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Biomedical subjects

A Carrascosa

Publications and source records attributed to A Carrascosa.

At least 37 records · Page 2Linked to original sources
PubMed1999

Sexual dimorphism in the maturation of the pituitary-gonadal axis, assessed by GnRH agonist challenge.

OBJECTIVE: To assess whether the maturational changes of the pituitary--gonadal axis in a healthy population show gender-specific changes and to establish normative data for the different Tanner stages. DESIGN: Prospective, cross-sectional study. METHODS: The GnRH agonist leuprolide acetate (500 microgram) was administered s.c. to 60 boys and 81 girls (age range, 5--17 years). Serum steroids and gonadotropins were determined at 0 and 24 h and at 0, 3 and 24 h after GnRH agonist challenge respectively, whereas IGF-I, IGF-binding protein-1 (IGFBP-1), IGFBP-3 and sex hormone-binding globulin were measured at baseline. RESULTS: Baseline and peak LH responses to the agonist in late puberty, and basal and peak FSH levels at all Tanner stages, were higher in girls than in boys. Girls showed higher IGF-I levels than boys throughout puberty, sharper decreases in IGFBP-1 and earlier and greater increases in 17-hydroxypregnenolone, dehydroepiandrosterone (DHEA) and DHEA-sulfate. Testosterone responses to the agonist increased during puberty in males, and showed no changes in females. Conversely, estradiol responses rose throughout puberty in females and remained unchanged until late puberty in males. CONCLUSION: Leuprolide acetate stimulates gonadotropin and gonadal steroid secretion during puberty in both sexes and increases FSH levels in prepubertal girls. Pubertal maturation of gonadotrope function is gender specific, as it appears to involve increases in both the releasable and reserve pools of LH in males, and of LH and FSH in females. The earlier increase in Delta(5)-steroids in girls may suggest a sharper rise in ovarian cytochrome P450c17 activity along the Delta(5)-steroid pathway, while the failure of estradiol to increase in response to leuprolide acetate in early pubertal males suggests a late maturation of aromatase activity.

Adolescent↗
PubMed1998

[Bone mass in patients with cystic fibrosis of the pancreas. Relationship with anthropometric parameters and genotype].

BACKGROUND: Cross-sectional study of bone mineral density (BMD) in children and adolescents with cystic fibrosis of the pancreas. The relationship of BMD values with nutritional status, respiratory function and the cystic transmembrane regulator genotype was also evaluated. PATIENTS AND METHODS: BMD expressed as grams of hydroxyapatite/cm2 was measured by dual-energy X-ray absorptiometry in the lumbar spine (L2-L4) in 41 patients (21 males and 20 women; age range: 4-21 years) with cystic fibrosis of the pancreas and compared with that of 471 normal controls (256 males and 215 women; age range: 1-20 years). Twenty patients were prepubertal, 9 pubertal and 12 young adults. RESULTS: Clinical repercussion of the disease evaluated by clinical and anthropometric data (weight, height and body mass index) and respiratory function was considered moderate. Height z score (mean [MSE]) was -0.53 (0.28), weight -0.81 (0.21) and body mass index -0.82 (0.12) BMD z score values (mean [MSE]) were -1.14 (0.17) and differed significantly (p < 0.001) from those of normal age- and sex-matched controls. No significant differences were observed between males and women or among prepubertal, pubertal and young adult patients. BMD z score values less than-1 z score were found in 53% and under -2 z score in 8%. Cystic transmembrane regulator genotype was studied in 36 patients (17 were F508/-, 10 F508/F508, 5 G542X/- and 4 diverse) and did not predict bone mineral status. A statistically significant correlation was found between BMD z score values and height z score, weight z score, body mass index z score and clinical assessment according to Shwachman criteria. A negative and statistically significant correlation was observed between BMD z score and functional score. CONCLUSIONS: The decrease in BMD values in CF patients begins early in life and appears to be related to the degree of clinical expression of the disease.

Adolescent↗
PubMed1998

Hyperinsulinaemia, dyslipaemia and cardiovascular risk in girls with a history of premature pubarche.

