Dehydroepiandrosterone Sulfate Concentrations Research Articles

Fetal sex and the development of gestational diabetes mellitus in polycystic ovarian syndrome gravidae

Polycystic ovarian syndrome is characterized by elevated androgens and is a well-known risk factor for the occurrence of gestational diabetes mellitus. Androgens (particularly dehydroepiandrosterone-sulfate) are crucial for the development and characteristics of the male reproductive tract during fetal life, and fetal dehydroepiandrosterone-sulfate enters the placenta where it is metabolized and functions as an estrogen substrate. Given this unique sex-specific relationship with androgens and the association of serum dehydroepiandrosterone-sulfate concentration with insulin resistance, we hypothesized that metabolic comorbidities in pregnancy might differ by fetal sex in gravidae with polycystic ovarian syndrome, notably in those with infertility. This study aimed to evaluate the data in a large population-based database to explore if fetal sex was significantly associated with gestational diabetes mellitus in gravidae with infertility and polycystic ovarian syndrome after controlling for confounders. This study was designed to evaluate the risk for the occurrence and rates of gestational diabetes mellitus among gravidae with infertility and a history of polycystic ovarian syndrome. We used a 2-hospital, single academic institution database comprising more than 30,000 subjects enrolled from September 2011 to June 2021 to identify all gravidae with diagnoses of infertility and polycystic ovarian syndrome at the time of delivery and to compare them with gravidae who lacked these comorbidities. Data on covariates, including but not limited to maternal age, body mass index, fetal sex, race, ethnicity, presence or absence of hypertensive disease, and presence or absence of gestational diabetes were identified. Unadjusted and adjusted odds rations were calculated. We found a statistically significant association between fetal female sex and the development of gestational diabetes mellitus in gravidae with polycystic ovarian syndrome (odds ratio for female vs male, 2.13; 95% confidence interval, 1.06-4.32; P=.03). After adjusting for potential confounders identified in our univariate analyses, there continued to be a statistically significant association between female fetuses and the development of gestational diabetes mellitus (adjusted odds ratio for female vs male, 2.10; 95% confidence interval, 1.04-4.41; P=.04). In contrast, there was no significant association between fetal sex and the development of gestational diabetes mellitus in our similar analysis of gravidae without infertility and polycystic ovarian syndrome (P=.99). Although the origin of gestational diabetes mellitus is multifactorial, we found that female fetal sex is associated with gestational diabetes mellitus in gravidae with infertility and polycystic ovarian syndrome but not in their comparative controls. Further research on the molecular mechanisms driving the association between female fetuses and the development of gestational diabetes mellitus in the context of maternal polycystic ovarian syndrome is warranted.

The Severity of Bone Loss: A Comparison Between Cushing’s Disease and Cushing’s Syndrome

Background: This study aimed to estimate the prevalence of osteoporosis among patients with adrenal Cushing’s syndrome (ACS) and Cushing’s disease (CD), to investigate whether there is a difference in the degree of osteoporosis between both groups; and if so, what factors may be responsible for this variation. Methods: This is a cross-sectional study in which data from 19 patients with CD and eight patients with ACS were analyzed. Osteoporosis was assessed using the bone mineral density (BMD) of the lumbar spine using dual-energy X-ray absorptiometry (DEXA). Results: Bone loss was present in 81.5% of the patients with Cushing’s syndrome. Osteoporosis is nearly three times more common in ACS (62.5%) than in CD (26.3%). BMD at the lumbar spine was lower in patients with ACS than in patients with CD. ACS had significantly lower levels of dehydroepiandrosterone sulfate (DHEA-S) than CD. In comparison to the CD group, the serum parathyroid hormone (PTH) concentration in the ACS group was significantly higher. In the entire patient population, there was a statistically significant correlation between the DHEA-S and the lumbar BMD values. Conclusions: Patients with ACS have more severe osteoporosis than patients with CD, and the difference in DHEA-S concentrations might be important in explaining this difference. BMD examinations should be prioritized to enable rapid recognition and intervention for osteoporosis. Measurement of bone turnover markers such as PTH may aid in the early diagnosis of the consequences of hypercortisolism on the bone. J Endocrinol Metab. 2023;13(1):33-38 doi: https://doi.org/10.14740/jem857

Age-related decrease in serum dihydrotestosterone concentration is accompanied by impaired vascular status

