PubMed Health⌕ Search

Biomedical subjects

A Carrascosa

Publications and source records attributed to A Carrascosa.

At least 55 records · Page 3Linked to original sources
PubMed1995

Growth hormone, insulin-like growth factor-I axis, and insulin secretion in hyperandrogenic adolescents.

OBJECTIVE: To assess GH and insulin-like growth factor I (IGF-I) axis variability in hyperandrogenic adolescents with different sources of androgen excess and their relationship with insulin resistance. DESIGN: Baseline IGF-I, insulin-like growth factor binding protein-1 (IGFBP-1), IGFBP-3, GH response to the exercise-propranolol test, and insulin responses to a standard oral glucose tolerance test were compared among patients with functional ovarian hyperandrogenism, hyperandrogenic nonfunctional ovarian hyperandrogenism patients, and age-matched controls. SETTING: Outpatient clinic in a medical center. PATIENTS: Twenty-one adolescents with ovarian (group A) and 17 with nonovarian (group B) hyperandrogenism, and 20 controls. RESULTS: Serum IGF-I and poststimulated GH levels were similar among groups, whereas serum IGFBP-3 levels were significantly lower in group A than in controls. Mean serum insulin levels were significantly higher in patients than in controls, whereas 24% of patients had abnormal insulin responses to glucose and/or insulin sensitivity indexes. Serum IGFBP-3 levels correlated negatively with the free androgen index (free androgen index = T/sex hormone-binding globulin [SHBG] x 100), whereas mean serum insulin levels correlated positively with the free androgen index and negatively with SHBG levels in all subjects. CONCLUSIONS: Hyperinsulinemia is common in hyperandrogenic adolescents and correlates with the degree of hyperandrogenism and not with the androgen source. Hyperinsulinemia and decreased IGFBP-3 levels may enhance IGF-I bioavailability, which in turn may both decrease SHBG levels and increase androgen production.

Adolescent↗
PubMed1994

Bone mineral density of the lumbar spine in white Mediterranean Spanish children and adolescents: changes related to age, sex, and puberty.

Bone mineral content was measured by dual-energy x-ray absorptiometry in the lumbar spine at the L2-L4 level with a Lunar DPX densitometer model in 471 healthy white Mediterranean Spanish children and adolescents (256 boys and 215 girls) randomly selected from the urban area of Barcelona. Ages ranged from 3 mo to 21 y. Weight, height, and pubertal development were in the normal age distribution. Bone mineral content values were corrected by the vertebral surface area scanned and expressed as bone mineral density (BMD) values. BMD increased progressively from infancy to adulthood, and values were similar in both sexes, with the only differences related to the earlier onset of puberty in girls. A statistically significant correlation (p < 0.001) was found between BMD values and age, height, and weight. BMD values increased annually, but the periods of higher increase were observed during the first 3 y of life and late puberty. A significant (p < 0.001) increase in BMD was observed between Tanner pubertal stages III and IV and between Tanner stage IV and adult values. Lumbar BMD values peaked in a similar way to growth height velocity during pubertal development. However, the BMD peak seemed to occur somewhat later than height velocity peak, particularly in girls. In conclusion, we report normative data for BMD values at the lumbar level in our normally growing pediatric population and show that the first 3 y of life and adolescence are critical periods for bone mineralization. These data provide a tool for the investigation and follow-up of pediatric populations at risk for low bone mineralization.

Absorptiometry, Photon↗
PubMed1994

Use of leuprolide acetate response patterns in the early diagnosis of pubertal disorders: comparison with the gonadotropin-releasing hormone test.

