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1.
J Endocrinol Invest ; 34(6): e126-30, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21042043

ABSTRACT

BACKGROUND: GH therapy response varies substantially among patients. Several models were developed to predict the efficacy of GH therapy in children. AIM: To evaluate the accuracy of a growth prediction model using data from an Italian pediatric GH deficiency (GHD) cohort (GeNeSIS, Growth Prediction Sub-study). METHODS: Open-label, multicenter study in 22 Italian pre-pubertal GH treatment- naïve patients with GHD (8 female, 14 male, 0.5 to 12.2 yr), 18 isolated GHD, 4 multiple pituitary hormone deficiency given recombinat human GH therapy (0.025-0.035 mg/kg/day) for 12 months. Growth prediction was performed, after 3 months of treatment, using baseline data [bone age (BA) and IGF-I], a urinary marker of bone turnover [deoxypyridinoline crosslinks (DPD)] at 4 weeks, and height velocity (HV) at 3 months. Results were expressed as 1st-yr HV using the following equation: 1-yr HV (cm) = 3.543 - (2.337 × BA) - (0.010 × IGF-I) + (0.100 × DPD) + (0.299 × 3-month HV). Predictions were compared to the 1st-yr HV and accuracy was calculated as percentage of the difference between mean calculated HV and the real 1st-yr HV. RESULTS: For females predicted HV was 12.98 ± 4.82 cm/yr and actually was 13.05 ± 3.91 cm/yr after the 1st year; for males predicted HV was 13.95 ± 5.39 cm/yr and actually was 12.93 ± 5.02 cm/yr. CONCLUSIONS: In this paediatric Italian cohort with GHD, a growth prediction model seems to be a valid tool to assess 1st-yr response to GH treatment in Italian children.


Subject(s)
Body Height , Growth Disorders/drug therapy , Human Growth Hormone/deficiency , Human Growth Hormone/therapeutic use , Adolescent , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Male , Prognosis , Prospective Studies , Puberty
2.
J Pediatr Endocrinol Metab ; 14 Suppl 1: 611-7, 2001.
Article in English | MEDLINE | ID: mdl-11393552

ABSTRACT

Maturity Onset Diabetes of the Young (MODY) is an autosomal dominant monogenic form of type 2 diabetes mellitus (DM) representing 5% of youth-onset DM in the Caucasian population. In young adults the disease can be present as either non-insulin dependent or insulin-dependent DM. The diagnosis of this genetic disorder in children and adolescents is rare because of the mild glucose metabolism disorder at this time. We performed a metabolic, autoimmune and genetic study in 40 offspring of young parents affected by insulin-dependent DM (Group A) and in 35 offspring of young parents affected by early-onset non-insulin-dependent DM (Group B). Two children of Group A (5%) were found to be affected by fasting hyperglycemia and carry a GCK gene mutation that in one case was present also in the diabetic father. Eighteen offspring of Group B (51%) were positive for GCK or HNF-1alpha gene mutations present in the affected parents. All but two of these young patients had impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). Eleven of them were younger than 16 years. We conclude that screening for DM in youth should be extended to MODY in young families with both non-insulin-dependent and insulin-dependent DM. The sensitivity of the metabolic tests will precede the genetic diagnosis.


Subject(s)
DNA-Binding Proteins , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/genetics , Nuclear Proteins , Adolescent , Blood Glucose/analysis , Child , Child, Preschool , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Fasting/blood , Glucokinase/genetics , Glucose Intolerance/etiology , Hepatocyte Nuclear Factor 1 , Hepatocyte Nuclear Factor 1-alpha , Hepatocyte Nuclear Factor 1-beta , Humans , Hyperglycemia , Mutation , Parents , Transcription Factors/genetics
3.
J Pediatr Endocrinol Metab ; 12(4): 487-97, 1999.
Article in English | MEDLINE | ID: mdl-10417964

ABSTRACT

The differential diagnosis of hyperglycemia in childhood and adolescence has to take into consideration early-onset non-insulin-dependent diabetes, defined as maturity onset diabetes of the young (MODY). To date, mutations in genes of five proteins have been shown to cause MODY: glucokinase (MODY2), hepatic nuclear factor-1 alpha (HNF-1 alpha) (MODY3), hepatic nuclear factor-4 alpha (HNF-4 alpha) (MODY1), insulin promoter factor 1 (IPF-1) (MODY4) and hepatic nuclear factor-1 beta (HNF-1 beta) (MODY5), but other MODY genes still await elucidation. Clinical and metabolic heterogeneity of these subtypes of type 2 diabetes need to be defined, as deficiency of each factor has its own phenotype. Pediatric diabetologists should be aware of the increasing importance of MODY as a possible cause of hyperglycemia in children and adolescents. This will allow for the early diagnosis of these metabolic conditions and for the appropriate follow-up and treatment.