IntroductionThe effect of androgens on the cardiovascular system in humans is ambiguous. Moreover, still little is known about the effects of the most potent androgen, dihydrotestosterone, on arterial stiffness and endothelial function. The aim of this study was to evaluate whether age-dependent alterations in serum concentration of dihydrotestosterone and its circulating metabolite are accompanied by changes in endothelial function and arterial stiffness. MethodsIn 12 young and 11 older men, basal serum concentrations of testosterone, dehydroepiandrosterone sulfate (DHAE-S), androstenedione (AE), dihydrotestosterone (DHT) and androstanediol glucuronide (ADG) were analyzed in relation to vascular status including cIMT — carotid intima media thickness, cAI — central augmentation index, crPWV — carotid radial pulse wave velocity, SI — stiffness index, endothelial and inflammatory markers. ResultsAlthough concentration of testosterone was not different between young and older group, it was demonstrated that DHT, DHEA-S, AE and ADG were significantly lower in older men in comparison to young men (p < 0.01). Interestingly the most surprising difference was found for DHT concentration, that was as much as 61 % lower in aged men that displayed significantly higher values of cIMT, AI, crPWV and SI (p < 10−4), suggestive of arterial stiffness. Furthermore, DHT was negatively correlated to all arterial wall parameters (cAI, crPWV, SI and cIMT), c-reactive protein (CRP) and hyaluronic acid (HA) concentration, as well as positively correlated to markers of endothelial function (MNA and 6-keto-PGF1α) in all studied individuals (n = 23). ConclusionsWe have shown that ageing leads to a significant decrease in DHT concentration that is accompanied by impaired arterial wall characteristics and worsened endothelial function. Therefore more attention should be paid to the DHT, DHEA-S and ADG concentrations as a biomarkers for vascular dysfunction in ageing men.

Assessment of dehydroepiandrosterone sulphate (DHEAS) and cortisol levels in saliva and their correlation to cervical vertebrae maturation method in males and females at different growth stages: a clinical study.

The aim of this in-vivo study was to assess the salivary dehydroepiandrosterone sulphate (DHEAS) and cortisol levels, and their correlation to the Cervical Vertebrae Maturation method (CVM) in males and females at pre-pubertal, pubertal and post-pubertal growth stages. 48 patients (24 males, 24 females) who were to undergo routine orthodontic treatment were screened according to the inclusion and exclusion criteria. Then subjects were grouped according to CVM stages, using lateral cephalogram, in pre-pubertal, pubertal and post-pubertal groups. Unstimulated saliva from the selected subjects was collected. DHEAS and cortisol levels in the salivary samples were estimated by Enzyme-Linked Immunosorbent assay (ELISA). Then they were compared to Cervical Vertebrae Maturation Method stages. One-way ANOVA test followed by Tukey's post-hoc test was used to compare the salivary DHEAS and cortisol levels between different CVM stages in males and females. Independent Student t-test was used to compare the mean salivary DHEAS and cortisol levels between different males and females in each CVM stage. There was a progressive increase in salivary DHEAS and cortisol concentration as skeletal maturation progressed from CVM stages 1 and 2, CVM stages 3 and 4, reaching the highest value at CVM stages 5 and 6. Their levels were higher in males than females. The salivary DHEAS and cortisol levels can be useful as a potential indicator of skeletal maturation, to aid in the assessment of pubertal status.

Hormones and depression in the advanced age.

In older people, depression and mental disability are more frequently present than in younger subjects. It is found that depressionis a risk factor for dementia, just as dementia is a risk factor for depression. In turn, both disturbances are known to be influenced by hormones. The present study aimed to see whether the hormonal changes in subjects over 75 years old correlate with the symptoms of depression measured using the Geriatric Depression Scale (GDS). In a group of patients aged over 75 years, concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestradiol, testosterone, dehydroepiandrosterone sulphate (DHEAs), and cortisol were measured in serum with the use of chemiluminescence. The symptoms of depression were estimated by GDS, and the mental functions were assessed by the Mini-Mental State Examination (MMSE). The correlations between the obtained results were estimated by Spearman's test. A significant correlation between GDS and MMSE scores was observed in the investigated patients. Some statistically significant correlations concerning cortisol and testosterone with GDS were observed in women, but not in men. On the other hand, no significant correlations between concentrations of FSH, LH, DHEAs, and oestradiol with GDS were noticed. Our data support the role of cortisol (possibly secreted during chronic stress) in the risk of depression. The gender difference in the mechanism of depression and stress in older age could be also hypothesized.

LBSAT59 Overnight Metyrapone Test And Urine Steroid Profiling In Patients Treated With Chronic Opioid Therapy: Prevalence Of Adrenal Insufficiency

