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Biomedical subjects

M E Escobar

Publications and source records attributed to M E Escobar.

At least 19 recordsLinked to original sources
PubMed2003

Interaction of sodium nitroprusside/liposome system with bovine serum albumin: a short-cut determination.

A rapid determination of protein-liposome binding was developed to predict the circulation time of the system within an animal, which is a function of the amount and type of protein bound. The binding pattern of albumin to liposomes, with and without sodium nitroprusside (SNP), was analyzed by SDS-PAGE. Liposomes were made of egg yolk lecithin, soybean lecithin and dimyristoyl lecithin, and contained SNP. They bound 58%, 26% and 100% bovine serum albumin, respectively, when compared to their corresponding controls lacking SNP. The method applied is simpler and significantly faster than ordinary chemical determinations.

Animals↗
PubMed2001

Disruption of the joint synchrony of luteinizing hormone, testosterone, and androstenedione secretion in adolescents with polycystic ovarian syndrome.

The present study explores the postulate that the polycystic ovarian syndrome (PCOS) is marked by failure of physiological feedforward and feedback signaling between pituitary LH and ovarian androgens. To this end, we appraised the 3-fold simultaneous overnight release of LH (assayed by high precision immunofluorometry), testosterone (RIA), and androstenedione (RIA) in 12 an- or oligoovulatory adolescents with PCOS (mean +/- SEM age, 16.4 +/- 0.47 yr) and 10 eumenorrheic girls (age, 16.5 +/- 0.45 yr). Gynecological (postmenarchal) ages (years) were also comparable at 4.8 +/- 0.39 (PCOS) and 4.0 +/- 3.6 (control; P = NS). Body mass index and fasting serum insulin and estradiol concentrations were indistinguishable in the two study cohorts. Mean overnight serum concentrations of LH (assayed by both immunofluorometry and Leydig cell bioassay), testosterone, androstenedione, and 17alpha-hydroxyprogesterone were each elevated significantly in patients with PCOS (all P </= 0.027). The bivariate cross-approximate entropy (cross-ApEn) statistic was used as a sensitive barometer of altered within-axis feedback. This scale-invariant metric is designed to quantitate the joint synchrony of putatively linked (neurohormone) time series in a lag-independent pattern-sensitive manner. Here, we applied cross-ApEn to the coupled release of LH and testosterone, LH and androstenedione, and testosterone and androstenedione. Statistical comparisons of the two adolescent study cohorts unveiled consistently elevated cross-ApEn in patients with PCOS, denoting disruption of the pairwise synchrony of LH and testosterone (P = 0.0055), LH and androstenedione (P = 0.0076), and testosterone and androstenedione (P = 0.014) secretion. As an analytically distinct technique to monitor coordinate hormone release, we also applied cross-correlation analysis with variable lag. This appraisal revealed that adolescents with PCOS further exhibit 1) loss of rapid feedforward coupling between LH and testosterone output, 2) erosion of the time-lagged positive linkages between LH and androstenedione secretion, and 3) attenuation of the coordinate relationship between testosterone and androstenedione release. In summary, based on complementary, but independent, statistical tools, the present two-variable analyses unmask vivid deterioration of the joint synchrony of LH-testosterone, LH-androstenedione, and testosterone-androstenedione secretion in adolescents with PCOS. The multiplicity of the bihormonal coupling defects points to impaired feedforward and feedback signaling interfaces among the hypothalamus, pituitary gland, and ovary. Disruption of interandrogen synchrony also identifies pathophysiological dissociation of testosterone and androstenedione cosecretion. Whether presumptive failure of integrative hypothalamo-pituitary-gonadal control emerges prepubertally in girls at risk for PCOS or persists in adults with PCOS is not known.

Adolescent↗
PubMed2001

Disruption of the synchronous secretion of leptin, LH, and ovarian androgens in nonobese adolescents with the polycystic ovarian syndrome.

