Biomedical subjects

F Antoniazzi

Publications and source records attributed to F Antoniazzi.

At least 19 recordsLinked to original sources

PubMed2000

Multicystic kidney dysplasia and Turner syndrome: two cases and a literature review.

Renal malformations occur in 33%-70% of cases of Turner syndrome (chromosome 45 and variants). We describe two cases of multicystic dysplastic kidney in Turner syndrome. A literature review of renal abnormalities in Turner syndrome shows the frequency of cystic disease to be 1.76%. In multicystic dysplastic kidney, diagnostic investigation of the contralateral kidney, including voiding cystourethrography, is necessary in view of the high incidence of associated diseases (15%-20% of cases, vesicoureteric reflux) and other anomalies.

Female↗

PubMed2000

Insulin-like growth factor binding protein-3 proteolysis and growth of athyreotic infants in the first weeks of life.

UNLABELLED: To gain a better understanding of the growth of athyreotic newborns in the first weeks of life, we evaluated auxological parameters and determined the serum levels of growth hormone (GH), insulin-like growth factor I (IGF-I) and free IGF-I, and IGF-binding protein-3 (IGFBP-3) in 15 hypothyroid infants (10 females) at a mean age of 25 d of life, immediately before the beginning of L-thyroxine therapy, and at 3 and 6 mo of life. Fourteen normal infants (9 females) of the same age were studied as controls. IGFBP-3 proteolytic activity was evaluated in 8 patients and in 8 controls at 25 d and 6 mo of life. There was no significant difference concerning weight and length between the patients and controls at birth, 25 d, 3 and 6 mo of life. The blood GH, IGF-I and IGFBP-3 levels were significantly lower in patients at diagnosis than in controls of the same age (p < 0.01 for all parameters), as well as IGFBP-3 studied by Western blotting. At diagnosis, the patients' free IGF-I level was within the control range, but the free IGF-I percentage of total IGF-I was higher than in the controls (p < 0.01). IGFBP-3 proteolytic activity was found to be greater in the patients (p < 0.01). At 6 mo of life, after therapy, none of these parameters was different from those of the controls. CONCLUSION: Increased IGFBP-3 proteolytic activity in our patients at diagnosis, favouring IGF-I bioavailability, could account for normal free IGF-I levels and in turn for their normal growth pattern during the first weeks of life and before the start of treatment.

Age Factors↗

PubMed2000

Etiology and age incidence of precocious puberty in girls: a multicentric study.

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

Abnormalities, Multiple↗

PubMed2000

When to stop GnRH analog therapy: the experience of the Italian Study Group for Physiopathology of Puberty.

Data reported in this study have been recently published elsewhere. The authors retrospectively analyzed the auxological response to GnRH agonist treatment and the final height (FH) outcome in 71 girls with idiopathic and truly precocious (onset before 8 years) central puberty (CTPP), who had been treated with the same therapy protocol (Decapeptyl Depot at the dose of 60 microg/kg i.m. every 28 days) for at least 2 years (since 7.0 +/- 1.3 yr) and followed until puberty was completed and FH was reached. During the entire treatment period we observed: A) a decrease of height standard deviation scores (SDS) (from 1.5+/-1.7 to 0.9+/-1.3 SDS, p<0.01); B) a striking deceleration of BA, revealed by the subnormal deltaBA:deltaCA ratio (0.2 +/- 0.1); C) an increase of predicted adult height (from 155.6+/-7.0 to 160.7+/-6.7 cm, p<0.0005). Treatment interruption was followed by notable catchdown growth, with FH (158.4 +/- 5.8 cm) lower (p < 0.025) with respect to that predicted at the end of therapy. However FH fell within the population norm and the target range in 87.3% and 90% of patients, respectively. The tallest FH was recorded in the patients who discontinued treatment at a BA of 12.0-12.5 years. We conclude that: 1) Most girls with idiopathic CTPP treated by GnRH agonists may achieve an adult height within the population norm and/or their target range; 2) The height gain from therapy onset until FH attainment, however, is generally rather limited (on average 2.9 cm) and only few patients are able to reach their target percentile; 3) The most favorable height prognosis with respect to target height (TH) is generally observed in the patients with the tallest H2 and the lowest BA2:CA2 ratio, due to the notable deterioration of height prognosis which frequently follows therapy interruption; 4) In order to strengthen the weak therapeutic effect of GnRH agonists in CTPP, this treatment should be discontinued at a BA of 12-12.5 years.

