Citations
All
Search in:AllTitleAbstractAuthor name
Publications
(358)
Patents
Grants
Pathways
Clinical trials
Publication
Journal: Clinica Chimica Acta
December/1/2013
Abstract
BACKGROUND
Since 2005, a newborn screening program for congenital adrenal hyperplasia (CAH) by measuring 17-alpha-hydroxyprogesterone (<em>17OHP</em>) in dried blood spots was introduced in Cuba.
METHODS
The hormone was measured by the <em>17OHP</em> Neonatal UMELISA method, in samples collected on the 5th day as average. Confirmatory test was performed to those neonates with <em>17OHP</em> values above 55 nmol/l. Some perinatal factors that can influence on <em>17OHP</em> levels were studied.
RESULTS
From January 2005 to December 2010, 621,303 newborns were screened and 39 CAH cases were detected. Coverage of the program reached 98%. The incidence of CAH in Cuba was 1:15,931, similar to that reported by other programs. A recall for suspected CAH was performed in 10,799 cases (1.74%). Therapy in classical CAH patients was started at the mean age of 22 days. <em>17OHP</em> levels were significantly higher in newborns with lower birth-weight (BW) and/or gestational age (GA). In addition, <em>17OHP</em> values were affected by the gender, twin status or mode of delivery.
CONCLUSIONS
In Cuba, the nationwide newborn screening program has allowed the early detection of CAH. The use of an optimized cut-off level for BW or GA could lead to a reduction in the percentage of recalled babies.
Publication
Journal: Journal of the Endocrine Society
June/12/2019
Abstract
Management of congenital adrenal hyperplasia (CAH) requires both glucocorticoid replacement and suppression of adrenal androgen synthesis. It is recommended that children with CAH be treated with hydrocortisone, but the appropriate glucocorticoid regimen in adults is uncertain. In order to review the outcomes of different glucocorticoid regimens in the management of CAH, a systematic search of PubMed/MEDLINE and Web of Science was conducted, including reports published up to 25 February 2019. Studies that compared at least two types of glucocorticoid preparation were included. The following information was extracted from each study: first author, year of publication, number and characteristics of patients and control subjects, types and doses of glucocorticoid regimen used, study design and outcomes [<i>e.g.,</i> biochemical tests, weight, height, body mass index (BMI), bone mineral density (BMD)]. A total of 23 studies were included in the qualitative synthesis, with 19 included in the quantitative synthesis. Dexamethasone was associated with the greatest degree of adrenal suppression; there was no significant difference in 17-hydroxyprogesterone (<em>17OHP</em>) and androstenedione levels between patients treated with hydrocortisone or prednisolone. Patients treated with dexamethasone had the lowest BMD and the highest BMI. Although dexamethasone therapy is associated with significantly lower <em>17OHP</em> and androstenedione levels, it is also associated with more adverse effects. There do not appear to be significant differences between hydrocortisone and prednisolone therapy, and the choice of agent should be based on individual patient factors.
Publication
Journal: Steroids
August/31/2015
Abstract
Although accumulating evidence indicates high expression of CYP17A1(P45017A1) allows castration resistant prostate cancer (CRPC) to maintain high intratumoral androgen levels, the potential P45017A1 activity has not been characterized yet. The aim of this study was to examine the potential CYP17A1 activity including 17α-hydroxylase and 17,20-lyase activities in human CRPC and the effect of a CYP17A inhibitor. We used three human CRPC cell lines: C4-2 and C4-2AT6 which was established from C4-2 under androgen ablation conditions for 6months, and PC3. To ascertain the potential CYP17A1 activity, we cultured with the steroid precursors: (13)C-[2,3,4]-progesterone (13C-Prog), and analyzed the sequential biosynthesis (13)C-[2,3,4]-17-hydroxyprogesterone (13C-<em>17OHP</em>) and (13)C-[2,3,4]-androstenedione(13C-Adione) by liquid chromatography/mass spectrometry (LC/MS/MS).The C4-2AT6 cells showed significantly higher CYP17A1 expression than C4-2 cells (p<0.001). LC/MS/MS analysis enabled us to detect the 13C-17-OHP and 13C-A-dione in these cell lines. The concentration ratio of 13C-Adione/13C-<em>17OHP</em> (Adione-<em>17OHP</em> ratio), which is thought to reflect the differences between 17-hydroxylase and 17,20-lyase activities, was then determined. The Adione-<em>17OHP</em> ratio in C4-2AT6 cells was significantly higher than that of C4-2 cells (p<0.001). Abiraterone were able to inhibit the CYP17A activities, although abiraterone did not have anti-proliferative effects on C4-2 and C4-2AT6 cells at clinically achievable concentrations of <1000nM in vitro. The present study clearly demonstrates CRPC have the dual activities of CYP17A1 mediated by 17-hydroxylase activity and 17,20-lyase activity. Abiraterone doesn't have an in vitro anti-proliferative efficacy in CRPC cells, suggesting limited efficacy in vitro.
