Normal Prepubertal Girls Research Articles

Pelvic Ultrasound in Diagnosing and Evaluating the Efficacy of Gonadotropin-Releasing Hormone Agonist Therapy in Girls With Idiopathic Central Precocious Puberty.

Background and Objective: Idiopathic central precocious puberty (ICPP) is characterized by early pubertal changes, the acceleration of growth velocity, and rapid bone maturation that often results in reduced adult height. Gonadotrophin-releasing hormone agonist (GnRHa) is currently considered to be an effective therapeutic agent. At present, GnRH stimulation test is adopted as a gold standard for the diagnosis of ICPP and the efficacy evaluation of GnRHa therapy. However, it is difficult to operate in practice due to the cumbersome procedures and multiple blood samples required. This study was conducted to establish the value of pelvic ultrasound in diagnosing ICPP and evaluating the efficacy of GnRHa therapy.Materials and Methods: One hundred and twenty-two girls with ICPP (ICPP group) were enrolled in the study. Pelvic ultrasound and levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were examined before and after GnRHa therapy for 3 months. Eighty normal prepubertal girls were enrolled as the control group. The difference in pelvic ultrasound parameters between the ICPP group before GnRHa therapy and the control group was compared by independent-sample t-test, while paired t-test for ICPP group before and after GnRHa therapy. Receiver operating characteristic (ROC) curve was used to explore the optimal pelvic ultrasound parameters for diagnosing ICPP. Pearson correlation analysis was performed between the pelvic ultrasound parameters and serum sexual hormone level.Results: The pelvic ultrasound parameters (length of the uterine body, anteroposterior diameter of the uterine body, transverse diameter of the uterine body, volume of the uterine body, uterine body-cervix ratio, length of the ovary, transverse diameter of the ovary, anteroposterior diameter of the ovary, volume of the ovary, number of increased follicles and maximum diameter of the follicle) in the ICPP group before GnRHa therapy were significantly larger than those of the control group (P < 0.05). All the above pelvic ultrasound parameters in the ICPP group were significantly decreased after GnRHa therapy compared with those before treatment (P < 0.05). The volume of the uterine body had the largest area under the ROC curve in differentiating between patients with ICCP and the control group. Pelvic ultrasound parameters were significantly correlated with serum sexual hormone levels (P < 0.05).Conclusion: This study indicates pelvic ultrasound is a simple and reliable tool to diagnose ICPP and evaluates the efficacy of GnRHa therapy by dynamically observing the morphology of internal genitalia. The volume of uterine body was the best ultrasound parameter to distinguish patients with ICPP from normal girls.

Anti-Müllerian Hormone in Girls with Premature Adrenarche: The Impact of Polycystic Ovary Syndrome History in their Mothers

To assess whether the serum levels of anti-Müllerian hormone (AMH) are increased in girls with premature adrenarche because they are at a higher risk of developing polycystic ovary syndrome (PCOS) later in life. We measured serum levels of AMH, dehydroepiandrosterone sulfate (DHEAS), testosterone, sex hormone binding globulin, androstenedione, and 17-hyroxyprogesterone in 89 girls with premature adrenarche aged 6.98 ± 1.60 years, and in 55 prepubertal normal girls aged 6.78 ± 1.60 years. AMH was significantly higher in girls with premature adrenarche (2.95 ± 1.20 ng/mL) compared with normal prepubertal girls (2.00 ± 0.95 ng/mL; P < .001), whereas their body mass index SD score was similar (P > .05). DHEAS, testosterone, and androstenedione were increased in premature adrenarche, whereas sex hormone binding globulin was decreased in girls with premature adrenarche. Among the 89 girls with premature adrenarche, 33 were daughters of mothers with a positive history of PCOS, whereas the mothers of the remaining 56 girls with premature adrenarche had a negative history of PCOS. The girls with a mother with a positive history of PCOS had significantly higher AMH serum levels compared with girls with a mother with a negative history of PCOS (3.37 ± 1.72 ng/mL vs 2.70 ± 1.25 ng/mL; P < .05) with no differences in testosterone, DHEAS, androstenedione, and sex hormone binding globulin. The serum concentration of AMH was only positively related to androstenedione (r = 0.538; P < .0001). Girls with premature adrenarche, especially those from mothers with a history of PCOS, could have a higher risk of developing PCOS later in life because they have increased serum AMH.

