Background: Changes and relationships of components of the cytokine and IGF systems have been sho... more Background: Changes and relationships of components of the cytokine and IGF systems have been shown in placenta and cord serum of fetal growth restricted (FGR) compared with normal newborns (AGA). This study aimed to analyse a data set of clinical and biochemical data in FGR and AGA newborns to assess if a mathematical model existed and was capable of identifying these two different conditions in order to identify the variables which had a mathematically consistent biological relevance to fetal growth.
Growth hormone ( G H ) pltultary reserve and magnetlc resonance imaqlng (MRI) flndinqs were studl... more Growth hormone ( G H ) pltultary reserve and magnetlc resonance imaqlng (MRI) flndinqs were studled in 22 short prepubertal slow growing c h~l d r e n (aged 6-11 yrs: males 1 4 ) . W e assessed GH r e s~o n s e s to a comblned adminlstrat~on of arqlnlne 10.5qIkql ~l u s GH-ieleaslng hormone (GHRH.lvg/kq) ( A~~~C H R H t e s t ) and.' mean spontaneous nocturnal G H secretlon (MGHC, normal=>3 nqlmll. Subjects were div~ded lhto 3 groups, comparable In ages, hilghts and growth rates: group I . 5 GH d e f~c~e n t c h~l d r e n , wlth reduced GH pltultary reserve (ArgtGtlRH GH peaks:<20 ngjml; meantSE values=8.4'0.8 ngjml) and low MGHC (2'0.2 ngjml); group 11, 9 GH d e f i c~e n t patlents, wlth normal G H pltultary reserve ((ArgtGHRH GH peaks= >20 nqlml; 58.327.9 ngjml) and low MGHC (1.9t0.3 ngjml); group 111. 8 slow growing chlldren, wlth normal GH.pitultary reserve (ArgtGHRH peak: 51.1113.2 ngjml) and normal MGHC (5.410.8 ngjml). MRI examlnatlon was performed to measure height, width, lenght and volumes of the pltultary gland. Results. All chlldren showed a normal pitultary anatomy wlthout stalk Interruptlon; mean gland measurements were not significantly different between the 3 groups (helght: 2.7?0.5, 3.5t0.3. 3.110.3 mm in groups I . 11. 111. respectlvely; volumes: 111.6 t 32. 124.5 1 15 and 126.3 t 20 m J . respectlvely). These data show that in subjects with normal pituitary anatomy and Intact stalk the GH pltultary reserve 1s not correlated w~t h magnetlc resonance imaglng f~n d l n g s .
The occurrence of circulating antibodies (IgG) against oxidatively modified LDL was investigated ... more The occurrence of circulating antibodies (IgG) against oxidatively modified LDL was investigated in a group of normocholesterolemic, healthy, cardiovascular risk-free children and in a comparable group of normal adults. An increased titer of IgG recognizing Cu++-oxidized or malondialdehyde (MDA)-derivatized LDL (MDA-LDL) was a constant feature in children. The antigenic epitopes recognized by these antibodies were generated rather late in the process of copper-mediated LDL oxidation, concomitantly with the formation of fluorescent adducts between reactive aldehydes (including MDA) and apo B100. MDA-LDL was not the only antigen recognized: derivatization of other structurally unrelated proteins, such as HDL, serum albumin, fibrinogen, and transferrin with MDA led to generation of recognizable epitopes. However, among the various modified proteins, LDL exhibited the highest binding activity for IgG present in the group of children. This was associated with an enhanced propensity of LDL isolated from children to undergo in vitro oxidation, despite normal levels of the endogenous antioxidant alpha-tocopherol. These findings indicate that circulating antibodies recognizing proteins modified with end-products of lipid peroxidation (including LDL) are present in healthy cardiovascular risk-free children. The possibility that LDL oxidation occurs in vivo already in childhood and may act as the real immunogen is an attractive but still unproven hypothesis.