Abstract Background Patients taking chronic opioids are at high risk of opioid induced adrenal insufficiency (OIAI). Previously, we showed that the prevalence of OIAI was 9% based on low morning cortisol, corticotropin (ACTH), and dehydroepiandrosterone sulfate (DHEAS). Data on the overnight metyrapone test to diagnose OIAI are sparse. We aimed to determine the prevalence of OIAI using overnight metyrapone test and identify changes in the steroid metabolome of patients treated with opioids. Methods Cross-sectional study of adult patients treated with opioid therapy of at least 20 morphine milligram equivalents (MME)/day for at least 3 months. Measurements included ACTH, cortisol, and DHEAS. Overnight metyrapone test was administered in all patients, and 24h urine steroid profiling was optional (25 steroids measured by liquid chromatography mass spectrometry1). All patients completed the quality-of-life survey (AddiQoL). Prevalence of OIAI was defined as sum of post-metyrapone 11-deoxycortisol and cortisol of &amp;lt;15 mcg/dL. Result: In 22 patients (median age 59 years [range, 38-74], 9, 41% women), median MME was 33 (20-161) mg, and median cumulative opioid exposure was 245 (10-2550) mg*years. Following the overnight metyrapone test, 7 (32%) patients were diagnosed with OIAI. Patients with OIAI had lower DHEAS concentrations (median of 21 mcg/dL[ 5-113] vs 54 [22-173], p =0. 03), but not cortisol (median 10[5.3-16] mcg/dL vs 13[5.3-22], p=0. 06) or ACTH (median 27[8.1-51] pg/mL vs 26[5.9-55], p=0.8). Patients with OIAI were treated with higher daily MME (100 mg[30-150] vs 30[20-161], p=0. 03) and had a higher cumulative exposure to opioids (median, 660 mg*years [250-2250] vs 150 [10-1288], p =0. 01). AddiQol scores were similar between groups (median of 68[56-84] vs 73[48-83], p= 0.97). Urine steroid profiling was performed in 18 patients. Patients with OIAI demonstrated 4 times lower total urine glucocorticoids (16334 mcg/24h vs 4377 mcg/24h, p=0. 003), all &amp;lt;10% of the reference range, and 3 times lower total urinary androgens (median of 805 mcg/24h vs 2320 mcg/24h, p=0.14). Conclusion Prevalence of OIAI using overnight metyrapone test is high at 32%. Patients diagnosed with OIAI were treated with higher doses of MME/day and had a higher cumulative exposure to opioids when compared to those without OIAI. Applying 24h urine steroid profiling we showed that total glucocorticoids are 4 times lower in those with OIAI (and all &amp;lt;10% of reference ranges) as opposed to those without OIAI. We showed that baseline measurements of ACTH, DHEAS, and cortisol may incorrectly exclude OIAI, and a dynamic test, such as overnight metyrapone test is needed when suspicion for OIAI is high. | 1. Hines JM, Bancos I, Bancos C, et al. High-Resolution, Accurate-Mass (HRAM) Mass Spectrometry Urine Steroid Profiling in the Diagnosis of Adrenal Disorders. Clin Chem. 2017;63(12): 1824-1835. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

`Association study of dehydroepiandrosterone sulfate, impulsivity personality traits and moderate alcohol consumption in men

This study focused on inspecting the relationship between impulsivity traits, salivary dehydroepiandrosterone sulfate (DHEA-S) concentrations, and moderate alcohol consumption in healthy subjects. In previous studies, impulsivity has been related to alcohol consumption and androgens. Limited research has focused on the sulfated form of DHEA-S and alcohol consumption or impulsivity. Moderate alcohol consumption can increase DHEA-S levels. Effects of alcohol, impulsivity and androgens levels may depend on age and gender. The participants were 120 healthy men (Mage = 44.39; SD = 12.88). The results showed positive correlations between DHEA-S and alcohol consumption (r = 0.22; p < .01) and an impulsivity factor (r = 0.22; p < .01) controlling for age. Regression analysis showed a significant relationship between DHEA-S (p < .001), impulsivity factor and AUDIT (p < .05). Analyzing the two extreme impulsivity groups, an association is observed between DHEA-S with AUDIT scores (R2 = 0.12; p < .05) in the high impulsivity group, but not in the low impulsivity one. It is therefore concluded that the effect of moderate alcohol consumption is cumulative and slightly associated with levels of impulsiveness and DHEA-S.

Nesfatin-1 as a potential marker for functional hypothalamic amenorrhea

Objective Nesfatin-1 plays an important role in regulating metabolism, appetite, gut motility, and eating behavior. It is suspected that abnormalities in nesfatin-1 secretion may be involved in the development of anorexia nervosa, and as such, this study aims to investigate the “circumstances of” nesfatin-1 in patients with functional hypothalamic amenorrhea (FHA). Materials and Methods One hundred and forty-seven patients with FHA were enrolled to the present study. A control group consisting of 88 healthy, age-matched subjects was used. Both study and control groups had blood samples drawn to establish baseline serum concentrations of luteinizing hormone, follicle-stimulating hormone, estradiol, prolactin, thyroid-stimulating hormone, fT4, morning cortisol, dehydroepiandrosterone sulfate, testosterone, glucose, and insulin. Nesfatin-1 was also measured with the use of enzyme-linked immunosorbent assay. Results Patients with FHA were found to have a significantly decreased concentration of serum nesfatin-1 when compared to healthy controls (6.21 ± 4.79 vs. 8.64 ± 6.63 respectively, p = 0.005). No statistically significant difference in nesfatin-1 levels was found between patients with normal and decreased BMI in the FHA group. Significant positive correlation was observed between serum nesfatin-1 concentration and 17-β-estradiol, while a significant negative correlation was observed between serum nesfatin-1 concentration and patient age, fasting glucose, and HDL levels. Conclusions This is the first known study to examine nesfatin-1 concentration in the context of clinical FHA. Patients with FHA were found to have decreased serum nesfatin-1 concentrations. This finding may prove instrumental in our future approach managing patients with FHA.