Subject(s)
DNA-Binding Proteins , Diabetes Mellitus, Type 2 , Homeodomain Proteins , Nuclear Proteins , Pediatrics , Adolescent , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors , Child , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/immunology , Glucokinase/genetics , Hepatocyte Nuclear Factor 1 , Hepatocyte Nuclear Factor 1-alpha , Hepatocyte Nuclear Factor 1-beta , Hepatocyte Nuclear Factor 4 , Humans , Insulin/metabolism , Insulin/pharmacology , Insulin Secretion , Mutation , Phosphoproteins/genetics , Trans-Activators/genetics , Transcription Factors/genetics
4.
J Endocrinol Invest ; 21(8): 494-500, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9801989

ABSTRACT

GH-releasing peptides (GHRPs) and their non-peptidly mimetics are synthetic molecules which possess marked, dose-related and reproducible GH-releasing effect even after oral administration. Their potent stimulatory effect on GH secretion suggested that GHRP could be useful as provocative test on the diagnosis of GH deficiency. We compared the GH response to the maximal effective dose of Hexarelin (2 micrograms/kg i.v.), an hexapeptide belonging to GHRP family, with that of GHRH (1 microgram/kg i.v.) alone and combined with arginine (ARG, 0.5 g/kg i.v.), which likely acts via inhibition of hypothalamic somatostatin release. We studied 6 prepubertal (4 boys and 2 girls, age 2.6-12.2 yr) and 6 pubertal children with normal short stature (3 boys and 3 girls, age 10.3-14.4 yr) as well as 12 normal young adults (6 males and 6 females, age 22-30 yr) and 12 normal elderly subjects (6 males and 6 females, age 53-79 yr). In prepubertal children, the GH response to HEX (19.0 +/- 4.6 micrograms/l; 611.5 +/- 121.4 micrograms/l/h) was lower than that to GHRH (27.4 +/- 12.7 micrograms/l; 1209.0 +/- 590.9 micrograms/l/h) but this difference did not attain statistical significance. Both these responses were, in turn, lower (p < 0.05) than that to ARG + GHRH (57.9 +/- 15.1 micrograms/l; 2483.6 +/- 696.6 micrograms/l/h). In pubertal children, the GH response to HEX (67.6 +/- 12.7 micrograms/l; 2755.3 +/- 547.3 micrograms/l/h) was higher than that to ARG + GHRH (49.1 +/- 8.9 micrograms/l; 2554.1 +/- 356.6 micrograms/l/h) but this difference did not attain statistical significance; both these responses were, in turn, clearly higher (p < 0.05) than that to GHRH alone (23.1 +/- 7.9 micrograms/l; 1004.8 +/- 214.3 micrograms/l/h). In young adults, the GH response to HEX 60.9 +/- 8.0 micrograms/l; 2401.0 +/- 376.2 micrograms/l/h) was similar to that to ARG + GHRH (68.9 +/- 11.7 micrograms/l; 3035.7 +/- 466.6 micrograms/l/h) and both were clearly higher (p < 0.001) than that to GHRH alone (21.6 +/- 3.6 micrograms/l; 790.0 +/- 137.0 micrograms/l/h). In elderly subjects, the GH response to HEX (22.4 +/- 4.9; 855.0 +/- 199.0 micrograms/l/h) was higher (p < 0.01) than that to GHRH (3.6 +/- 0.8 micrograms/l; 151.8 +/- 24.6 micrograms/l/h) but lower (p < 0.05) than that to ARG + GHRH (48.1 +/- 4.6 micrograms/l; 1758.2 +/- 149.1 micrograms/l/h). In conclusion, GHRPs are a powerful stimulus of GH secretion in pubertal children and young adults only. On the other hand, the age-related variations in the GH response to GHRPs probably limit their reliability for the evaluation of GH releasable pool in prepubertal children and elderly subjects.