To assess whether the quantitative and qualitative aspects of cortisol, 17-hydroxyprogesterone (1... more To assess whether the quantitative and qualitative aspects of cortisol, 17-hydroxyprogesterone (17-OHP), and androstenedione (D4A) secretion in patients with nonclassic congenital adrenal hyperplasia (NCCAH) differ from those in normal children, 24-hour serum concentrations of these steroids were measured in five prepubertal patients with NCCAH and five normal prepubertal children. Adrenal steroid profiles obtained by 30-minute sampling were analyzed by the Pulsar program. In comparison to normal children, the 24-hour quantitative parameters of 17-OHP and D4A secretion were significantly greater in NCCAH patients, but serum cortisol concentrations were similar in the two groups. When daytime and nighttime hormone releases were separately analyzed, a significant nocturnal elevation of the cortisol area under the curve above zero level (AUCo) and 12-hour mean and 17-OHP AUCo, AUC above baseline, mean peak height, amplitude, area, and 12-hour mean was detected in normal subjects only. Conversely, NCCAH patients exhibited an increased frequency and number of 17-OHP secretory peaks at night together with a reduction of the interpeak interval. No significant day/night differences in D4A concentrations were detected either in normals or in the patients. In conclusion, the results of the present study indicate that patients with NCCAH have a distinct pattern of adrenal steroid secretion characterized by a high-frequency 17-OHP release accompanied by a relative nocturnal cortisol deficiency.
We evaluated the 12 month growth of 18 pubertal children with familial short stature randomly ass... more We evaluated the 12 month growth of 18 pubertal children with familial short stature randomly assigned to clinical follow-up (group A), GH treatment alone (group B) and GH+LHRH analogue (LHRHa) treatment (group C). Height velocity increased significantly compared to baseline in groups A and B (4.7 +/- 0.4 vs 6.6 +/- 0.6 and 4.4 +/- 0.3 vs 8 +/- 1 respectively), but not in C (5 +/- 0.5 vs 6.5 +/- 0.4). Moreover in group B height and height prognosis standard deviation score SDS) also were higher (-2.2 +/- 0.2 vs -1.7 +/- 0.2 and 1.8 +/- 0.3 vs -1 +/- 0.2, respectively). Comparisons among the groups showed a significant increase in group B vs the other groups of height velocity SDS (3.9 +/- 1.3 vs 0.4 + 1 and 0.3 +/- 0.7) and of height prognosis SDS (-1 +/- 0.2 vs -2.4 +/- 0.3 and -2.4 +/- 0.3). In conclusion, after one-year treatment, GH seems to be more effective in stimulating growth than GH +/- LHRHa, even if studies of longer duration and/or follow-up are needed.
To define the role of somatostatin and dopamine in TSH suppression induced by L-thyroxine, 16 chi... more To define the role of somatostatin and dopamine in TSH suppression induced by L-thyroxine, 16 children (12 F, 4 M) on suppressive doses of L-thyroxine (3-4 microg/kg/day) for endemic goiter were studied. Firstly a conventional TRH test was performed in all subjects, in order to evaluate TSH, PRL and GH (basal study). A week later a second TRH test was carried out; one hour before the test, however, group A (9 patients) was given 60 mg pyridostigmine bromide po (pyridostigmine study) and group B (7 patients) 10 mg metoclopramide po (metoclopramide study). In the basal study, TSH was suppressed in both groups and levels did not increase following TRH administration, while PRL increased significantly and GH levels remained stable. In the pyridostigmine study, TSH levels did not increase following TRH administration, while PRL and GH levels were both significantly raised. In the metoclopramide study, TSH and GH levels were not raised following TRH administration, while a significantly greater increase of PRL was observed. In conclusion, suppressive doses of L-thyroxine inhibit the TSH response to TRH, while they do not seem to affect GH and PRL secretion. Somatostatin and/or dopamine do not seem to play a significant role in the L-thyroxine-induced TSH suppression.
