Acylated and unacylated ghrelin levels in normal weight and obese children: influence of puberty and relationship with insulin, leptin and adiponectin levels.

BACKGROUND: Ghrelin circulates in blood as acylated (AG) and unacylated (UAG) ghrelin. The physiological role of the two forms is poorly understood, in particular in childhood. Aim of the study was to evaluate the AG and UAG levels in obese and normal weight (NW) children, pre-pubertal and pubertal, and their relationship with insulin, leptin and adiponectin levels. SUBJECTS AND METHODS: A population based study in which AG, UAG, leptin, adiponectin, glucose, insulin, testosterone or estradiol levels, insulinemic indexes were evaluated in 82 NW and 58 obese (OB) children. RESULTS: Both ghrelin forms in NW were higher (AG, p<0.02; UAG, p<0.0001) than in OB subjects, with similar ratio AG/UAG . While no differences were observed for gender, puberty AG (p<0.01) and UAG (p<0.0001) levels were higher in pre-pubertal than pubertal NW and OB subjects. Adiponectin levels in NW subjects were higher (p<0.001), while leptin and insulin levels were lower (p<0.0001) than in OB subjects. NW children showed homeostasis model assessment (HOMA) and HOMAß indices lower than OB children (p<0.0001) with a higher a quantitative insulin sensitivity check index (p<0.0001). AG and UAG levels correlated to each other (p<0.0001), each showing a negative correlation to age, height, weight and body mass index. Both forms, but more strongly UAG, correlated with adiponectin, leptin, and insulin. CONCLUSIONS: OB children show lower levels of both AG and UAG when compared to NW subjects, with lower levels during puberty. These results demonstrate a peculiar strong relationship between UAG levels and metabolic parameters in the pediatric population, suggesting a role for UAG in metabolic functions.

Interleukin-10 and transforming growth factor-beta1 in cord blood: relationship with paternal allergy and cesarean section.

AIM: To measure Interleukin-10 (IL-10) and transforming growth factor-beta1 (TGF-beta1) in cord blood and assess their relationship with parental allergy and perinatal characteristics. METHODS: In a neonatal care unit 212 consecutive full-term and appropriate for gestational age newborns were recruited. IL-10 and TGF-beta1 levels were determined in cord blood by high sensitivity ELISA. Perinatal characteristics, mode of delivery and presence of allergy in parents were recorded. RESULTS: Out of 212 newborns, 136 were of non-allergic parents and 76 (35.8%) of one or both allergic parents. In newborns of allergic fathers median IL-10 levels tended to be lower (0.67 vs. 1.06 pg/mL, p = 0.07) and TGF-beta1 levels were significantly lower (40.9 vs. 45.3 ng/mL, p = 0.008) than in newborns of non-allergic parents. Multiple general regression analysis showed that presence of paternal allergy (beta=-0.19, p = 0.003) to be born by cesarean section (beta=-0.21, p = 0.03) and younger gestational age (beta= 0.14, p = 0.04) independently contributed to decrease TGF-beta1 levels (multiple R = 0.38, p < 0.0001). CONCLUSION: Paternal allergy and cesarean section are associated to decreased TGF-beta1, which might be the mediator of the increased risk of atopy development. Cord blood IL-10 and TGF-beta1 levels of our newborn series could be used as reference values for further studies on these relationships.

Prevalence and risk factors for overweight and obesity in a population of Italian schoolchildren: a longitudinal study.

Prevalence of childhood overweight and obesity have dramatically increased worldwide in the last decades. Overweight and obesity are the result of a complex interaction between genetic and environmental factors. The aim of our longitudinal study was to assess the prevalence of overweight and obesity in a population of Italian schoolchildren followed for 2 years and to identify main risk factors for obesity onset and persistence in childhood. We enrolled 632 children (males /females= 345/287), aged 3 to 8 yr.Weight and height were measured at time 0, 1 (1 yr later), and 2 (2 yr later). Overweight and obesity were defined using body mass index (BMI) (Italian growth charts). Data collected included: birth weight, gestational age,maternal weight gain during pregnancy, breast feeding, parents' BMI, educational level, and occupation type. At time 0, 1, and 2 the prevalence of overweight was 22%, 22%, and 25%, respectively, and the prevalence of obesity was 7%, 8%, and 8%, respectively. During follow-up 62%of children remained normal weight, 24% was always overweight or obese, 9% became overweight, while only 5% of overweight subjects became normal weight. Male gender, maternal weight gain during pregnancy >10 kg, parental overweight/obesity were positively associated with the presence of overweight during the entire follow-up. On the contrary, being small for gestational age at birth was negatively related to persistence of overweight. No influence was found for being breastfed, for parental low educational level, and manual occupation. A large prevalence of overweight/obesity was observed in Italian schoolchildren. Gender, maternal weight gain during pregnancy, and parents' BMI were the strongest predictors of the persistence of child overweight and obesity.