Girls with a history of premature pubarche, i.e. appearance of pubic hair before 8 years of age, show hyperinsulinism in response to an oral glucose tolerance test. As hyperinsulinaemia has a major role in dyslipaemia, and is considered an independent risk factor for cardiovascular disease, we assessed the patterns of plasma insulin concentration after a standard oral glucose tolerance test as well as fasting serum lipid, lipoprotein, and sex hormone-binding globulin concentrations in girls (n = 81) with premature pubarche compared with girls (n = 55) matched with them for stage and bone age to ascertain their metabolic states to identify those potentially at risk for the development of premature cardiovascular disease. Mean serum insulin concentrations were higher in patients at all pubertal stages, and associated with elevated serum triglyceride, very low density cholesterol and very low density triglyceride concentrations (p value range 0.04 to < 0.0001) but reduced sex hormone-binding globulin. Premature pubarche patients also displayed higher low density to high density lipoprotein cholesterol ratios compared with control subjects (p = 0.004 to 0.008). In conclusion, hyperinsulinaemia, decreased sex hormone-binding globulin concentrations and an unfavourable lipid pattern are common features in premature pubarche girls supporting the contention that atherogenic abnormalities composing the metabolic syndrome could start in childhood. To determine the clinical sequelae of such clustering of metabolic deviations, girls who were identified need to be followed up for the potential development of premature cardiovascular disease.

Adolescent↗
PubMed1998

Diagnosis and treatment in utero of goiter with hypothyroidism caused by iodide overload.

A fetal goiter was detected by ultrasonography in a woman receiving potassium iodide. After this medication was discontinued at 29 weeks, a fetal hypothyroidism was confirmed by cordocentesis, and two doses of levothyroxine were administered by amniocentesis. At 34 weeks repeated cordocentesis showed fetal euthyroidism and ultrasonography shrinkage of the goiter. Growth and development normal at 1 year.

Adult↗
PubMed1998

Leptin in relation to resumption of menses in women with anorexia nervosa.

Serum levels of leptin are decreased in underweight AN patients and increase with weight restoration. To assess the relationship of decreased leptin levels with other hormonal abnormalities in AN and to evaluate the possible role of increasing leptin levels, alone or in combination with other hormones, in the resumption of menses that accompanies weight gain, we studied cross-sectionally sixty-five consecutively enrolled AN patients. Subjects were divided in three groups: (I) underweight and amenorrheic; (II) weight-recovered but still amenorrheic; and (III) weight-recovered and eumenorrheic women. Patients in group I had decreased BMI, serum leptin, estradiol (E2), insulin-like growth factor 1 (IGF-1) and urinary growth hormone (GH) levels and increased sex hormone-binding globulin (SHBG) levels, compared to AN patients in groups II and III. Moreover, although no differences in leptin levels or BMI were observed between amenorrheic and eumenorrheic weight-recovered patients (groups II and III), free E2 and GH levels were higher (P<0.02) in weight-recovered, eumenorrheic women. Thus, it appears that leptin is a necessary, but not a sufficient, factor for the resumption of menses in AN patients.

Adult↗
PubMed1998

Down's syndrome: altered chondrogenesis in fetal rib.

Down's syndrome (DS), a human genetic abnormality usually caused by an extra chromosome 21, presents a wide range of major and minor anomalies, the most significant of which are mental retardation and congenital heart defects. The anomalous phenotype also includes short stature and neck, thin calvaria, and cartilage hypoplasia. The genesis of these skeletal features is unknown. Histopathologic sections of fetal cartilage from skull, vertebra, rib, and femur were studied in 16 fetuses with DS (17-22 wk old) and 13 control non-DS fetuses (19-22 wk old) with other pathologies not directly affecting skeletal growth. Rib growth cartilage morphology showed a previously unreported structural anomaly in DS, an increase in the hypertrophic portion with a concomitant decrease in proliferative and resting zones. The hypertrophic chondrocytic zone was markedly increased in DS compared with non-DS (149 +/- 68 microm versus 36 +/- 20 microm, and 26 +/- 12 versus 7 +/- 3 expressed in percent of the total length; p < 0.0001), whereas the proliferative zone (114 +/- 58 microm versus 165 +/- 43 microm, 20 +/- 10 versus 33 +/- 4 in percent of the total length; p < 0.001) and the resting zone (53 +/- 4 versus 59 +/- 6 in %, p < 0.009) were decreased. These features were not found in the femoral epiphyseal growth plate or in cartilage from vertebra and skull. Our results demonstrate an imbalance toward the hypertrophic phenotype. This abnormality, found in DS fetuses 17-22 wk old, may represent an early manifestation of an abnormal growth cartilage maturation pattern, which manifests postnatally in long bones, leading to diminished growth rates.

