scholarly journals SUN-073 Urine Steroid Profile of Girls with Premature Adrenarche

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Grit Sommer ◽  
Marco Janner ◽  
Michael Groessl ◽  
Christa E Flueck

Abstract Background: Adrenarche describes the development of the human adrenal cortex when the zona reticularis increases the synthesis of C19 steroids (DHEA/-S). Girls with premature adrenarche have a higher risk to develop adverse outcomes including polycystic ovary syndrome and metabolic syndrome later in life. The role of novel biosynthetic pathways of androgen production in health and disease remains largely unsolved. Objective: This study aimed to compare the urinary steroid metabolome between girls with premature adrenarche and healthy girls with focus on metabolites originating of novel, alternate androgen pathways. Methods: In 23 girls with premature adrenarche (median age 7 years) and 22 healthy, age-matched girls, we measured 39 steroid metabolites comprising progesterones, corticosterones, aldosterone, androgens, estrogens and glucocorticoids in the urine collected over 24 h by gas chromatography mass spectrometry. We compared metabolites and metabolite ratios between both groups of girls using Mann-Whitney tests with Bonferroni correction to account for multiple testing. Results: Girls with premature adrenarche were heavier than healthy girls (median weight 26.2 kg vs. 21.5 kg, p=0.003) and had a higher BMI SDS (0.8 vs -0.3, p=0.013). Gestational age and birth weight was similar between groups. Overall androgen excretion was different between groups, in particular amounts of androsterone, etiocholanolone, androstanediol, dehydroepiandrosterone, androstenediol, androstenetriol and pregnenetriol were higher in girls with premature adrenarche than in healthy girls (p<0.05). Some of these metabolites originate from alternate androgen pathways, e.g. androsterone. We found no differences in progesterones, corticosterones, aldosterone, estrogens and glucocorticoids, except for 20β-dihydrocortisone, which was higher in girls with premature adrenarche. Activities of 17βHSD and of 17,20-lyase via the Δ4pathway were higher in girls with premature adrenarche than in healthy girls. Conclusions: Girls with premature adrenarche produce more androgens than healthy girls of similar age. The urinary steroid signature of adrenarche includes metabolites of alternate pathways. Androstanediol seems a marker of adrenarche. Future studies should assess whether the steroid signature of adrenarche is just appearing earlier in girls with premature adrenarche or earlier and different compared to adrenarche at normal timing.

2020 ◽  
Vol 105 (12) ◽  
pp. e4439-e4451
Author(s):  
Marco Janner ◽  
Grit Sommer ◽  
Michael Groessl ◽  
Christa E Flück

Abstract Context Girls with premature adrenarche (PA) may have a higher risk of developing polycystic ovary syndrome (PCOS) and metabolic syndrome. The biological purpose of adrenarche is unknown and the role of novel biosynthetic pathways remains unclear. Objective To compare the urinary steroid metabolome and enzyme activities of girls with PA to age-matched control girls and to published steroid values of girls with normal adrenarche and of women with PCOS and their newborn daughters. Design Prospective observational study from 2009 to 2014. Setting Academic pediatric endocrinology referral center. Participants Twenty-three girls with PA and 22 healthy, age-matched girls. Main Outcome Measures Steroid metabolites in 24-hour urine samples, including 4 progesterones, 5 corticosterones, aldosterone, 13 androgens, 2 estrogens, 14 glucocorticoids, and enzyme activities represented by metabolite ratios. Results Girls with PA had a higher body mass index (mean standard deviation scores 0.9 vs -0.3, P = 0.013). Androgen excretion was higher in PA girls than in control girls (median 3257 nmol/24 hours vs 1627 nmol/24 hours, P < 0.001), in particular metabolites from alternate androgen pathways. The amount of progesterone, corticosterone, aldosterone, estrogen, and cortisol metabolites were similar between groups. Activities of 17β-hydroxysteroid-dehydrogenase and of 17,20-lyase were higher in girls with PA. Activities of 3β-hydroxysteroid-dehydrogenase, 21-hydroxylase, and 5α-reductase activity were not different between groups, in contrast to published results on girls with normal adrenarche or PCOS females. Conclusions Metabolites and enzymes involved in alternate androgen pathways appear to be markers of PA. Prospective studies should assess whether steroid production in PA also differs from adrenarche at normal timing and persists into adulthood.