The present study probes putative disruption of hypothalamic control of multihormone outflow in polycystic ovarian syndrome by quantitating the joint synchrony of leptin and LH release in adolescents with this syndrome and eumenorrheic controls. To this end, hyperandrogenemic oligo- or anovulatory patients with polycystic ovarian syndrome (n = 11) and healthy girls (n = 9) underwent overnight blood sampling every 20 min for 12 h to monitor simultaneous secretion of leptin (immuno-radiometric assay), LH (immunofluorometry), and androstenedione and T (RIA). Synchronicity of paired leptin-LH, leptin-androstenedione, and leptin-T profiles was appraised by two independent bivariate statistics; viz., lag-specific cross-correlation analysis and pattern-sensitive cross-approximate entropy. The study groups were comparable in chronological and postmenarchal age, body mass index, fasting plasma insulin/glucose ratios, and serum E2 concentrations. Overnight mean (+/- SEM) serum leptin concentrations were not distinguishable in the two study groups at 30 +/- 4.8 (polycystic ovarian syndrome) and 32 +/- 7.4 microg/liter (control). Serum LH concentrations were elevated at 9.5 +/- 1.4 in girls with polycystic ovarian syndrome vs. 2.8 +/- 0.36 IU/liter in healthy subjects (P = 0.0015), androstenedione at 2.8 +/- 0.30 (polycystic ovarian syndrome) vs. 1.2 +/- 0.11 ng/ml (control) (P = 0.0002), and T at 1.56 +/- 0.29 (polycystic ovarian syndrome) vs. 0.42 +/- 0.06 ng/ml (P < 0.0001). Cross-correlation analysis shows that healthy adolescents maintained a positive relationship between leptin and LH release, wherein the latter lagged by 20 min (P < 0.01). No such association emerged in girls with polycystic ovarian syndrome. In eumenorrheic volunteers, leptin and androstenedione concentrations also covaried in a lag-specific manner (0.0001 < P < 0.01), but this linkage was disrupted in patients with polycystic ovarian syndrome. Anovulatory adolescents further failed to sustain normal time-lagged coupling between leptin and T (P < 0.01). Approximate entropy calculations revealed erosion of orderly patterns of leptin release in polycystic ovarian syndrome (P = 0.012 vs. control). Cross-entropy analysis of two-hormone pattern regularity disclosed marked disruption of leptin and LH (P = 0.0099), androstenedione and leptin (P = 0.0075) and T-leptin (P = 0.019) synchrony in girls with polycystic ovarian syndrome. In summary, hyperandrogenemic nonobese adolescents with oligo- or anovulatory polycystic ovarian syndrome manifest: 1) abrogation of the regularity of monohormonal leptin secretory patterns, despite normal mean serum leptin concentrations; 2) loss of the bihormonal synchrony between leptin and LH release; and 3) attenuation of coordinate leptin and androstenedione as well as leptin and T output. In ensemble, polycystic ovarian syndrome pathophysiology in lean adolescents is marked by vivid impairment of the synchronous outflow of leptin, LH and androgens. Whether analogous disruption of leptin-gonadal axis integration is ameliorated by therapy and/or persists into adulthood is not known.

17-alpha-Hydroxyprogesterone↗
PubMed2001

[Molecular analysis of the most frequent mutations associated with congenital adrenal hyperplasia secondary to 21-hydroxylase enzyme deficiency].

Most cases (90%) of congenital adrenal hyperplasia (CAH) are secondary to steroid 21-hydroxylase enzyme deficiency (P450c21). In human, the P450c21 gene (CYP21B) is present along with a non functional pseudogene (CYP21A). These genes, located in chromosome 6, present a sequence homology of 98%. This high homology and the complexity of this gene locus brings about considerable difficulties in its molecular analysis and in the interpretation of the results. The aim of the present study was to elaborate an adequate strategy for the analysis of the most frequent mutations described in the CYP21B gene. A total of 77 patients with clinical and biochemical diagnosis of CAH secondary to P450c21 enzyme deficiency, as well as 170 unaffected relatives, were studied. They belonged to 73 unrelated families (146 chromosomes). The strategy allowed for the differentiation of patients with homozygous point mutations (PM), with PM in one allele and deletions, conversions, Ex3 or Cluster Ex6 PM in the other, even though parents were not always available for the study. Furthermore, it allowed for the discrimination of heterozygous deletions or conversions of the CYP21B gene from duplications of the non functional gene CYP21A, as well as CYP21B and A deletions from normal copies of the two genes. An exhaustive molecular analysis of this gene is necessary for an adequate characterization of the alterations present in this locus.