Premature Thelarche in Taiwanese Girls

This study was conducted to understand the clinical features and natural course of Taiwanese girls with premature thelarche (PT). The medical records of 91 Taiwanese girls with PT who were diagnosed younger than six and have been regularly followed up for more than two years were reviewed. For comparison, GnRH test was also done in 25 girls with central precocious puberty (CPP) and 10 normal prepubertal girls. The age of onset of these patients was 1.5 +/- 1.6 years and 79% of them developed PT before the age of two. Girls with PT had intermediate degree of hypothalamic-pituitary-ovarian activity between prepuberty and CPP with FSH-predominant response to GnRH stimulation. 87% of patients have complete regression of breast development during 3.8 +/- 2.5 years' follow-up but 19% of them have progressed to CPP during follow-up. We conclude that Taiwanese girls with PT more often developed within the first two years of life. Activation of hypothalamic-pituitary-gonadal axis with predominant FSH activity during infancy may contribute to its development. In addition, PT is not always a benign self-limited condition, and clinicians should be cautious about pubertal development of these patients.

Diagnostic Utility of a Low-Dose Gonadotropin-Releasing Hormone Test in the Context of Puberty Disorders

Objectives: The 10-µg gonadotropin-releasing hormone (GnRH) test assesses pituitary gonadotroph responsiveness, whereas the 100-µg dose assesses maximal secretory capacity. Our aims were to establish normative data for the low-dose test in children and to evaluate the test in diagnosing common pubertal disorders. Methods: We retrospectively classified 107 children who underwent 10-µg GnRH tests into normal prepubertal (20 boys, 10 girls), normal early pubertal (10 boys, 16 girls), constitutional delay of puberty (CDP, 13 prepubertal boys >12 years), hypogonadotropic hypogonadism (HH, 5 prepubertal boys >12 years), central precocious puberty (CPP, 19 girls) or premature thelarche/variant (13 girls). Results: Peak LH response was higher in prepubertal boys >12 years compared with younger boys (p < 0.01) but showed no further change in early puberty. CDP boys had LH responses similar to prepubertal boys >12 years. HH boys showed an absent LH response which diagnosed HH with 100% sensitivity and 96% specificity. Thelarche girls had LH:FSH peak ratios lower than normal prepubertal (p = 0.001), pubertal (p < 0.05) or CPP (p = 0.001) girls. Conclusions: We have established normative values for the low-dose GnRH test in children. The test successfully differentiated HH from CDP in boys, and contributed to the differential diagnosis of CPP and premature thelarche in girls.

Early Adrenarche in Normal Prepubertal Girls: A Prospective Longitudinal Study

To study basal and ACTH stimulated levels of dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), and cortisol (F) in healthy girls during prepuberty. Six prepubertal girls, ages 3.7-10.9 years. The six girls underwent a physical examination and an acute ACTH stimulation test on a yearly basis. Serum DHEA, DHEAS, A4, and F at 0 min (Steroid0) and 60 min (Steroid60) after 0.25 mg ACTH1-24 i.v., and the net increment (delta Steroid60-0) were calculated. DHEAS0, DHEAS60, DHEA0, DHEA60 and A40 were positively correlated to chronological age. DHEAS0 and DHEAS60 levels rose gradually beginning at 6.1-7.0 years of chronological age, and were found to be significantly different at 9.1-10.0 years and 10.1-11.0 years of age, compared to the median values obtained at < or =6.0 years of age. There was a tendency for DHEA0, DHEA60, and A40 to increase beginning at 9.1-10.0 years of age. Net increment values of all hormones did not change throughout the study. An increase in the circulating level of DHEAS appears to be the first event observed during adrenarche, prior to clinical evidence of the process.

Relationship between the growth hormone/insulin-like growth factor-I axis, insulin sensitivity, and adrenal androgens in normal prepubertal and pubertal girls.