Heterozygous mutation of HESX1 causing hypopituitarism and multiple anatomical malformations without features of septo-optic dysplasia.

Isolated GH deficiency or combined pituitary hormone deficiencies have been associated with mutations in transcription factors encoding genes that control organogenesis or cell differentiation. Among these factors, Hesx1 is essential for the development of the optic nerve and regulates some of the earliest stages in pituitary development and is intimately involved in orchestrating the expression of other factors involved in pituitary organogenesis. Mutations in HESX1 are reported in patients with hypopituitarism either with typical septo-optic dysplasia (SOD) or with neuromorphological abnormalities not included in classical SOD. The present report describes clinical features, biochemical parameters, and characterization of a missense mutation (Gln6His) in exon1 of HESX1 in a pre-pubertal child who progressively developed multiple hypopituitarism, firstly GH and, afterwards, TSH and ACTH deficiencies, in a pluri-malformative syndrome characterized by short stature and anatomical malformations not associated with a classical SOD phenotype. This finding further supports the necessity to stay alert in evaluating a gene that plays a minor role in the pathogenesis of sporadic hypopituitarism, such as HESX1 gene even when the phenotype does not fit in with a classical SOD syndrome.

Ghrelin secretion in preterm neonates progressively increases and is refractory to the inhibitory effect of food intake.

CONTEXT: Ghrelin, a natural GH secretagogue, is mainly characterized by nonendocrine activities such as orexigenic effect and modulation of the endocrine and metabolic response to variations in energy balance. Ghrelin levels have been reported to be negatively associated with insulin secretion, enhanced in anorexia, and reduced in obesity. Ghrelin levels in newborns were shown to be similar to those found in children and adults without any gender-related difference. OBJECTIVE: The aim of this study was to evaluate ghrelin variations in preterm newborns as a function of fasting and feeding. METHODS: To this end, in 31 preterm neonates (13 males and 18 females) categorized as appropriate for gestational age, total ghrelin levels were measured in cord blood and then on the fourth day of life before and after meals. RESULTS: Ghrelin levels in cord blood [(median 25th-75th centile) 184; 122-275 pg/ml] were higher (P < 0.006) than levels measured in the mothers at delivery (167.0; 89-190 pg/ml). In newborns on the fourth day of life, ghrelin levels in fasting conditions (451; 348-649 pg/ml) were higher (P < 0.0004) than those in cord blood. The meal did not at all modify ghrelin levels (476; 302-775 pg/ml), which were unchanged, compared with those in fasting condition. Total ghrelin levels in cord blood were not associated with weight and length; conversely, on the fourth day of life ghrelin levels in newborns were negatively correlated to birth weight as well as the present weight (P = 0.05, r = -0.4). Ghrelin levels were independent of gender, type of delivery, and the kind of feeding regimen. CONCLUSIONS: The secretion of total ghrelin increases from delivery to the fourth day of life when it is refractory to the inhibitory effect of food intake, but it is negatively correlated to body weight.

A systematic review of Helicobacter pylori eradication treatment schedules in children.