Adrenal Hyperplasia, Congenital↗
PubMed2000

Clinical assessment and serum hormonal profile in prepubertal hypertrichosis.

Twenty-two prepubertal girls with hypertrichosis were studied and compared to 10 prepubertal normal girls. Hypertrichosis was assessed according to a score that considers the amount and the distribution of vellus hair in androgen- and non-androgen-sensitive areas. Serum androgen profile and free androgen index (FAI) were determined in both groups. The hypertrichosis score was higher in patients than in the normal girls. Testosterone levels and FAI were increased in patients when compared to control; 3alpha-androstanediol glucuronide levels above 2 SD from the control mean were found in 10 girls and all hormonal parameters falling in the normal range were found in 4 girls. The new score designed to assess the degree of hypertrichosis was useful to differentiate between normal and pathological hair growth. Although most of the girls with prepubertal hypertrichosis showed an increased androgen bio-availability, a slight increase in peripheral 5alpha-reductase activity and a completely normal androgen profile was also associated with a pathological hair growth.

Androgens↗
PubMed2000

Estrogen priming effect on growth hormone (GH) provocative test: a useful tool for the diagnosis of GH deficiency.

We have studied the effect of estradiol (E2) on the GH-insulin-like growth factor (GH-IGF) axis in 15 prepubertal GH deficiency (GHD) children and 44 prepubertal or early pubertal children with idiopathic short stature (SS). All of them received a daily dose of micronized E2 (1 or 2 mg) or placebo, for 3 days, before a sequential arginine-clonidine test. In SS children, GH maximal responses were 17.8+/-10.9 on placebo and 27.9+/-14.5 microg/L on estrogen (P < 0.0001). The lower 95% confidence limits for GH maximal response changed from 3.7 microg/L (without E2) to 8.3 microg/L (on E2). In GHD children, no significant stimulatory effect of estrogen on GH levels was observed. After placebo, a cut-off limit of 3.7 microg/L (the lower 95% confidence interval limit) resulted in 73% sensitivity, 95% specificity, and an overall 90% diagnostic efficiency. After E2, a cut-off limit of 8.3 microg/L resulted in a sensitivity of 87%, a specificity of 98%, and a diagnostic efficiency of 95%. After placebo, 68% of SS showed normal IGF-I levels, and the mean did not change on E2 (13.7+/-6.3 vs. 14.3+/-6.8 nmol/L, not significant). In 93% of SS, IGF binding protein (IGFBP)-3 levels were normal during placebo. On E2, mean IGFBP-3 did not change (2.63+/-0.70 vs. 2.70+/-0.70 mg/L, not significant). In 14 of 15 GHD patients, IGF-I values were below normal on placebo, and the mean of the group did not change after E2. During placebo, 13 of 15 GHD children presented low IGFBP-3 values. During E2, there was a small significant increase in IGFBP-3 values (1.06+/-0.58 vs. 1.20+/-0.69 mg/L, P < 0.02). The highest diagnostic efficiencies for IGF-I and IGFBP-3 were observed during placebo (75% and 91%, respectively). We conclude that GH stimulation tests after E2 priming had the highest diagnostic efficiency. Our findings suggest that the effect of estrogen priming on GH stimulated levels, by reducing the number of false nonresponders, might be useful to better discriminate between normal and abnormal GH status in SS children.

Adolescent↗
PubMed1999

A preponderance of basic luteinizing hormone (LH) isoforms accompanies inappropriate hypersecretion of both basal and pulsatile LH in adolescents with polycystic ovarian syndrome.