Publication
Journal: Clinical and Experimental Rheumatology
April/21/2008
Abstract
OBJECTIVE
In patients with rheumatoid arthritis (RA), long-term therapy with anti-tumor necrosis factor (TNF) antibodies sensitizes the pituitary gland and improves adrenal androgen secretion in prednisolone-naïve patients. However, whether this is similar in psoriatic arthritis (PsA) is not known. The aim of this study was to assess the effect of 12 weeks of etanercept treatment upon the function of the HPA axis in patients with PsA.
METHODS
Eleven prednisolone-naïve patients (mean age 47.3+/-8.9 years) with PsA were included. We measured serum levels of adrenocorticotropic hormone (ACTH), 17-hydroxyprogesterone (<em>17OHP</em>), cortisol, and androstenedione (ASD), at baseline and at 4 and 12 weeks after initiation of anti-TNF therapy (etanercept, 50 mg every week as a single dose by sc. injection). Clinical improvement was assessed using the Disease Activity Score-28 (DAS-28).
RESULTS
Mean levels of serum ACTH, serum cortisol, serum <em>17OHP</em> and serum ASD did not markedly change during 12 weeks of etanercept treatment. Similarly, the ratio of serum cortisol divided by serum ACTH did not change during 12 weeks of anti-TNF treatment. However, an increase of serum cortisol relative to serum <em>17OHP</em> or ASD was related to clinical improvement. This indicates that improvement was linked to higher serum cortisol levels relative to others adrenal hormones.
CONCLUSIONS
This is the first study to demonstrate baseline serum levels and the course of HPA axis-related hormones in patients with PsA. An increase of serum cortisol relative to others adrenocortical hormones (i.e., androstenedione and ACTH) was accompanied by clinical improvement.
Publication
Journal: American Journal of Obstetrics and Gynecology
July/3/2016
Abstract
BACKGROUND
Racial/ethnic disparities in preterm birth remain a major public health challenge in the United States. While 17-alpha hydroxyprogesterone caproate (<em>17OHP</em>-C) is recommended for preterm birth prevention in women with a prior preterm birth, non-Hispanic black women continue to experience higher rates of recurrent preterm birth than white women receiving the same treatment. Further investigation of disparities in <em>17OHP</em>-C use and adherence is warranted.
OBJECTIVE
We sought to evaluate whether racial and ethnic disparities exist in the use of and adherence to <em>17OHP</em>-C within a population of eligible women.
METHODS
This was a retrospective cohort study of women with a prior spontaneous, singleton preterm birth who were eligible for <em>17OHP</em>-C for preterm birth prevention and received care at a single institution from 2010 through 2014. Associations between self-identified race/ethnicity (non-Hispanic black vs women in all other racial/ethnic groups) and documented counseling about <em>17OHP</em>-C, receipt of any <em>17OHP</em>-C, and adherence to <em>17OHP</em>-C administration were each estimated by bivariable analysis and multivariable logistic regression. Adherence to <em>17OHP</em>-C was defined as not >1 missed dose, initiation <20 weeks' gestational age, and continuation until 37 weeks or delivery.
RESULTS
Of 472 women who were clinically eligible for <em>17OHP</em>-C, 72% (N = 296) had documented <em>17OHP</em>-C counseling and 48.9% (N = 229) received <em>17OHP</em>-C. There were no differences in likelihood of <em>17OHP</em>-C counseling or receipt of <em>17OHP</em>-C based on race/ethnicity. While overall 83% (N = 176) of women were adherent to <em>17OHP</em>-C, only 70% (N = 58) of non-Hispanic black women were adherent, compared to 91% (N = 118) of all other women (P < .001). Non-Hispanic black women had more missed doses (2.4 vs 0.4 doses, P < .001) and later initiation of care (12.0 vs 10.2 weeks, P < .001) than women in other racial/ethnic groups. After adjustment for potential confounders, non-Hispanic black women were significantly less likely to be adherent to <em>17OHP</em>-C (adjusted odds ratio, 0.16; 95% confidence interval, 0.04-0.65). A significant interaction between non-Hispanic black race/ethnicity and public insurance was identified (adjusted odds ratio, 0.16; 95% confidence interval, 0.05-0.52).
CONCLUSIONS
In a diverse cohort of women eligible for preterm birth prevention, non-Hispanic black women are at an increased risk of nonadherence to <em>17OHP</em>-C. Non-Hispanic black women with public insurance are at a particularly increased risk of nonadherence.
Publication
Journal: British Journal of Clinical Pharmacology
July/11/2020
Abstract
Aim: To characterize the pharmacokinetic/pharmacodynamic relationships of cortisol and the adrenal biomarkers 17-hydroxyprogesterone and androstenedione in children with congenital adrenal hyperplasia (CAH).