METHODS: We systematically reviewed all available data in the paediatric literature on treatment for Helicobacter pylori infection to determine overall efficacy of different schedules. A comprehensive search of all published articles and letters from 1987, and of abstracts presented at three main meetings on this topic between 1997 and 1999, was carried out. Results from all English and French papers, letters and abstracts were extracted and analysed. RESULTS: Only 30 full articles and 16 abstracts were found, with results on eradication of H. pylori in 870 and 1552 children, respectively. Monotherapy or dual therapy with an antisecretory drug plus one antibiotic showed a very low efficacy. Dual therapies with bismuth plus one antibiotic (either amoxycillin or a nitro- imidazole) or two antibiotics when administered for 2 or more weeks were as effective as either bismuth-based or proton pump inhibitor-based triple therapies. Triple therapies were less effective than in adults, and while bismuth-based triple therapies were more effective when given for 2 weeks than for one week, proton pump inhibitor-based triple therapies have a similar efficacy irrespective of the duration. CONCLUSION: In children dual therapies seemed as effective as triple therapies, and longer courses of proton pump inhibitor-base triple therapies are not better than shorter ones.

Usefulness of Helicobacter pylori stool antigen test to monitor response to eradication treatment in children.

BACKGROUND: The monitoring of the results of eradication treatment is a crucial step for patients with Helicobacter pylori gastritis. A non-invasive test for H. pylori antigens in stools (HpSA) was recently validated for children. AIM: To evaluate the accuracy of HpSA in monitoring eradication treatment in children. METHODS: In 60 children, H. pylori gastritis was diagnosed by endoscopy and the 13C-urea breath test. The children were treated and returned for a follow-up (13)C-urea breath test 6 weeks after the end of treatment. Children were considered cured when the (13)C-urea breath test was negative. Stool were collected at baseline, and at 2 and 6 weeks. Stool antigens were measured by HpSA. RESULTS: According to (13)C-urea breath test, 6 weeks after the end of treatment 49 children were cured and 11 were still H. pylori-positive. The sensitivity and specificity of HpSA on stools collected 2 weeks after therapy were 100%. At 6 weeks specificity was 93.9 and sensitivity 100%. Results by visual reading were concordant with the plate-reader in all but two cases at baseline. CONCLUSIONS: HpSA is accurate for monitoring treatment in children as early as 2 weeks after therapy, when information is most useful and unachievable with other tests. Results by visual reading are accurate, and this can make the test cheaper and more practical.

Ghrelin gene polymorphisms and ghrelin, insulin, IGF-I, leptin and anthropometric data in children and adolescents.

BACKGROUND: Previous investigations on the ghrelin gene reported three common polymorphisms (Arg51Gln, Leu72Met, and Gln90Leu), but their role in overweight and obese individuals remains to be clarified. OBJECTIVE: To ascertain whether these genetic variants could influence ghrelin secretion and play a part in predisposing to earlier onset of obesity or in modulating the overweight phenotype in childhood. DESIGN AND METHODS: Mutational analysis of the entire ghrelin gene and total and acylated plasma determinations were performed in 81 obese or overweight children and adolescents (46 were obese and 35 overweight: Ob/Ow). We also recruited 168 normal-weight healthy controls (72 young adults and 96 children) for mutational or plasma ghrelin analysis. RESULTS: Median total and acylated plasma ghrelin concentrations were significantly lower in Ob/Ow individuals than in controls (175 pg/ml compared with 345 pg/ml, P<0.0001, and 95 pg/ml compared with 114 pg/ml, P<0.0001, respectively). The ghrelin gene variants showed similar allele frequencies in the Ob/Ow individuals and in controls; in the former, they were not associated with any change in total and acylated circulating ghrelin concentrations or anthropometric data. The Leu72Met status was associated with a positive family history for obesity (75% for Leu72Met compared with 39% for Leu72Leu, P=0.03) and with a greater percentage of newborns born 'large for gestational age' (33% for Leu72Met compared with 5% for Leu72Leu, P=0.03), but in the control group it was related to a lower mean body mass index z-score (-0.03 for Leu72Met and -0.47 for Leu72Leu, P=0.04). CONCLUSION: Our present findings do not support the hypothesis that the ghrelin gene polymorphisms have a relevant impact in the secretion of total and acylated ghrelin.

Neonatal transient hypothyroidism: aetiological study. Italian Collaborative Study on Transient Hypothyroidism.