Body Height↗

PubMed2000

End results in central precocious puberty with GnRH analog treatment: the data of the Italian Study Group for Physiopathology of Puberty.

We report some end results with GnRH agonist (GnRHa) treatment in central precocious puberty (CPP), in terms of final height (FH), ovarian function, peak bone mass, body composition and psychological problems. The two studies reported (Study I and II) are part of the activity of the Italian Study Group for Physiopathology of Puberty. Study L Growth data were analyzed of three groups of patients: treated with i.n. spray buserelin, i.m. triptorelin and untreated. Both GnRHa administration modes were effective in arresting pubertal development and all girls had complete recovery of the reproductive axis after therapy. Treated patients showed an improvement in final height in comparison with untreated patients and compared to predicted height at the start of treatment with both agonist treatments. However, patients treated with the long-acting slow release preparation had a better improvement in adult height and reached or exceeded the genetic height potential. Study II. In a retrospective evaluation of the outcome in 71 girls with idiopathic CPP treated with triptorelin, we found that FH fell within the population norm and the target range in 87.3% and 90% of the patients respectively. The tallest FH was recorded in the patients who started therapy at less than 6 years of age and in those who discontinued treatment at a bone age of 12.0-12.5 yr. Finally, we and other groups have recently found normal values of bone mineral density in girls at the end of GnRHa treatment in the great majority of patients.

Aerosols↗

PubMed1999

Prevention of bone demineralization by calcium supplementation in precocious puberty during gonadotropin-releasing hormone agonist treatment.

We have previously demonstrated a negative impact on peak bone mass in girls with precocious puberty treated with GnRH agonist (GnRHa). Several studies have shown that a high calcium intake positively influences bone mass in prepubertal girls and leads to a higher peak bone mass. The aim of this study was to evaluate the effect of calcium supplementation in girls with precocious puberty during GnRHa treatment. Forty girls affected by true central precocious puberty and treated with the GnRHa triptorelin were studied for 2 yr. After diagnosis, the patients were randomly assigned to three groups: group A, treated only with GnRHa; group B, treated for 12 months solely with GnRHa and then supplemented with calcium gluconolactate/carbonate (1 g calcium/day in two doses) for 12 months; and group C, treated from the beginning with combined GnRHa and calcium. Bone mineral density (BMD) at the lumbar spine was measured by dual energy x-ray absorptiometry at the beginning of the study and after 12 and 24 months and was expressed as the calculated true volumetric density (BMDv) in milligrams per cm3. Group A showed a decrease in absolute BMDv levels, in SD score for chronological age (CA), and even more in SD score for bone age (BA). Group B showed the same behavior during the first year, but this trend was reversed in the second year, when calcium supplementation was added to GnRHa treatment. Group C showed an increase in absolute BMDv levels and in SD score for CA and BA. BMDv variations (expressed as absolute values, SD score for CA, and SD score for BA) became statistically significant at 24 months between groups C and A (P = 0.036, P = 0.032, and P = 0.025, respectively). The behavior of the lumbar spine BMDv in the three groups is consistent with a positive effect of calcium supplementation during GnRHa treatment. In calcium-supplemented patients, the normal process of bone mass accretion at puberty is preserved despite GnRHa treatment. Therefore, the reduction in BMD during GnRHa treatment in girls with precocious puberty is at least completely reversible and preventable if calcium supplementation is associated from the beginning.

