreased but the adrenal androgens were unaffected. In four patients who showed progression of the angrogen-dependent signs (adrenarche), despite suppression of gonadotrophins, increasing the dosage of the LHRH analogue was ineffective and combined therapy with CyA was reinstituted in three of them because of accelerated growth and bone maturation. It is concluded that at present the treatment of choice for precocious puberty is the daily administration of a superactive LHRH analogue such as D-TRP6-LHRH, together with CyA in the initial stage, and at a later state if adrenarche progresses too rapidly.     

PUBERTAL DEVELOPMENT IN THE PRADER-LABHART-WILLI SYNDROME

ABSTRACT. The sexual maturation in the Prader-Labhart-Willi (PLW) syndrome was investigated in 14 patients, 10 females and 4 males. A wide variability in the pattern of pubertal development was found including delayed puberty in 5 patients and normal puberty in 4 patients; sexual precocity was also observed in 5 patients, true precocious puberty in one patient and incomplete sexual precocity in the form of precocious pubarche in 4 patients. In 5 patients, 3 of them with precocious pubarche, the appearance of the pubertal signs was followed by a delay or arrest in their future development. An LH-RH stimulation test was performed in 11 patients. In the 6 patients who eventually developed normal puberty, the basal levels and the peak responses of both LH and FSH were within the range of those observed in normal controls of the same pubertal stage. In 4 patients showing marked delay or arrest of puberty, the basal levels were normal or low and the responses of LH and FSH to LH-RH were blunted. Priming with repeated LH-RH stimulation in one of the male patients led to an augmented LH response, suggesting a hypothalamic hypogonadotrophism. It is concluded that the lack of uniformity in the pattern of sexual maturation in the PLW syndrome is due to a variability in the location and extent of a hypothalamic lesion, which may comprise an active process continuing beyond the perinatal period.