Hormonal profile changes induced by pesticide mixture exposure in female rats revealed by hair analysis.

Pesticide exposure has been associated with hormonal disruption in both animals and humans. However, there is limited knowledge of the combined effects of complex mixtures of pesticides on endogenous hormone levels. Here, we used hair analysis to assess the impact of a pesticide mixture comprising 19 components from multiple chemical classes at eight doses of 0-400μg/kg body weight (bw) three times per week per component on concentrations of 36 steroid and thyroid hormones in female rats over a 90-day exposure period. We detected 13 hormones in rat hair, namely estradiol (E2), androstenedione (AD), testosterone (T), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), pregnenolone (P5), progesterone (P4), 11-deoxycorticosterone (11-DOC), corticosterone (CORT), 3,3'-l-diiodothyronine (T2), 3,5,3'-l-triiodothyronine (T3), 3,3',5'-l-triiodothyronine (rT3), and 3,5,3',5'-l-tetraiodothyronine (T4). In comparison to the control group, hair E2 concentration was significantly lower in the two highest (200 and 400μg/kg bw) exposure groups, whereas hair DHEAS and CORT concentrations were significantly higher in the 40μg/kg bw and the highest exposure groups, respectively. Results from generalized additive models suggest that pesticide exposure resulted in monotonic dose responses in hair E2 concentration, CORT concentration and DHEA/CORT molar ratio but nonmonotonic dose responses in hair T concentration, DHEAS concentration, P4/P5 and DHEA/DHEAS molar ratios. The associations of E2, CORT and DHEA/CORT ratio with exposure intensity were confirmed by their significant linear relationships with hair concentrations of at least 23 of the 25 exposure biomarkers analyzed. Our results demonstrate that exposure to low levels of the pesticide mixture evaluated here can alter hair reproductive and adrenal hormones levels.

The Association Between Circulating Sex Hormones and Central Serous Chorioretinopathy: A Case-Control Study.

BackgroundCentral serous chorioretinopathy (CSC) is preferential cocurated in males, however the associations between sex hormones and CSC incidence or progression remains unclear. The sex hormone concentration assessments in CSC cases and healthy controls will update the knowledge in CSC management.MethodsThis case-control study included 59 CSC cases and 30 healthy controls, from January 2019 to December 2020. The CSC cases would be defined as spontaneous resolved if the subretinal fluid were absorbed within three months. The concentrations of total testosterone (TT), free testosterone (FT), estradiol (E2), sex hormone-binding globulin (SHBG), progesterone, leuteinizing hormone (LH) and dehydroepiandrosterone sulfate (DHEA-S) were detected in all the participants. The relationships between sex hormone concentrations and CSC-related characteristics were analyzed with Pearson correlation analyses.ResultsSignificantly increased TT, FT, FT/E2 ratio, SHBG concentrations as well as decreased DHEA-S level were detected in non-resolved CSC group compared with the control group. Comparing with the resolved ones, it was found that TT, FT and SHBG concentrations were increased in the non-resolved CSC. A significant positive correlation between TT concentrations and CMT (R2=0.168, P=0.031) as well as SRF height (R2=0.146, P=0.045) were detected in the non-solved CSC group.ConclusionDifferent concentrations of TT, FT, FT/E2 ratio, DHEA-S and SHBG were detected in resolved and non-resolved CSC cases. Sex hormones were related to CSC symptom durations and related parameters.

Short-time intensive insulin therapy upregulates 3 beta- and 17 beta-hydroxysteroid dehydrogenase levels in men with newly diagnosed T2DM.