Body Height↗

PubMed1999

Analysis of the factors affecting auxological response to GnRH agonist treatment and final height outcome in girls with idiopathic central precocious puberty.

The aim of this retrospective study was to analyze the factors which affected the auxological response to GnRH agonist treatment and the final height (FH) outcome in 71 girls with idiopathic and truly precocious (onset before 8 years) central puberty (CTPP) who had been treated with the same therapy protocol (Decapeptyl Depot, 60 microg/kg i.m. every 28 days) for at least 2 years (since 7.0+/-1. 3 (S.D.) years of age) and followed until puberty was completed and FH was reached. During the entire treatment period we observed: (a) a decrease of height standard deviation scores (SDS) (from 1.5+/-1.7 to 0.9+/-1.3 SDS, P<0.01); (b) a striking deceleration of bone age (BA), revealed by the subnormal DeltaBA:Deltachronological age (CA) ratio (0.2+/-0.1); (c) an increase of predicted adult height (from 155.6+/-7.0 to 160.7+/-6.7 cm, P<0.0005). Treatment interruption was followed by an important catch-down growth, with an FH (158.4+/-5.8 cm) lower (P<0.025) than that predicted at the end of therapy. However, FH fell within the population norm and the target range in respectively 87.3 and 90% of the patients. The tallest FH was recorded in the patients who started therapy at less than 6 years of age and in those who discontinued treatment at a BA of 12.0--12.5 years. At stepwise regression analysis, FH in the whole study population was positively affected by the following independent factors: (a) height at the end of therapy (F=45.45, P<0.0001); (b) pretreatment height (F=13.91, P<0.0005); (c) treatment duration (F=8. 51, P<0.005); (d) target height (TH) (F=7.70, P<0.01). We conclude that: (i) most girls with idiopathic CTPP treated by GnRH agonists may achieve an adult height within the population norm and/or their target range; (ii) the height gain from therapy onset until FH attainment, however, is generally rather limited (on average 2.9 cm) and only few patients are able to reach their target percentile; (iii) the most favorable height prognosis with respect to TH is generally observed in the subjects with the tallest height at the end of treatment and the lowest BA2:CA2 ratio, due to the important deterioration of height prognosis which frequently follows therapy interruption; (iv) FH is also significantly conditioned by both TH and treatment duration; (v) in order to strengthen the weak therapeutic effect of GnRH agonists in CTPP this treatment should be started as early as possible and discontinued at a BA of 12.0--12.5 years.

Age Factors↗

PubMed1998

Determination of thyroxine in the hair of newborns by radioimmunoassay with high-performance liquid chromatographic confirmation.

Hair analysis is often used in forensic toxicology to study, retrospectively, chronic exposure of individuals to drugs, and consequently newborn hair may become an ideal sample to study intrauterine exposure to xenobiotics as well as to endogenous compounds. As a tool to investigate a supposed maternal thyroxine (T4) supply to the congenital hypothyroid fetus, we devised to use the analysis of T4 extracted from newborn hair. In the present paper, the analytical method based on T4 extraction from hair followed by a radioimmunoassay is described. To verify the nature of the T4-like immunoreactive material present in newborn hair, it was further studied by HPLC fractionation with radioimmunoassay of the eluted fractions. On the basis of a clear correspondence between retention times of T4 standard and T4-immunoreactive compound extracted from hair, we assigned this immunoreactive material to T4. Then, we determined T4 hair concentrations in 19 control newborns at birth and 12 congenital hypothyroid infants at 22 days of life. Values obtained from hypothyroid infants (31.47+/-8.8 pg/mg(hair), mean+/-S.D.) were not significantly lower than those obtained from healthy newborns at birth (36.10+/-13.2 pg/mg(hair)). Such results are in agreement with the hypothesis of a maternal supply of thyroxine to the fetus through placental crossing.

