We review the etiology and age incidence of precocious puberty in 438 girls examined between 1988-1998; 428 (97.7%) had central precocious puberty (CPP), the remaining 10 (2.3%) gonadotropin-independent precocious puberty (GIPP) of ovarian origin. The majority of CPP girls (59.6%) were aged between 7-7.9 yr, 22.4% were 6 year olds, and only 18% were under 6 years old. Cranial CT and/or MRI performed in 304/428 girls, showed neurogenic abnormalities in 56/304 (18.4%) CPP girls; 30 (9.9%) were due to previously diagnosed intracranial abnormalities and the remaining 26 (8.5%) were detected at the diagnosis of CPP. The frequency of neurogenic CPP tended to be higher in girls under 4 years of age while the frequency of idiopathic CPP tended to be higher in girls aged between 7-7.9 years, but no statistically significant differences were found. Interestingly, some CNS anomalies either of tumoral or congenital origin were detected at presentation in 7% of the girls aged over 7 years. Other related or coincidental clinical anomalies, mainly due to genetic diseases, were observed in 22/304 (7.2%) patients. History of precocious maternal menarche was found in 12/304 (4%) girls. In conclusion, idiopathic CPP was observed in 74% of the girls in this study. Neurogenic anomalies or other coincidental or related clinical findings were observed in the remaining 26%. The increased frequency of idiopathic CPP in girls aged over 7 years may suggest an early, but otherwise normal onset of puberty in many of these girls as a consequence of the trend towards earlier maturation. Nonetheless, the finding of CNS anomalies also in the older patients, raises the question of whether these patients should undergo a complete diagnostic work-up.

We have evaluated the plasma GH response to a single injection of 1 microgram/kg of GH-releasing hormone (GHRH)-40 in 15 obese children and 15 age-matched control children. Most of the obese children showed a subnormal plasma GH response to GHRH and the mean plasma GH integrated area (IC-GH) following stimulation was significantly smaller in obese than control children. Plasma somatomedin-C (SM-C) levels were significantly higher in obese than control children, and were negatively correlated with the peak plasma GH levels (r = -0.616, P less than 0.01) and the IC-GH (r = -0.554, P less than 0.02) after GHRH. Non-esterified fatty acids (NEFA) and fasting plasma insulin levels were also elevated in obese children, but did not correlate with the extent of plasma GH response to GHRH. These data confirm previous observations on the refractoriness of obese children to release GH after GHRH, and imply that it may be due to the feedback inhibition operated by the elevated plasma levels of SM-C.

The aim of this retrospective study was to analyze the factors which affected the auxological response to GnRH agonist treatment and the final height (FH) outcome in 71 girls with idiopathic and truly precocious (onset before 8 years) central puberty (CTPP) who had been treated with the same therapy protocol (Decapeptyl Depot, 60 mg/kg i.m. every 28 days) for at least 2 years (since 7.0 Ϯ 1.3 (S.D.) years of age) and followed until puberty was completed and FH was reached.During the entire treatment period we observed: (a) a decrease of height standard deviation scores (SDS) (from 1.5 Ϯ 1.7 to 0.9 Ϯ 1.3 SDS, P < 0.01); (b) a striking deceleration of bone age (BA), revealed by the subnormal DBA:Dchronological age (CA) ratio (0.2 Ϯ 0.1); (c) an increase of predicted adult height (from 155.6 Ϯ 7.0 to 160.7 Ϯ 6.7 cm, P < 0.0005). Treatment interruption was followed by an important catch-down growth, with an FH (158.4 Ϯ 5.8 cm) lower (P < 0.025) than that predicted at the end of therapy. However, FH fell within the population norm and the target range in respectively 87.3 and 90% of the patients. The tallest FH was recorded in the patients who started therapy at less than 6 years of age and in those who discontinued treatment at a BA of 12.0-12.5 years. At stepwise regression analysis, FH in the whole study population was positively affected by the following independent factors: (a) height at the end of therapy (F = 45.45, P < 0.0001); (b) pretreatment height (F = 13.91, P < 0.0005); (c) treatment duration (F = 8.51, P < 0.005); (d) target height (TH) (F = 7.70, P < 0.01).We conclude that: (i) most girls with idiopathic CTPP treated by GnRH agonists may achieve an adult height within the population norm and/or their target range; (ii) the height gain from therapy onset until FH attainment, however, is generally rather limited (on average 2.9 cm) and only few patients are able to reach their target percentile; (iii) the most favorable height prognosis with respect to TH is generally observed in the subjects with the tallest height at the end of treatment and the lowest BA2:CA2 ratio, due to the important deterioration of height prognosis which frequently follows therapy interruption; (iv) FH is also significantly conditioned by both TH and treatment duration; (v) in order to strengthen the weak therapeutic effect of GnRH agonists in CTPP this treatment should be started as early as possible and discontinued at a BA of 12.0-12.5 years.

The circadian rhythm of circulating melatonin was determined in 38 children, aged 1-18 yr. Serum melatonin concentrations at 2400 and 0300 h in children aged 1-5 yr were significantly (P less than 0.001) higher than those in older children [6-10 yr, puberty stage 1 (P1)]. Nocturnal melatonin levels also were significantly (P less than 0.01) higher in P1 subjects than in P2 subjects aged 9-12 yr. A further small decline was found from P2 to P4/P5 (P less than 0.05). Thus, the decline in the nocturnal melatonin surge is not exclusively related to pubertal development, but begins in infancy.