Subject(s)
Aging , Human Growth Hormone/metabolism , Oligopeptides , Puberty , Adolescent , Adult , Aged , Arginine/administration & dosage , Child , Child, Preschool , Female , Growth Hormone-Releasing Hormone/administration & dosage , Growth Substances , Humans , Male , Middle Aged , Oligopeptides/administration & dosage , Oligopeptides/adverse effects
5.
J Pediatr Endocrinol Metab ; 10(5): 491-7, 1997.
Article in English | MEDLINE | ID: mdl-9401905

ABSTRACT

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.


Subject(s)
Aging , Human Growth Hormone/metabolism , Oligopeptides/pharmacology , Adolescent , Adult , Child , Female , Growth Hormone-Releasing Hormone/adverse effects , Growth Hormone-Releasing Hormone/pharmacology , Growth Substances/pharmacology , Humans , Infant, Newborn , Insulin-Like Growth Factor I/metabolism , Male , Oligopeptides/adverse effects
6.
Clin Endocrinol (Oxf) ; 47(1): 61-4, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9302373

ABSTRACT

OBJECTIVE: It is widely accepted that arginine is a potent GH secretagogue in man, probably acting via inhibition of hypothalamic somatostatin release. Although many other amino acids are known to stimulate GH secretion, their effects and mechanisms of action have not been extensively studied in humans. The aim of the present study was to clarify the effect, if any, of methionine (MET) on GH secretion in children with normal short stature (normal height velocity and IGF-1 > 100 micrograms/l). DESIGN: We studied the effect of MET (0.2 g/kg intravenously (i.v.) over 30 min) on both basal and GHRH (1 microgram/kg i.v. at 0 min)-induced GH secretion (group A) comparing its effect with that of arginine (ARG) at low and classical doses 0.2 and 0.5 g/kg i.v. over 30 min) (groups B and C). The effect of the combined administration of MET and ARG (0.5 g/kg i.v. over e0 min) (group D) on GH secretion was also studied. PATIENTS: Thirty-four children (20 male and 14 female, age 12.8-14.0 years), divided into four groups. MEASUREMENTS: Serum Gh was measured in duplicate by immunoradiometric assay. RESULTS: In group A, MET increased basal Gh levels (peak, mean +/- SEM 14.6 +/- 2.6 vs 2.6 +/- 0.6 mU/l; P < 0.01) and potentiated the GH response to 1 microgram/kg i.v. GHRH (78.0 +/- 17.6 vs 41.6 +/0 9.8 mU/I; P < 0.02). In group B, ARG (0.2 g/kg) increased basal GH levels (16.2 +/- 5.2 vs 2.4 +/- 0.6 mU/I; P < 0.03) and potentiated the GH response to GHRH (119.6 +/- 20.4 vs 48.8 +/- 14.2 mU/I; P < 0.01). In group C, ARG (0.5 g/kg) induced a clear GH rise (28.0 +/- 3.8 vs 2.0 +/- 0.6 mU/I; P < 0.001) and potentiated the GH response to GHRH (93.4 +/- 10.0 vs 34.2 +/- 4.6 mU/I; P < 0.001). The GH responses to MET and ARG alone in groups A and B were similar and lower than that to ARG in group C. The GH responses to MET or ARG combined with GHRH in groups A, B and C were similar. In group D MET failed to modify the GH response to 0.5 g/kg i.v. ARG (10.8 +/- 6.4 vs 9.6 +/- 6.0 mU/I). CONCLUSION: Methionine potentiates both basal and GHRH-induced Gh secretion in children as effectively as arginine. As methionine has no interaction with arginine, our data suggest that these amino acids act via a common mechanism.


Subject(s)
Growth Disorders/drug therapy , Growth Hormone-Releasing Hormone/therapeutic use , Growth Hormone/metabolism , Methionine/therapeutic use , Adolescent , Arginine/therapeutic use , Child , Drug Synergism , Drug Therapy, Combination , Female , Growth Disorders/blood , Growth Disorders/physiopathology , Growth Hormone/blood , Humans , Immunoradiometric Assay , Male
7.
Eur J Endocrinol ; 137(6): 635-42, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9437229