The effects of a single injection (500 micrograms sc) of the GnRH agonist leuprolide acetate on gonadotropin secretion and those induced by a GnRH test were analyzed in 32 children (11 males and 21 females) referred for possible pubertal developmental disorders and in 9 prepubertal controls [group C; 4 males and 5 females; chronological age (CA), 7.4 +/- 1.2 yr]. The pituitary-gonadal secretory responses to the GnRH agonist were characterized in all subjects and in a control group in early puberty [10 females (Tanner breast stage II; CA, 11.3 +/- 1.1 yr) and 6 males (Tanner pubertal stage II; CA, 13.5 +/- 0.4 yr); group D]. Twelve girls (CA, 7.1 +/- 0.7 yr) presented with precocious breast development, 11 patients [6 boys (CA, 10.9 +/- 0.4 yr) and 5 girls (CA, 9.3 +/- 0.5 yr)] had advanced puberty and predicted adult heights below -2.0 SD score, and 9 patients [5 boys (CA, 14.6 +/- 0.3 yr) and 4 girls (CA, 14.4 +/- 1.1 yr)] had delayed puberty. Less than 6 months had elapsed since the appearance of pubertal signs in all patients with pubertal development. After a follow-up period of 12.9 +/- 2.0 months, 20 patients showed progression of pubertal signs (group A, progressive puberty), and in 12, puberty regressed or did not progress (group B, nonprogressive puberty). The results of hormonal tests in all patients were analyzed retrospectively according to their clinical outcome. Patients in group A had a mean plasma peak LH response significantly higher after leuprolide acetate stimulation than after GnRH challenge (13.1 +/- 0.2 vs. 7.3 +/- 0.9 IU/L; P < 0.003). Those in groups B and C had similar peak LH responses after both tests (3.3 +/- 0.2 vs. 3.1 +/- 0.4, and 1.5 +/- 0.1 vs. 1.8 +/- 0.4 IU/L, respectively). No differences in basal and poststimulated LH levels were found between boys and girls in the same group. In patients in groups A and D, LH consistently peaked 3 h postleuprolide acetate challenge; in those in groups B and C, the LH peak occurred 3-6 h postinjection. Maximal gonadal responses were elicited 24 h poststimulation. No overlap in poststimulated estradiol or testosterone values occurred between patients in groups A and D and those in groups B and C.(ABSTRACT TRUNCATED AT 400 WORDS)

Child↗
PubMed1994

Source localization of androgen excess in adolescent girls.

Functional ovarian hyperandrogenism (FOH) is characterized by an abnormal ovarian response to challenge with the GnRH analogs nafarelin and leuprolide acetate, similar to that observed in women with well defined polycystic ovary syndrome, regardless of whether elevated LH levels or polycystic ovaries are present. We studied an unselected group of 42 hyperandrogenic adolescents (age range, 14-22 yr; mean, 18.1 +/- 2.5 yr) 1) to determine FOH incidence through the assessment of ovarian-steroidogenic response to a single dose of leuprolide acetate, 2) to assess the clinical characteristics of patients according to their responses to GnRH analog stimulation, and 3) to evaluate adrenal steroidogenic function and its relation to ovarian hyperandrogenism in patients with either normal or abnormal responses to leuprolide acetate challenge. All patients underwent leuprolide acetate and ACTH testing, dexamethasone and ovarian suppression tests, and pelvic ultrasonography. Twenty-four (58%) patients had supranormal plasma 17-hydroxyprogesterone (17-OHP) responses to leuprolide acetate characteristic of FOH, and in 18, the 17-OHP response was similar to that of controls (n = 24; age, 17.1 +/- 2.3 yr). Seven patients (5 with FOH and 2 with normal responses to leuprolide acetate) had an abnormal response to ACTH, but only 1 had conclusive evidence of 21-hydroxylase deficiency. In 16 patients, the response to both stimulation tests was normal. Only 13 (54%) of the 24 FOH patients had polycystic ovaries on ultrasonography, and in 11 (46%), basal plasma LH levels were elevated. In FOH patients, reduction in testosterone and androstenedione plasma levels was significantly greater after ovarian suppression than after dexamethasone challenge (P < 0.0005 and P < 0.02, respectively). Peak plasma 17-OHP levels postleoprolide acetate simulation correlated with dexamethasone-suppressed plasma testosterone concentrations, dexamethasone-suppressed plasma androstenedione levels, and the free androgen index postdexamethasone treatment (r = 0.4, P = 0.01; r+ 0.4, P < 0.05; and r = 0.41, P = 0.007, respectively), Plasma sex hormone-binding globulin levels after dexamethasone administration correlated negatively with the baseline free androgen index (r = -.0.67; P < 0.0001). Considering our diagnostic criteria, 26 (62%) of our collective of 42 patients had abnormal responses to one or both stimulation tests, whereas 16 (37%) had normal response. FOH is the most common cause in (58%) of androgen excess in adolescence. Short term leuprolide acetate stimulation is a reliable tool fro identification of the ovary as the source of their hyperandrogenism.

17-alpha-Hydroxyprogesterone↗
PubMed1993

Postpubertal outcome in girls diagnosed of premature pubarche during childhood: increased frequency of functional ovarian hyperandrogenism.