Chromatography, High Pressure Liquid↗

PubMed1998

[Growth hormone deficiency. Treatment with growth hormone and body composition].

Increased fat mass, decreased lean mass, muscular mass and bone mineral density are characteristic of the body composition in GH deficiency, GH treatment reverses these abnormalities. Body composition was determined in 20 young adults with GHD diagnosed in childhood, whose GH treatment was stopped 1 year earlier. Reevaluation of GH secretion in these patients showed that 12 remained GH deficient (confirmed GHD) while eight recovered normal GH secretion (transient GHD). One year after stopping the GH treatment, patients with confirmed GHD showed an increased fat mass as compared with value at the end of the treatment; in addition a decreased bone mineral content was observed in the patients with low physical activity. There was no increased fat mass in transient GHD; however, these patients presented with low bone mineral content, as previously reported in adults with history of delayed growth and adolescence.

Adolescent↗

PubMed1998

[Somatotropin function in term and premature newborns during the first month of life].

Neonatal somatotropic function is characterized by a discrepancy between elevated growth hormone (GH) levels and low IGF I levels. This study aimed at explaining this discrepancy, particularly to examining if it could result from low GH bioactivity. Serum concentrations of bioactive GH (bio GH), GH measured by radioimmunoassay (riGH), GH binding protein (GHBP), IGF I and IGF binding proteins (IGFBP) were determined in 27 premature and term newborns during the first month of life. At day 4, riGH and bio GH concentrations were elevated in both premature and term newborns as compared with normal prepubertal children; GHBP and IGF I levels were low, with a positive correlation with gestational age (P < 0.001). There was a positive correlation between GHBP and IGF I levels. IGFBP-1 and IGFBP-2 levels were elevated and negatively correlated with gestational age (P < 0.005). IGFBP-3 levels were within the range of prepubertal children values and positively correlated with gestational age (P < 0.005). During the first month, riGH and bio GH levels decreased in all infants, while IGFI levels increased in premature infants only, and GHBP levels in term infants only. The elevated levels of bio GH during the first days of life appear to be related to the low levels of IGF I due to a reduced number or function of GH receptors. In premature infants the decrease in GH levels observed afterwards appears to be secondary to the increase in IGF I levels. In term infants, in the absence of increase in IGFI levels other(s) factor(s) seem(s) to be involved.

Age Factors↗

PubMed1997

Growth hormone-binding proteins, IGF-I and IGF-binding proteins in children and adolescents with type 1 diabetes mellitus.

Growth hormone binding proteins, insulin-like growth factor I and insulin-like growth factor binding proteins were determined in 54 children and adolescents affected by type 1 diabetes mellitus (25 prepubertal and 29 pubertal) showing reduced height velocity and the results were compared to those of 104 matched controls. Growth hormone binding proteins were similar in prepubertal and pubertal subjects but were significantly lower in the prepubertal diabetic group than in controls. Insulin-like growth factor I was low both in prepubertal and pubertal diabetic subjects. Insulin-like growth factor binding protein 3 was similar to controls, while insulin-like growth factor binding protein 1 and 2 were always high in diabetic children. Insulin-like growth factor binding protein 4 was high only in the prepubertal diabetic group. In conclusion, a low insulin-like growth factor I in diabetic children seems to depend on a GH receptor and/or a postreceptor defect. A low insulin-like growth factor I together with a normal insulin-like growth factor binding protein 3 and high levels of insulin-like growth factor binding proteins 1, 2 and 4 results in a reduced bioavailability of insulin-like growth factor I to target tissues. This could be a possible contributing factor to the reduced height velocity seen in our diabetic children.

Adolescent↗

PubMed1996

Gonadal function and response to growth hormone (GH) in boys with isolated GH deficiency and to GH and gonadotropins in boys with multiple pituitary hormone deficiencies.

