Growth hormone-releasing activity of hexarelin, a new synthetic hexapeptide, before and during puberty.

The objective of this study was to verify the GH-releasing activity of a synthetic hexapeptide, hexarelin (HEX), before and during puberty. Ninety-six children (54 boys and 42 girls, aged 4.1-17.4 yr) were studied. Fifty-two of the children were prepubertal, and the other 44 were in pubertal stage II-IV. The GH response to 2 micrograms/kg HEX, iv (n = 56), was higher (P < 0.001) than that induced by 1 microgram/kg GHRH, iv (n = 33). The iv dose of 2.0 micrograms/kg HEX induced a greater GH increase (P < 0.02) than the 1.0 microgram/kg dose. The GH-releasing effect of 10 mg HEX, orally, was greater (P < 0.03) than that of 1.0 microgram/kg GHRH, iv (n = 7). The iv dose of 2 micrograms/kg HEX elicited an increase in GH levels that was higher in pubertal children than in prepubertal children (77.5 +/- 8.5 vs. 39.4 +/- 4.4 micrograms/L; P < 0.001). Before puberty, there was no sex-dependent difference in the GH response to HEX. It increased during puberty (P < 0.05 and P < 0.002 for boys and girls, respectively), when it was higher (P < 0.05) in girls than in boys. In contrast, GH responses to GHRH were not related to sex differences and/or puberty. In conclusion, HEX is a potent and reproducible stimulus of GH secretion in children. The effect of HEX increases in puberty, with girls showing a more marked GH response.

Enhancement of cholinergic tone by pyridostigmine promotes both basal and growth hormone (GH)-releasing hormone-induced GH secretion in children of short stature.

Increased cholinergic tone induced by pyridostigmine (PD) increases basal plasma GH levels and potentiates the GH response to GHRH in normal adults. In this study the effects of PD (60 mg, orally) on both basal and GHRH (1 microgram/kg)-induced GH secretion in seven children with familial short stature (FSS), six with GH deficiency (GHD) and 10 with constitutional growth delay (CGD) were studied and compared with results obtained by stimulation with insulin-induced hypoglycemia (IH) and GHRH alone. The mean peak plasma GH levels were variable, but individual values were frequently low in all groups after both IH [FSS, 9.7 +/- 1.3 (+/- SEM) ng/mL; GHD, 1.6 +/- 0.4 ng/mL; CGD, 7.0 +/- 0.8 ng/mL] and GHRH (FSS, 23.8 +/- 6.6 ng/mL; GHD, 11.1 +/- 5.8 ng/mL; CGD, 15.1 +/- 4.5 ng/mL) administration. PD induced GH responses (FSS, 14.5 +/- 1.6 ng/mL; GHD, 3.8 +/- 0.8 ng/mL; CGD, 18.3 +/- 3.2 ng/mL) that in many children in the FSS and CGD groups were higher than those after IH and GHRH treatment. PD clearly increased the GH response to GHRH in all children [FSS, 69.5 +/- 9.4 ng/mL (P less than 0.01 vs. other stimuli); GHD, 18.0 +/- 7.5 ng/mL; CGD, 50.0 +/- 8.5 ng/mL (P less than 0.01 vs. other stimuli)]. We conclude that in children with short stature, as in adults, enhancement of cholinergic tone increases both basal and GHRH-induced GH secretion, and that PD plus GHRH is the best provocative stimulus for evaluating the somatotroph response.

Retesting young adults with childhood-onset growth hormone (GH) deficiency with GH-releasing-hormone-plus-arginine test.