Abortion, Therapeutic↗
PubMed1998

Oxidative stress at onset and in early stages of type 1 diabetes in children and adolescents.

OBJECTIVE: In diabetes, the persistence of hyperglycemia has been reported to cause increased production of oxygen free radicals through glucose autooxidation and nonenzymatic glycation. The aim of this study was to determine whether oxidative cellular damage occurs at the clinical onset of diabetes and in later stages of the disease in young patients. RESEARCH DESIGN AND METHODS: Indicative parameters of lipoperoxidation, protein oxidation, and changes in the status of antioxidant defense systems were evaluated in single blood samples from 54 diabetic children, adolescents, and young adults and 60 healthy age- and sex-matched control subjects. RESULTS: Malondialdehyde and protein carbonyl group levels in plasma were progressively higher in diabetic children and adolescents than in control subjects (P < 0.0001). The highest erythrocyte superoxide dismutase (SOD) activity was found in diabetic children at onset of clinical diabetes. In diabetic adolescents, SOD was also significantly higher (P < 0.0001) than in control subjects. Erythrocyte glutathione peroxidase was significantly lower in diabetic children and adolescents compared with control subjects (P < 0.002). A significant decline in blood glutathione content at the recent onset of diabetes was found (P < 0.0001). Furthermore, our results demonstrated progressive glutathione depletion during diabetes evolution. The plasma alpha-tocopherol/total lipids ratio and beta-carotene levels during diabetes development (P < 0.001) were low. CONCLUSIONS: This cross-sectional study in young diabetic patients showed that systemic oxidative stress is present upon early onset of type 1 diabetes and is increased by early adulthood. Decreased antioxidant defenses may increase the susceptibility of diabetic patients to oxidative injury. Appropriate support for enhancing antioxidant supply in these young diabetic patients may help prevent clinical complications during the course of the disease.

Adolescent↗
PubMed1998

[Bone mineral density in nursing infants and young children (0-4 years old) at the level of the lumbar spine. The normal patterns].

OBJECTIVE: A cross-sectional study of bone mineral density was conducted in a normal population of children with ages ranging from the neonatal period to 4 years with the aim of establishing normal bone mineral density (BMD) patterns. PATIENTS AND METHODS: Bone mineral content density was measured by dual-energy X-ray absorptiometry at the level of the lumbar spine (L2-L4) in 147 normal children (69 boys, 78 girls, age range: 15 days to 4 years) randomly selected from the urban area of Barcelona. RESULTS: Weight, length and height were in the normal age distribution. Bone mineral content values were corrected by the vertebral surface area scanned and expressed as bone mineral density values (grams of hydroxyapatite/cm2). Bone mineral density values increased progressively from birth to 4 years and values were similar in both sexes. A statistically significant correlation was found between BMD values and age (r = 0.82, p < 0.001), weight (r = 0.87, p < 0.001) and length or height (r = 0.79, p < 0.001). Lumbar bone mineral density values increased annually, but the periods of higher increase were observed during the first 2 years of life. Bone mineral density values showed a similar pattern to height growth velocity. CONCLUSIONS: We report normative data for bone mineral density at the lumbar spine in our normally-growing pediatric population from the neonatal period to 4 years. These data provide a tool for the study and follow-up of pediatric populations at risk for low bone mineralization during early childhood.

Absorptiometry, Photon↗
PubMed1997

[Adult height, pattern of growth and pubertal development in patients with congenital adrenal hyperplasia, salt losing form].

BACKGROUND: The height growth pattern in 24 patients with the salt-wasting from of congenital adrenal hyperplasia was retrospectively evaluated from the neonatal period to attainment of adult height. PATIENTS AND METHODS: All patients were on mineralcorticoid therapy and received hydrocortisone (mg/m2 body surface and day. Mean +/- SD): 34.53 +/- 8.2 during the first year of life, 22.83 +/- 4.1 from then to the puberty onset and 21.83 +/- 3.6 during puberty. Height was measured every 3-4 months and compared with that of the normal age- and sex-matched controls. RESULTS: Height differences with respect to reference population (M +/- SD) were: +0.38 +/- 0.82 in the neonatal period; -2.21 +/- 1.1 at one year of age; -0.76 +/- 1.25 at three years of age; -0.45 +/- 0.99 at the onset of puberty and -1.34 +/- 0.79 at attainment of adult height. Adult height differed significantly (p < 0.01) from control values and in girls from those of their mothers (p < 0.05). Hyperandrogenism, evaluated through urinary 17-ketosteroids, testosterone, delta 4 androstenedione and DA-S, was not documented during prepuberty and puberty. CONCLUSIONS: Our patients showed a lower growth rate than those of the control population during the two periods of higher growth potentiality: the first year of life and puberty, and this results in adult height impairment.