The postpubertal outcome of a group of girls diagnosed of premature pubarche during childhood was assessed 1) to determine the incidence of functional ovarian hyperandrogenism (FOH) through the ovarian-steroidogenic response to the GnRH agonist leuprolide acetate, 2) to validate leuprolide acetate stimulation in FOH diagnosis, and 3) to ascertain whether FOH-predictive biochemical markers exist at the diagnosis of premature pubarche. Of 35 patients (age, 15.4 +/- 1.5 yr), 16 showed hirsutism, oligomenorrhea, and elevated baseline testosterone and/or androstenedione (delta 4-A) levels. Subcutaneous administration of leuprolide acetate (500 micrograms) produced similar increases in gonadotropin levels in oligomenorrheic patients, regularly menstruating patients (n = 19), and controls (n = 12; age, 15.3 +/- 1.3 yr) when tested at 6 h. Of all of the steroids measured, 17-hydroxyprogesterone (17-OHP) and delta 4-A levels 24 h postleuprolide acetate stimulation were significantly higher in oligomenorrheic patients than in the other two groups (P < 0.0001). No overlapping in 17-OHP responses occurred between oligomenorrheic patients and the other groups. Baseline dehydroepiandrosterone sulfate and delta 4-A levels at the diagnosis of premature pubarche correlated with 17-OHP values postleuprolide acetate challenge (r = 0.47; P < 0.005 and r = 0.67; P < 0.0001, respectively). These results show a distinct leuprolide acetate challenge response in 45% of the postpubertal premature pubarche girls studied, suggestive of an increased incidence of FOH, and support the need for continued routine postmenarcheal evaluation of this group of patients. Responses of 17-OHP to leuprolide acetate challenge facilitate the identification of FOH patients, establish this test as a reliable diagnostic tool in FOH diagnosis, and confirm the ovaries as the source of hyperandrogenemia in most patients with androgen excess. Although increased 17-OHP responses after leuprolide acetate stimulation seem to occur more frequently in girls with elevated dehydroepiandrosterone sulfate and/or delta 4-A levels at the diagnosis of premature pubarche, specific biochemical markers predictive of FOH in this group of patients are still lacking.

Androgens↗
PubMed1992

Clinical usefulness of urinary growth hormone measurements in normal and short children according to different expressions of urinary growth hormone data.

To assess the clinical usefulness of urinary growth hormone (UGH) measurements, a UGH determination technique, including dialysis, ultrafiltration, and measurement by polyclonal-coated tube RIA, was established. Sixty-three short children were studied: 56 idiopathic growth retarded (37 prepubertal and 19 pubertal) and seven prepubertal with classic GH (growth hormone) deficiency. Forty-two healthy children (32 prepubertal and 10 pubertal) served as controls. Two groups of adults were studied: eight with active acromegaly and 11 healthy controls. UGH was measured in 24-h urine samples from all patients and controls. Mean +/- SD UGH excretion expressed as ng/24 h was significantly lower in the GH-deficient group compared with prepubertal growth-retarded and control children (p less than 0.01). No differences were found between UGH excreted by controls and by the growth-retarded groups. Pubertal children excreted significantly higher amounts of GH when UGH was expressed as ng/24 h (p less than 0.02 and p less than 0.03, respectively), but this difference disappeared when UGH was expressed as ng/g creatinine. UGH was significantly higher in acromegalic patients compared with adult controls (p less than 0.001). Differences between day, night, and 24-h UGH were studied in 23 children. UGH in night urine was significantly lower whether expressed as the total amount or as ng/g creatinine. The effect of recombinant hGH administration on UGH was studied in 13 children after 6 and 12 mo of treatment. UGH increased significantly under recombinant hGH treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1992

Somatostatin effects on cultured human fetal epiphyseal chondrocytes.

Somatostatin effects on cultured human fetal epiphyseal chondrocytes were evaluated by studying the effects of somatostatin on DNA synthesis. Cultured epiphyseal chondrocytes from human fetuses (12-40 wk old) were incubated for 48 h in Ham's F-12 serum-free medium. After this, the medium was replaced by MCDB-104 serum-free medium and the cells were incubated for an additional 48 h in the presence or absence of somatostatin 1 pM to 10 microM, with the addition of 3H-thymidine (5 microCi/mL) for the last 24 h of incubation. A significant (p < 0.02) inhibitory effect of somatostatin (1 nM to 10 microM) on 3H-thymidine DNA incorporation was observed in cultured chondrocytes from fetuses of all gestational ages studied (12-40 wk), with no significant differences among fetal ages. In conclusion, our results show that somatostatin exerts a biologic effect on cultured human fetal epiphyseal chondrocytes, as it does in its target cells. These results suggest that somatostatin could regulate human skeletal growth not only by growth hormone secretion regulation, but also by acting directly on chondrocyte metabolism. However, the physiologic significance of the latter remains to be elucidated.