ObjectiveOur previous study has found that short-term intensive insulin therapy in patients with newly diagnosed type 2 diabetes mellitus (T2DM) increased serum testosterone levels, but the underlying mechanisms remain unclear.Design and methodsIn this self-controlled study, 43 men with newly diagnosed drug naïve T2DM, aged 18-60 years, with HbA1c >9.0% were treated with continuous subcutaneous insulin infusion (CSII) to normalize blood glucose within one week. Venous blood specimens were collected for measuring of serum total testosterone, dehydroepiandrosterone sulfate (DHEA-S), 3β- and 17β-hydroxysteroid dehydrogenase (3β- and 17β-HSD) concentrations before and after insulin therapy.ResultsTestosterone increased from 13.0 (11.3, 14.6) nmol/L to 15.7 (13.9, 17.5) nmol/L after intensive insulin therapy (p<0.001), while the levels of DHEA-S decreased significantly after treatment (from 6.5 (5.7, 7.3) μmol/L to 6.0 (5.3, 6.7) μmol/L, p=0.001). The ratio of testosterone/DHEA-S increased significantly (2.4 (2.0, 2.8) vs. 3.1 (2.6, 3.7) nmol/μmol, p<0.001). After blood glucose normalization with the short-term CSII therapy, 3β-HSD increased from 11.0 (9.5, 12.5) pg/mL to 14.6 (13.5, 15.7) pg/mL, p=0.001, and 17β-HSD increased from 20.7 (16.3, 25.2) pg/mL to 28.2 (23.8, 32.5) pg/mL, p=0.009.ConclusionsBlood glucose normalization via short-term intensive insulin therapy increases plasma total testosterone levels in men with newly diagnosed type 2 diabetes, associated with a decreased level of DHEA-S, probably because of the enhanced conversion from DHEA to testosterone catalyzed by 3β-HSD and 17β-HSD.

P-613 Association between basal androgen concentrations and number of follicles on the day of triggering final oocyte maturation in poor responders undergoing IVF; A prospective study

Abstract Study question Are basal androgen concentrations associated with the number of follicles on the day of triggering final oocyte maturation in poor responders undergoing in vitro fertilization (IVF)? Summary answer A significant negative association is present between (dehydroepiandrosterone sulfate) DHEAS concentrations and the number of follicles on the day of triggering final oocyte maturation. What is known already Studies in animals have shown that androgens promote early follicular development and granulosa cell proliferation, by augmenting follicle-stimulating hormone (FSH) receptor expression in granulosa cells. Several retrospective studies have evaluated the association between basal androgen concentrations and follicular development in normal and poor responders undergoing ovarian stimulation for IVF with conflicting results. Study design, size, duration This prospective study was performed between 02/2020 and 01/2022 in 103 poor responders according to the Bologna criteria. Androgens, including total testosterone, sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), Δ4-androstenedione and 17-OH progesterone (17-OHP), were measured at the initiation of ovarian stimulation, using the automated Elecsys immunoanalyser (Roche Diagnostics, Mannheim, Germany). Ovarian stimulation was performed using a fixed dose of 300 IU of recombinant gonadotrophins and gonadotrophin-releasing hormone (GnRH) analogues. Participants/materials, setting, methods Triggering of final oocyte maturation was performed in the presence of three follicles of ≥ 17mm. The primary outcome measure was the number of follicles ≥11mm on the day of triggering final oocyte maturation. The association between androgen concentrations and the number of follicles ≥11mm on the day of triggering was evaluated using generalized estimating equations, accounting for female age and body mass index (BMI). Values were expressed as coefficient (coef) or mean (95% confidence interval). Main results and the role of chance Female age was 41.9 (41.2-42.6) years, while BMI was 26.1 (24.9-27.3) kg/m2. The duration of ovarian stimulation was 10.3 (9.7-10.8) days and the total dose of gonadotrophins required was 3058 (2903-3213) IU. The number of follicles ≥11 mm on the day of triggering final oocyte maturation was 6.1 (5.3-7.0). The number of COCs retrieved was 3.9 (3.2-4.6), the number of MII oocytes was 3.4 (2.8-3.9) and the number of 2pn oocytes was 2.5 (2.1-2.8). No significant association was found between basal testosterone (coef: -0.008, -0.019 to + 0.003, p = 0.17), 17-OHP (coef: -0.044, -0.391 to + 0.303, p = 0.80), SHBG (coef: -0.002, -0.007 to + 0.002, p = 0.25) Δ4-androstenedione (coef: -0.101, -0.306 to + 0.104, p = 0.33) concentrations and the number of follicles ≥11mm on the day of triggering final oocyte maturation. In contrast, a significant negative association was found between basal DHEAS (coef: -0.011, -0.019 to -0.003, p = 0.007) concentrations and the number of follicles ≥11 mm on the day of triggering final oocyte maturation. Higher DHEAS concentrations were associated with the development of fewer follicles ≥11 mm. Limitations, reasons for caution This prospective study evaluated the association between basal androgen concentrations and the number of follicles on the day of triggering final oocyte maturation in poor responders stimulated with a fixed dose of recombinant FSH. However, the precision of the estimates could be increased by analyzing a larger study population. Wider implications of the findings DHEA supplementation in poor responders undergoing IVF has not been shown to improve ovarian response. Given the significant negative association between DHEAS concentrations and the number of follicles on the day of triggering final oocyte maturation, future studies on DHEA supplementation should consider basal DHEAS concentrations. Trial registration number N/A