Methods: A nonlinear mixed-effect modeling approach was used to analyze cortisol, 17-hydroxyprogesterone and androstenedione concentrations obtained over six hours from children with CAH (n=50). A circadian rhythm was evident and the model leveraged literature information on circadian rhythm in untreated children with CAH. Indirect response models were applied in which cortisol inhibited the production rate of all three compounds using an Imax model.
<strong class="sub-title"> Results: </strong> Cortisol was characterized by a one-compartment model with apparent clearance and volume of distribution estimated at 22.9L/h/70kg and 41.1L/70kg, respectively. The IC<sub>50</sub> values of cortisol concentrations for cortisol, 17-hydroxyprogesterone, and androstenedione were estimated to be 1.36, 0.45 and 0.75ug/dL, respectively. The inhibitory effect was found to be more potent on <em>17OHP</em> than D4A, and the IC<sub>50</sub> values were higher in salt-wasting subjects than simple virilizers. Production rates of cortisol, 17-hydroxyprogesterone, and androstenedione were higher in simple-virilizer subjects. Half-lives of cortisol, 17-hydroxyprogesterone, and androstenedione were 60, 47, and 77 minutes, respectively.
Conclusion: Rapidly changing biomarker responses to cortisol concentrations highlight that single measurements provide volatile information about a child's disease control. Our model closely captured observed cortisol, 17-hydroxyprogesterone, and androstenedione concentrations. It can be used to predict concentrations over 24 hours and allows many novel exposure metrics to be calculated, e.g., AUC, AUC-above-threshold, time-within-range, etc. Our long-range goal is to uncover dose-exposure-outcome relationships that clinicians can use in adjusting hydrocortisone dose and timing.
Keywords: Endocrinology; NONMEM®; Population pharmacokinetics-pharmacodynamics; compartmental analysis; mathematical modeling; pediatric; pharmacometrics; steroids.
Publication
Journal: Steroids
April/23/2008
Abstract
OBJECTIVE
Androgen excess carries varied clinical manifestations in women. Although testosterone and dehydroepiandrostendionesulfate (DHEAS) determination is considered useful in diagnostic workup, there is no laboratory definition that sufficiently describes androgen excess.
METHODS
We studied 464 hirsute women with a Ferriman and Gallwey score of at least 8 between 2000 and 2005. Our examination included clinical data, total testosterone (T), sex hormone-binding globulin (SHBG), the free androgen index (FAI), and DHEAS. Additionally, androstendione, 17alpha-hydroxyprogesterone (<em>17OHP</em>), dehydroepiandrostendione (DHEA), and 11-deoxycortisol were determined at baseline and 60min after corticotropin challenge (250microg synacthen).
RESULTS
Of 464 women, 77.6% fulfilled the clinical criteria for hyperandrogenemia. Of these 360 women, 78.1% had hyperandrogenic hirsutism. Of these 281 women, 43.4% showed increased stimulation of <em>17OHP</em> to 250microg of synacthen. Another 37.4% showed adrenal steroid biosynthesis defects other than 21alpha-hydroxylase deficiency, such as defective 11beta-hydroxylation or 3beta-hydroxysteroid dehydrogenase malfunction. The diagnosis of polycystic ovary syndrome was applicable to 12.4%. In addition, our results show that 72% of 281 patients with secondary hirsutism had normal T concentrations, and 55% had a normal FAI. Only 5% of hirsute patients with a normal FAI had elevated DHEAS values. However, 40% showed elevated DHEA levels, while 26% of the women with normal FAI showed androstendione values over the maximal levels in the 79 controls.
CONCLUSIONS
Our data suggest that in addition to testosterone and FAI, androstendione and DHEA are significantly helpful parameters in diagnosing hyperandrogenemia in hirsute women. DHEAS was not found to be helpful.
Publication
Journal: Journal of Pediatrics
October/15/2014
Abstract
OBJECTIVE
To characterize the urinary steroid metabolome of neonates and infants born either at term or preterm.
METHODS
We retrospectively analyzed urinary steroid hormone metabolites determined by gas chromatography-mass spectrometry of 78 neonates and infants born at term and 83 neonates and infants born preterm (median 34 weeks of gestational age). The subjects' 11β-hydroxylase and 21-hydroxylase activities were assessed on the basis of urinary metabolite substrate-to-product ratios.
RESULTS
Preterm neonates and infants had elevated urinary concentrations of 17α-hydroxyprogesterone (<em>17OHP</em>) metabolites (P<.001) but lower urinary concentrations of the 21-deoxycortisol metabolite pregnanetriolone (PTO) (P<.01). One reason was lower 11β-hydroxylase activity in preterms. We could demonstrate a correlation between low 11β-hydroxylase activity and high urinary concentrations of <em>17OHP</em> metabolites (r=0.51, P<.001) but low urinary concentrations of the 21-deoxycortisol metabolite PTO (r=-0.24, P=.03) in preterms.