AIMS: To define the aetiology of neonatal transient hypothyroidism (NTH) and recommend preventive measures. METHODS: Maternal and perinatal clinical data on the use of antiseptics, drugs, and contrast agents containing iodine were collected from 40 subjects. Thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroxine (T4), thyroglobulin (TG), TSH receptor antibodies, thyroid peroxidase antibodies and urinary iodine were measured in random neonatal samples. In the mothers with known or suspected thyroid disorders, TSH, FT4, TSH receptor antibodies and thyroid peroxidase antibodies were also measured. RESULTS: The NTH aetiology was identified in 85% of cases. More than 50% of the babies with transient hypothyroidism had been exposed to iodine; maternal transfer of antibodies had occurred in a third of them. CONCLUSIONS: It is suggested that the practice of using iodine containing disinfectants should be withdrawn, and chlorhexidine substituted instead; that pregnant women should be advised of the adverse effects of using iodine products; and that thyroid function should be monitored whenever iodine is used.

IGF-1 and IGFBP-3 in congenital and acquired hypothyroidism after long-term replacement treatment.

BACKGROUND: Thyroid hormones are involved in the regulation of the GH/IGF axis. Hypothyroidism is associated with a reduction in GH pulsatility and in GH-response to stimulatory tests. In hypothyroidism, serum levels of IGF-I and IGFBP-3 fall and these changes are reserved after short-term replacement with L-T4. This study was undertaken to determine the effect of long-term replacement therapy with T4 in IGF-1 and IGFBP-3 serum levels. METHODS: The study included 12 patients affected with hypothyroidism and in replacement treatment with T4. They were divided into 3 groups according to age at the beginning of treatment. Group A consisted of 4 pre-pubertal subjects with Congenital Hypothyroidism (CH) diagnosed with neonatal screening, where T4 treatment was started within 15 days of life. Group B consisted of 5 young adults where CH was clinically diagnosed at the median age of 6 months and replacement therapy started at this age. Group C consisted of 3 subjects affected with hypothyroidism secondary to thyroiditis where diagnosis and replacement treatment were delayed at age 11, 12 and 14 respectively. All subjects were matched with a control of the same age, sex, weight and pubertal stage. RESULTS: FT3, FT4 and TSH were in the normal range both in patients and in controls. No correlation was found between FT3 or FT4 and IGF-1 or IGFBP-3 serum levels. IGF-1 serum levels in group A (198 +/- 122 ng/ml) were significantly lower than that in group B (624 +/- 105, p < 0.001) and in group C (649 +/- 98, p=0.003). IGFBP-3 serum levels in group A (1.98 +/- 0.56 microgram/ml) were significantly lower than in group B (3.65 +/- 1.10, p=0.03) and in group C (4.13 +/- 0.49, p=0.003). The increase of IGF-1 and IGFBP-3 levels was seen also in control groups B and C when compared with control group A. IGF-1 and IGFBP-3 were positively correlated with age both in patients and in controls. A linear correlation was found between IGF-1 and IGFBP-3 which was positive for controls (r=0.946, p < 0.001) and patient group A and B (r=0.839, p = 0.005) but tended to be negative for patient group C (r=0.65, n.s.). CONCLUSIONS: : Our data demonstrate that long-term replacement therapy in children with hypothyroidism is associated with a physiological increase in IGF-1 and IGFBP-3. The positive correlation between IGF-1 and IGFBP-3 levels in group A and B confirm the efficacy of long-term replacement treatment on the IGF-1/BP-3 axis in pre- and post-pubertal patients treated for CH. However, this correlation tended to be negative in patients with hypothyroidism secondary to thyroiditis, suggesting that the cause of thyroid insufficiency and/or the age at the beginning of replacement therapy may have a role in the post-pubertal hormonal status in IGF-1 and IGFBP-3 balance.

IGF-1 and IGFBP in congenital and acquired hypothyroidism after long-term replacement treatment.