Adrenal Hyperplasia, Congenital↗
PubMed1997

Vitreous levels of vascular endothelial growth factor are not influenced by its serum concentrations in diabetic retinopathy.

Vascular endothelial growth factor (VEGF) plays a major role in the development of neovascularization in proliferative diabetic retinopathy (PDR). The source of intravitreous VEGF is presumably ischaemic retina, but increased levels derived from serum cannot be excluded. The aim of the study is to determine the intravitreous concentrations of VEGF in diabetic patients with PDR and to investigate whether serum VEGF could contribute to the intravitreous concentration. For this purpose, we studied 20 diabetic patients (5 IDDM and 15 NIDDM) with PDR in whom a vitrectomy was performed (group A). Non-diabetic patients (n = 13) with other conditions requiring vitrectomy served as a control group (group B). In both groups, VEGF was determined in serum and undiluted vitreous samples obtained simultaneously. Furthermore, serum VEGF was determined in 69 healthy control subjects (group C) and 39 diabetic patients without microvascular complications (group D). Vitreous and serum VEGF was determined by ELISA (R & D Systems, Abingdon, UK); intra-assay CV 3.8%, interassay CV 5.1%. Intravitreous concentrations of VEGF were strikingly higher in group A (median 1.75 ng/ ml, range 0.33-6.66) in comparison with group B (median 0.009 ng/ml, range 0.009-0.038); p < 0.0001. This difference remained significant after adjusting for intravitreous protein concentration (p < 0.05). Differences in serum VEGF among the groups included in the study were not found. We conclude that the high vitreous levels of VEGF observed in diabetic patients with PDR cannot be attributed to serum diffusion across the blood-retinal barrier. Therefore, intraocular synthesis is the main contributing factor for the high vitreous VEGF concentrations observed in PDR.

Adult↗
PubMed1997

Girls diagnosed with premature pubarche show an exaggerated ovarian androgen synthesis from the early stages of puberty: evidence from gonadotropin-releasing hormone agonist testing.

OBJECTIVE: To assess the gonadotropin and ovarian steroid responses to the GnRH agonist (GnRH-a) leuprolide acetate (LA) in premature pubarche girls and in Tanner stage- and bone age-matched controls to ascertain whether the ovarian 17-hydroxyprogesterone (17-OHP) hyper-response to GnRH-a challenge present in some subsets of adolescent premature pubarche girls is detectable during puberty and whether these patients have a distinct pattern of pituitary-ovarian maturation. DESIGN: Cross-sectional study. SETTING: A university teaching hospital. PATIENT(S): Seventy-six premature pubarche girls (early pubertal [B2; n = 31], midpubertal [B3; n = 15], late pubertal [B4; n = 12], and postmenarcheal [B5; n = 18]) and 45 controls. INTERVENTION(S): Gonadotropins and plasma steroid hormones (17-OHP, 17-OH-pregnenolone [17-Preg], androstenedione [A], T, DHEA, DHEAS, E2, and cortisol) were measured before and 3 and 24 hours, respectively, after LA challenge (500 micrograms SC). MAIN OUTCOME MEASURE(S): Ovarian-steroidogenic responses to GnRH-a challenge. RESULT(S): Luteinizing hormone responsiveness increased significantly during puberty in all subjects whereas FSH levels changed less consistently. Peak E2 levels differed among pubertal stages and were significantly higher in premature pubarche girls than in controls at B4 and at B5. Both peak and incremental increases of 17-Preg and DHEA throughout puberty and of 17-OHP and A at B4 were significantly higher in premature pubarche girls than in controls. This pattern of ovarian-steroidogenic response was most evident during midpuberty and late puberty and resembled the adrenal hyper-response to ACTH of exaggerated adrenarche, suggestive of increased ovarian activity of both the 17 alpha-hydroxylase and the 17,20 lyase functions of cytochrome P450c17 alpha. CONCLUSION(S): Pubertal girls with a history of premature pubarche show a distinct pattern of ovarian maturation characterized by an exaggerated ovarian androgen synthesis throughout puberty.