CONCLUSIONS
Low 11β-hydroxylase activity may explain increased <em>17OHP</em> but decreased 21-deoxycortisol metabolite excretion in preterms. Our analysis clarifies, first, why preterms have higher <em>17OHP</em> levels and thus higher rates of false-positive screening results for congenital adrenal hyperplasia than do term infants, and, second, why 21-deoxycortisol or its urinary metabolite PTO is more specific than <em>17OHP</em> for the diagnosis of 21-hydroxylase deficiency.
Publication
Journal: Journal of Endocrinological Investigation
July/30/1997
Abstract
3 alpha-androstanediol glucuronide (3 alpha diolG) is a marker of peripheral tissue androgen metabolism. There are no previous data regarding complete paediatric reference ranges for 3 alpha diolG. In order to obtain reference values for 3 alpha diolG we have measured serum levels of 3 alpha diolG in 283 healthy children and adolescents, 146 boys and 137 girls, age 1 month to 20 years and 28 adults. A non-extraction, solid phase radioimmunoassay employing a polyclonal antiserum that is specific for 3 alpha diolG was used to measure serum 3 alpha diolG levels (intra assay variation 5.1-10.1%, inter assay variation 2.7-9.0%). There was a strong sex and age dependence (r = 0.8; p < 0.0001) of 3 alpha diolG levels throughout childhood and adolescence with males showing significantly higher levels of the androgen than females (p < 0.05). 3 alpha diolG serum levels (nmol/l +/- SD) correlated significantly with pubertal stage (p < 0.01). Interestingly, in 35 children with CAH serum 3 alpha diolG levels correlated well with clinical and metabolic status, i.e. <em>17OHP</em> serum levels. In summary, we have established percentile curves for 3 alpha diolG levels in healthy children and adolescents. We hypothesize that on the basis of our reference values the single measurement of serum 3 alpha diolG could serve as a means to determine androgen status in children with disorders of puberty and sexual development.
Publication
Journal: Rapid Communications in Mass Spectrometry
November/14/2005
Abstract
17alpha-Hydroxyprogesterone (<em>17OHP</em>) is considered to be the biomarker of congential adrenal hyperplasia (CAH). Screening for CAH in newborns by measuring levels of the biomarker of <em>17OHP</em> has become routine. In the work, a rapid, simple and sensitive technique was developed for the diagnosis of neonatal CAH by the quantitative analysis of <em>17OHP</em> in neonatal blood spots. The technique was based on microwave-assisted silylation (MAS) followed by gas chromatography/mass spectrometry (GC/MS). In the method, fast derivatization of <em>17OHP</em> with N,O-bis(trimethylsilyl)trifluoroacetamide was performed by using microwave irradiation, and the trimethylsilyl derivative thus formed was analyzed by GC/MS. The results of the experiment indicate that MAS followed by GC/MS analysis is a rapid, simple and sensitive method for the determination of <em>17OHP</em> in blood samples. The proposed technique has been shown to have potential as a powerful tool for the rapid diagnosis of neonatal CAH.
Publication
Journal: Journal of Pediatric Endocrinology and Metabolism
July/12/2007
Abstract
OBJECTIVE
Functional ovarian hyperandrogenism (FOH) is considered to be a form of polycystic ovary syndrome (PCOS) at adolescence. There are almost no data in the prepubertal period, although one of the earliest manifestations of PCOS is premature pubarche. Prepubertal girls with obesity or insulin resistance are also at risk to develop the full PCOS phenotype after puberty. The aim of this study was to evaluate prepubertal girls with premature pubarche and/or obesity for PCOS or FOH.
METHODS
Twenty-seven prepubertal girls with premature pubarche and/or obesity aged >6 years were evaluated. FOH was defined as abnormal ovarian <em>17OHP</em> response to challenge with GnRH analog of >2 ng/ml after exclusion of adrenal dysfunction. All patients underwent a pelvic ultrasound examination.
RESULTS
Sixteen patients had premature pubarche, seven were obese, and four had both premature pubarche and obesity. Eleven of 27 patients (40.7%) showed high (>2 ng/ml) <em>17OHP</em> response to GnRH challenge. Three patients (11%) with FOH also showed PCO morphology on pelvic ultrasound examination.
CONCLUSIONS
In prepubertal girls who carry risk factors, including genetic polymorphisms and/or particular environmental factors, FOH/PCOS could develop at a high rate.
Publication
Journal: Annals of Clinical Biochemistry
August/9/2015
Abstract
BACKGROUND
Monitoring of treatment for patients diagnosed with congenital adrenal hyperplasia (CAH) can be performed by measuring the concentration of 17α-hydroxyprogesterone (<em>17OHP</em>) in bloodspots collected on filter papers. A method is described here for measuring <em>17OHP</em> by liquid chromatography tandem mass spectrometry (LCMSMS).