BACKGROUND: Thyroid hormones are involved in the regulation of the GH/IGF axis. Hypothyroidism is associated with a reduction in GH pulsatility and in GH-response to stimulatory tests. In hypothyroidism, serum levels of IGF-1 and IGFBP-3 fall and these changes are reversed after short term replacement with L-T4. This study was undertaken to determine the effect of long term replacement therapy with T4 in IGF-1 and IGFBP-3 serum levels. METHODS: The study included 12 patients affected with hypothyroidism and in replacement treatment with T4. They were divided into 3 groups according to age at the beginning of treatment. Group A consisted of 4 pre-pubertal subjects with Congenital Hypothyroidism (CH) diagnosed with neonatal screening, where T4 treatment was started within 15 days of life. Group B consisted of 5 young adults where CH was clinically diagnosed at the median age of 6 months and replacement therapy started at this age. Group C consisted of 3 subjects affected with hypothyroidism secondary to thyroiditis where diagnosis and replacement treatment were delayed at age 11, 12 and 14 respectively. All subjects were matched with a control of the same age, sex, weight and pubertal stage. RESULTS: FT3, FT4 and TSH were in the normal range both in patients and in controls. No correlation was found between FT3 or FT4 and IGF-1 or IGFBP-3 serum levels. IGF-1 serum levels in group A (198 +/- 122 ng/ml) were significantly lower than that in group B (624 +/- 105, p < 0.001) and in group C (649 +/- 98, p = 0.003). IGFBP-3 serum levels in group A (1.98 +/- 0.56 micrograms/ml) were significantly lower than in group B (3.65 +/- 1.10, p = 0.03) and in group C (4.13 +/- 0.49, p = 0.003). The increase in IGF-1 and IGFBP-3 levels was seen also in control groups B and C when compared with control group A. IGF-1 and IGFBP-3 were positively correlated with age both in patients and in controls. A linear correlation was found between IGF-1 and IGFBP-3 which was positive for controls (r = 0.946, p < 0.001) and patient group A and B (r = 0.839, p = 0.005) but tended to be negative for patient group C (r = -0.65, n.s.). CONCLUSIONS: Our data demonstrate that long term replacement therapy in children with hypothyroidism is associated with a physiological increase in IGF-1 and IGFBP-3. The positive correlation between IGF-1 and IGFBP-3 levels in group A and B confirm the efficacy of long term replacement treatment on the IGF-1/BP-3 axis in pre- and post-pubertal patients treated for CH. However, this correlation tended to be negative in patients with hypothyroidism secondary to thyroiditis, suggesting that the cause of thyroid insufficiency and/or the age at the beginning of replacement therapy may have a role in the post-pubertal hormonal status in IGF-1 and IGFBP-3 balance.

Measurement of urinary iodine excretion to reveal iodine excess in neonatal transient hypothyroidism.

This study was undertaken to confirm the importance of iodine excess in neonatal transient hypothyroidism. In 30 transient hypothyroid newborns at screening we measured urinary iodine excretion and TSH. They were divided into two groups: group A consisted of 21 newborns who had been exposed to iodine; group B of 9 non-exposed newborns. The two groups were significantly different only for median urinary iodine excretion (p = 0.001). In 61.5% of newborns of group A, iodine exposure caused iodine excess (urinary iodine excretion higher than 185 micrograms/l); this correlated with a higher prevalence of prematurity and a lower mean gestational age. Clinical records should reveal iodine exposure, but only urinary iodine excretion shows iodine excess. We suggest that evaluation at birth of urinary iodine excretion in every newborn with high TSH could help in predicting a good prognosis, since hypothyroidism due to the Wolff-Chaikoff effect is always spontaneously reversible, even if treatment may be suggested.

[Prevalence of goiter and urine iodine in a school population in an area of the Bolognese Apennines]. / Prevalenza di gozzo e ioduria nella popolazione della scuola dell'obbligo in un'area dell'Appennino bolognese.

We evaluated goiter prevalence and urinary iodine excretion (UIE) in schoolchildren living in three villages of the Appennines in the Bologna district-Castel d'Aiano (CA), Gaggio Montano (GM) and Pietracolora (PC). 175 age-matched schoolchildren living in the urban area of Bologna were considered as control group. In the control area the presence of goiter was documented in 11 out of 175 subjects (6.3%). In the mountain area the presence of goiter was documented in 42 out of 233 subjects (18%) (p < 0.0001 vs control area). In the urban control area the UIE was 159 micrograms/l (median; range 19-298). In the mountain area the UIE was 119 micrograms/l (median; range 10-286) (p < 0.001 vs control area). We observed the highest prevalence of goiter and UIE levels < 100 micrograms/l only in the village of PC, which is still characterized by geographical isolation and rural economy.

[Increasing prevalence of celiac children with negative serum antigliadin antibodies]. / Aumento dei bambini con malattia celiaca e anticorpi antigliadina negativi: studio delle caratteristiche cliniche.