17-alpha-Hydroxypregnenolone↗
PubMed1997

Pubertal changes in insulin secretion and peripheral insulin sensitivity.

Using a simple and standardized method we estimated both insulin secretion and insulin sensitivity in peripheral tissues in relation to Tanner pubertal stages. Early insulin response, mean blood glucose (MBG), mean serum insulin (MSI), glucose uptake rate in peripheral tissues and insulin sensitivity index (SI) in response to the standard oral glucose tolerance test were evaluated in 73 normal girls. Study subjects were divided into 4 groups: group 1 (Tanner stage I, n = 20); group 2 (Tanner stage II, n = 14); group 3 (Tanner stages III and IV, n = 15), and group 4 (Tanner stage V, n = 24). Steroid levels and insulin-like growth factors were determined to characterize clinical pubertal development. MBG was similar in all groups but MSI increased at stage II and retained similar values throughout puberty, with those of group I being statistically lower than in the other groups (p < 0.001). When MSI values were adjusted per kilogram of body weight, a significant increase was observed in group II (p < 0.05). The MSI adjusted values were: group 1, 1.0 +/- 0.4; group 2, 1.4 +/- 0.4; group 3, 1.0 +/- 0.3, and group 4, 1.0 +/- 0.4 mU/l/kg. SI values were similar in groups 1 and 2 and significantly lower than in groups 3 and 4 (p < 0.001). Our results confirm both that insulin secretion is related to age and that an insulin-resistant state occurs during puberty. Thus, the insulin-resistant state coincides with Tanner stage II. In conclusion, this mathematical approach is considered to be a simple and reliable method for analyzing the possible alterations in insulin secretion and action in children and adolescents in whom more sophisticated procedures must be limited in this early period of life for ethical reasons.

Adolescent↗
PubMed1997

Hyperinsulinemia and decreased insulin-like growth factor-binding protein-1 are common features in prepubertal and pubertal girls with a history of premature pubarche.

The fasting insulin resistance index, mean blood glucose, mean serum insulin (MSI), early insulin response to glucose, glucose uptake rate in peripheral tissues, and insulin sensitivity indexes in response to a standard oral glucose tolerance test; serum insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), IGFBP-3, and sex hormone binding-globulin (SHBG) levels; and the free androgen indexes were evaluated in 98 girls with premature pubarche [PP; prepubertal (B1; n = 32), early pubertal (B2; n = 27), midpubertal (B3; n = 23), and postmenarcheal (B5; n = 16)] and in 86 Tanner stage- and bone age-matched controls. We ascertained whether hyperinsulinemia is already present in PP girls before or during pubertal development and whether these patients show a similar pattern of growth factor secretion as normal girls. Body mass indexes did not differ significantly between patients and controls within the same pubertal stage. MSI levels showed a significant increase with pubertal onset in all subjects, as expected. Patients showed significantly higher MSI values than controls at all Tanner stages (P < 0.03, P = 0.03, P = 0.03, and P < 0.05 for B1, B2, B3, and B5, respectively); higher insulin response to glucose at B1, B2, and B3 (P < 0.03, P = 0.03, and P < 0.05, respectively); higher glucose uptake rate in peripheral tissues at B1 and B2 (P < 0.04 and P = 0.02, respectively); and a later rise in insulin sensitivity compared to controls. PP girls also showed lower IGFBP-1 levels at B1 and B5 (P < 0.01 and P = 0.02, respectively), lower SHBG concentrations at B5 (P < 0.0005), and higher free androgen indexes at B1, B3, and B5 (P < 0.01, P < 0.05, and P < 0.001, respectively) compared to controls. Among others, significant correlations between SHBG and MSI levels (r = -0.49; P < 0.0001) and between SHBG and IGFBP-1 levels (r = 0.41; P < 0.0001) were found in all subjects. Hyperinsulinemia, increased early insulin responses to glucose, increased glucose uptake rate in peripheral tissues, elevated free androgen indexes, and decreased SHBG and IGFBP-1 levels are present in most girls with PP from childhood. These findings lend strong support to the concept that PP is not a benign condition, and long term follow-up of these patients into adulthood is recommended. The possible causal role of hyperinsulinemia in adrenal and/or ovarian androgen hypersecretion remains to be established.