The aim of this study was to analyze the possible implication of changes in the GH/IGF-I axis and in insulin sensitivity for the regulation of adrenal androgen secretion of normal prepubertal and adolescent girls. A total of 61 normal girls were evaluated in prepuberty [Group (Gr)1, n = 33; early (Gr1A, n = 16) and late (Gr1B, n = 17)]; puberty (Gr3, n = 28), early (Gr3A, n = 9) and late (Gr3B, n = 19); and during the transition between prepuberty and puberty (Gr2, n = 26). Insulin sensitivity was estimated by the fasting glucose/insulin ratio (G/I). In Gr1, G/I was significantly higher, and the mean serum IGF-I and serum dehydroepiandrosterone sulfate (DHEAS) were significantly lower than in Gr3 (P < 0.0001). Mean G/I in Gr1A and Gr3A was significantly higher than in Gr1B (P < 0.01) and Gr3B (P < 0.02), respectively, and ratios in Gr1B were also significantly higher than in Gr3A (P < 0.02). However, body mass index (BMI) in Gr1A, Gr1B, and Gr3A was not significantly different, although a significant increment was observed between late prepuberty (Gr1B) and late puberty (Gr3B; P < 0.0001). On the other hand, serum IGF-I levels in Gr1A and Gr3A were significantly lower than those in Gr1B (P < 0.01) and Gr3B (P < 0.02), respectively. The mean serum DHEAS level in Gr1A and Gr3A was significantly lower than in Gr1B (P < 0.01) and Gr3B (P < 0.02), respectively, and the level in Gr1B was also significantly lower than in Gr3A (P < 0.02). Correlation studies within Gr1, Gr2, and Gr3 were also performed. There was a significant positive correlation between serum DHEAS and age and a significant negative correlation between serum DHEAS and G/I in the three groups. However, a significant positive correlation between serum DHEAS and serum IGF-I was only found in Gr1. Furthermore, a significant negative correlation between BMI and the G/I was found in Gr2 and Gr3. Therefore, changes in insulin sensitivity might be involved in adrenal androgen synthesis both in prepuberty and in puberty, as well as during the transition from prepuberty to puberty. Changes in BMI suggest that adiposity might be a mediator of this effect, particularly during late puberty. On the other hand, the GH/IGF axis might be an important metabolic signal involved in the maturational changes of human adrenal androgens during prepuberty, at the time of adrenarche. Indeed, a significant negative correlation between G/I and serum IGF-I was found in Gr1, as well as in Gr2. In conclusion, the findings of this study indicate that the GH/IGF-I axis and insulin resistance might be involved in the mechanism of adrenarche during prepuberty in normal girls. Because these relationships had not been seen in boys, we proposed that prepubertal ovarian estrogens might be responsible for the sex difference. The relationship between insulin resistance and adrenal androgens persists during the transition from prepuberty to puberty, as well as during puberty.

Estradiol levels in girls with Turner's syndrome compared to normal prepubertal girls as determined by an ultrasensitive assay.

Based on growing evidence that estradiol is produced in small amounts even in the prepubertal ovary, we hypothesized that estradiol levels in girls with Turner's syndrome (TS) are lower than in normal prepubertal girls secondary to the lack of normally functioning ovaries. Estradiol levels in untreated girls with TS have not been previously well defined because of the lack of adequate sensitivity of previously available estradiol assays. We utilized an ultrasensitive assay to study estradiol levels in 34 girls with TS and 34 normal age-matched prepubertal girls between the ages of 5 and 12 years. The average estradiol level in the girls with TS (6.4 +/- 4.9 pmol/l estradiol equivalents) was significantly lower than in the normal prepubertal girls (12.7 +/- 10.8 pmol/l estradiol equivalents; p < 0.01). Girls with TS were significantly shorter, and weighed less than the normal prepubertal girls, as expected. The estradiol level was not significantly correlated with height, bone age, or degree of bone age delay. In conclusion, girls with TS have significantly lower estradiol levels than normal age-matched prepubertal girls. This report is consistent with the hypothesis that the lack of normal ovarian function in girls with TS is evident even before puberty.

Serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 in girls with premature thelarche.