We recently demonstrated that adolescent girls with polycystic ovarian syndrome (PCOS) exhibit augmented LH secretion due to an increase in immunofluorometric and deconvolution-estimated LH secretory burst mass and pulse frequency. Concurrently, we inferred either a prolongation of apparent (endogenous) LH half-life or elevated basal (nonpulsatile) LH release in PCOS. The in vivo half-life of LH molecules can be affected by the oligosaccharide side-chains, which also modify in vitro bioactivity and electrostatic change. Accordingly, as a surrogate estimator of altered endogenous LH half-life and/or biopotency in PCOS, we characterized the isoelectric properties of secreted LH isoforms and determined their in vitro biological activity in adolescent girls with PCOS compared with healthy age-matched eumenorrheic controls. To this end, 12-h (overnight) serum samples from PCOS patients (n = 12) and normal adolescents (n = 10) were pooled by subject. Bioactive LH concentrations were then quantitated in a rat Leydig cell in vitro bioassay, and immunological activity was determined by immunofluorometry. The distribution of LH isoforms was evaluated by preparative chromatofocusing (pH window, 10.5 to <4.0) of samples further combined to yield three independent serum pools for each of the patient and control groups. Fasting serum concentrations of 17-hydroxyprogesterone (17-OHP), androstenedione, testosterone, estrone, estradiol, and sex hormone-binding globulin were determined as possible endocrine correlates of LH isotypes. Mean serum concentrations of immunoreactive and bioactive LH in adolescents with PCOS were 3 and 2 times higher than values in controls: immunoreactive: PCOS, 7.8+/-0.9; controls: 2.6+/-0.3 IU/L (P < 0.001); and bioactive: PCOS, 52+/-10; controls, 25+/-4.1 IU/L (P = 0.002), respectively. Bioactive LH concentrations correlated positively with 17-OHP (P = 0.022), androstenedione (P = 0.012), and testosterone (P = 0.046) concentrations in PCOS. Chromatofocusing of LH isoforms disclosed greater LH immunoreactivity at pI values greater than 8 and 7.99-7.0 in adolescents with PCOS compared with controls (P = 0.031). The percentage of basic LH isoforms was related positively to serum concentrations of 17-OHP (P = 0.032), androstenedione (P = 0.046), and testosterone (P = 0.040). In conclusion, the present isotype analysis demonstrates elevated in vitro LH bioactivity and a preponderance of basic LH isoforms in girls with PCOS. Since previously reported heterologous in vivo assays of LH kinetics point toward accelerated removal of such alkaline isotypes, our findings would favor the earlier alternative hypothesis of inappropriate hypersecretion of basal (interpulse) LH rather than prolongation of the LH half-life as the mechanism for elevated interpulse serum LH concentrations in adolescents with PCOS. In ensemble, the foregoing data thus suggest 3-fold amplification of basal LH secretion as well as both a heightened amplitude and frequency of the pulsatile mode of LH release in PCOS.

17-alpha-Hydroxyprogesterone↗
PubMed1998

Peripheral catecholamine alterations in adolescents with polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCO) is one of the most common endocrine disorders affecting women. Several lines of evidence have suggested the involvement of the sympathetic nervous system (SNS) in this condition. The present work was designed to assess neurochemically SNS activity in patients during the early stages of PCO. DESIGN AND PATIENTS: Fourteen patients with PCO (aged 14 to 21 years) were studied on a random day and 9 normal regularly cycling adolescents (aged 14 to 20 years) were studied during the early follicular phase (days 2 to 5). MEASUREMENTS: Hormonal profile was determined in basal conditions. LH and FSH were also measured after i.v. administration of 100 micrograms GnRH. Plasma concentrations of dihydroxyphenylalanine (Dopa), noradrenaline (NA), adrenaline (A), total dopamine (DA) and dihydroxyphenylglycol (DHPG) were determined in basal conditions and in response to GnRH by HPLC with electrochemical detection or a radioenzymatic method. Basal urinary Dopa, catecholamines and catechol metabolites (DHPG, vanillylmandelic acid (VMA), 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), metanephrine (MN) and normetanephrine (NMN)) were determined by HPLC with electrochemical detection. RESULTS: Basal plasma LH, testosterone, androstenedione, oestrone and LH/FSH ratio were higher (P < 0.01) and serum sex hormone-binding globulin (SHBG) were lower (P < 0.01) in PCO patients than in control subjects. Basal and GnRH-stimulated plasma free Dopa, A, NA and total DA were similar in patients and controls. Plasma DHPG was lower (P < 0.01) in PCO patients (4.20 +/- 0.30 nmol/l) than in controls (8.0 +/- 1.0 nmol/l) throughout the study. Urinary A, NA, DA, Dopa, MN, MHPG, HVA, and VMA were similar in patients and controls. Urinary DHPG was lower (P < 0.01) in PCO patients (0.50 +/- 0.02 mumol/d) than in controls (0.73 +/- 0.09 mumol/d). On the other hand PCO patients had a higher urinary excretion of NMN than controls (PCO: 1.20 +/- 0.10; C: 0.78 +/- 0.10 mumol/d, P < 0.05). CONCLUSIONS: Our results show the same endocrinological features in adolescent PCO patients as those reported in adults. The results also demonstrate a peripheral catecholaminergic alteration which suggests an alteration in noradrenaline deamination and/or uptake in adolescent patients. This study however does not permit us to conclude that PCO is primarily caused by this sympathetic alteration.