2018 ◽  
Vol 61 (1) ◽  
pp. 109-117 ◽  
Author(s):  
Marta Marcos-Serrano ◽  
Guillermo Olcina ◽  
Carmen Crespo ◽  
Darrell Brooks ◽  
Rafael Timon

AbstractThe aim of this study was to determine variations in the urinary steroid profile of triathletes following an Ironman event. A total of 10 male participants (age = 36.0 ± 1.27 years; body height = 179.29 ± 10.77 cm; body mass = 74.50 ± 1.04 kg) completed an Ironman Championship. Urine samples were collected before, immediately after, and 24 hours following the race. Gas chromatography-mass spectrometry (GC/MS) was used to detect and quantify catabolic and anabolic hormones: Androsterone, Dehydroepiandrosteone (DHEA), Androstenedione and Testosterone (T), Betaestradiol, Estrone, Progesterone, Cortisol (C), Cortisone, Tetrahydrocortisol (THE) and Tetrahydrocortisone (THF). These were measured in their glucuroconjugated and free forms. Androsterone (3297.80 ± 756.83 vs. 2154.26 ± 1375.38), DHEA (47.80 ± 19.21 vs. 32.62 ± 15.96) and Beta-estradiol (59.36 ± 11.7 vs. 41.67 ± 10.59) levels decreased after the event. The significant decrease of DHEA (47.80 ± 19.21 vs. 32.11 ± 14.03) remained at 24 hours. Cortisol (200.38 ± 56.60 vs. 257.10 ± 74.00) and THE (238.65 ± 81.55 vs. 289.62 ± 77.13) increased after exercise and remained elevated 24 hours later (200.38 ± 56.60 vs. 252.48 ± 62.09; 238.65 ± 81.55 vs. 284.20 ± 66.66). The following anabolic/catabolic ratios fell after exercise: T/C (0.85 ± 0.54 vs. 0.54 ± 0.29), T/THE (0.66 ± 0.29 vs. 0.40 ± 0.08), T/THE+THF (0.38 ± 0.17 vs. 0.24 ± 0.06), DHEA/THE (0.22 ± 0.05 vs. 0.12 ± 0.05), DHEA/THF (0.34 ± 0.02 vs. 0.21 ± 0.01) and DHEA/THE+THF (0.12 ± 0.02 vs. 0.08 ± 0.03). The steroid profile showed that athletes were fatigued after finishing the competition and a catabolic state remained 24 hours later.


Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1489 ◽  
Author(s):  
Melinda Fernando ◽  
Stacey J. Ellery ◽  
Clara Marquina ◽  
Siew Lim ◽  
Negar Naderpoor ◽  
...  

Vitamin D-binding protein (VDBP), the main carrier of vitamin D, has recently been implicated in reproductive health and pregnancy outcomes including endometriosis, polycystic ovary syndrome (PCOS), pre-eclampsia, and gestational diabetes mellitus (GDM). Improved methods for measuring VDBP and an increased understanding of its role in biological processes have led to a number of newly published studies exploring VDBP in the context of pregnancy. Here, we synthesize the available evidence regarding the role of VDBP in reproductive health and pregnancy, and we highlight areas requiring further study. Overall, low levels of maternal serum VDBP concentrations have been associated with infertility, endometriosis, PCOS and spontaneous miscarriage, as well as adverse pregnancy outcomes including GDM, pre-eclampsia, preterm birth and fetal growth restriction. However, increased VDBP concentration in cervicovaginal fluid has been linked to unexplained recurrent pregnancy loss and premature rupture of membranes. Some genetic variants of VDBP have also been associated with these adverse outcomes. Further studies using more accurate VDBP assays and accounting for ethnic variation and potential confounders are needed to clarify whether VDBP is associated with reproductive health and pregnancy outcomes, and the mechanisms underlying these relationships.


2020 ◽  
Vol 69 (5) ◽  
pp. 27-38
Author(s):  
Natalya V. Vorokhobina ◽  
Lyudmila I. Velikanova ◽  
Olga B. Glavnova ◽  
Ekaterina V. Malevanaya ◽  
Ravilya K. Galakhova ◽  
...  