We report on a survey carried out in 65 pediatric and adult endocrinological centers concerning: ... more We report on a survey carried out in 65 pediatric and adult endocrinological centers concerning: 1) the modalities of the transfer of children with chronic endocrine diseases from pediatricians to adult endocrinologists, 2) opinions and suggestions from physicians of the Centers, and 3) specific details regarding GH deficiency. The main results are: 1) The mean age of transfer is around 18 yr of age. 2) The reasons for the transfer are personal convincement of pediatricians in 47%, administrative reasons in 37% and patient&#39;s desire in 16% of cases 3) In the majority of cases a discharge summary is sent by the pediatrician to the endocrinologist often followed by a phone call, whereas 30% of endocrinologists do not send a report back to pediatricians. 4) Less than half of the Centers are satisfied with the modalities of the transfer and the remainder complain about the lack of communication, no common guidelines, and differences in the management of patients. However, all are willing to try to improve this important time for adolescents with chronic diseases. 5) As far as GH deficiency is concerned, the main differences between pediatric and adult endocrinological centers are the different tests used to re-evaluate the diagnosis and the higher doses of GH used by pediatricians to treat young adults. In conclusion, considering the interest and desire of physicians, a structural intervention of the scientific societies to help to overcome problems is highly desirable.
Growth hormone-releasing peptide 6 (GHRP-6) is a synthetic hexapeptide with a potent GH-releasing... more Growth hormone-releasing peptide 6 (GHRP-6) is a synthetic hexapeptide with a potent GH-releasing activity after intravenous, subcutaneous, intranasal and oral administration in man. Previous data showed its activity also in some patients with GH deficiency. The aim of our study was to verify the GH-releasing activity of oral GHRP-6 administration on GH secretion in children with normal short stature. The effect of oral GHRP-6 (300 micrograms/kg) was compared with that of the maximally effective dose of intravenous GH-releasing hormone (GHRH-29, 1 microgram/kg). As the GHRH-induced GH rise in children is potentiated by arginine (ARG), even when administered by oral route at low dose (4 g), we studied also the interaction of oral GHRP-6 and ARG administration. We studied 13 children (nine boys and four girls aged 6.2-10.5 years, pubertal stage I) with normal short stature (height less than -2 SD score; height velocity more than -2 SD score; normal bone age; insulin-like growth factor I &gt; 70 micrograms/l). In a first group of children (N = 7), oral GHRP-6 administration induced a GH response (mean +/- SEM; peak at 60 min vs baseline: 18.8 +/- 3.0 vs 1.1 +/- 0.3 micrograms/l, p &lt; 0.0006; area under curve: 1527.3 +/- 263.9 micrograms l-1 h-1) which was similar to that elicited by GHRH (peak at 45 min vs baseline: 20.8 +/- 4.5 vs 2.2 +/- 0.9 micrograms/l, p &lt; 0.007; area under curve: 1429.4 +/- 248.2 micrograms l-1 h-1).(ABSTRACT TRUNCATED AT 250 WORDS)
Aim: To compare the results of ultrasound and computed peripheral tomography in evaluating bone m... more Aim: To compare the results of ultrasound and computed peripheral tomography in evaluating bone mass in a population of normal children. Methods: Seven hundred and twenty-six healthy school children (260 males; age 8.3-20.9 y) underwent calcaneous ultrasound and peripheral computed tomography at the ultradistal radius. Broadband ultrasound attenuation (BUA) and areal and volumetric bone mineral density (aBMD and vBMD) were evaluated. The results were compared and correlated among them and with auxological parameters (height, BMI and pubertal stages) using the software package SPSS for Windows. Results: The three variables examined (BUA, aBMD and vBMD) all showed a progressive increase with age and a positive correlation with age, height and BMI. When the population was subdivided according to pubertal stages, all variables showed a progressive increase, the difference being significant when stages 1-2 were compared with stages 4-5. A significant correlation was present among BUA, aBMD and vBMD even if the Pearson correlation coefficient was not high.