OBJECTIVE: [corrected] To evaluate spermatogenesis in patients with isolated GH deficiency and multiple pituitary hormone deficiencies. DESIGN: Treatment of isolated GH-deficient patients with recombinant human GH (weekly dose of 0.7 IU/kg) for 5.3 +/- 0.4 (mean +/- SD) years and cotreatment of multiple pituitary deficient patients with GH at the same dosage for 8.0 +/- 0.4 years and hCG (2,000 IU, three times per week) and hMG (500 IU, two times per week) for 13.7 +/- 1.1 months. SETTING: Endocrine Pediatric Unit. PATIENTS: Eight patients affected by isolated GH deficiency and seven by multiple pituitary hormone deficiencies. MAIN OUTCOME MEASURES: Serum LH, FSH, and T, testicular volume, semen volume, density, count, and motility. RESULTS: Patients with isolated GH deficiency completed their pubertal development in 19.0 +/- 3.5 months and patients with multiple pituitary hormone deficiencies in 13.7 +/- 1.1 months. At the end of puberty, the two groups of patients had similar testicular volume, penis size, sperm concentration, motility, and morphology, although T levels and seminal volume were lower in isolated GH-deficient patients than in multiple pituitary deficient patients. CONCLUSIONS: The two groups of patients, treated specifically for their identified hormonal deficiencies, in the end had similar satisfactory reproductive results.

Adolescent↗

PubMed1996

Growth hormone treatment in osteogenesis imperfecta with quantitative defect of type I collagen synthesis.

OBJECTIVES: We studied growth rate, bone density, and bone metabolism in patients affected by type I osteogenesis imperfecta (OI) with quantitative defect in type I collagen synthesis during treatment with human growth hormone (hGH), being aware of its collagen-stimulating synthesis activity in vitro. STUDY DESIGN: Fourteen patients (6 boys; ages 4.8 to 10.8 years) were studied. Any structural alteration in the collagen chains was excluded, and reduced production of structurally normal type I collagen (increase in type III/type I collagen; reduction in the messenger ribonucleic acid alpha 1 (I)/ alpha 2 (I) ratio) was demonstrated. The patients were divided into two groups comparable in sex, age, height, and clinical severity of OI; seven patients (three boys) were treated for 12 months with hGH at a dosage of 0.2 mg/kg per week (0.6 IU/kg per week), in six injections subcutaneously, and seven were followed as control subjects. Auxologic data were measured every 3 months, and bone age was determined at the start, after 1 year of treatment, and 1 year after its completion. Every 3 months, serum insulin-like growth factor type I, osteocalcin, carboxyterminal propeptide of type I procollagen, alkaline phosphatase, calcium, and phosphorus levels and urinary hydroxyproline and calcium levels were determined. Bone mass measurements were carried out at the start of the study in all patients and repeated after 12 months in treated patients at the lumbar spine by dual-energy x-ray absorptiometry and by anteroposterior (second, third, and fourth lumbar vertebrae) and lateral (third lumbar vertebra) scan. Results were expressed as areal (anteroposterior and lateral) bone density (in milligrams per square centimeter) and as calculated true density (in milligrams per cubic centimeter). RESULTS: After 12 months, linear growth velocity in treated patients increased significantly in comparison with the pretreatment period (from 3.57 +/- 0.55 to 6.04 +/- 0.69 cm/yr; p < 0.05) and with the untreated group (p < 0.05). Bone age did not advance faster than chronologic age. The fracture index per year was low before treatment, and during therapy no patient had any fractures. Serum osteocalcin levels were statistically lower than in control subjects before treatment and increased significantly after 12 months (3.3 +/- 1.0 vs 2.1 +/- 0.9 nmol/L; p < 0.05). Serum levels of carboxyterminal propeptide of type I procollagen were significantly lower than normal values before treatment (164.6 +/- 46.7 vs 310.3 +/- 97.6 ng/ml; p < 0.05) and rose, but not significantly, during and after treatment. Before therapy, patients with OI had significantly lower lumbar anteroposterior, lateral, and calculated true bone density than the normal population of the same sex compared for both age and height. After hGH treatment, bone density increased significantly in the lumbar spine, in anteroposterior and lateral scans (+2.6 +/- 2.5% and +9.8% +/- 14.0%, respectively; p < 0.05). CONCLUSIONS: From our results, we conclude that hGH treatment in moderate OI does not increase the fracture risk in treated patients in the short term, significantly increases the rate of linear growth velocity, and increases bone turnover and mineral content in trabecular bone at the lumber spine.