Premature thelarche (PT) is characterised by precocious breast development without any other sign of puberty, normal height velocity (HV) and normal bone maturation, while girls with central precocious puberty (CPP) show increased HV, bone maturation and increased serum IGF-I and IGFBP-3 levels. This prompted us to study serum IGF-I and IGFBP-3 concentrations in girls with PT. Thirty-nine girls with premature breast development were studied and classified as PT or CPP according to clinical and laboratory evaluation. Normal prepubertal and pubertal girls were studied as controls. Serum IGF-I and IGFBP-3 were determined in all girls by IRMA. IGF-I levels in PT (155 +/- 61 microg/l) were lower than in CPP (337 +/- 149 microg/l) or late-pubertal controls (355 +/- 84 microg/l) and similar to those found in prepubertal (113 +/- 72 microg/l) and early-pubertal (222 +/- 81 microg/l) girls. Considering the SDS of IGF-I for chronological age (CA), the values observed in PT were in an intermediate position between CPP and prepubertal controls and statistically similar to those observed in CPP and prepubertal girls. IGFBP-3 levels in PT (2.1 +/- 0.5 mg/l) were similar to those found in CPP (2.5 +/- 0.8 mg/l), but only the latter were higher than in prepubertal girls (1.9 +/- 0.9 mg/l). IGF-I/IGFBP-3 molar ratios in PT were in an intermediate position between CPP and prepubertal controls. In conclusion, IGF-I and IGF-I/IGFBP-3 values in PT are intermediate between those observed in prepubertal children and in CPP, suggesting that PT could be a very early stage of puberty with slight but real changes in the GH-IGF axis.

A new recombinant cell bioassay for ultrasensitive determination of serum estrogenic bioactivity in children.

The evaluation of estrogenic status is necessary for many physiological and pathological conditions in pediatric as well as adult endocrinology. Because current immunoassays exclusively measure E2--and with a sensitivity that is insufficient for prepubertal children--we developed a new recombinant cell bioassay for ultrasensitive determination of serum estrogenic bioactivity. This assay is based on human uterine cervix carcinoma cells, HeLa cells, that do not naturally express E2 receptor. These cells were transfected with plasmids encoding the human ERalpha or beta, along with an estrogen-responsive promoter fused to the luciferase gene, and called HELNalpha and HELNbeta for HeLa estrogen-responsive element luciferase neomycin alpha and beta. HELNalpha and HELNbeta are able to respond to estrogens and various compounds having estrogenic activity but, because of the importance of ERalpha in the reproductive function, we chose to work with the HELNalpha cell line. The luciferase activity we obtained was compared with an E2 standard curve specific for each serum sample and established with stripped serum. The estrogenic bioactivity was expressed in picograms of E2 equivalents, and the detection limit was < 1 pg x ml(-1) E2 equivalents. The intra and interassay error was lower than 10% and 20%, respectively. We measured estrogenic bioactivity in 18 normal prepubertal boys (age = 9.7 +/- 2.4 yr), 18 normal prepubertal girls (age = 9.2 +/- 1.7 yr) and 18 normal pubertal girls (age = 13.6 +/- 1.8 yr). The estrogenic bioactivity in the prepubertal girls was significantly higher than in the boys, i.e. 3.53 +/- 2.23 pg x ml(-1) vs. 1.44 +/- 0.87 pg x ml(-1) (P < 0.01). A significant difference was found between the pre- and pubertal girls, i.e. 3.53 +/- 2.23 pg x ml(-1) vs. 26.77 +/- 18.32 pg x ml(-1) (P < 0.01). This ultrasensitive bioassay measures total estrogenic bioactivity of serum with very high sensitivity. It has numerous potential applications in pediatric and adult endocrinology. In addition, this assay may help to evaluate excess estrogenic activity related to aromatase overexpression or contamination by environmental chemicals.