Background: Changes and relationships of components of the cytokine and IGF systems have been sho... more Background: Changes and relationships of components of the cytokine and IGF systems have been shown in placenta and cord serum of fetal growth restricted (FGR) compared with normal newborns (AGA). This study aimed to analyse a data set of clinical and biochemical data in FGR and AGA newborns to assess if a mathematical model existed and was capable of identifying these two different conditions in order to identify the variables which had a mathematically consistent biological relevance to fetal growth.
Growth hormone ( G H ) pltultary reserve and magnetlc resonance imaqlng (MRI) flndinqs were studl... more Growth hormone ( G H ) pltultary reserve and magnetlc resonance imaqlng (MRI) flndinqs were studled in 22 short prepubertal slow growing c h~l d r e n (aged 6-11 yrs: males 1 4 ) . W e assessed GH r e s~o n s e s to a comblned adminlstrat~on of arqlnlne 10.5qIkql ~l u s GH-ieleaslng hormone (GHRH.lvg/kq) ( A~~~C H R H t e s t ) and.' mean spontaneous nocturnal G H secretlon (MGHC, normal=>3 nqlmll. Subjects were div~ded lhto 3 groups, comparable In ages, hilghts and growth rates: group I . 5 GH d e f~c~e n t c h~l d r e n , wlth reduced GH pltultary reserve (ArgtGtlRH GH peaks:<20 ngjml; meantSE values=8.4'0.8 ngjml) and low MGHC (2'0.2 ngjml); group 11, 9 GH d e f i c~e n t patlents, wlth normal G H pltultary reserve ((ArgtGHRH GH peaks= >20 nqlml; 58.327.9 ngjml) and low MGHC (1.9t0.3 ngjml); group 111. 8 slow growing chlldren, wlth normal GH.pitultary reserve (ArgtGHRH peak: 51.1113.2 ngjml) and normal MGHC (5.410.8 ngjml). MRI examlnatlon was performed to measure height, width, lenght and volumes of the pltultary gland. Results. All chlldren showed a normal pitultary anatomy wlthout stalk Interruptlon; mean gland measurements were not significantly different between the 3 groups (helght: 2.7?0.5, 3.5t0.3. 3.110.3 mm in groups I . 11. 111. respectlvely; volumes: 111.6 t 32. 124.5 1 15 and 126.3 t 20 m J . respectlvely). These data show that in subjects with normal pituitary anatomy and Intact stalk the GH pltultary reserve 1s not correlated w~t h magnetlc resonance imaglng f~n d l n g s .
The occurrence of circulating antibodies (IgG) against oxidatively modified LDL was investigated ... more The occurrence of circulating antibodies (IgG) against oxidatively modified LDL was investigated in a group of normocholesterolemic, healthy, cardiovascular risk-free children and in a comparable group of normal adults. An increased titer of IgG recognizing Cu++-oxidized or malondialdehyde (MDA)-derivatized LDL (MDA-LDL) was a constant feature in children. The antigenic epitopes recognized by these antibodies were generated rather late in the process of copper-mediated LDL oxidation, concomitantly with the formation of fluorescent adducts between reactive aldehydes (including MDA) and apo B100. MDA-LDL was not the only antigen recognized: derivatization of other structurally unrelated proteins, such as HDL, serum albumin, fibrinogen, and transferrin with MDA led to generation of recognizable epitopes. However, among the various modified proteins, LDL exhibited the highest binding activity for IgG present in the group of children. This was associated with an enhanced propensity of LDL isolated from children to undergo in vitro oxidation, despite normal levels of the endogenous antioxidant alpha-tocopherol. These findings indicate that circulating antibodies recognizing proteins modified with end-products of lipid peroxidation (including LDL) are present in healthy cardiovascular risk-free children. The possibility that LDL oxidation occurs in vivo already in childhood and may act as the real immunogen is an attractive but still unproven hypothesis.