Cells, Cultured↗
PubMed1992

Natural history of premature pubarche: an auxological study.

The natural history of girls with premature pubarche is reported to be normal, but the effects on puberty and on final height are not well documented. We assessed the outcome of a group of girls with premature pubarche from two Latin populations in whom 21-hydroxylase deficiency had been ruled out by an ACTH test. Patients comprised 127 girls (70 Northern-Italian and 57 Northern-Spanish), of whom 69 had entered puberty and 38 had attained adult height. Height, bone age, onset and progression of puberty, height prognosis, adult height, and baseline plasma androgen levels were evaluated. Advanced skeletal maturation and tall stature were constant features during the first years of follow-up and subsequently declined. Puberty began at 9.7 +/- 0.9 yr, and age at menarche (12.0 +/- 1.0 yr) was comparable to maternal and population menarcheal ages. The appearance and chronology of pubertal milestones in both populations were very similar. Adult heights correlated with the height prognosis at diagnosis and at onset of puberty, and were above midparental heights. Premature pubarche produces a transient acceleration in growth and bone maturation with no negative effects on the onset and progression of puberty and final height.

Adolescent↗
PubMed1992

Effects of triiodothyronine (T3) and identification of specific nuclear T3-binding sites in cultured human fetal epiphyseal chondrocytes.

The effects of T3 on cultured human fetal epiphyseal chondrocytes were assessed by studying its effects on DNA synthesis and alkaline phosphatase activity. DNA synthesis was evaluated as follows: after 48-h incubation in Ham's F-12 serum-free medium, cultured chondrocytes were incubated with or without T3 (0.1-100 nM) in MCDB-104 serum-free medium for different periods of time (2-10 days), with the addition of [3H]thymidine (5 microCi/mL) for the last 24 h. Confluent cultured chondrocytes in 25-cm2 tissue culture flasks were incubated in Ham's F-12 serum-free medium for up to 9 days with or without T3 (0.1-100 nM); the cellular cytoplasmic fraction was obtained, and alkaline phosphatase activity was evaluated using paranitrophenylphosphate as a substrate. No significant effects of T3 (0.1-100 nM) on DNA-[3H]thymidine incorporation were observed in any experiment (n = 17) for any gestational age (12-39 weeks) or for any incubation period studied (2-10 days). However, a significant (P less than 0.025 or more) stimulatory effect of T3 (0.1-100 nM) on alkaline phosphatase activity was observed after 9 days of incubation. This effect was highest for 5 nM T3 and was present in cultured chondrocytes from human fetuses of all ages studied (13-40 weeks). Cultured human fetal epiphyseal chondrocytes from human fetuses 12-40 weeks old (n = 8) showed specific nuclear binding sites for T3. The binding capacity was 27.14 +/- 2.84 fmol/100 micrograms DNA, and the Kd was 0.66 +/- 0.14 x 0.1 nM (mean +/- SEM), with no significant differences among fetal ages. In conclusion, our results show that T3 elicits a biological response in cultured human fetal epiphyseal chondrocytes and has specific nuclear binding sites. Since alkaline phosphatase is closely related to the mineralization of epiphyseal cartilage, these results suggest that thyroid hormones could regulate this process.

Alkaline Phosphatase↗
PubMed1990

Assay-dependent results of immunoassayable spontaneous 24-hour growth hormone secretion in short children.

Forty-eight children, referred for evaluation of short stature, underwent 24-hour spontaneous growth hormone (GH) secretion studies. The GH level in pooled sera was assessed for each child, using up to 11 commercial immunoassays. In a group of 15 children, the mean GH values obtained by nine of the assays were compared with the mean value given by a polyclonal radioimmunoassay (RIA) from Sorin: four gave higher results (p less than 0.0001), three gave comparable results and two gave lower results (p less than 0.001). The assay yielding the highest results (Nichols: 5.9 +/- 2.3 ng/ml, mean +/- SD) gave values that were approximately triple those obtained by the assay yielding the lowest results (Hybritech: 1.8 +/- 0.8 ng/ml; p less than 0.0001); both of these are monoclonal immunoradiometric assays (IRMAs). The GH concentrations measured in 24-hour pools from 32 children using a monoclonal IRMA from Biomérieux were similar to those obtained using a polyclonal RIA from Farmos (2.8 +/- 1.1 ng/ml and 2.9 +/- 1.4 ng/ml, respectively) but significantly lower than those measured by another polyclonal RIA from Sorin (3.5 +/- 1.5 ng/ml). Two polyclonal assays (Biomérieux and Sorin) were then used to measure the GH levels in all of the 30-minute samples and in the day, night and 24-hour pools from the secretion studies of 22 children. The ratio of the results of the two assays remained fairly constant for a given child (although the GH levels in different 30-minute samples differed considerably). However, the ratios between different children showed quite wide variation (from 2.03 to 1.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Biological effects of androgens and identification of specific dihydrotestosterone-binding sites in cultured human fetal epiphyseal chondrocytes.