Hypothesis/aims of study. Polycystic ovary syndrome (PCOS) is a common disease. Depending on the diagnostic criteria, the disease is seen in 10-20% of women of reproductive age and accounts for 70-80% of all forms of hyperandrogenic syndrome. PCOS is a heterogeneous condition of multifactorial etiology characterized by various clinical, endocrine and metabolic disorders. Therefore, it is important to clarify the specific features of steroid hormone biosynthesis and metabolism and steroidogenesis enzyme activity, as well as to search for new laboratory criteria for early diagnosis and prompt treatment. The aim of this study was to perform metabolic profiling of androgens, progestins and glucocorticoids using gas chromatography-mass spectrometry (GC-MS) in obese and non-obese women with PCOS. Study design, materials and methods. We examined 53 women of reproductive age diagnosed with PCOS. The first group included 30 women aged 22 to 29 years with normal body weight. The second group comprised 23 obese patients aged 25 to 33 years with an average body mass index (BMI) of 35.3 0.4 kg/m2. The control group consisted of 25 healthy women aged 26 0.6 years having a normal BMI without clinical and biochemical signs of hyperandrogenism. Immunoassay methods were used to determine the serum levels of luteinizing hormone, follicle-stimulating hormone, free testosterone, 17-hydroxyprogesterone, and sex hormone-binding globulin. A glucose tolerance test was performed to determine glucose and insulin levels before and after load. Urine steroid profiles were studied by GC-MS with the optimization of the sample preparation schedule. Statistical data processing was performed using the STATISTICA for WINDOWS software system (version 10). The main quantitative characteristics of the patients are presented as the median (Me), the 25th percentile and the 75th percentile (Q25Q75). To compare the results obtained in the study groups, the nonparametric Mann-Whitney test was used. The 95% confidence interval was considered statistically significant. Results. The article presents a metabolomics analysis of androgens, glucocorticoid hormones and progestins in women with PCOS compared to the control group. It was revealed that non-obese patients with PCOS had increased urinary excretion of androstenedione metabolites, dehydroepiandrosterone and its metabolites, 17-hydroxypregnanolone, pregnantriol, and 5-ene-pregnenes, while obese patients with PCOS had increased that of androsterone and dehydroepiandrosterone metabolites (16-oxo-androstenediol and androstenediol-17) compared to the control group findings. Decreased ratios of cortisol and cortisone tetrahydro metabolite amount to the levels of 11-oxo-pregnanetriol, pregnanetriol and 17-hydroxypregnenolone, when compared to the control group, was obtained in non-obese patients with PCOS, which indicates 21-hydroxylase deficiency. In obese patients with PCOS, four signs of increased 5-reductase activity were obtained, and in PCOS patients with a normal BMI, three signs were obtained, which indicates varying 5-reductase activity in PCOS patients depending on the BMI. Conclusion. Quantitative evaluation of androgen and progestin metabolites, as well as 5- and 5-metabolites of androstenedione and glucocorticoids in the study of urine steroid profiles by GC-MS method opens new opportunities for PCOS diagnostics.


2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Paula Kuivasaari-Pirinen ◽  
Kaisa Raatikainen ◽  
Maritta Hippeläinen ◽  
Seppo Heinonen

In vitro fertilization (IVF) is a risk factor for pregnancy, but there have been few studies on the effect of infertility’s aetiology. Thus, we have assessed the role of aetiology on IVF pregnancy outcomes in a retrospective cohort study comparing the outcomes of IVF singleton pregnancies with those of spontaneous pregnancies in the general Finnish population. The study group consisted of 255 women with births resulting from singleton IVF pregnancies. Six subgroups were formed according to the following causes of infertility: anovulation (27%), endometriosis (19%), male factor (17%), tubal factor (15%), polycystic ovary syndrome (11%), and unexplained infertility (12%). The reference group consisted of 26,870 naturally conceived women. Adjusted odds ratios (AORs), for confounding factors such as age and parity, were estimated using logistic regression analysis. Women with endometriosis and anovulation had increased risks of preterm birth (AOR 3.25, 95% CI 1.5–7.1 and AOR 2.1, and 95% CI 1.0–4.2, resp.), while women in couples with male factor infertility had a twofold risk of admission to neonatal intensive care (AOR 2.5, 95% CI 1.2–5.3). The findings show that the aetiology of infertility influenced the obstetrics outcome, and that pooling results may obscure some increased risks among subgroups.


2020 ◽  
Vol 14 (1) ◽  
pp. 4-13
Author(s):  
Ilya E. Shcherbakov ◽  
Roman A. Chernikov ◽  
Vladimir F. Rusakov ◽  
Elysey A. Fedorov ◽  
Uriy N. Fedotov ◽  
...  