Adolescent↗
PubMed1998

Characterization of serum SHBG isoforms in prepubertal and pubertal girls.

OBJECTIVE: SHBG is a circulating glycoprotein that binds dihydrotestosterone, testosterone and oestradiol with high affinity and low capacity. In girls, serum concentrations of SHBG gradually decrease with age due to a true fall in concentration and not to a change in the binding characteristics. The aim of our study was to determine the pattern of serum SHBG isoforms in normal girls in early childhood (ECh), late childhood (LCh) and puberty (P). SUBJECTS: Fifteen normal girls were studied. They were divided into three groups according to their age: ECh: 3.7 +/- 0.9 years (mean +/- SD, n = 5); LCh: 6.4 +/- 0.5 years (n = 5); and P: 13.4 +/- 1.5 years (n = 5). METHODS AND MEASUREMENTS: Preparative isoelectric focusing was used to isolate SHBG isoforms according to their isoelectric point (pI). Three groups of isoforms were isolated: SI: pI 5.2-5.4; SII: pI 5.4-5.6 and SIII: pI 5.6-5.8. Steroid levels in serum were determined by RIA. RESULTS: The relative distribution of SHBG isoforms (% of the total SHBG recovered, mean +/- SD) in the three groups of girls studied was: ECh: SI: 25.8 +/- 9.9, SII: 53 +/- 10.5 and SIII: 21.2 +/- 1.6; LCh: SI: 8.8 +/- 3.1, SII: 58.8 +/- 12.2 and SIII: 31.8 +/- 8.6; P: SI: non-detectable; SII: 51.6 +/- 12.6 and SIII: 48.4 +/- 12.6. CONCLUSION: These results indicate that serum SHBG is more heterogeneous before puberty. A considerable proportion of acidic isoforms are present early in life; they decrease during the prepubertal period and disappear when sexual development is completed. After puberty the glycoprotein is more homogeneous and an important proportion of more basic isoforms is present. At puberty serum SHBG not only falls in concentration but also has an altered sialic acid content which modulates its circulating half-life.

Adolescent↗
PubMed1998

Augmented frequency and mass of LH discharged per burst are accompanied by marked disorderliness of LH secretion in adolescents with polycystic ovary syndrome.