ABSTRACT

Hexarelin (HEX) is a synthetic growth hormone-releasing peptide (GHRP) which acts on specific receptors at both the pituitary and the hypothalamic level to stimulate GH release in an age-dependent manner. Like other GHRPs, HEX possesses also prolactin (PRL) and ACTH/cortisol-releasing activity. similar to that of human corticotropin-releasing hormone (hCRH). The mechanisms underlying the stimulatory effect of GHRPs on lactotrope and corticotrope secretion are even less clear and the influence of age on these endocrine activities of GHRPs is unknown. To clarify this point we studied the GH, PRL, ACTH and cortisol responses to the maximal effective dose of HEX (2.0 micrograms/kg i.v.) in: 12 prepubertal children (Pre-C, 8 male, 4 female, age 5.8-12.1 years); 12 pubertal normal short children (Pub-C, 5 male, 7 female, age 9.7-15.5 years, pubertal stage II-IV); 20 normal young adults (Young, 6 males, 14 females, age 23-32 years); and in 16 normal elderly people (Elderly, 5 male, 11 female, age 66-81 years). The GH response to HEX was clear in Pre-C (0-120 min area under curve, mean +/- S.E.M. 769.5 +/- 122.2 micrograms*min/l) but strikingly increased (P < 0.001) in Pub-C (1960.2 +/- 283.5 micrograms*min/l). The HEX-induced GH rise in Young (1829.7 +/- 243.1 micrograms*min/l) persisted similar to that in Pub-C, but decreased in Elderly (951.1 +/- 232.9 micrograms*min/I, P < 0.005); the latter was, in turn, similar to that in Pre-C. HEX induced a significant PRL increase which, however, showed no age-related variations, being similar in Pre-C (512.1 +/- 88.0 micrograms*min/l), Pub-C (584.0 +/- 106.0 micrograms*min/l), Young (554.9 +/- 56.0 micrograms*min/l) and Elderly (523.9 +/- 59.6 micrograms*min/l). The ACTH-releasing activity of HEX was present in Pre-C (1356.6 +/- 204.9 pg*min/ml) and was clearly enhanced (P < 0.02) in Pub-C (2253.5 +/- 242.8 pg*min/ml). The ACTH rise after HEX in Young (1258.1 +/- 141.2pg*min/ml) was lower (P < 0.02) than that in Pub-C and similar to that in Pre-C, while the ACTH response to HEX in Elderly (1786.5 +/- 340.1 pg*min/ml) showed a further trend toward increase, being similar to that in Pub-C. On the other hand, the cortisol response to HEX showed no significant age-related variations, being not different in Pre-C (7747.2 +/- 1031.6 micrograms*min/l), Pub-C (6106.0 +/- 862.9 micrograms*min/l), Young (6827.5 +/- 509.6 micrograms*min/I) and Elderly (7950.6 +/- 658.3 micrograms*min/l). In conclusion, our present data demonstrate that in humans the GH- and ACTH-releasing activities of HEX undergo different age-related variations, while its PRL-releasing activity is not dependent on age. These finding suggest that actions at different levels and/or on different receptor subtypes mediate the different age-related hormonal effects of GHRPs.


Subject(s)
Adrenocorticotropic Hormone/metabolism , Growth Hormone-Releasing Hormone/administration & dosage , Human Growth Hormone/metabolism , Hydrocortisone/metabolism , Oligopeptides/administration & dosage , Prolactin/metabolism , Adolescent , Adult , Age Factors , Aged , Child , Female , Humans , Male , Secretory Rate/drug effects
8.
J Pediatr Endocrinol Metab ; 9(5): 523-31, 1996.
Article in English | MEDLINE | ID: mdl-8961128

ABSTRACT

Of the amino acids arginine is the most potent GH secretagogue in man. It potentiates the GH response to GHRH, exerts a weaker PRL-releasing effect, stimulates insulin and glucagon and induces a biphasic glucose variation. The potency and effects of other amino acids on pituitary and pancreatic hormones need to be clarified. In 43 children with normal short stature (5.3-14.0 yr; 30 M and 13 F) the effects of the infusion of phenylalanine (Phe, 0.08 g/kg), histidine (His, 0.1 g/kg), and leucine (Leu, 0.08 g/kg) on basal and GHRH-stimulated GH secretion and on PRL, insulin and glucose levels were studied and compared with those of arginine at high (hArg, 0.5 g/kg) or low dose (lArg, 0.2 g/kg). Phe increased basal (p < 0.05) but not GHRH-stimulated GH levels, induced PRL and insulin rises (p < 0.03 and p < 0.03), and did not change glycemia. Though a trend toward an increase in basal GH levels was found after His, His and Leu did not significantly modify either basal or GHRH-induced GH secretion nor basal PRL, insulin and glucose levels. Both hArg and lArg increased basal (p < 0.0001 and p < 0.05, respectively) and GHRH-stimulated GH levels (p < 0.006 and p < 0.006). hArg increased both PRL (p < 0.002) and insulin levels (p < 0.005) more (p < 0.0005 and p < 0.004) than lArg (p < 0.005 and p < 0.005), while glucose levels showed a similar increase followed by a similar decrease. We conclude that in childhood: a) Phe significantly increases GH secretion but, differently from Arg, does not potentiate the response to GHRH, suggesting different mechanisms of action of these amino acids; b) differently from His and Leu, Phe is a PRL and insulin secretagogue but is less potent than Arg; c) Arg has the highest stimulatory effect on pituitary and pancreatic hormones.