Adolescent↗
PubMed1997

Bone mineral density in prepubertal and in adolescent and young adult patients with the salt-wasting form of congenital adrenal hyperplasia.

OBJECTIVE: To evaluate bone mineral density (BMD) in prepubertal and in adolescent and young adult patients with the salt-wasting form of congenital adrenal hyperplasia (CAH). DESIGN: A relationship between bone mineral content and risk for osteoporotic fractures has been observed in adulthood. Infancy, childhood, and adolescence are critical periods for skeletal mineralization; thus, chronic diseases may impair bone mass peaking, particularly if children and adolescents are overexposed to glucocorticoids, as may occur in patients with CAH. Lumbar L2-L4 BMD values were measured by dual x-ray absorptiometry and compared with those of 471 age- and sex-matched controls. PATIENTS: Thirty-three patients with the salt-wasting form of CAH were studied. Sixteen (10 girls and 6 boys; age range, 1.5 to 8.3 years) were prepubertal and 17 (13 women and 4 men; age range, 17.1 to 28.2 years) were adolescent and young adults who had reached final height and had presented normal pubertal development and normal gonadal function thereafter. The average doses of hydrocortisone (mg/m body surface/day) received from diagnosis in the neonatal period to BMD evaluation were 21.2 +/- 2.2 and 22.3 +/- 2.6, respectively. RESULTS: Mean BMD Z score values were 0.16 +/- 1.01 in prepubertal patients and 0.06 +/- 1.02 in adolescent and young adult patients with no statistically significant differences with age- and sex-matched controls. Mean height Z score values were -0.03 +/- 1.13 in prepubertal patients and -1.13 +/- 0.62 in adolescent and young adult patients with significant differences between the latter and their respective age- and sex-matched controls. CONCLUSION: Long-term glucocorticoid therapy does not impair bone mass peaking in CAH patients with normal gonadal function, even though their adult height values are low.

Adolescent↗
PubMed1996

Ovarian 17-hydroxyprogesterone hyperresponsiveness to gonadotropin-releasing hormone (GnRH) agonist challenge in women with polycystic ovary syndrome is not mediated by luteinizing hormone hypersecretion: evidence from GnRH agonist and human chorionic gonadotropin stimulation testing.

Women with polycystic ovary syndrome (PCOS: hyperandrogenism and oligomenorrhea) have been shown to have exaggerated ovarian 17-hydroxyprogesterone (17-OHP) responses after GnRH agonist stimulation, suggestive of disordered ovarian cytochrome P450c17 alpha activity. However, most hyperandrogenic women also have an exaggerated LH response to both native GnRH and GnRH agonists. To assess whether the known LH hyperresponsiveness in PCOS patients mediates their exaggerated 17-OHP response to GnRH agonist challenge or whether the 17-OHP response can be duplicated by direct stimulation of the ovary with a fixed amount of hCG, 25 PCOS women [age, 20.6 +/- 1.1 yr; body mass index (BMI), 24.9 +/- 1.3 kg/m2] and 5 controls (age, 29.4 +/- 2.3 yr; BMI, 29.2 +/- 3.0) underwent both GnRH agonist (leuprolide acetate) and hCG testing. In addition, 23 normal women (age, 26.5 +/- 1.5 yr; BMI, 27.2 +/- 1.7 kg/m2) underwent hCG testing, and 21 other normal women (age, 19.3 +/- 0.5 yr; BMI, 23.0 +/- 0.8 kg/m2) underwent leuprolide acetate challenge. Blood was sampled before and 24 h after (the previously determined time of the peak response) leuprolide acetate (500 micrograms, sc) and hCG (5000 IU, im) stimulation tests. The tests were administered during the early follicular phase in women who were ovulatory and in randomized order in the subjects receiving both stimuli. Peak serum 17-OHP levels did not differ between leuprolide acetate or hCG stimulation in PCOS patients or controls when measured at 24 h (324.9 +/- 41.9 vs. 360.4 +/- 54.0 in PCOS; 183.2 +/- 19.6 vs. 141.2 +/- 11 ng/dL in controls). Peak 17-OHP levels after hCG challenge and GnRH agonist stimulation were highly correlated (r = 0.82; P < 0.001) in the subjects receiving both stimuli. Although leuprolide acetate elicited a higher estradiol (E2) response than hCG in all subjects, serum E2 levels increased significantly after hCG treatment in both patients and controls (P < 0.001 and P < 0.0001). The small, but significant, increase in serum E2 after hCG stimulation suggests that a rigid two-cell model of ovarian steroidogenesis may be an oversimplification of in vivo physiology. Our results suggest that exaggerated 17-OHP responses to GnRH agonist stimulation in hyperandrogenic women are not mediated by the known hyperresponsiveness of LH in these patients, but are due to increased ovarian androgen sensitivity to LH stimulation.