To assess whether the quantitative and qualitative aspects of cortisol, 17-hydroxyprogesterone (1... more To assess whether the quantitative and qualitative aspects of cortisol, 17-hydroxyprogesterone (17-OHP), and androstenedione (D4A) secretion in patients with nonclassic congenital adrenal hyperplasia (NCCAH) differ from those in normal children, 24-hour serum concentrations of these steroids were measured in five prepubertal patients with NCCAH and five normal prepubertal children. Adrenal steroid profiles obtained by 30-minute sampling were analyzed by the Pulsar program. In comparison to normal children, the 24-hour quantitative parameters of 17-OHP and D4A secretion were significantly greater in NCCAH patients, but serum cortisol concentrations were similar in the two groups. When daytime and nighttime hormone releases were separately analyzed, a significant nocturnal elevation of the cortisol area under the curve above zero level (AUCo) and 12-hour mean and 17-OHP AUCo, AUC above baseline, mean peak height, amplitude, area, and 12-hour mean was detected in normal subjects only. Conversely, NCCAH patients exhibited an increased frequency and number of 17-OHP secretory peaks at night together with a reduction of the interpeak interval. No significant day/night differences in D4A concentrations were detected either in normals or in the patients. In conclusion, the results of the present study indicate that patients with NCCAH have a distinct pattern of adrenal steroid secretion characterized by a high-frequency 17-OHP release accompanied by a relative nocturnal cortisol deficiency.
We evaluated the 12 month growth of 18 pubertal children with familial short stature randomly ass... more We evaluated the 12 month growth of 18 pubertal children with familial short stature randomly assigned to clinical follow-up (group A), GH treatment alone (group B) and GH+LHRH analogue (LHRHa) treatment (group C). Height velocity increased significantly compared to baseline in groups A and B (4.7 +/- 0.4 vs 6.6 +/- 0.6 and 4.4 +/- 0.3 vs 8 +/- 1 respectively), but not in C (5 +/- 0.5 vs 6.5 +/- 0.4). Moreover in group B height and height prognosis standard deviation score SDS) also were higher (-2.2 +/- 0.2 vs -1.7 +/- 0.2 and 1.8 +/- 0.3 vs -1 +/- 0.2, respectively). Comparisons among the groups showed a significant increase in group B vs the other groups of height velocity SDS (3.9 +/- 1.3 vs 0.4 + 1 and 0.3 +/- 0.7) and of height prognosis SDS (-1 +/- 0.2 vs -2.4 +/- 0.3 and -2.4 +/- 0.3). In conclusion, after one-year treatment, GH seems to be more effective in stimulating growth than GH +/- LHRHa, even if studies of longer duration and/or follow-up are needed.
To define the role of somatostatin and dopamine in TSH suppression induced by L-thyroxine, 16 chi... more To define the role of somatostatin and dopamine in TSH suppression induced by L-thyroxine, 16 children (12 F, 4 M) on suppressive doses of L-thyroxine (3-4 microg/kg/day) for endemic goiter were studied. Firstly a conventional TRH test was performed in all subjects, in order to evaluate TSH, PRL and GH (basal study). A week later a second TRH test was carried out; one hour before the test, however, group A (9 patients) was given 60 mg pyridostigmine bromide po (pyridostigmine study) and group B (7 patients) 10 mg metoclopramide po (metoclopramide study). In the basal study, TSH was suppressed in both groups and levels did not increase following TRH administration, while PRL increased significantly and GH levels remained stable. In the pyridostigmine study, TSH levels did not increase following TRH administration, while PRL and GH levels were both significantly raised. In the metoclopramide study, TSH and GH levels were not raised following TRH administration, while a significantly greater increase of PRL was observed. In conclusion, suppressive doses of L-thyroxine inhibit the TSH response to TRH, while they do not seem to affect GH and PRL secretion. Somatostatin and/or dopamine do not seem to play a significant role in the L-thyroxine-induced TSH suppression.