Subject(s)
Arginine/pharmacology , Growth Hormone-Releasing Hormone/pharmacology , Histidine/pharmacology , Human Growth Hormone/metabolism , Leucine/pharmacology , Phenylalanine/pharmacology , Adolescent , Arginine/adverse effects , Blood Glucose/metabolism , Body Height , Child , Child, Preschool , Drug Synergism , Female , Histidine/adverse effects , Humans , Insulin/blood , Leucine/adverse effects , Male , Phenylalanine/adverse effects , Prolactin/blood , Puberty
9.
J Clin Endocrinol Metab ; 81(9): 3323-7, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8784091

ABSTRACT

The reliability of provocative stimuli of GH secretion in the diagnosis of GH deficiency is still controversial. Until now, normative values of GH response to various stimuli have not been established properly. In 472 children and adolescents with normal stature (n = 295, height SDS range -1.5 to 1.2) or normal short stature (n = 177, height SDS range -3.7 to -1.8), we studied the GH response to physical exercise, insulin-induced hypoglycemia, arginine (ARG), clonidine, levodopa, glucagon, pyridostigmine (PD), GHRH, PD + GHRH, and ARG + GHRH. The peak GH responses (range) to various stimuli were: 1) physical exercise: 3.0-28.3 micrograms/L; 2) insulin-induced hypoglycemia: 2.7-46.4 micrograms/L; 3) ARG: 0.5-48.4 micrograms/L; 4) clonidine: 3.8-86.0 micrograms/L; 5) levodopa: 1.9-40.0 micrograms/L; 6) glucagon: 1.9-49.5 micrograms/L; 7) PD: 2.5-35.0 micrograms/L; 8) GHRH: 2.7-102.7 micrograms/L; 9)PD + GHRH: 19.6-106.0 micrograms/L; and 10) ARG + GHRH: 19.4-120.0 micrograms/L. Our results show that all conventional stimuli of GH secretion frequently failed to increase GH levels, showing values lower than that arbitrarily assumed, so far, as minimum normal GH peak, i.e. 7 or 10 micrograms/L. When combined with PD or ARG (substances inhibiting hypothalamic somatostatin release), GHRH becomes the most powerful test to explore the secretory capacity of somatotrope cells (the GH response being always higher than 19 micrograms/L). Therefore, only GHRH combined with PD or ARG may be able to clearly differentiate normal children from patients with GH deficiency, though a normal GH response to these tests cannot rule out the existence of GH hyposecretory state because of hypothalamic dysfunction.


Subject(s)
Growth Hormone/metabolism , Adolescent , Arginine , Child , Child, Preschool , Clonidine , Exercise/physiology , Female , Glucagon , Growth Hormone/deficiency , Growth Hormone-Releasing Hormone , Humans , Hypoglycemia , Insulin , Insulin-Like Growth Factor I/metabolism , Levodopa , Male , Pyridostigmine Bromide , Reproducibility of Results
10.
J Clin Endocrinol Metab ; 80(4): 1090-4, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7714074

ABSTRACT

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.


Subject(s)
Growth Hormone/metabolism , Oligopeptides/pharmacology , Puberty/metabolism , Adolescent , Child , Child, Preschool , Dose-Response Relationship, Drug , Female , Growth Substances/pharmacology , Humans , Male , Oligopeptides/adverse effects , Reproducibility of Results
11.
J Endocrinol Invest ; 17(11): 849-54, 1994 Dec.
Article in English | MEDLINE | ID: mdl-7745232