Massive adrenocortical carcinoma presenting as peripheral edema: a case report

BackgroundAdrenocortical carcinoma is a rare, but potentially lethal, malignancy that is usually detected as an incidental finding on abdominal imaging studies or owing to hormonal complications. This report recounts an unusual presentation with leg edema due to compression of the inferior vena cava. The dearth of proven effective treatment is also addressed.Case presentationA 65-year-old White male physician presented with severe, bilateral pitting edema that extended from the toes to the thighs. It progressed over several months. He also experienced paroxysmal dyspnea. Evaluation of cardiac, hepatic, and renal function failed to determine a cause. Computed tomography revealed a tumor above the right kidney, with compression of the intrahepatic inferior vena cava and upstream distension. Serum cortisol and dehydroepiandrosterone sulfate concentrations were elevated, 24-hour urinary cortisol level was elevated, and serum adrenocorticotropic hormone and testosterone concentrations were suppressed. A 27-cm tumor, the right lobe of the liver, the right kidney, and 26 lymph nodes were resected. Histological study confirmed the diagnosis of adrenocortical carcinoma. Ki67 proliferation index was 26.7% (worse prognosis associated with index > 10%). Lymph nodes were negative for malignancy, but a separate 2.7-cm tumor was found near the renal hilum. Adjuvant mitotane chemotherapy was prescribed. Serum testosterone concentration returned to normal. High-dose hydrocortisone administration was needed because of adrenal suppression and CYP 3A4 induction by mitotane.ConclusionImaging of the abdomen and pelvis should be conducted in cases of unexplained leg edema. In this case, a large adrenal cancer compressed the vena cava. Iron deficiency followed resection of the large tumor. Advanced stages of adrenocortical carcinoma are associated with poor prognosis. Mitotane chemotherapy is a standard but unproven adjuvant treatment that is associated with many complications, and its induction of hepatic CYP 3A4 enzymes necessitates adjustment of other medications.

Simultaneous Determination of Steroids and Glucocorticoids in Human Urine by Ultra-High-Performance Liquid Chromatography – Tandem Mass Spectrometry (UPLC–MS/MS)

Prostate cancer is a hormone-dependent disease and therefore androgens play a critical role in its development. For both research on clinical conditions as well as diagnostic and monitoring purposes, accurate measurement of steroid hormones is essential. This study aimed to develop a sensitive and selective method for simultaneously detecting nine sex steroids and two glucocorticoids in human urine and to evaluate the alterations of urinary endogenous steroid hormones induced by prostate cancer. A total of 97 Chinese subjects were randomly recruited for this study, including 66 patients with prostate cancer and 31 healthy controls. The concentrations of steroid hormones, including dehydroepiandrosterone, dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, dihydrotestosterone (DHT), estrone, estradiol, estriol (E1), progesterone, cortisol (F), and cortisone (E), were simultaneously determined by ultra-high-performance liquid chromatography – tandem mass spectrometry with atmospheric pressure chemical ionization in the positive mode (UPLC–APCI+–MS/MS). The population analysis indicated that prostate cancer patients showed significantly higher DHEAS, DHT, E1, and E than healthy controls. Furthermore, the levels of DHEAS and E1 were significantly positively correlated with serum levels of prostate-specific antigen (PSA), which is considered to be the best conventional prostate cancer marker in the current study. In summary, we validated the use of urine samples for multiple steroid profiling by UPLC–MS/MS. Two steroids were significantly altered and correlated with PSA in the prostate cancer population. These findings open further investigation of the potential role of sex steroids in prostate cancer diagnosis. Studying large samples and determining these steroid hormones in the urine are still necessary.

Hair Cortisol and DHEA-S in Foals and Mares as a Retrospective Picture of Feto-Maternal Relationship under Physiological and Pathological Conditions.