METHODS
<em>17OHP</em> was extracted by liquid-liquid extraction and analysed by LCMSMS. The method was validated for sensitivity, specificity, linearity, recovery, ion suppression, precision and bias.
RESULTS
The standard curve was linear from 0 to 400 nmol/L. Intra-assay %CVs were <10 and inter-assay %CVs were <15 over the range 10-200 nmol/L. Limit of quantitation was 6 nmol/L. No ion suppression was detected. The only interfering compound detected was deoxycorticosterone, an intermediate steroid with the same molecular weight as 17α-hydroxyprogesterone. The method was more accurate and precise than an existing radioimmunoassay. There was poor correlation between the two assays.
CONCLUSIONS
We have developed a sensitive and specific assay suitable for quantitation of <em>17OHP</em> in bloodspots. This method performs better than radioimmunoassay and allows smaller samples to be used.
Publication
Journal: JBRA assisted reproduction
December/12/2016
Abstract
The aim of this study as to analyze published evidence regarding the effectiveness of aromatase inhibitor therapy on improving spermatogenesis in infertile men. We carried out a systematic review of randomized controlled trials. The date of the most recent search was October 4, 2015. Two authors independently selected relevant clinical trials, assessing their methodological quality and extracting data. Three studies were included in this review with a total of 100 participants; however, we were able to include data from only 54 participants in the analysis. In the representation of meta-analysis with a single study comparing testolactone versus placebo, related to the hormone concentrations, there was a statistically significance difference favoring the use of testolactone for Luteinizing Hormone (LH); Estrogen (E2); free Testosterone (free T); free Estrogen (free E2); 17-Hydroxyprogesterone (<em>17OHP</em>); prolactin (PRL). In another analysis from a single study comparing letrozole versus anastrozole, there was also a statistically significance difference favoring the use of letrozole for the increase in both the sperm count and LH. There is only low quality evidence regarding the effectiveness of aromatase inhibitor therapy in infertile men. Further trials are needed with standardized interventions and outcomes.
Publication
Journal: Journal of Clinical Endocrinology and Metabolism
September/10/2017
Abstract
The classic androgen synthesis pathway proceeds via dehydroepiandrosterone, androstenedione, and testosterone to 5α-dihydrotestosterone. However, 5α-dihydrotestosterone synthesis can also be achieved by an alternative pathway originating from 17α-hydroxyprogesterone (<em>17OHP</em>), which accumulates in congenital adrenal hyperplasia (CAH). Similarly, recent work has highlighted androstenedione-derived 11-oxygenated 19-carbon steroids as active androgens, and in CAH, androstenedione is generated directly from <em>17OHP</em>. The exact contribution of alternative pathway activity to androgen excess in CAH and its response to glucocorticoid (GC) therapy is unknown.
We sought to quantify classic and alternative pathway-mediated androgen synthesis in CAH, their diurnal variation, and their response to conventional GC therapy and modified-release hydrocortisone.
We used urinary steroid metabolome profiling by gas chromatography-mass spectrometry for 24-hour steroid excretion analysis, studying the impact of conventional GCs (hydrocortisone, prednisolone, and dexamethasone) in 55 adults with CAH and 60 controls. We studied diurnal variation in steroid excretion by comparing 8-hourly collections (23:00-7:00, 7:00-15:00, and 15:00-23:00) in 16 patients with CAH taking conventional GCs and during 6 months of treatment with modified-release hydrocortisone, Chronocort.
Patients with CAH taking conventional GCs showed low excretion of classic pathway androgen metabolites but excess excretion of the alternative pathway signature metabolites 3α,5α-17-hydroxypregnanolone and 11β-hydroxyandrosterone. Chronocort reduced <em>17OHP</em> and alternative pathway metabolite excretion to near-normal levels more consistently than other GC preparations.
Alternative pathway-mediated androgen synthesis significantly contributes to androgen excess in CAH. Chronocort therapy appears superior to conventional GC therapy in controlling androgen synthesis via alternative pathways through attenuation of their major substrate, <em>17OHP</em>.
Publication
Journal: Journal of Pediatric Endocrinology and Metabolism
May/19/2010
Abstract
To determine the influence of age, gestational age, gender and methodological protocol on serum <em>17OHP</em> and cortisol concentrations. <em>17OHP</em> in non-extracted (NE) and extracted (E) sera was measured by RIA in 319 full-term (FT) (1 d-5 yr) infants, 38 pre-term (PT) and in 19 neonates with classical CAH at diagnosis. <em>17OHP</em> (NE- and E-) decreased with age in normal children. The extraction procedure significantly reduced <em>17OHP</em> by eliminating interfering steroids in children < 1 year. Sexual dimorphism was only observed in NE-<em>17OHP</em>. <em>17OHP</em> in PT was always higher than in FT up to 2 months of age (p < 0.001). Neither NE- nor E-<em>17OHP</em> in CAH overlapped with those of FT or PT (p < 0.001) allowing to omit the extraction procedure to confirm CAH diagnosis. Cortisol levels were within normal range in neonates with CAH, thus not adding useful information about adrenal function. Chronological and gestational age, gender, and extraction for <em>17OHP</em> measurement are important factors to know when assessing adrenal function during the first year of life.