ABSTRACT

In order to verify the true GH-releasing effect of glucagon and to explain the mechanism underlying this effect, we studied the effect of glucagon (GLU, 1 mg) administered either iv or im on both basal and GHRH (1 microgram/kg)-induced GH rise in 48 normal short children and adolescents. Moreover, the in vitro effect of GLU on rat anterior pituitary cells was studied. Intravenous administration of GLU induced no significant GH rise. On the other hand, im GLU administration induced a clear-cut GH increase (mean +/- SE GH peak after GLU vs placebo = 25.7 +/- 3.9 vs 10.1 +/- 3.6 micrograms/L, p < 0.01). Intravenous administration of GLU failed to modify the GHRH-induced GH rise either when coadministered with the neurohormone (35.2 +/- 4.1 vs 34.1 +/- 6.0 micrograms/L) or when given 60 min earlier (20.2 +/- 5.8 vs 21.1 +/- 8.3 micrograms/L). Differently from iv GLU, im GLU strikingly potentiated the GH response to GHRH given 90 min later (57.5 +/- 6.3 vs 24.7 +/- 9.1 micrograms/L, p < 0.01). Mean plasma glucose levels increased 30 min after GLU, administered either iv or im, and returned to basal levels 60 min later. GH secretion from dispersed rat pituitary cells was unaffected by incubation with GLU (10(-10)-10(-4) mol/L). Incubation of the cells with 10(-7) mol/L GHRH induced instead a clear-cut stimulation of GH release. In conclusion, our data demonstrate that glucagon per se has not GH-releasing activity as indicated by its uneffectiveness to release GH in vitro and after intravenous administration.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Glucagon/pharmacology , Growth Hormone/metabolism , Pituitary Gland, Anterior/drug effects , Adolescent , Animals , Blood Glucose/analysis , Cells, Cultured , Child , Child, Preschool , Female , Glucagon/administration & dosage , Growth Hormone/blood , Humans , Infusions, Intravenous , Injections, Intramuscular , Male , Pituitary Gland, Anterior/cytology , Pituitary Gland, Anterior/metabolism , Rats , Time Factors
12.
Diabetes Care ; 17(5): 432-5, 1994 May.
Article in English | MEDLINE | ID: mdl-8062612

ABSTRACT

OBJECTIVE: To provide reliable data concerning the incidence of insulin-dependent diabetes mellitus (IDDM) in children from the Marche Region in Italy and contribute to a better understanding of its geographical variability throughout Italy and Europe. RESEARCH DESIGN AND METHODS: All newly diagnosed cases of IDDM in children 0-14 years of age in the Marche Region between 1 January 1990 and 31 December 1992 were recorded. The primary source of ascertainment was clinical records from the 59 hospitals of the region. Secondary and tertiary independent sources included local and national associations for diabetic children and local district centers of the National Health System. RESULTS: Over the 3-year study period, the overall IDDM incidence rate was 8.1 per 100,000/year. No significant sex-related difference in incidence was noted, with a male:female ratio of 0.9. The completeness of ascertainment was estimated at 100%. CONCLUSIONS: The Marche Region appears to have a slightly elevated incidence of IDDM among noninsular Italian regions.


Subject(s)
Diabetes Mellitus, Type 1/epidemiology , Adolescent , Age Factors , Child , Child, Preschool , Female , Geography , Humans , Incidence , Infant , Italy/epidemiology , Male , Sex Characteristics , Sex Factors
13.
J Endocrinol Invest ; 17(3): 189-93, 1994 Mar.
Article in English | MEDLINE | ID: mdl-8051341

ABSTRACT

To examine pulsatile TSH secretion, serum TSH was determined every 30 min for 24 h in eight short normal prepubertal children (3 males and 5 females, age 4.0-12.6 yr). All children exhibited a clear circadian pattern of TSH secretion. Pulsatile TSH secretion was identified in all subjects with a mean (+/- SD) TSH pulse frequency of 6.9 +/- 1.2 pulses/24 h. The group mean TSH pulse amplitude was 1.4 +/- 0.3 mU/L. Mean TSH concentration was higher during the night hours (2.1 +/- 0.8 mU/L) than during the day hours (1.3 +/- 0.4 mU/L, p < 0.005), and significantly more pulses were detected during the night (mean 4.7 +/- 1.4) than during the day hours (2.1 +/- 0.6, p < 0.005). On average, 62 to 68% of the peaks were detected in the night hours. Mean TSH pulse amplitude during the night hours was not significantly different from that during the day hours. Our findings indicate that, as previously shown in adults, a pulsatile pattern of TSH secretion is present in children. In our study group, the nocturnal TSH surge is associated with an increase in pulse frequency but not amplitude.