We report on a survey carried out in 65 pediatric and adult endocrinological centers concerning: ... more We report on a survey carried out in 65 pediatric and adult endocrinological centers concerning: 1) the modalities of the transfer of children with chronic endocrine diseases from pediatricians to adult endocrinologists, 2) opinions and suggestions from physicians of the Centers, and 3) specific details regarding GH deficiency. The main results are: 1) The mean age of transfer is around 18 yr of age. 2) The reasons for the transfer are personal convincement of pediatricians in 47%, administrative reasons in 37% and patient&#39;s desire in 16% of cases 3) In the majority of cases a discharge summary is sent by the pediatrician to the endocrinologist often followed by a phone call, whereas 30% of endocrinologists do not send a report back to pediatricians. 4) Less than half of the Centers are satisfied with the modalities of the transfer and the remainder complain about the lack of communication, no common guidelines, and differences in the management of patients. However, all are willing to try to improve this important time for adolescents with chronic diseases. 5) As far as GH deficiency is concerned, the main differences between pediatric and adult endocrinological centers are the different tests used to re-evaluate the diagnosis and the higher doses of GH used by pediatricians to treat young adults. In conclusion, considering the interest and desire of physicians, a structural intervention of the scientific societies to help to overcome problems is highly desirable.
Growth hormone-releasing peptide 6 (GHRP-6) is a synthetic hexapeptide with a potent GH-releasing... more Growth hormone-releasing peptide 6 (GHRP-6) is a synthetic hexapeptide with a potent GH-releasing activity after intravenous, subcutaneous, intranasal and oral administration in man. Previous data showed its activity also in some patients with GH deficiency. The aim of our study was to verify the GH-releasing activity of oral GHRP-6 administration on GH secretion in children with normal short stature. The effect of oral GHRP-6 (300 micrograms/kg) was compared with that of the maximally effective dose of intravenous GH-releasing hormone (GHRH-29, 1 microgram/kg). As the GHRH-induced GH rise in children is potentiated by arginine (ARG), even when administered by oral route at low dose (4 g), we studied also the interaction of oral GHRP-6 and ARG administration. We studied 13 children (nine boys and four girls aged 6.2-10.5 years, pubertal stage I) with normal short stature (height less than -2 SD score; height velocity more than -2 SD score; normal bone age; insulin-like growth factor I &gt; 70 micrograms/l). In a first group of children (N = 7), oral GHRP-6 administration induced a GH response (mean +/- SEM; peak at 60 min vs baseline: 18.8 +/- 3.0 vs 1.1 +/- 0.3 micrograms/l, p &lt; 0.0006; area under curve: 1527.3 +/- 263.9 micrograms l-1 h-1) which was similar to that elicited by GHRH (peak at 45 min vs baseline: 20.8 +/- 4.5 vs 2.2 +/- 0.9 micrograms/l, p &lt; 0.007; area under curve: 1429.4 +/- 248.2 micrograms l-1 h-1).(ABSTRACT TRUNCATED AT 250 WORDS)
Aim: To compare the results of ultrasound and computed peripheral tomography in evaluating bone m... more Aim: To compare the results of ultrasound and computed peripheral tomography in evaluating bone mass in a population of normal children. Methods: Seven hundred and twenty-six healthy school children (260 males; age 8.3-20.9 y) underwent calcaneous ultrasound and peripheral computed tomography at the ultradistal radius. Broadband ultrasound attenuation (BUA) and areal and volumetric bone mineral density (aBMD and vBMD) were evaluated. The results were compared and correlated among them and with auxological parameters (height, BMI and pubertal stages) using the software package SPSS for Windows. Results: The three variables examined (BUA, aBMD and vBMD) all showed a progressive increase with age and a positive correlation with age, height and BMI. When the population was subdivided according to pubertal stages, all variables showed a progressive increase, the difference being significant when stages 1-2 were compared with stages 4-5. A significant correlation was present among BUA, aBMD and vBMD even if the Pearson correlation coefficient was not high.
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Papers by C. Volta