Reduced spontaneous growth hormone secretion in patients with Turner's syndrome

Pirazzoli P, Mazzanti L, Bergamaschi R, Perri A, Scarano E, Nanni S, Zucchini S, Gualandi S, Cicognani A, Cacciari E. Reduced spontaneous growth hormone secretion in patients with Turner's syndrome. Acta Pædiatr 1999; 88: 610‐3. Stockholm. ISSN 0803‐5253We evaluated growth hormone (GH) secretion in 81 patients with Turner's syndrome (TS) (mean age 10.7 ± 3.6 y) with respect to karyotype, auxological characteristics and growth response to GH treatment (1 IU/kg/wk). None of the patients had spontaneous puberty or had started replacement therapy with estrogens. Thirty‐nine patients (48%) had monosomia 45X, 29 (36%) structural abnormalities of the X chromosome and 13 (16%) X mosaicism. Before the start of GH therapy, each patient underwent an evaluation of mean nocturnal GH concentration (MGHC) and 75 patients also underwent 2 pharmacological tests. MGHC of the TS patients did not differ from that of 29 prepubertal GH‐deficient girls (GH peaks &lt; 8 μg/l after pharmacological tests) and both groups were lower (p &lt; 0.0001 and p &lt; 0.0005, respectively) than MGHCs of 27 short normal girls (GH peak &gt; 8 μg/l). MGHC of the patients with TS was negatively correlated (p &lt; 0.001) with bodyweight excess (BWE) at multiple regression analysis. MGHC of the TS patients with BWE &lt; 20% was significantly higher (p &lt; 0.02) than that of the TS patients with BWE &gt; 20%, but again did not differ from that of the GH‐deficient patients and was lower (p &lt; 0.001) than that of the short normal girls. MGHC did not significantly differ between the 3 groups subdivided according to karyotype. Forty‐four percent of the TS patients showed GH responses to pharmacological tests &lt; 8 μg/l. Height velocity SDS at first and second year of therapy was not influenced by MGHC levels, chronological or bone age, target height or BWE. In conclusion, spontaneous secretion in our patients with TS was lower than that of the short normal prepubertal girls and did not differ from that of GH‐deficient subjects, even if we excluded overweight patients. The level of GH secretion was unable to predict GH response to treatment. □Bodyweight excess, growth hormone secretion, growth hormone therapy, Turner's syndrome

Estrogen levels in girls with premature thelarche compared with normal prepubertal girls as determined by an ultrasensitive recombinant cell bioassay

Objective: Estradiol levels in girls with premature thelarche have not previously been well defined because of the lack of adequate sensitivity of previously available estradiol assays. The ultrasensitive recombinant cell bioassay for estradiol has made the study of estradiol levels in premature thelarche possible. We hypothesized that girls with premature thelarche have higher estradiol levels than normal prepubertal girls. Study design: We used an ultrasensitive recombinant cell bioassay to study estradiol levels in 20 girls with premature thelarche and 15 normal prepubertal girls less than 3 years of age. The 2 groups were compared by Student t test. Results: Estradiol levels were significantly greater in the girls with premature thelarche (8.4 ± 4.5 pmol/L estradiol equivalents) than in the normal prepubertal girls (3.3 ± 3.5 pmol/L estradiol equivalents; P < .01). The estradiol level was not significantly correlated with age, height, weight, body mass index, age at onset of thelarche, or the presence or absence of ovarian cysts. Conclusion: Girls with premature thelarche have significantly higher estradiol levels than normal prepubertal girls. This is consistent with the hypothesis that the mechanism of premature thelarche involves increased estradiol levels rather than increased sensitivity of breast tissue to normal estradiol levels. (J Pediatr 1999;134:190-2)

Reduced spontaneous growth hormone secretion in patients with Turner's syndrome.