Within an appropriate clinical context, severe GH deficiency (GHD) in adults has to be defined biochemically by provocative testing of GH secretion. Patients with childhood-onset GHD need retesting in late adolescence or young adulthood to verify whether they have to continue recombinant human GH treatment. GHRH + arginine (GHRH+ARG) is the most reliable alternative to the insulin-induced hypoglycemia test (ITT) as a provocative test for the diagnosis of GHD in adulthood, provided that appropriate cut-off limits are assumed (normal limits, 16.5 microg/L as 3rd and 9.0 microg/L as 1st centile). We studied the GH response to a single GHRH (1 microg/kg iv) + ARG (0.5 g/kg iv) test in 62 young patients who had undergone GH replacement in childhood, based on the following diagnosis: 1) organic hypopituitarism with GHD (oGHD) In = 18: 15 male (M), 3 female (F); age, 26.8+/-2.2 yr; GH peak < 10 microg/L after two classical tests]; 2) idiopathic isolated GHD (iGHD) [n = 23 (15 M, 8 F); age, 23.0+/-1.5 yr; GH peak < 10 microg/L after two classical tests]; and 3) GH neurosecretory dysfunction (GHNSD) [n = 21 (10 M, 11 F); age, 25.1+/-1.6 yr; GH peak > 10 microg/L after classical test but mGHc < 3 microg/L]. The GH responses to GHRH+ARG in these groups were also compared with that recorded in a group of age-matched normal subjects (NS) [n = 48 (20 M, 28 F); age, 27.7+/-0.8 yr]. Insulin-like growth factor I levels in oGHD subjects (61.5+/-13.7 microg/L) were lower (P < 0.001) than those in iGHD subjects (117.2+/-13.1 microg/L); the latter were lower than those in GHNSD subjects (210.2+/-12.9 microg/L), which, in turn, were similar to those in NS (220.9+/-7.1 microg/L). The mean GH peak after GHRH+ARG in oGHD (2.8+/-0.8 microg/L) was lower (P < 0.001) than that in iGHD (18.6+/-4.7 microg/L), which, in turn, was clearly lower (P < 0.001) than that in GHNSD (31.3+/-1.6 microg/L). The GH response in GHNSD was lower than that in NS (65.9+/-5.5 microg/L), but this difference did not attain statistical significance. With respect to the 3rd centile limit of GH response in young adults (i.e. 16.5 microg/L), retesting confirmed GHD in all oGHD, in 65.2% of iGHD, and in none of the GHNSD subjects. With respect to the 1st centile limit of GH response (i.e. 9.0 microg/L), retesting demonstrated severe GHD in 94% oGHD and in 52.1% of iGHD. All oGHD and iGHD with GH peak after GHRH+ARG lower than 9 microg/L had also GH peak lower than 3 microg/L after ITT. In the patients in whom GHD was confirmed by retesting, the mean GH peak after GHRH+ARG was higher than that after ITT (3.4+/-0.5 vs. 1.9+/-0.4). In conclusion, given appropriate cut-off limits, GHRH+ARG is as reliable as ITT for retesting patients who had undergone GH treatment in childhood. Among these patients, severe GHD in adulthood is generally confirmed in oGHD, is frequent in iGHD, but never occurs in GHNSD.

[The age of menarche]. / L'epoca del menarca.

PIP: A review of the literature concerning age at menarche is presented, and the various methods for measuring age at menarche are described. Factors considered include genetic and ethnic factors, family characteristics, physique, geographic factors, morbidity, and socioeconomic factors. The results of a wide range of studies from historical times to the present are summarized. The geographic focus is worldwide. (summary in ENG)^ieng

Chromosomal aberrations, sister chromatid exchanges and high frequency cells in young patients with neurofibromatosis 1 (NF1).

Chromosomal aberrations (CAs), sister chromatid exchanges (SCEs) and high frequency cells (HFCs) have been assessed in peripheral blood lymphocytes of 10 neurofibromatosis (NF1) patients and 10 healthy controls. In both groups, the spontaneous rates and the induced (bleomycin for CA and MMC for SCE) frequencies were analyzed. No differences between cells from NF1 patients and controls were observed with respect to spontaneous or bleomycin induced CA. Spontaneous or MMC induced SCE frequencies were also similar in NF1 patients and controls. HFCs, on the contrary, were statistically lower in NF1 patients.

A patient with early puberty associated with Chiari 1 malformation.

A boy is described with early puberty and Chiari 1 malformation. It is not known whether there was an etiological relationship between these two conditions, or whether they were coincidental. This report emphasizes the utility of MRI when early puberty is diagnosed, particularly in males.

The GH-releasing effect of Hexarelin, a synthetic hexapeptide, in newborns is lower than in young adults.

The aim of the present study was to verify the GH-releasing effect of Hexarelin, a synthetic hexapeptide, in newborns who are known to have GH hypersecretion likely due to hyperactivity of GHRH-secreting neurons while somatostatinergic activity seems not fully operative. We studied in 6 newborns (NB, 2.5 +/- 2.1 days), 12 prepubertal children (PC, 9.8 +/- 0.45 yr) and 12 young adults (YA, 28.2 +/- 0.2 yr) the GH response to Hexarelin (HEX, 2 micrograms/kg i.v.) compared to that observed after GHRH (1 microgram/kg i.v.) in 6 NB (4.2 +/- 0.4 days), 12 PC (9.9 +/- 0.6 yr) and 12 YA (31.0 +/- 1.3 yr). GH levels were assayed basally and 30 and 60 min after drug administration. In NB, mean (+/- SEM) basal GH levels were higher while IGF-I levels were lower than those recorded in PC and YA (GH: 34.8 +/- 1.9 vs 2.8 +/- 0.4 vs 1.4 +/- 0.4 micrograms/l, p < 0.0006; IGF-I: 36.3 +/- 1.9 vs 152.0 +/- 11.5 vs 175.8 +/- 15.3 micrograms/l, p < 0.0007); in the last two groups GH and IGF-I levels were similar. The mean delta GH peak after HEX in NB (32.8 +/- 4.7 micrograms/l) was similar to that in PC (34.6 +/- 4.3 micrograms/l) and lower (p < 0.01) than that in YA (56.2 +/- 7.4 micrograms/l). Delta GH peak after GHRH in NB (60.1 +/- 1.5) was higher than those in PC and YA (20.8 +/- 4.8 and 22.8 +/- 3.4 micrograms/l) (p < 0.005 and < 0.002, respectively). In NB, the GH response to HEX was lower (p < 0.005) than to GHRH while in PC and YA the somatotrope response to HEX was higher (p < 0.03 and 0.0004, respectively) than to GHRH. These data demonstrate that the GH-releasing effect of Hexarelin undergoes age-dependent variation being lower in newborns than in young adults, opposite to that observed after GHRH administration. The evidence that Hexarelin releases less GH than GHRH in newborns but not in prepubertal children and in young adults makes unlikely the hypothesis that the GH-releasing effect of this hexapeptide is mediated via endogenous GHRH release.