BACKGROUND: X-ray diagnostics methods are important in detection of adrenal neoplasms malignant nature. The sensitivity and specificity of these methods are high enough. However the hormonal tests are also necessary to make an accurate clinical diagnosis with the high diagnostic efficiency of modern X-ray methods for adrenal tumors diagnosing. The urine steroid profile violations are detected with the adrenal glands various pathologies (primary hyperaldosteronism, hypercorticism, congenital hyperplasia of the adrenal cortex and adrenocortical cancer). Urine steroid profile tests in patients with diagnosed adrenal neoplasms are intended primarily to confirm or refute the adrenocortical cancer risk. At the same time in the medical community to date there are a number of disagreements accumulated regarding the accuracy and significance of the urine steroid profile tests. AIMS: The study aims to determine the urine steroid profile determination accuracy limits for the adrenocortical cancer diagnosis. MATERIALS AND METHODS: In total 62 samples were tested for urine steroid profile by gas chromatography-mass spectrometry. 58 patients had morphologically confirmed adrenal neoplasms. The study was blind prospective. To increase the study accuracy the 30 patients with adrenocortical adenomas (n = 17) and adrenocortical cancer (n = 13) were selected out of 58 tested persons. The sensitivity, specificity and accuracy of the urine steroid profile were determined in order to assess information content of such method for the adrenocortical carcinoma diagnosis. RESULTS: The possibilities of the urine steroid profile determining for the adrenocortical cancer diagnosis are estimated. The method sensitivity was 46.2%, specificity and accuracy were 70.6% and 60% respectively. The most reliable of adrenocortical cancer markers were tetrahydro-11-deoxycortisol and dehydroepiandrosterone (38.5% of cases) increasing concentrations. CONCLUSIONS: The present study demonstrates relatively low diagnostic efficacy of the urine steroid profile as a primary diagnostic method for adrenocortical cancer determining. This is especially evident in comparison with X-ray diagnostic methods. The technique interpretation is complex and accessible only to specialists with extremely high qualifications. Such fact complicates the distribution and widespread use in clinical practice of this testing method. At the same time the urine steroid profile determination in the future (after additional study) may be apply as an auxiliary diagnostic method which in some cases determines the treatment tactics for patients undergoing adrenocortical cancer adrenalectomy treatment.KEYWORDS: dPheochromocytoma; intraoperative hemodynamic instability; laparoscopic adrenalectomy; Endovascular embolization of preoperative; сase report.


Author(s):  
J W Honour ◽  
C G D Brook

For a number of rare adrenal disorders, some of which are life threatening in childhood, laboratories need access to specialist endocrine investigations. Measurements of hormones in blood samples may be diagnostic in some cases but not all of the requisite steroid hormone assays are available. Multiple plasma steroid measurements may be required to prove the nature of a steroid biosynthetic disorder but in newborn children immunoassays, performed without prior solvent extraction, can be misleading. A urine steroid profile by gas chromatography coupled with mass spectrometry examines many steroid metabolites simultaneously and provides specific diagnostic information. A urine steroid profile can provide precise information of the secretory nature of tumours and causes of virilization, salt loss and hypertension often from a spot urine sample rather than a 24 h collection. However, a steroid profile is not helpful in making a diagnosis in neonatal genetic males with poorly developed genitalia.


Author(s):  
Daniela Menichini ◽  
Gianpiero Forte ◽  
Beatrice Orrù ◽  
Giuseppe Gullo ◽  
Vittorio Unfer ◽  
...  

Abstract. Vitamin D is a secosteroid hormone that plays a pivotal role in several metabolic and reproductive pathways in humans. Increasing evidence supports the role of vitamin D deficiency in metabolic disturbances and infertility in women with polycystic ovary syndrome (PCOS). Indeed, supplementation with vitamin D seems to have a beneficial role on insulin resistance and endometrial receptivity. On the other hand, exceedingly high levels of vitamin D appear to play a detrimental role on oocytes development and embryo quality. In the current review, we summarize the available evidence about the topic, aiming to suggest the best supplementation strategy in women with PCOS or, more generally, in those with metabolic disturbances and infertility. Based on the retrieved data, vitamin D seems to have a beneficial role on IR, insulin sensitivity and endometrial receptivity, but high levels and incorrect timing of administration seem to have a detrimental role on oocytes development and embryo quality. Therefore, we encourage a low dose supplementation (400–800 IU/day) particularly in vitamin D deficient women that present metabolic disturbances like PCOS. As far as the reproductive health, we advise vitamin D supplementation in selected populations, only during specific moments of the ovarian cycle, to support the luteal phase. However, ambiguities about dosage and timing of the supplementation still emerge from the clinical studies published to date and further studies are required.


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