Subject(s)
Thyrotropin/metabolism , Child , Child, Preschool , Circadian Rhythm , Female , Humans , Male , Reference Values , Thyrotropin/blood , Triiodothyronine/blood
14.
Am J Med Genet ; 49(1): 108-10, 1994 Jan 01.
Article in English | MEDLINE | ID: mdl-8172236

ABSTRACT

We report on a case of ring chromosome 5 in a 36-month-old girl with severe growth retardation, clinodactyly, mild psychological abnormalities, and normal facial appearance. Endocrine tests showed partial growth hormone deficiency. Cytogenetic investigation failed to demonstrate any apparent microscopic deletion of either short or long arm of chromosome 5 as consequence of ring formation. In 12% of cells examined, the ring was either absent or present in multiple copies. Only 3 previous cases of ring chromosome 5 have been reported in association with short stature of prenatal onset and minor anomalies, without mental retardation.


Subject(s)
Chromosome Aberrations/genetics , Chromosomes, Human, Pair 5/ultrastructure , Dwarfism, Pituitary/genetics , Ring Chromosomes , Abnormalities, Multiple/genetics , Child, Preschool , Chromosome Disorders , Face/abnormalities , Female , Growth Hormone/deficiency , Humans , Intellectual Disability/genetics
15.
J Endocrinol Invest ; 16(7): 521-5, 1993.
Article in English | MEDLINE | ID: mdl-8227981

ABSTRACT

Aim of this study was to verify whether arginine (ARG), which likely inhibits hypothalamic somatostatin release, has an enhancing effect on the GHRH-induced GH rise, even when administered orally at low dose. To this goal we studied the effects of 4 g orally administered ARG, either hydrochloride (ARG-H) or aspartate (ARG-A), on both basal and GHRH (1 microgram/Kg i.v.)-stimulated GH secretion in 31 children with familial short stature (11 males and 20 females, aged 5.5-13.8 yr, pubertal stage I-III, and compared the results with those of i.v. infusion of 0.5 g/kg ARG-H. Oral ARG-H (Group A, n = 11) induced a significant increase of basal GH levels (4.2 +/- 1.3 vs 1.0 +/- 0.4 micrograms/L, p < 0.02) and enhanced the GH response to GHRH (41.1 +/- 8.6 vs 25.3 +/- 6.7 micrograms/L, p < 0.02). Oral ARG-A (Group B, n = 10) induced a slight, but not statistically significant increase in serum GH levels (3.4 +/- 1.5 vs 1.0 +/- 0.3 micrograms/L) and enhanced the GHRH-induced GH rise (49.7 +/- 9.8 vs 26.1 +/- 8.4 micrograms/L, p < 0.05). Intravenous ARG-H (Group C, n = 10) stimulated basal GH levels (6.2 +/- 1.2 vs 1.2 +/- 0.3 micrograms/L, p < 0.005) and increased the GHRH-induced GH rise (46.7 +/- 5.0 vs 17.1 +/- 2.3 micrograms/L, p < 0.005). This response was similar to those after oral ARG-H or ARG-A plus GHRH. No variation was observed in PRL levels after oral ARG (either ARG-H or ARG-A) and/or GHRH.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Arginine/administration & dosage , Body Height , Growth Hormone-Releasing Hormone/administration & dosage , Growth Hormone/metabolism , Prolactin/metabolism , Administration, Oral , Adolescent , Arginine/pharmacology , Child , Child, Preschool , Female , Growth Hormone/drug effects , Humans , Injections, Intravenous , Male , Prolactin/drug effects
16.
Hum Hered ; 42(2): 134-9, 1992.
Article in English | MEDLINE | ID: mdl-1349299

ABSTRACT

The somatostatin (SST) gene was analyzed to detect possible molecular variations in subjects with familial isolated growth hormone deficiency type I (IGHD I). No gross alterations in restriction fragments were observed with 18 used enzymes. The association with two RFLPs closely linked to the SST gene was also negative, adding weight to the evidence that the SST gene is not involved in the etiology of IGHD I. The nucleotide variability of a 23-kb DNA segment containing the SST gene and its flanking sequences was studied by restriction analysis of a sample of 19 Italians. The data suggest that approximately 1 in 400 bp is variant in this region.


Subject(s)
Growth Hormone/deficiency , Polymorphism, Restriction Fragment Length , Somatostatin/genetics , DNA Restriction Enzymes , DNA-Cytosine Methylases , Deoxyribonuclease EcoRI , Gene Frequency , Haplotypes , Humans , Nucleotides/genetics , Restriction Mapping
17.
Minerva Pediatr ; 43(9): 605-9, 1991 Sep.
Article in Italian | MEDLINE | ID: mdl-1758399

ABSTRACT

The authors report two cases of Turner syndrome with clinical evidence of only primitive hypogonadism and short stature. Karyotype analysis showed X ring mosaicism which is present only in 5% of cases of Turner syndrome. The authors agree with the hypothesis suggesting no relationship between break points on the X chromosome and phenotypical aspect. An earlier diagnosis is auspicious so that, using correct therapy, final height should be improved.