We evaluated growth hormone (GH) secretion in 81 patients with Turner's syndrome (TS) (mean age 10.7+/-3.6 y) with respect to karyotype, auxological characteristics and growth response to GH treatment (1 IU/kg/wk). None of the patients had spontaneous puberty or had started replacement therapy with estrogens. Thirty-nine patients (48%) had monosomia 45X, 29 (36%) structural abnormalities of the X chromosome and 13 (16%) X mosaicism. Before the start of GH therapy, each patient underwent an evaluation of mean nocturnal GH concentration (MGHC) and 75 patients also underwent 2 pharmacological tests. MGHC of the TS patients did not differ from that of 29 prepubertal GH-deficient girls (GH peaks < 8 microg/l after pharmacological tests) and both groups were lower (p < 0.0001 and p < 0.0005, respectively) than MGHCs of 27 short normal girls (GH peak > 8 microg/l). MGHC of the patients with TS was negatively correlated (p < 0.001) with bodyweight excess (BWE) at multiple regression analysis. MGHC of the TS patients with BWE < 20% was significantly higher (p < 0.02) than that of the TS patients with BWE > 20%, but again did not differ from that of the GH-deficient patients and was lower (p < 0.001) than that of the short normal girls. MGHC did not significantly differ between the 3 groups subdivided according to karyotype. Forty-four percent of the TS patients showed GH responses to pharmacological tests < 8 microg/l. Height velocity SDS at first and second year of therapy was not influenced by MGHC levels, chronological or bone age, target height or BWE. In conclusion, spontaneous secretion in our patients with TS was lower than that of the short normal prepubertal girls and did not differ from that of GH-deficient subjects, even if we excluded overweight patients. The level of GH secretion was unable to predict GH response to treatment.

DHEA-S, IGF-I, and IGFBP-1 and -3 Relationships to Insulin and Body Fat in Normal Prepubertal Caucasian, African-American, and Hispanic Girls † 427

Although premature adrenarche (defined as precocious appearance of pubic or axillary hair) is more common in African-American girls, ethnic differences in adrenal androgen secretion in normal prepubertal girls have not been described. We examined ethnic differences in circulating serum levels of DHEA-S, IGF-1, IGFBP-1 and -3, and insulin in healthy prepubertal [Tanner stage I] Caucasian, African-American and Hispanic girls. Body fat was determined by dual-energy x-ray absorptiometry. Forty-seven girls (19 Caucasian, 9 African-American, 19 Hispanic) between the ages of 7.5 and 9 yr were enrolled. Age, weight, height, insulin, glucose-insulin ratios, and IGFBP-3 levels were not statistically different among groups. Body mass index and% fat were higher in Hispanic girls (p<0.017; p<0.004, respectively) but not different between African-Americans and Caucasians. Despite similar insulin levels among groups, IGFBP-1 levels were higher in Caucasian than in Hispanic (p<0.002) and African-American (p<0.0001) girls. DHEA-S levels in the African-Americans were twofold higher than in the Caucasians(p<0.004), despite the fact that African-Americans and Caucasians were equally lean (16.1% vs 19.4% body fat; p=0.138), whereas those of Hispanics were intermediate. Plasma IGF-I levels also were higher in African-Americans than in Caucasians (319 ng/ml vs 219 ng/ml; p<0.02) while no significant difference was seen between the Caucasians and Hispanics. Conclusions: (1) In African-American girls, DHEA-S concentrations are higher than those of Caucasian girls, even without clinical evidence of premature adrenarche; (2) These ethnic differences are unrelated to body fat or insulin resistance; (3) Elevated DHEA-S and IGF-I levels in African-American girls may be indicative of an influence not only of gonadal but also of adrenal steroids on the GH/IGF-I axis.

Diagnostic Value of Basal and Stimulated Levels of Gonadotropins Measured By An Immunofluorometric Assay (Ifma) in the Differential Diagnosis of Precocious Puberty. 20

The new immunofluorometric kits such as DELFIA (Wallac, Turku, Finland) have an improved sensitivity and may allow a better discrimination between patients with gonadotropin dependent (GDPP) and independent (IGPP) precocious puberty. Normal prepubertal girls had gonadotropin levels measured by DELFIA kits under basal conditions (n = 20) and after stimulation with 100 μg iv GnRH (n = 10). Basal LH and FSH levels were 0.7 U/L) and FSH (> 3.4 U/L) may establish the diagnosis of GDPP, precluding the use of GnRH stimulation tests. In contrast, basal prepubertal concentrations of LH and FSH may occur in both GDPP and IGPP, indicating the need to perform GnRH stimulation tests.

Vitamin D-receptor gene polymorphisms and bone density in prepubertal American girls of Mexican descent.