The aim of this study was to quantify pulsatile LH secretion, burst frequency and mass, LH half-life, and the approximate entropy (ApEn) or (dis-) orderliness of LH release in adolescents with polycystic ovary syndrome (PCOS), combining a high-precision immunofluorimetric LH assay with deconvolution techniques. We sampled LH concentration profiles every 20 min overnight in 12 girls with PCOS (mean +/- S.E.M. age 16.4+/-0.57 years, body mass index (BMI) 24.4+/-1.6 kg/m2) and 11 eumenorrheic early-follicular-phase controls (mean +/- S.E.M. age 16.5+/-0.47 years, BMI 22.2+/-1.0 kg/m2). Fasting serum levels of androstenedione, testosterone, 17-hydroxyprogesterone (17-OHP), estrone, estradiol, FSH and sex hormone-binding globulin (SHBG) were determined. Compared with euandrogenic girls, PCOS adolescents had significantly (P<0.005) elevated serum LH/FSH ratios, 17-OHP, androstenedione, esterone and testosterone levels, decreased SHBG, and similar estradiol. PCOS subjects exhibited a 3-fold higher mean serum LH concentration with almost no overlap with controls (8.8+/-1.2 and 2.8+/-0.3 IU/l respectively, P<0.001). We initially used a conventional serum hormone concentration peak analysis method (Cluster) to evaluate the characteristics of pulsatile LH release. Cluster analysis disclosed a significant increase in serum LH concentration maximal peak height, a higher LH peak frequency and a higher mean serum LH concentration in interpulse nadirs in the PCOS group. Deconvolution analysis of mechanisms underlying the foregoing showed higher frequency in the PCOS group than the controls (7.9+/-0.4 and 5.7+/-0.6 pulses/12 h respectively, P<0.05). The mass of LH released per secretory event was also significantly higher in PCOS subjects than controls (5.4+/-0.57 and 3.4+/-0.56 IU/l respectively, P<0.05). Since the pulsatile production rate is the product of the mean mass of hormone secreted per pulse and the number of pulses per day, we estimated a significantly higher mean pulsatile production rate of (endogenous) LH in the PCOS group (41+/-4.2 IU/l per day in the PCOS group vs 18+/-2.3 IU/l per day in the controls, P<0.01). The mean estimated half-life of endogenous LH disappearance was also significantly higher in patients with PCOS than in controls (110+/-8.5 and 77+/-3.7 min respectively, P<0.01). To quantify the orderliness of LH release, we used ApEn. PCOS patients had remarkably increased disorderliness (higher ApEn) of LH release (1.09+/-0.04 vs 0.77+/-0.08 in controls, P = 0.002). Mean serum LH concentration, mass of LH secreted per burst, and LH production rate in PCOS, but not in normal adolescents, correlated positively with androstenedione (P<0.02, 0.02 and 0.05 respectively). The same parameters also correlated positively with 17-OHP (P<0.05, 0.02 and 0.05 respectively). Stepwise regression analysis unmasked a negative influence of BMI in PCOS on both mass of LH secreted per burst (r = -0.77, P<0.005) and LH production rate (r = -0.70, P<+/0.01). We conclude that PCOS adolescents secrete LH molecules with amplified frequency and burst mass and with markedly disrupted orderliness. A rise in basal (non-pulsatile) LH release, more basic LH isoforms, and/or a prolongation or asymmetry of the LH secretory burst could account for the apparently prolonged LH half-life. Determining whether disorderliness of the amplified pituitary LH release process is an intrinsic abnormality in PCOS. or reflects androgen excess, may help to clarify the pathophysiology of this oligo-ovulatory syndrome in young women.

Adolescent↗
PubMed1997

Persistence of autonomous ovarian activity after discontinuation of therapy for precocious puberty in McCune-Albright syndrome.

OBJECTIVE: The aim of this study was to evaluate the possibility of persistence of autonomous ovarian activity in girls with McCune-Albright syndrome (MAS) after withdrawal of medroxyprogesterone therapy administered for precocious puberty. DESIGN, SETTING, AND PARTICIPANTS: Five girls with MAS were followed-up 1.2 to 8.5 years after the end of treatment. The girls underwent luteinizing hormone-releasing hormone (LH-RH) tests, estradiol (E2) basal measurement, and pelvic ultrasound two times in the follow-up period. RESULTS: Menses resumed in four of five girls, 1.4 +/- 0.9 years after the end of treatment, at chronologic age of 11.3 +/- 1.3 years. Cycles for all girls were irregular. Three patients presented inadequate E2 levels (from 56 to 320 pg/mL) associated with low or absent gonadotropin response to LH-RH tests. The pelvic ultrasound showed ovarian cysts at the time of the study. CONCLUSION: These hormonal and ultrasonographic findings provide evidence of persistence of autonomous ovarian activity in some young women with MAS.

Child↗
PubMed1997

Gonadotropin secretion in prepubertal normal and agonadal children evaluated by ultrasensitive time-resolved immunofluorometric assays.