Subject(s)
Ring Chromosomes , Turner Syndrome/diagnosis , X Chromosome , Adolescent , Child , Female , Humans , Karyotyping , Mosaicism/genetics , Sex Chromosome Aberrations/diagnosis , Sex Chromosome Aberrations/genetics , Turner Syndrome/genetics
18.
Minerva Pediatr ; 43(6): 465-9, 1991 Jun.
Article in Italian | MEDLINE | ID: mdl-1886533

ABSTRACT

The authors analyzed the clinical and psychological effects of GH (group 1) and GH plus oxandrolone (group 2) in a group of 11 Turner girls aged 6.3-14 years. The results showed a significant improvement of posttreatment height velocity vs pretreatment height velocity for both study groups. No significant differences were found between the two groups. A girl of group 2 manifested a defect of sexual identification.


Subject(s)
Growth Hormone/therapeutic use , Oxandrolone/therapeutic use , Turner Syndrome/drug therapy , Adolescent , Body Height/drug effects , Child , Drug Evaluation , Drug Therapy, Combination , Female , Humans , Time Factors
19.
Pediatr Med Chir ; 13(3): 277-8, 1991.
Article in Italian | MEDLINE | ID: mdl-1945995

ABSTRACT

Since thymic factor activity can modulate immunoglobulin production, thymomodulin effect on IgE secretion was studied in thirty children (20 atopic and 10 control patients). Before treatment circadian variability of IgE was verified in all the children. Thymomodulin (3 mg/kg/die) was given daily for 30 days in both groups. Disappearance of circadian IgE variability were observed in atopic children, while no change of serum IgE circadian levels occurred in control group. On the basis of our results an improvement of IgE disregulation in atopic children may be postulated.


Subject(s)
Circadian Rhythm/drug effects , Hypersensitivity/drug therapy , Immunoglobulin E/analysis , Thymus Extracts/pharmacology , Child , Child, Preschool , Female , Humans , Immunoglobulin E/drug effects , Male , Thymus Extracts/therapeutic use
20.
Pediatr Med Chir ; 13(1): 67-71, 1991.
Article in Italian | MEDLINE | ID: mdl-2052459

ABSTRACT

Metabolic control and psychological parameters in forty insulin-dependent diabetic adolescents were evaluated during a sequential crossover study comparing two insulin regimens: a) 6 months of conventional insulin therapy (CIT) (T0-T1) using twice-daily mixture of short-acting and intermediate-acting insulins (AcHM and MoHM); b) 6 months of intensified insulin therapy (IIT) (T1-T2) using two pre-meal injections of short-acting insulin (AcHM) and one pre-dinner mixture of short-acting plus ultralente-acting insulin (AcHM + UtHM). Twenty patients received the pre-meal short-acting insulin with a pen-injector (group A) and twenty with conventional syringes (group B). All of participant received the pre-dinner insulin mixture with traditional syringes. Fasting blood glucose (BG), fructosamine, HbA1c, anxiety, depression levels and patient daily life adjustment (T1, T2) were investigated. The metabolic parameters showed similar results in both groups. There was no fasting BG variation during IIT, while post-meal (lunch and dinner) BG reduction (p less than 0.01) was observed. HbA1c levels didn't decrease but fructosamine levels significantly decreased at T2 time. Severe hypoglycemia where never observed, while the frequency of slight hypoglycaemic reactions didn't change during the study. The psychological parameters showed no differences at T0 and T1, while the differences became remarkable between the groups at T2 time. Home anxiety slightly decreased in group A and increased in group B (p less than 0.05). In group A an improvement of self-care initiative (self-injections) occurred too. In conclusion this study showed that, in a limited group of insulin-dependent diabetic adolescents, IIT with three daily injections improved fructosamine and post-meal BG levels.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Diabetes Mellitus, Type 1/blood , Insulin/administration & dosage , Adolescent , Blood Glucose/analysis , Child , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/psychology , Evaluation Studies as Topic , Female , Fructosamine , Glycated Hemoglobin/analysis , Hexosamines/blood , Humans , Injections, Intramuscular/instrumentation , Male , Peptides/blood , Psychological Tests , Syringes , Time Factors
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