Alkaline Phosphatase↗

PubMed1996

Growth hormone-binding proteins and insulin-like growth factor-binding proteins in protein-energy malnutrition, before and after nutritional rehabilitation.

To clarify the influence of nutrition on the GH-IGF axis in protein-energy malnutrition (PEM), we determined the serum levels of GH, GH-binding proteins (BP) (GHBPs), IGF-I, and IGFBPs in nine children with kwashiorkor and 13 with marasmus, before and after nutritional rehabilitation. In a basal condition, the GH level was significantly higher in the two malnourished groups than in controls (p < 0.01); in contrast, the second fraction of GHBP was lower and seemed to be related to the high GH and to a reduction in GH receptors. After refeeding, the GH level increased and the second fraction of GHBP decreased. The IGF-I basal level was higher in kwashiorkor than in marasmus subjects (p < 0.05), but in both groups it was significantly lower than in controls (p < 0.01); after refeeding it increased. IG-FBP-3, measured by RIA and Western blotting techniques, was in the control range in the kwashiorkor group but in the marasmic group it was significantly lower than in controls; after refeeding it decreased in kwashiorkor (p < 0.01 versus basal values) and increased in marasmus (p < 0.05 versus prerefeeding level). When sera of malnourished patients were mixed with adult control sera, incubated for 5 h at 37 degrees C, and assessed by ligand blotting, a low IGFBP-3 level in marasmus was found to be due to increased adaptive proteolysis of IGFBP-3; in contrast, in kwashiorkor the IGFBP-3 proteolytic activity was very low, probably because of inhibition by aflatoxins. These findings confirm that malnutrition affects the GH-IGF axis.

Adult↗

PubMed1995

Use of the gonadotropin-releasing hormone agonist triptorelin in the diagnosis of delayed puberty in boys.

To differentiate gonadotropin deficiency from delayed puberty in teenage boys, 0.1 mg/m2 of triptorelin, a gonadotropin-releasing hormone agonist, was administered subcutaneously at 4 AM. Serum gonadotropins and testosterone levels were determined at baseline and 4 hours after the injection. The increase in blood gonadotropin and testosterone levels was significantly greater in patients with delayed puberty than in those with gonadotropin deficiency.

Adolescent↗

PubMed1995

Use of combined Gn-RH agonist and hGH therapy for better attining the goals in precocious puberty treatment.

We studied 30 girls (age 6.36 +/- 1.21 years, range 4.6-8.8) affected by idiopathic precocious puberty with significant reduction of height velocity (below the 25th centile) at the end of 1 year of Gn-RHa (triptorelin intramuscular depot) treatment, to evaluate GH-IGF-I axis activity and the effects of combined Gn-RHa plus hGH therapy. After 12 months, 15 patients continued Gn-RHa and started hGH therapy for 12 months, while 15 continued treatment with Gn-RHa alone (control group). We evaluated height velocity, bone age, urinary GH, serum IGF-I and IGFBP-3 levels throughout the study; plasma GHBP levels were determined only in the first 12 months of Gn-RHa treatment. Height velocity decreased significantly during Gn-RHa treatment; it increased significantly and became higher than the control group after 12 months of Gn-RHa plus hGH treatment. During Gn-RHa therapy alone, bone age progressed less than chronological age, while in the 12 months of Gn-RHa plus hGH treatment there was a slight nonsignificant increase in bone age progression in comparison to controls. Serum IGF-I and IGFBP-3 levels decreased significantly at 12 months of Gn-RHa therapy and increased significantly after Gn-RHa plus hGH treatment. Urinary GH levels showed the same behavior. Plasma GH binding to peak II-BP, slightly lower than the prepubertal normal range before treatment, significantly increased after 12 months of Gn-RHa treatment. Therefore, in these girls, during Gn-RHa treatment alone, we have a reduction in GH-IGF-I axis activity. During Gn-RHa plus hGH therapy there was a significant increase in height velocity, in urinary GH levels, in serum IGF-I and IGFBP-3 levels. Bone age did not seem to advance faster than chronological age and this may imply a better prediction in adult height. In our opinion, only in a small percentage of patients affected by precocious puberty (with a very low predicted adult height or an important reduction of growth velocity during Gn-RHa treatment) may an association with hGH therapy be useful.