17-alpha-Hydroxyprogesterone↗
PubMed1996

Hyperinsulinemia in postpubertal girls with a history of premature pubarche and functional ovarian hyperandrogenism.

Previous studies have documented the association of insulin resistance and hyperandrogenism in adult women with functional ovarian hyperandrogenism (FOH) or polycystic ovary syndrome (a form of FOH). However, the possible impact of adrenal hyperandrogenism development during childhood in premature pubarche (PP) patients on postpubertal insulin secretion patterns remains unclear. The fasting insulin to glucose ratio, C peptide, early insulin response to glucose (IRG), mean blood glucose, mean serum insulin (MSI), glucose uptake rate in peripheral tissues (M), and insulin sensitivity indexes (SI) in response to a standard oral glucose tolerance test were evaluated in 13 PP girls with FOH (group A; age, 17.2 +/- 0.5 yr), 11 eumenorrheic nonhirsute PP girls (group B; age, 16.6 +/- 0.5 yr), and 21 age-matched controls (group C). Body mass indexes (BMI) were similar in the 3 groups (group A, 23.3 +/- 0.8; group B, 22.5 +/- 0.6; group C, 20.6 +/- 0.5 kg/m2). MSI values were significantly higher in FOH patients than in controls (74.7 +/- 17.6 vs. 45.7 +/- 4.1 mU/L; P < 0.01), but were not different from those in group B (63.3 +/- 11.1 mU/L). Thirty-eight percent of FOH patients (group A) and 27% of non-FOH patients (group B), all of whom had normal BMI, showed MSI levels well above the upper normal limit for controls (> 83.3 mU/L). MSI correlated with the degree of ovarian hyperandrogenism [defined by an abnormal 17-hydroxyprogesterone response to challenge with the GnRH analog leuprolide acetate; group A] and with the free androgen index [testosterone (nanomoles per L)/sex hormone-binding globulin (nanomoles per L) x 100; groups A and B)]. Although IRG, glucose uptake rate in peripheral tissues, mean blood glucose, and SI values were not significantly different in the 3 groups, 3 patients in group A and 1 patient in group B showed decreased insulin sensitivity and/or an enhanced early IRG. Among others, significant correlations between MSI and free androgen index values (r = 0.6; P < 0.002; groups A and B) and between BMI and SI (r = -0.53; P < 0.05; groups A and B) were found. Peak 17-hydroxyprogesterone responses to ACTH at PP diagnosis correlated positively with SI in both groups of patients (r = 0.53; P < 0.007). Hyperinsulinemia is a common feature in adolescent PP patients with FOH and appears to be directly related to the degree of androgen excess. Long term follow-up of PP patients into adulthood is warranted to ascertain whether hyperinsulinemia actually precedes FOH development and whether overt insulin resistance ensues.

Adolescent↗
PubMed1996

Growth hormone secretion assessment in the diagnosis of short stature.

Growth hormone (GH) secretion assessment in the diagnosis of short stature presents certain problems in relation to the protocols designed for it and the interpretation of results. GH measurement in serum may be accompanied by IGF-I and IGFBP-3 measurements, and in some patients by GHBP measurement. Protocols for evaluating GH response to acute stimuli or spontaneous secretion are tedious, sometimes hazardous and difficult to interpret. This is due to the wide variation in responses observed in normally-growing children, to the age-dependent changes in these parameters and, in the case of GH, to the wide variation in immunoassay results. New techniques able to measure biologically-active GH molecules circulating in blood may help to simplify diagnosis. Severe idiopathic or organic GH deficiency poses no diagnostic problems. GH secretory insufficiency may be diagnosed as partial, idiopathic, isolated GH deficiency or as neurosecretory dysfunction. Clear cut-off values for these diagnoses and the possibility of a transient reversible pathology are not well established. Analysis of large series of children with different diagnoses in whom the growth pattern, either spontaneous or under rhGH treatment, final height and GH secretion re-evaluation at the end of growth were studied will help to clarify GH secretion or action abnormalities in these patients.

Adolescent↗