To analyze a possible gonadal effect on the control of gonadotropin secretion during the prepubertal period, we have measured the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) serum concentrations in children with primary gonadal failure (PGF). We measured them using an ultrasensitive immunofluorometric assay (IFMA) in a single daytime serum sample and compared the results with those obtained with a radioimmunoassay (RIA) technique. The patients were 22 children with PGF (13 girls and 9 boys) aged 0.56-15.4 years and 58 normal children (28 girls and 30 boys) aged 0.08-16 years. In the normal group there were significant changes in serum LH and FSH concentrations in relation to sex and pubertal development. These changes were more evident especially in LH concentrations when using IFMA. We observed that during the prepubertal period the normal LH levels (mean +/- SD) were detectable with this method at concentrations well below the limit RIA could detect (girls 0.026 +/- 0.012 IU/l, and boys 0.025 +/- 0.01 IU/l), while at the onset of puberty these LH levels rose significantly in both sexes (girls 1.0 +/- 0.79 IU/l, boys 1.7 +/- 0.7 IU/l; p < 0.01 vs. prepubertal group), reaching similar values to those observed in FSH concentrations (prepubertal girls 1.9 +/- 0.89 IU/l, boys 0.73 +/- 0.41 IU/l; early pubertal girls 3.1 +/- 0.9 IU/l, boys 2.6 +/- 1.3 IU/l). At prepubertal age, most PGF patients showed normal gonadotropin serum levels (particularly LH) when measured by RIA. However, these same samples-when measured by IFMA-showed LH and FSH levels clearly higher than normal in almost all-10 of 12-patients (PGF girls, n = 8, LH 1.1 +/- 1.0 IU/l, FSH 34 +/- 30 IU/l; PGF boys, n = 4, LH 0.13 +/- 0.12 IU/l, FSH 6.5 +/- 5.7 IU/l). We conclude that, during the so-called 'juvenile pause' when the gonadotropin concentrations could be reliably measured, supranormal gonadotropin levels could be observed during a single daytime serum sample in patients with PGF. These findings suggest that during this period of life the gonads contribute to the negative feedback regulation of gonadotropin levels.

Adolescent↗
PubMed1995

Bone age at discontinuation of medroxyprogesterone acetate therapy in girls with precocious puberty: effect on final height.

To determine the final height of patients with precocious puberty treated with medroxyprogesterone acetate (MPA; 150 mg every week) for a period > 1 year (mean +/- SD = 3.24 +/- 1.85 years), data from a group of 26 girls were analyzed. The attained final height was 155.6 +/- 8.06 cm (-1.1 SD of the normal population). In a group of 8 untreated girls with precocious puberty, adult height was 149.2 +/- 5.07 (-2.16 SD, p < 0.02). In 9 patients in whom treatment was stopped at a bone age < or = 12 years, final height was 159.2 +/- 10.05 cm, while in 16 girls who had a bone age > 12 years at the end of treatment, the final height was 153.03 +/- 6.28 cm. Our data demonstrate the effectiveness of MPA treatment on ultimate height. The better height observed in those patients who stopped treatment with a bone age < 12 years suggests the advantage of discontinuing therapy before reaching a more advanced degree of skeletal maturation.

Age Determination by Skeleton↗
PubMed1987

Long-term endocrine sequelae after surgery, radiotherapy, and chemotherapy in children with medulloblastoma.

Thirteen children with medulloblastoma, were studied after 2 to 62 months off radiotherapy and chemotherapy with methotrexate and BCNU. Ages at time of study ranged from 2.3 to 15.7 years. Eleven patients, followed for a mean of 22 months, showed a significant decrease of height score, whereas nine patients had deficient growth hormone (GH) response to provocative tests. Clinical pubertal progression was normal in all patients, and three of five girls with advanced pubertal development had menarche. No evidences of gonadotropin disturbances were found in five patients whereas seven had raised basal follicle-stimulating hormone (FSH) level or FSH response to luteinizing hormone-releasing hormone (LH-RH). Abnormalities in thyrotrophin (TSH) secretion were found in 9 of 13 patients. This study shows that poor growth and GH deficiency were frequent in our patients. The high frequency of thyroid disturbances observed point out the need of evaluating thyroid function for adequate replacement therapy. Perhaps modification of adjuvant chemotherapy in the future can diminish drug-induced gonadal damage.