Bone mass is under strong genetic control, and recent studies in adults have suggested that allelic differences in the gene for the vitamin D receptor may account for inherited variability in bone mass. We studied the relations of the vitamin D-receptor genotype to skeletal development and variation in the size, volume, and density of bone in children. We identified three allelic variants of the vitamin D-receptor gene using the polymerase chain reaction and three restriction enzymes (ApaI, BsmI, and TaqI) in 100 normal prepubertal American girls of Mexican descent. We then determined the relations of the different vitamin D-receptor genotypes (AA, Aa, aa, BB, Bb, bb, TT, Tt, and tt) to the cross-sectional area, cortical area, and cortical bone density of the femoral shaft and the cross-sectional area and density of the lumbar vertebrae. The vitamin D-receptor genotype was associated with femoral and vertebral bone density. Girls with aa and bb genotypes had 2 to 3 percent higher femoral bone density (P=0.008 and P=0.04, respectively) and 8 to 10 percent higher vertebral bone density (P=0.01 and P=0.03, respectively) than girls with AA and BB genotypes. There was no association between the cross-sectional area of the vertebrae or the cross-sectional or cortical area of the femur and the vitamin D-receptor genotype. The chronologic age, bone age, height, weight, body-surface area, and body-mass index did not differ significantly among girls with different vitamin D-receptor genotypes. Vitamin D-receptor gene alleles predict the density of femoral and vertebral bone in prepubertal American girls of Mexican descent.

Estrogen Levels in Girls with Premature Thelarche Compared to Age Matched Normal Prepubertal Girls as Determined by an Ultrasensitive Recombinant Cell Bioassay. † 395

Estrogen Levels in Girls with Premature Thelarche Compared to Age Matched Normal Prepubertal Girls as Determined by an Ultrasensitive Recombinant Cell Bioassay. † 395

EVALUATION OF HYPOTHALAMIC-PITUITARY-GONADAL (HPG) FUNCTION IN PATIENTS WITH TURNER SYNDROME (TS) WITH THE GnRH ANALOG (GnRHa) SUBACUTE TEST

We have previously described that a GnRH test (100 ug of SC Buserelin acetate administered twice at a 24 hs interval) can be used to evaluate the HPG axis in normal prepubertal girls (J Pediat 122:46,1993). In order to evaluate ovarian steroidogenic capacity and the role of sex steroids (SS) in the regulation of pituitary gonadotropins LH and FSH at late prepuberty (Pre), a GnRHa test was carried on in 14 girls with TS and bone ages (BA) between 6.16 and 12 years (y). Serum LH, FSH and E2 was evaluated in basal (B) conditions. 24 hs after the first and 4, 6 and 24 hs after the second injection of Buserelin. A positive response of serum E2 (E2≥55 pmol/L) was only detected in 4 patients. To evaluate LH and FSH responses, patients were divided into 2 groups (Gr) as a function of E2 response: Gr1(E2 ≥55pmol/L), mean±SD chronological age (CA) 9.94±1.84 y and BA 7.41±1.33 y and Gr2 (E2 <55pmol/L, n=10), CA 11.5±3.34 y and BA 9.97±2.49 y. BA was similar in the two groups. B LH and FSH in Gr1 was significantly lower than in Gr2: Median(M) LH was 0.31 (r:0.15-0.49) and 6.79 (r:0.1-54.1) while M FSH was 12.5(r:8.07-17.5) and 43.8(r:8.81-135) U/L, respectively, p<0.05 Dunn's test. Serum LH response to GnRHa was significantly different between Gr1 and Gr2 only 24 hs after the second stimulation (median 1.09, r:0.31-6.6 and 5.1, r:1.21-58, respectively, p<0.05). FSH was similar in the two groups at every sampling time. Conclusions: 1) the GnRHa test in TS is useful to evaluate the steroidogenic capacity of the ovary, 2) lack of difference in FSH response to GnRHa in the two groups would suggest similar ovarian inhibin deficiency, and 3) the differences between Gr1 and Gr2 in B LH and in LH 24 hs after the second GnRHa stimulation suggest that ovarian SS play a role in the regulation of LH secretion in late prepuberty as well as in early puberty.