Variation of bone age progression in healthy children.

Bone age assessments were related to auxological variables in 407 Italian boys, between 7 and 12 years of age, in order to elucidate the factors that affect the rate of skeletal maturation and to examine the possibility of using measures of skeletal maturation of evaluate individual patients. Using the radius-ulna-short bones (RUS) method of assessment, bone age velocity was greater in the Italian boys than for the UK reference standards, although there was considerable interindividual dispersion around the mean. Bone age velocity and height velocity were poorly correlated, and there was little correlation between skeletal and pubertal maturation. There was a slight positive correlation between bone age velocity and height SDS and between bone age velocity and body mass index. Bone age estimations using RUS were greater than those obtained using the carpus. In conclusion, the marked interindividual deviation in measured bone ages makes it difficult to relate data on an individual basis to other measures of growth and maturation

Incidence and prevalence rate estimation of GH treatment exposure in Piedmont pediatric population in the years 2002-2004: Data from the GH Registry.

OBJECTIVE: The aim of this study is to estimate the annual incidence and prevalence rate of the GH treatment exposure in patients under the age of 18 treated for hypopituitarism or isolated GH deficiency (GHD) in Piedmont, during the period January 1, 2002 to December 31, 2004. METHODS: The selection criteria for recombinant human GH (rhGH) treatment in childhood were approved by the Ministry of Health in Italy in the yr 1998. The present analysis is based on data from the Registry of subjects receiving GH therapy (GH Registry) made up of the 918 pediatric patients (age <18 yr) with a diagnosis of GHD (excluding Prader-Willi and Turner syndromes and other conditions), diagnosed in the period January 1, 2002 - December 31, 2004. The case series has been described as regards the number of cases per year of diagnosis; the prevalence and incidence rates, calculated per 10,000 (per ten thousand) inhabitants, are given for each year of the study period. RESULTS: The prevalence rate increases slightly from 8.62 per thousand in 2002 to 9.44 per thousand in 2004 and the incidence rates estimated were 2.49 per ten thousand, 1.86 per ten thousand and 1.97 per ten thousand in the yr 2002, 2003 and 2004, respectively. CONCLUSION: The Piedmont GH Registry represents the first database available in Italy and could set an example for the other Italian regions as well.

Diagnosis by the numbers: what's between the lines can be critical.

The government has laid down the rules. The ICD-9-CM diagnosis codes are to be used on all Medicare Part B claim forms. Physicians not accepting assignments can be fined and ultimately excluded from the Medicare program.

Final height in sexually precocious girls after therapy with an intranasal analogue of gonadotrophin-releasing hormone (buserelin).

Twenty-two girls affected by sexual precocity with impaired final height prognosis were followed until they achieved final height. Twelve of them were treated with an intranasal (D-Ser6)-gonadotrophin-releasing hormone (GnRH) analogue (buserelin) administered at a mean dose of 25 micrograms/kg/day (range 20-32) for a mean period of 14 months (range 8-18). Ten girls refused treatment. Mean final height of the treated girls was 157.3 +/- 8.2 cm, significantly (p = 0.03) higher than the 149.7 +/- 5.5 cm of untreated patients. Treated girls surpassed midparental height (+1.7 cm) while untreated girls reached the lower part of target zone (-3.5 cm). Our data suggest that intranasal buserelin treatment preserves final height in girls with sexual precocity and initially impaired height prognosis.

[Obstetrico-pediatric aspects of physiopathology of lipid metabolism. I. Synthesis of the physiological bases with special regard to hormonal regulation and classification of dyslipidemias]. / Aspetti ostetrico pediatrici della fisiopatologia del metabolismo lipidico. Nota I: sintesi delle basi fisiologiche con particolare riguardo alla regolazione ormonale e classificazione delle dislipidemie

PIP: This work is the 1st of a research program on the behavior of lipid metabolism during pregnancy and in the 1st years of life. Theories on the subject of the biochemistry of cholesterol and triglycerides are summarized and lipid physiology, particularly from the viewpoint of hormone regulation and the behavior of some important enzyme systems, is examined. Lipid transport systems, in the form of lipoproteins, is discussed, followed by a description and classification of hyper- and hypolipemia and of the relation between some forms of hyperlipemia and atherosclerosis. It is concluded that it would be very useful to obtain an early identification of subjects with a high risk of atherosclerosis in order to begin prophylactic treatment, if possible, during early infancy or even during pregnancy.^ieng