Publication
Journal: Journal of Mass Spectrometry
July/20/2014
Abstract
Electrospray ionization coupled with collision-induced dissociation (CID) and tandem mass spectrometry (MS/MS) is a commonly used technique to analyze the chemical composition of steroids. However, steroids are structurally similar compounds, making it difficult to interpret their product-ion spectra. Electron transfer dissociation (ETD), a relatively new technique for protein and peptide fragmentation, has been shown to provide more detailed structural information. In this study, we compared the ability of CID with that of ETD to differentiate between eight 3,20-dioxosteroids that had been derivatizated with a quaternary ammonium salt, Girard reagent P (GirP), at room temperature or after exposure to microwave irradiation to generate doubly charged ions. We found that the derivatization of steroid with GirP hydrazine occurred in less than 10 min when the reaction was carried out in the presence of microwave irradiation compared to 30 min when the reaction was carried out at room temperature. According to the MS/MS spectra, CID provided rich, structurally informative ions; however, the spectra were complex, thereby complicating the peak assignment. In contrast, ETD generated simpler spectra, making it easier to recognize individual peaks. Remarkably, both CID and ETD were allowed to differentiate of steroid isomers, 17α-hydroxyprogesterone (<em>17OHP</em>) and deoxycorticosterone (DOC), but the signature ions obtained from CID were less intense than those generated by ETD, which generated much clearer spectra. These results indicate that ETD in conjunction with CID can provide more structural information for precise characterization of steroids.
Publication
Journal: Journal of Endocrinological Investigation
July/24/1984
Abstract
We describe 5 adult women with severe hirsutism due to late onset 21-hydroxylase deficiency. Diagnosis was performed on the finding of high serum 17-hydroxyprogesterone (<em>17OHP</em>) levels with a marked hyperresponse to an ACTH test. The endocrine study showed in most patients a gonadotropin behavior similar to that observed in classical polycystic ovary (PCO) syndrome. Prolactin levels were slightly increased in basal conditions and presented an exaggerated response to TRH stimulation.
Publication
Journal: Journal of Pediatric Endocrinology and Metabolism
April/29/2008
Abstract
OBJECTIVE
To report the experience of the neonatal screening program for congenital adrenal hyperplasia (CAH) carried out in Buenos Aires, Argentina, from 1997 to 2006.
METHODS
17-Hydroxyprogesterone (<em>17OHP</em>) was measured with an immunofluorometric assay in filter paper blood samples collected at neonatal maternity discharge. Filter paper blood levels <40 nmol/l were considered normal. <em>17OHP</em> levels from 40-90 nmol/l triggered a new assessment to decide on a course of action. Confirmation of CAH was made with levels >90 nmol/l. This led to clinical follow up. For preterm (PT) infants, data were adjusted according to percentiles for gestational age and/or birth weight.
RESULTS
From 80,436 screened newborns (46.8% girls), 8848 (11%) were PT. 15 term (T) and 3 PT infants were recalled (0.022%). Nine were confirmed as having CAH (8 T and 1 PT) (female/male: 0.8; incidence 1:8937). Mean ages of screening and treatment were 5.7 and 13 days. Only 33% of affected children were clinically suspected of having CAH prior to screening. Four boys and two girls presented salt-wasting forms and severe adrenal insufficiency crises were prevented as a result of the screening.
CONCLUSIONS
Our findings confirm the benefits of CAH neonatal screening in our country with a high incidence of the classical form. Established criteria of screening and follow up allowed us to detect unrecognized affected males and females and to successfully prevent salt-wasting crises.
Publication
Journal: Hormone and Metabolic Research
January/16/2014
Abstract
The question of the contribution of CYP21A2 heterozygosity to the development of polycystic ovary syndrome (PCOS) has repeatedly been raised in the literature. The available data, however, do not offer a satisfactory answer. The discrepancy must be attributed, primarily, to the small number of subjects in the various studies, the type of selected phenotype, and the number of searched mutations. The aim of the study was to define the contribution of CYP21A2 heterozygous mutations to the pathogenesis of PCOS. We searched for 14 molecular defects of the CYP21A2 gene in 197 PCOS women, employing allele specific PCR. Androgen levels were determined at baseline by appropriate methodology in the follicular phase. PCOS women with 17-hydroxyprogesterone (<em>17OHP</em>) basal values >2 ng/ml and/or post-ACTH >10 ng/ml were excluded. Appropriate controls were included. The frequency of the CYP21A2 heterozygous mutations in PCOS women and in controls was 7.6% and 5.9%, respectively [p-value (PCOS vs. controls): 0.663]. Homozygosity for CYP21A2 gene defects was not detected. In conclusion, the contribution of CYP21A2 heterozygous mutations to the pathogenesis of PCOS is not substantiated by our data. Moreover, 17-hydroxyprogesterone values of < 10 ng/ml post-ACTH exclude homozygosity of CYP21A2 mutations.