Simple SummaryHair hormone concentrations represent an attractive alternative for studies focusing on the prenatal period because a single measurement from hair collected at birth could provide data from a wide but datable prenatal period. Our aim is to evaluate cortisol, dehydroepiandrosterone-sulfate concentrations and their ratio in the trichological matrix of mares and foals to assess maternal and fetal hypothalamus-pituitary-adrenal axis activity in relation to the clinical condition of the neonate and the housing place at parturition. Mare’s endocrine setting influences hormone concentrations detected in foal’s hair, and foals classified as sick at birth have different hormone concentrations than healthy ones. On the other hand, hormone concentrations detected in the hair of mares hospitalized for attended parturitions do not reflect a different hypothalamus-pituitary-adrenal axis activity from those foaled at the breeding farm. Although the specific role of cortisol and dehydroepiandrosterone-sulfate in foals and mares under pathological conditions remains under investigation, this study opens up the use of neonate’s hair as an attractive non-invasive retrospective calendar for the assessment of prenatal adrenal activity in the equine species.Equine fetal hair starts to grow at around 270 days of pregnancy, and hair collected at birth reflects hormones of the last third of pregnancy. The study aimed to evaluate cortisol (CORT) and dehydroepiandrosterone-sulfate (DHEA-S) concentrations and their ratio in the trichological matrix of foals and mares in relation to their clinical parameters; the clinical condition of the neonate (study 1); the housing place at parturition (study 2). In study 1, 107 mare-foal pairs were divided into healthy (group H; n = 56) and sick (group S; n = 51) foals, whereas in study 2, group H was divided into hospital (n = 30) and breeding farm (n = 26) parturition. Steroids from hair were measured using a solid-phase microtiter radioimmunoassay. In study 1, hair CORT concentrations measured in foals did not differ between groups and did not appear to be influenced by clinical parameters. A correlation between foal and mare hair CORT concentrations (p = 0.019; r = 0.312, group H; p = 0.006; r = 0.349, group S) and between CORT and DHEA-S concentrations in foals (p = 0.018; r = 0.282, group H; p < 0.001; r = 0.44, group S) and mares (p = 0.006; r = 0.361, group H; p = 0.027; r = 0.271, group S) exists in both groups. Increased hair DHEA-S concentrations (p = 0.033) and decreased CORT/DHEA-S ratio (p < 0.001) appear to be potential biomarkers of chronic stress in the final third of pregnancy, as well as a potential sign of resilience and allostatic load in sick foals, and deserve further attention in the evaluation of prenatal hypothalamus-pituitary-adrenal (HPA) axis activity in the equine species. In study 2, hormone concentrations in the hair of mares hospitalized for attended parturition did not differ from those that were foaled at the breeding farm. This result could be related to a too brief period of hospitalization to cause significant changes in steroid deposition in the mare’s hair.

Serum concentrations of 17-hydroxyprogesterone and dehydroepiandrosterone sulfate in women with polycystic ovary syndrome and their relation to the parameters of glucose metabolism

Serum concentrations of 17-hydroxyprogesterone and dehydroepiandrosterone sulfate in women with polycystic ovary syndrome and their relation to the parameters of glucose metabolism

Adrenal androgens versus cortisol for primary aldosteronism subtype determination in adrenal venous sampling

ObjectiveWe examined if measurement of adrenal androgens adds to subtype diagnostics of primary aldosteronism (PA) under cosyntropin‐stimulated adrenal venous sampling (AVS).DesignA prospective pre‐specified secondary endpoint analysis of 49 patients with confirmed PA, of whom 29 underwent unilateral adrenalectomy with long‐term follow‐up.MethodsConcentrations of androstenedione, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) were measured during AVS in addition to aldosterone and cortisol. Subjects with lateralisation index (LI) of ≥4 were treated with unilateral adrenalectomy, and the immunohistochemical subtype was determined with CYP11B2 and CYP11B1 stains. The performance of adrenal androgens was evaluated by receiver operating characteristics (ROC) curve analyses in adrenalectomy and medical therapy groups.ResultsDuring AVS, the correlations between cortisol and androstenedione, DHEA and DHEAS for LI and selectivity index (SI) were highly significant. The right and left side SIs for androstenedione and DHEA were higher (p < .001) than for cortisol. In ROC analysis, the optimal LI cut‐off values for androstenedione, DHEA and DHEAS were 4.2, 4.5 and 4.6, respectively. The performance of these LIs for adrenal androgens did not differ from that of cortisol.ConclusionsUnder cosyntropin‐stimulated AVS, the measurement of androstenedione and DHEA did not improve the cannulation selectivity. The performance of cortisol and adrenal androgens are confirmatory but not superior to cortisol‐based results in lateralisation diagnostics of PA.

IL-15 Participates in the Pathogenesis of Polycystic Ovary Syndrome by Affecting the Activity of Granulosa Cells.