27 ANDROGEN PATTERN IN PREPUBERTAL HYPERTRICHOSIS

The cause of prepubertal hypertrichosis (H) is unknown. Plasmatic androgen levels were determined in 17 girls with H, (ca: X±SD: 5.5±1.41 years), 11 girls with precocious pubarche (PP) and 9 normal prepubertal girls (CP). All of them were assesed according to their distribution score of vellus hair. Group H. was characterized by excessive growth of vellus hair (score>7), CP showed normal distribution and PP group had pubic hair II-III without excessive growth of vellus hair (score<5)17OH Progesterone, Androstenedione (A), DHEA-S, Testosterone (T), SHBG and 3 Androstanediol glucoronide(3 AG)were measured by RIA. Normal levels of A and DHEA-S and elevated 3 AG levels suggest an increase in the peripheral activity of 5 reductase in most prepubertal girls with hypertrichosis.

MONTHLY URINARY GONADOTROPIN AND OVARIAN HORMONE SECRETORY PATTERNS IN NORMAL CHILDREN AND PATIENTS WITH IDIOPATHIC PRECOCIOUS PUBERTY

We have already reported a simple and improved method for the quantification of urinary gonadotropins needed in amounts of urine smaller than those previously reported. Good correlation was observed between urinary gon-adotropin and ovarian steroid/creatinine ratios in first morning voided(FMV) urine and 24-h urine collections in children. Using consecutive 30-d FMV urine specimens from 29 normal children and from 9 patients with idiopathic precocious puberty, we have studied the monthly patterns of nighttime gonadotropin and ovarian steroid excretions. Urinary LH levels in normal prepubertal girls were low with few fluctuations. FSH levels were higher and showed remarkable, episodic fluctuations. In early pubertal girls, urinary LH and FSH excreted with alternate every other day variations at the same time. Their urinary total estrogen excretions remained low levels. In mid-pubertal girls, urinary LH excretion increased to near the levels of urinary FSH and they fluctuated with alternate every other day variations. Urinary total estrogen also increased and fluctuated with an opposite way to these variations in urine LH and FSH. With progressive sexual maturation, urine LH excretion increased. The cycle of a normal postmenarcheal girl aged 14 years showed a pattern similar to those of normal adults. In patients with idiopathic precocious puberty, those hormonal patterns showed similar to those of normal subjects matched for sexual stage. Measuring monthly urinary gonadotropins and ovarian steroids seems to be useful to investigate the process of sexual maturation and the endocrine requirements for ovulation.

Decreased Metabolic Clearance of Endogenous Growth Hormone and Specific Alterations in the Pulsatile Mode of Growth Hormone Secretion Occur in Prepubertal Girls with Turner's Syndrome*

We have used deconvolution analysis to test the hypothesis that specific facets of GH secretion and clearance differ in young patients with Turner's syndrome and normal prepubertal girls. To this end, we sampled blood at 20-min intervals for 12 h overnight in 50 girls, 37 of whom had Turner's syndrome and 13 of whom were healthy Tanner stage I controls. Deconvolution analysis revealed that the half-life of endogenous GH in Turner's syndrome was significantly prolonged at 14 +/- 0.93 vs. 11 +/- 0.44 min in normal girls (P = 0.029). The number of significant GH secretory bursts was reduced in Turner's patients to 4.7 +/- 0.27 vs. 6.8 +/- 0.60 events/12 h in healthy girls (P less than 0.01). GH secretory burst half-duration was significantly prolonged in Turner's syndrome, viz. 23 +/- 1.3 vs. 15 +/- 0.87 min (controls; P less than 0.001). The changes in GH secretory burst frequency, duration, and half-life were specific, since neither the mass of GH secreted per burst nor the maximal rate of GH secretion attained per burst (amplitude of the secretion pulse) was significantly different in the 2 study groups. Thus, although 12-h GH secretion rates corrected for body weight were similar (3.9 +/- 0.76 in Turner's patients and 3.3 +/- 0.76 micrograms/L.kg/12 h in the control girls), equivalent GH production rates were achieved by different mechanisms in the 2 groups. We conclude that specific alterations in GH secretory burst frequency and duration and endogenous GH half-life can be documented in young girls with Turner's syndrome.