Publication
Journal: Urological research
July/17/1989
Abstract
Serum levels of testosterone (T), 17 alpha-hydroxyprogesterone (<em>17OHP</em>), 4-androstene-3,17-dione (A-4), dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS) and cortisol were measured before and after 6 months of treatment in prostatic cancer patients treated by orchidectomy (ORX) or with oral + parenteral estrogens (OE), single parenteral estrogens (PE; 160 or 320 mg polyestradiol phosphate i.m. every fourth week), estramustine phosphate (ECYT) or LHRH agonist without (LHRH) or with (LHRH-F) flutamide. Castration values of T and 170HP were reached in all types of treatment (PE at the higher dose). A-4 levels were suppressed by all treatment regimens except ECYT; DHA by OE and LHRH-F and DHAS by ORX, OE and LHRH-F. The most pronounced suppression was found in the LHRH-F group. Cortisol levels were markedly increased by OE and ECYT. The observed effects on the adrenal androgens A4, DHA and DHAS and on cortisol probably reflect different degrees of liver interaction rather than interaction with adrenocortical steroid synthesis.
Publication
Journal: Gynecological Endocrinology
May/9/2017
Abstract
Polycystic ovary syndrome (PCOS) is a heterogeneous disorder that demonstrates ethnic and regional differences. To assess the phenotypic variability among Indian PCOS women, we evaluated clinical, biochemical and hormonal parameters of these women being followed in two tertiary care institutions located in Delhi and Srinagar. A total of 299 (210 PCOS diagnosed by Rotterdam 2003 criteria and 89 healthy) women underwent estimation of T4, TSH, LH, FSH, total testosterone, prolactin, cortisol, <em>17OHP</em>, and lipid profile, in addition to post OGTT, C-peptide, insulin, and glucose measurements. Among women with PCOS, mean age, age of menarche, height, systolic, diastolic blood pressure, and serum LH were comparable. PCOS women from Delhi had significantly higher BMI (26.99 ± 5.38 versus 24.77 ± 4.32 kg/m(2); P = 0.01), glucose intolerance (36 versus 10%), insulin resistance as measured by HOMA-IR (4.20 ± 3.39 versus 3.01 ± 2.6; P = 0.006) and QUICKI (0.140 ± 0.013 versus 0.147 ± 0.015; P = 0.03) while PCOS from Srinagar had higher FG score (12.12 ± 3.91 versus 10.32 ± 2.22; P = 0.01) and serum total testosterone levels (0.65 ± 0.69 versus 0.86 ± 0.41 ng/ml; P = 0.01. Two clear phenotypes, i.e. obese hyperinsulinaemic dysglycemic women from Delhi and lean hyperandrogenic women from Srinagar are emerging. This is the first report on North Indian women with PCOS showing phenotypic differences in clinical, biochemical and hormonal parameters despite being in the same region.
Publication
Journal: Journal of reproductive medicine, The
July/12/1999
Abstract
OBJECTIVE
To determine the incidence of late-onset congenital adrenal hyperplasia (LOCAH) due to 21-hydroxylase deficiency among hirsute women and to evaluate the results of the ACTH stimulation test with the clinical characteristics.
METHODS
Prospective, controlled study. One hundred women with hirsutism and 14 normally cycling women without hirsutism were included in this study at the Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Cerrahpasa School of Medicine, Istanbul University. After basal serum progesterone (P) and 17 hydroxyprogesterone (<em>17OHP</em>) levels were determined, an ACTH stimulation test was performed on cycle day 3-5. The same parameters were checked 30 minutes later. We estimated the 21 hydroxylase activity by calculating the change in <em>17OHP</em> (<em>17OHP</em> 30-0) and the summed rate of the change in P and <em>17OHP</em> ([P30-0] + [<em>17OHP</em>30-01/30 minutes). The 95th percentile for these estimates in normal women were calculated, and values above three times the 95th percentile were considered to distinguish women with LOCAH due to 21-hydroxylase deficiency.
RESULTS
The 95th percentile for <em>17OHP</em> 30-0 and (P30-0) + (<em>17OHP</em>30-0)/30 minutes in normal women was 1.6 and 8.9 ng/dL/min, respectively. Regarding <em>17OHP</em> 30-0 values, three women with hirsutism had levels above three times the 95th percentile of these estimates, and 28 women had estimates of more than the 95th percentile but less than threefold. Seventeen of 28 women had oligomenorrhea, and all had severe hirsutism. The women with severe hirsutism and oligomenorrhea had significantly higher ACTH-stimulated serum <em>17OHP</em> levels and values for <em>17OHP</em> 30-0 and (P30-0 + (<em>17OHP</em>30-0)/30 min) than did normally cycling women.