AIM: In the last few years we noted an increasing number of children with celiac disease with negative serum anti-gliadin antibodies (AGA) a useful serologic test to monitor compliance to gluten-free diet. The aim of this study was to verify diagnostic accuracy of AGA and compare clinical characteristics of AGA-negative with AGA-positive celiac children. METHODS: The authors analyzed serum of AGA-negative celiac children with 3 Elisa kits, and compared clinical and anthropometric data of AGA-negative with AGA-positive celiac children. Celiac disease was diagnosed with small bowel biopsy, and total IgA were determined. Children with IgA-deficiency were excluded. RESULTS: When retested with two other commercial kits, serum values of AGA-negative children were confirmed in all but one. In the last 14 years a diagnosis of celiac disease was performed in 166 children, in 56 of them (33.7%) antigliadin antibodies were negative. Preva-lence of AGA-negative celiac children increased significantly in the last years (from 23% before 2002 to 39.8% after 2002, P=0.04). AGA-negative children were significantly older (7.8 years vs. 3.7 years, P=0.0007) they complained more frequently of abdominal pain (55%, vs. 25,4% P=0.04) and less frequently of anaemia (8% vs. 24.5% P=0.012) and were less likely to have a classical celiac triad (5.3 vs. 22%, P=0.004) than AGA-positive children. CONCLUSION: Serum AGA seem no longer useful for monitoring compliance to gluten-free diet. In children where AGA are negative at diagnosis, when the child eats a normal amount of gluten, they are going to remain negative even after poor compliance.

[Iodine status in historically iodine deficiency area]. / Apporto iodico in un'area storicamente iodocarente.

AIM: The median urinary iodine concentration (UIC) for schoolchildren was 90 microg/L in Biella and 136 microg/L in Novara in survey carried out in 1995-1996. Biella resulted as iodine deficiency area and Novara as iodine sufficient area. Aim of our study was to assess goiter prevalence by ultrasonography in Biella and Novara schoolchildren and to evaluate median UIC in Biella schoolchildren. METHODS: A total of 829 Biella schoolchildren and 310 Novara schoolchildren, aged 7-15 years, were submitted to thyroideal ultrasonography. Biella schoolchildren were submitted to morning-spot urine sample's collection for UIC's determination. RESULTS: The ultrasound goiter prevalence as function of age resulted 15.7% in Biella and 14.8% in Novara (P = 0.7, chi 2 test). The ultrasound goiter prevalence as function of body surface area resulted 17.1% in Biella and 7.1% in Novara (P < 0.0001, chi 2 test). UIC (25-75 degrees ) for Biella schoolchildren who attended third and fifth year of primary school was 159 microg/L (107-228 microg/L) while for Biella schoolchildren who attended second year of secondary school was 150 microg/L (92-218 microg/L). CONCLUSIONS: Based on the results of UIC, Biella is considered as iodine sufficient area. Based on the results of goiter prevalence by ultrasonography, both Biella and Novara resulted as iodine deficiency area. UIC and goiter prevalence, however, provide different informations about iodine status: UIC supplies informations about present iodine status while goiter prevalence assesses past iodine status.

Oral glucose load inhibits circulating ghrelin levels to the same extent in normal and obese children.

OBJECTIVE: The presence of both the GH secretagogue (GHS) receptor and ghrelin in the pancreas indicates an involvement of this hormone in glucose metabolism. Ghrelin secretion is increased by fasting and energy restriction, decreased by food intake, glucose load, insulin and somatostatin in normal adults; however, food intake is not able to inhibit circulating ghrelin levels in children, suggesting that the profile of ghrelin secretion in children is different from that in adults. Moreover, how ghrelin secretion is regulated in childhood as a function of fat mass is still unclear. DESIGN AND SUBJECTS: We studied the effect of oral glucose load (75 g solution orally) on circulating total ghrelin levels in 14 obese children (group A, four boys and 10 girls, aged 9.3 +/- 2.3 years) and 10 lean children (group B, five boys and five girls, aged 9.7 +/- 3.8 years). MEASUREMENTS: In all the sessions, blood samples were collected every 30 min from 0 up to +120 min. GH, insulin and glucose levels were assayed at each time point. RESULTS: Glucose peaks following an oral glucose tolerance test (OGTT) in groups A and B were similar; however, both basal and OGTT-stimulated insulin levels in group A were higher than in group B (P < 0.05). Basal total ghrelin levels in group A (281.3 +/- 29.5 pg/ml) were lower (P < 0.0005) than in group B (563.4 +/- 81.5 pg/ml). In both groups A and B, the OGTT inhibited total ghrelin levels (P < 0.005). In terms of absolute values, total ghrelin levels in group A were lower (P < 0.0005) than those in group B at each time point after glucose load. The percentage nadir in total ghrelin levels recorded in group A (-25% at 90 min) was similar to that recorded in group B (-31% at 120 min). Total ghrelin levels were negatively associated with BMI (r = 0.5, P < 0.005) but not with glucose or insulin levels. CONCLUSION: Ghrelin secretion is reduced in obese children. It is, however, equally sensitive in both obese and lean children to the inhibitory effect of oral glucose load.