BackgroundLow-grade chronic inflammation may contribute to the pathogenesis of polycystic ovary syndrome (PCOS). Interleukin-15 (IL-15) is a proinflammatory cytokine involved in the development of chronic inflammation leading to obesity-associated metabolic syndrome. However, the concentration of IL-15 in follicular fluid of patients with PCOS has yet been evaluated.ObjectivesThe aim of this study is to evaluate the expression level of IL-15 in both patients with PCOS and PCOS mice model and investigate the functional effect of IL-15 on ovarian granulosa cells.MethodsThe level of IL-15 in follicular fluid (FF) was measured using cytokine array and enzyme linked immunosorbent assay (ELISA) in two cohorts from 23 PCOS patients and 18 normo-ovulatory controls. PCOS mice model was induced by subcutaneously implanted with letrozole pellet for 21 days. The expression level of IL-15 in serum, ovarian, and subcutaneous adipose tissue in PCOS mice model was measured by ELISA, real-time polymerase chain reaction (RT-PCR), immunohistochemistry (IHC), and immunofluorescence. The effect of IL-15 on the proliferation and apoptosis of the KGN cells and mouse ovarian granulosa cells (GCs) were detected by CCK-8 assay and flow cytometry, respectively. Transcript expression of 17α-hydroxylase17,20-lyase (CYP17A1), cytochrome P450 family 19 subfamily A member 1(CYP19A1), FSH receptor (FSHR), steroidogenic acute regulatory protein (StAR), and proinflammatory cytokine were quantified using RT-PCR. The protein level and phosphorylation level of p38 MAPK and JNK are detected by Western blot. Concentration of dehydroepiandrosterone sulfate (DHEAS) and progesterone (P)were measured by ELISA.ResultsIL-15 expression in follicular fluid of patients with PCOS was significantly elevated compared with the control group, and similar results were observed in the ovarian and subcutaneous adipose tissue of PCOS mice models. Furthermore, the elevated FF IL-15 levels have a positive correlation with the serum testosterone levels. FSHR co-localized with IL-15 indicating that IL-15 production originate from ovarian granulose cells. IL-15 treatment inhibited proliferation and promoted apoptosis of KGN cells and mouse GCs. Moreover, IL-15 upregulated the transcription levels of CYP17A1, IL-1b and Ifng KGN cells. Similar results were observed in mouse GCs except concentration of DHEAS was higher in IL-15 treatment. IL-15 promoted p38 MAPK and JNK phosphorylation in KGN cells, treating KGN cells with p38 MAPK inhibitor SP600125 and JNK inhibitor SB203580 could reverse the effect of IL-15 on the proliferation and function of KGN cells.ConclusionThe results indicate that IL-15 is involved in the pathogenesis of PCOS potentially by affecting survival, the inflammation state and steroidogenesis of granulosa cells. The practical significance of this association between IL-15 and the pathogenesis of PCOS needs further investigation.

DHEA-S production capacity in relation to perceived prolonged stress

We and other research groups have previously described that levels of the anabolic hormone dehydroepiandrosterone sulfate (DHEA-S) are lowered in individuals who report prolonged stress. We have also shown that the DHEA-S production capacity during acute stress is attenuated in individuals reporting high prolonged stress. This study aimed to further investigate the DHEA and DHEA-S production capacity in relation to prolonged stress. Eighty-one healthy participants in the age 20–50 years old were included in the study and divided into a low stress (n = 45) and a high stress group (n = 36) according their response to a single question regarding perceived stress during the preceding month. They underwent the Trier Social Stress Test while blood samples were drawn before, during and after the stress test. The concentration of DHEA, DHEA-S, cortisol and ACTH was measured. The results showed that the high stress group exhibited a significantly lower response of DHEA-S (40% lower) than the low stress group, while DHEA, cortisol and ACTH responses did not differ between the groups. Reduced DHEA-S production may constitute one of the links between stress and poor health.

The Relation of Serum Dehydroepiandrosterone Sulfate Level to Protein Energy Wasting in Hemodialysis Patients

Protein-energy wasting (PEW) is a major risk for morbidity and mortality in hemodialysis (HD) patients. The change in the concentration of dehydroepiandrosterone sulfate (DHEA-S) may play a role in PEW. The aim of this work was to study the possible relationship between serum DHEA-S levels and various nutritional and inflammatory parameters in a cohort of HD patients. In total, 78 HD patients (47 males and 31 females) were included in this crosssectional observational study. In addition to taking their history, clinical examinations, and routine laboratory investigations, the nutritional status was assessed, and their serum DHEA-S was measured. Nutritional status was assessed by anthropometric measures, bioelectrical impedance analysis, malnutrition inflammation scores, and subjective global assessments. A diagnosis of malnutrition was made based on the recommendations of the International Society of Renal Nutrition and Metabolism. The relationship between DHEA-S and various nutritional parameters was analyzed. Eighteen patients (23.1%) suffered from PEW. Those with PEW had a longer duration of HD (P = 0.04), and lower serum levels of creatinine (P = 0.003), hemoglobin (P = 0.01), albumin (P &lt;0.0001), cholesterol (P = 0.02), and DHEA-S (P = 0.01). Among the variables, serum DHEA-S levels were significant predictors of PEW in this cohort (odds ratio: 0.976; 95% confidence interval: 0.954–1.0; P = 0.04). PEW is frequently encountered in HD patients. Decreased serum DHEA-S levels were associated with PEW in male HD patients. Further studies are needed to assess the effect of hormone supplementation on this serious disorder in HD patients.