CONCLUSIONS
The incidence of LOCAH due to 21-hydroxylase deficiency and mild 21-hydroxylase deficiency is 3% and 28%, respectively, in women with hirsutism. Clinical characteristics are not helpful in determining 21-hydroxylase deficiency. However, the incidence of 21-hydroxylase deficiency is more common among women with severe hirsutism and oligomenorrhea. The change in serum <em>17OHP</em> 30-0 seems to be greater than the summed rate of change in serum <em>17OHP</em> and P in the detection of 21-hydroxylase enzyme deficiency.
Publication
Journal: Clinical Chemistry and Laboratory Medicine
August/20/2017
Abstract
BACKGROUND
Salivary androgen testing represents a valuable source of biological information. However, the proper measurement of such low levels is challenging for direct immunoassays, lacking adequate accuracy. In the last few years, many conflicting findings reporting low correlation with the serum counterparts have hampered the clinical application of salivary androgen testing. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) makes it possible to overcome previous analytical limits, providing new insights in endocrinology practice.
METHODS
Salivary testosterone (T), androstenedione (A), dehydroepiandrosterone (DHEA) and 17OHprogesterone (<em>17OHP</em>) were extracted from 500µL of saliva, separated in 9.5 min LC-gradient and detected by positive electrospray ionization - multiple reaction monitoring. The diurnal variation of salivary and serum androgens was described by a four paired collection protocol (8 am, 12 am, 4 pm and 8 pm) in 19 healthy subjects.
RESULTS
The assay allowed the quantitation of T, A, DHEA and <em>17OHP</em> down to 3.40, 6.81, 271.0 and 23.7 pmol/L, respectively, with accuracy between 83.0 and 106.1% for all analytes. A parallel diurnal rhythm in saliva and serum was observed for all androgens, with values decreasing from the morning to the evening time points. Salivary androgen levels revealed a high linear correlation with serum counterparts in both sexes (T: R>0.85; A: R>0.90; DHEA: R>0.73 and <em>17OHP</em>: R>0.89; p<0.0001 for all).
CONCLUSIONS
Our LC-MS/MS method allowed a sensitive evaluation of androgen salivary levels and represents an optimal technique to explore the relevance of a comprehensive androgen profile as measured in saliva for the study of androgen secretion modulation and activity in physiologic and pathologic states.
Publication
Journal: American Journal of Obstetrics and Gynecology
August/1/2016
Abstract
BACKGROUND
Preterm birth (PTB) remains a significant cause of neonatal morbidity and mortality. Women with a prior PTB are at risk for recurrent PTB. Treatment with 17-alpha hydroxyprogesterone caproate (<em>17OHP</em>-C) has become standard of care for women with prior PTB to help reduce this risk. Factors that affect a woman's decision to use this medication are largely unknown.
OBJECTIVE
The objective of our study was to investigate patient-level barriers to <em>17OHP</em>-C. We studied a cohort of women eligible for <em>17OHP</em>-C with the hypothesis that <em>17OHP</em>-C is underutilized and certain patient characteristics, such as obstetrical history, influence its use.
METHODS
A cross-sectional study of all women seen at a specialty prematurity clinic from 2009 through 2013 was performed. Women with a singleton pregnancy were included if they had a prior spontaneous PTB (sPTB). The χ(2) tests were performed for univariate analyses. Multivariable logistic regression was used to control for confounders.
RESULTS
In all, 243 women had <em>17OHP</em>-C recommended to them based on obstetrical history. There were 218 women with a pregnancy during our study period that were included in our analysis. A total of 163 (74.7%) had documented <em>17OHP</em>-C use. Women were more likely to accept <em>17OHP</em>-C if they had a history of a second-trimester loss only (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.17-4.58) or received recommendation for cerclage due to a short cervical length (OR, 4.12; 95% CI, 1.55-10.99). Women with a prior full-term birth were less likely to accept <em>17OHP</em>-C (OR, 0.48; 95% CI, 0.26-0.89), especially when the prior full-term birth was subsequent rather than prior to the PTB (OR, 0.19; 95% CI, 0.08-0.47). Race, obesity, and insurance status did not impact <em>17OHP</em>-C use. There was no difference in the rate of sPTB between those who used and did not use <em>17OHP</em>-C (37.2 vs 34.0%, P = .7).
CONCLUSIONS
Obstetric history impacted <em>17OHP</em>-C use. This study identifies biases regarding <em>17OHP</em>-C at the patient level and can be used to develop strategies to increase its use. However, the similarity in the sPTB rate between users and nonusers highlights the importance of identifying specific populations where <em>17OHP</em>-C is and is not effective in preventing PTB.
Pulse
Views:
1
Posts:
No posts
Rating:
Not rated
load more...