Puberty onset in Northern Italy: a random sample of 3597 Italian children.

Entering puberty is one of the most important milestones in life. Studies from around the world have shown that age of pubertal changes onset can vary with race and ethnicity, environmental conditions, geographical location and nutrition. In the last century, the onset of puberty progressively shifted back towards younger ages in several European countries, with a levelling off in the last decades. The aim of our study was to describe the prevalence of secondary sexual characteristics in a group of children living in Northern Italy comparing them with the percentile values published by Tanner in 1976. We enrolled 3496 children drawn from public schools and evaluated height, weight and pubertal stages. The analysis of our data evidenced that the 50th percentile age of puberty onset in both sexes decreased by about 1 yr compared to data published by Tanner. Mean body mass index (BMI) z-score was significantly higher (p = 0.01) in pubertal than in pre-pubertal girls, on the contrary it was higher (p = 0.005) in pre-pubertal than in pubertal boys. In conclusion, our study found that girls and boys of our region are beginning pubertal development about 1 yr earlier than Tanner's British population. Taking into consideration the 3rd percentile age for Tanner's breast stage 2 in girls and testicular volume (TV) of 4 ml in boys, the current internationally used cut-off age for precocious puberty, i.e. 8 yr for girls and 9 yr for boys, can be maintained in our population.

The impact of gender, puberty and body mass on reference values for urinary growth hormone (GH) excretion in normally growing non-obese and obese children.

OBJECTIVE: There is a lack of normal reference data on urinary GH (u-GH) excretion in children. We have investigated the impact of age, gender, pubertal development and body mass on reference values for u-GH excretion in normally growing non-obese and obese children. STUDY DESIGN: u-GH levels were evaluated in 1153 healthy normal children (aged 5-14) and in 684 obese children (body mass index, BMI: > 75th). u-GH levels (ng/8 h) were determined by ELISA as the mean value of three consecutive first morning voidings. RESULTS: Reference values (5-95th centile) for u-GH excretion in obese and non-obese children of both sexes are reported. In normal prepubertal children median u-GH levels were relatively stable and superimposable in the two sexes; subsequently, u-GH levels increased, reaching a peak value at 13 years in both sexes. Significant increments (P < 0.0001) in u-GH levels were shown at B2 for females and at G3 for males. A slight decline was evident at 14 years. In obese children, median u-GH concentrations were significantly lower than those recorded in normal children of prepubertal age and at all stages of puberty (except in females at B2), in spite of their comparable normal height. u-GH levels significantly increased at puberty also in obese children, although the pubertal rise was significantly (P < 0.001) lower (1.7-fold in both sexes) than that observed in normal children (2.5-fold in boys and 2.3-fold in girls). A multiple regression analysis showed that both chronological age (beta: 0.20), BMI (beta: - 0.11), gender (beta: - 0.04) and pubertal stage (beta: 0.25) contributed significantly to the physiological variation in u-GH levels (multiple R: 0.44, P < 0.00001). CONCLUSIONS: This study provides reference values for u-GH in normally growing non-obese and obese children, analysing the impact of gender, puberty and body mass on this parameter. In agreement with previous studies, which demonstrate blunted GH-responses to provocative stimuli and reduced nocturnal GH concentration, obese children have significantly lower u-GH levels than age-matched normal weight children, both before and during puberty.