Body Height↗

PubMed1995

Bone mineral metabolism in girls with precocious puberty during gonadotrophin-releasing hormone agonist treatment.

Bone mineral metabolism and mineralization before and during treatment were studied in 10 girls aged 6.9-8.4 years affected by central precocious puberty and treated with gonadotrophin-releasing hormone agonist (GnRHa) leuprolide acetate depot, in order to understand better the consequences of oestrogen deficiency and the reduction of growth hormone (GH)-insulin-like growth factor I (IGF-I) axis activity. Before and after 12 months of therapy, the patients underwent a clonidine stimulation test and a 4-day calcitriol osteoblast stimulation test. On day 0, day 5 and at 3-month intervals thereafter, serum calcium, phosphate, alkaline phosphatase, IGF-I, IGF binding protein 3 (IGFBP-3), GH, GH binding protein and osteocalcin levels were measured; urinary calcium, phosphate and hydroxyproline levels were evaluated in fasting spot samples. Trabecular and cortical bone mass variations, measured by dual X-ray absorptiometry in the lumbar spine and by dual photon absorptiometry in the radius, respectively were evaluated before the start and after 12 months of therapy. During treatment, a decrease of serum oestradiol levels from pubertal to prepubertal levels was observed. The GH peak following clonidine diminished significantly after 1 year. Growth hormone binding protein showed a slight increase, and IGF-I and IGFBP-3 decreased, although not significantly. Osteocalcin levels decreased significantly after 9 and 12 months of treatment, but they did not change significantly after calcitriol load, either before or after GnRHa therapy. Urinary hydroxyproline decreased significantly after 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Height↗

PubMed1994

A base substitution at IVS-19 3'-end splice junction causes exon 20 skipping in pro alpha 2(I) collagen mRNA and produces mild osteogenesis imperfecta.

Molecular investigations on a young patient and her family were undertaken to identify the molecular defect responsible for a mild form of osteogenesis imperfecta (OI) with blue sclerae, dentinogenesis imperfecta and joint laxity. Analysis of collagenous proteins from the proband's fibroblasts showed the presence of two populations of alpha 2(I) chains, one normal and one migrating faster on SDS gels, thereby suggesting deletion of amino acid sequences. The faster migrating chains were retained mainly in the cell layer and not found in the extracellular matrix deposited by cultured fibroblasts. Chemical cleavage of mismatch (CCM) analysis on the patient's pro alpha 2(I) mRNA: normal cDNA heteroduplexes localized the molecular defect. cDNA sequencing revealed a deletion of exon 20 (54 bp) in about half of the molecules. Genomic DNA sequencing revealed heterozygosity for a G-to-C transversion of the last nucleotide of intron 19, which changed the 3' consensus splicing site. As a consequence pro alpha 2(I)mRNA was abnormally spliced from the last codon of exon 19 to the first codon of exon 21. To our knowledge, this is the first acceptor site mutation so far described in an OI patient. Restriction analysis indicated that the mutation was present also in three other affected family members. The full sequence of COL1A2 introns 19 and 20 are reported.

Base Sequence↗