The biological effects of dihydrotestosterone (DHT) and testosterone (T) on cultured human fetal epiphyseal chondrocytes were assessed by studying the ability of these androgens to promote DNA synthesis. DNA synthesis was evaluated by measuring [3H]thymidine incorporation into DNA. After 48-h incubation in Ham's F-12 serum-free medium, chrondrocytes were incubated with or without DHT (10(-11)-10(-8) M) or T (10(-11)-10(-8) M) in MCDB-104 serum-free medium for a further 48 h, with the addition of [3H]thymidine (5 microCi/mL) for the last 24 h. In chondrocytes from five male fetuses (12-40 weeks' gestation) DHT and T significantly stimulated DNA synthesis. The maximum stimulatory effect was obtained for DHT at 10(-10) M (P less than 0.01) and for T at 10(-6) M (P less than 0.02). In chondrocytes from four female fetuses the stimulatory effect was significant only for DHT and was maximum at 10(-10) M (P less than 0.02), whereas no effect was observed for T. Cultured chondrocytes from both male and female fetuses show the presence of proteins with high affinity and limited binding capacity (Bmax) for DHT (male fetuses: Bmax, 4.9 +/- 1.9 x 10(-15) M/mg protein; Kd, 0.43 +/- 0.24 x 10(-9) M; female fetuses: Bmax, 4.8 +/- 1.6 x 10(-15) M/mg protein; Kd, 0.63 +/- 0.19 x 10(-9) M) with no significant differences between sexes. In conclusion, our results show that androgens elicit a biological response in cultured human fetal epiphyseal chondrocytes and that DHT-binding sites are present in these cells. DHT, rather than T, seems to be the active androgen. A sex difference in the degree of androgen action is also documented.

Androgen-Binding Protein↗
PubMed1987

Chronic growth retardation with normal growth hormone response to provocative stimuli and low somatomedin activity. Long-term therapy with human growth hormone.

Four prepubertal children with chronic growth retardation (growth velocities less than or equal to 4 cm/yr), normal growth hormone (GH) response to provocative stimuli and low basal but increased somatomedin activity values after GH administration, received continuous GH-therapy (4 IU/three times a week) for an 18-24-month period. Growth velocity doubled during the first 12 months of therapy and remained 4-6 cm/yr until the end. Bone age progressed according to chronological age and adult height predictions improved. No thyroid function or carbohydrate and lipid metabolism anomalies were observed. After completion of this GH-therapy period, patients remained off treatment during the following six months. Growth velocities were similar to pre-GH-treatment values in two patients, lower in the third and higher in the fourth, who was by then pubertal. Thus, in these patients, long-term GH-therapy promoted growth and improved adult height prediction.

Child↗
PubMed1987

Evidence for a direct in vitro action of sex steroids on rabbit cartilage cells during skeletal growth: influence of age and sex.

A direct effect of sex steroid hormones on in vitro cartilage cell metabolism was demonstrated. Cells were derived from rabbit fetuses on day 20 of gestation, and from male and female rabbits aged from 2 to 80 days. Testosterone (T), dihydrotestosterone (DHT), or 17 beta-estradiol (E2) (10(-9) -10(-9) M) were added to primary culture of epiphyseal articular chondrocytes. They showed an age-dependent stimulatory effect on [35S]sulfate incorporation into newly synthesized proteoglycans. In cultured rabbit fetal cartilage cells, the maximum active concentration of T and DHT was 10(-9) M with a 40% stimulating effect over control values. E2 was even more active with 80% stimulating effect when added at 10(-8) M. Chondrocytes from animals aged up to 5 days responded poorly and those from animals aged 5-30 days not at all. The response of cells from older animals varied with animal age and sex. T and DHT stimulated chondrocytes from males aged 32-55 days and females aged 40-52 days to about the same extent. E2 stimulated cells from animals of the same ages, but the response of female-derived cells was twice that of male-derived cells. The stimulating effect was dose dependent from 10(-11) to 10(-8) M and maximal at 10(-9) M for T and DHT and at 10(-8) M for E2. Puromycin completely abolished the effect.

Aging↗