Adolescent↗
PubMed1987

Validity of the calculation of non-sex hormone-binding globulin-bound estradiol from total testosterone, total estradiol and sex hormone-binding globulin concentrations in human serum.

Recent evidences indicate that biologically available serum testosterone (T) and estradiol (E2) include not only the free fractions but also most of the albumin-bound fractions. These two serum T or E2 fractions constitute most of non-sex hormone-binding globulin (SHBG)-bound T or E2, respectively. It has been reported that the estimation of serum non-SHBG-bound T gives identical results when it is assayed experimentally or when it is calculated by a formula derived from the law of mass action assuming two binding systems (T-SHBG and T-albumin). In the present work, we have compared the results of the experimental measurement of non-SHBG-bound E2 with the calculated value derived by an equation based on the law of mass action considering four binding systems (E2-SHBG, T-SHBG, E2-albumin, T-albumin). It was found that the two estimations of non-SHBG-bound E2 correlated closely in normal men (r = 0.80), normal women (r = 0.90) and hirsute women (r = 0.98). When compared with a more complex calculation which includes 21 steroids and 3 binding proteins results also agreed closely. Values for the different T and E2 fractions in these groups of subjects are given. These calculations could be used, not only for clinical research, but also in clinical practice as an useful tool for evaluation of the sex hormone status of patients.

Estradiol↗
PubMed1987

Evaluation of gonadal function following long-term treatment for acute lymphoblastic leukemia in girls.

Twenty-four girls were studied following long-term treatment (mean: 50 months) for acute lymphoblastic leukemia; 14 were prepubertal and 10 pubertal. Follow-up during endocrine studies ranged from 2 months to 6.7 years (mean: 2.3 years). Five of 14 prepubertal patients started clinical pubertal development at a normal age and were reevaluated during puberty, increasing the pubertal group to 15 patients. Thirteen of 15 pubertal patients had received cranial radiotherapy. Ten of 15 pubertal patients started menses during the endocrine study. Although age of menarche was normal, in nine patients it was below the normal mean. Except for the remaining patient, all had received cranial cobalt therapy. In 6 of 19 patients bone age was significantly accelerated. Serum gonadotrophin response to LH-RH was normal in 13 prepubertal patients and in 10 pubertal patients. In 3 of 10 pubertal patients follicle-stimulating hormone (FSH) values were temporarily elevated. Only one pubertal patient had oligoamenorrhea. Five patients were studied by measuring serum progesterone on days 19-22 of the cycle to determine corpus luteum function. Three of them showed progesterone levels compatible with adequate corpus luteum function (6, 19, and 12 ng/ml, respectively) and two presented low progesterone levels (2 ng/ml), probably because of their short gynecological age (0.24 and 0.3 years, respectively). This study suggests that neither the disease nor the long-term antileukemia therapy seems to injure gonadal function in girls. A tendency to early sexual development was observed, which may be related to cranial cobalt therapy.

Acute Disease↗
PubMed1987

Growth in Turner's syndrome: long term treatment with low dose ethinyl estradiol.

The growth response to 100 ng/kg BW X day ethinyl estradiol (2-4 micrograms/day) given for 18 months was studied in a group of nine patients with Turner's syndrome, aged 8.6-13.3 yr. All patients were prepubertal and had elevated gonadotropin levels. Growth velocity increased from 3.09 +/- 1.05 (+/-SD) to 7.09 +/- 1.47 cm/yr in the first 6 months, 6.08 +/- 1.78 cm/yr in the second 6 months, and 4.03 +/- 1.65 cm/yr in the third 6 months. Bone age increased a mean of 0.82 +/- 0.34, 0.89 +/- 0.79, and 0.74 +/- 0.59 yr, respectively, in the three 6-month periods. Predicted height prognosis did not change after any period. All patients had pubertal changes, limited in most to slight breast development. Mean diurnal spontaneous GH secretion did not change during treatment. Plasma somatomedin-C levels were low before treatment, and ethinyl estradiol did not significantly increase somatomedin-C values. Our data confirm the ability of a low dose of ethinyl estradiol to increase growth velocity in girls with Turner's syndrome, although the effect diminished with time, and the excess bone age advancement precluded improvement of predicted height.

Adolescent↗