Serum Dehydroepiandrosterone Research Articles

A PROSPECTIVE, OPEN-LABEL, NON-RANDOMISED STUDY TO ASSESS THE EFFICACY AND SAFETY OF ZERO TENSION TABLETS IN PATIENTS WITH STRESS, ANXIETY AND INSOMNIA DISORDERS

Introduction: Passiflora incarnata, Valeriana wallichii and Withania somnifera are known to have psychotropic effects. These plants have been reported to alleviate stress, anxiety, and insomnia. This study aimed to evaluate the safety and efficacy of Zero Tension tablets in patients with mild to moderate stress, anxiety, and insomnia disorders. Methods: This study was a prospective, open-label, non-randomised study on patients (n = 100) with mild to moderate stress, anxiety, and insomnia disorders. All participants received two tablets with lukewarm water daily at night for 56 days. Primary outcomes were changes in the Hamilton anxiety scale (HAM-A), perceived stress scale (PSS), insomnia severity index, general health scores, serum levels of cortisol and dehydroepiandrosterone (DHEA) from day 0 to day 56. Secondary outcomes included adverse effects, changes in vital signs, haematological parameters, and serum biochemistry. Datasets were analysed at different assessment points using a t-test and one-way analysis of variance (ANOVA), as applicable. Results: Consumption of Zero Tension tablets significantly (p<0.001) reduced HAM-A, PSS, insomnia severity, and general health scores. Most participants experienced reduced stress, anxiety, and insomnia symptoms after 56 days of treatment. The serum cortisol and DHEA levels were also mildly reduced. No significant adverse effects or changes in vital signs, haematological, or blood biochemistry parameters were observed. Conclusion: The results suggested that the Zero Tension tablet is safe and could be an effective alternative to improve stress, anxiety and sleep disorders.

Mechanism of leptin-NPY on the onset of puberty in male offspring rats after androgen intervention during pregnancy.

The time of onset of puberty has been increasingly earlier, but its mechanism is still unclear. This study aimed to reveal the mechanism of leptin and NPY in the onset of puberty in male offspring rats after androgen intervention during pregnancy. Eight-week-old specific pathogen-free (SPF) healthy male Sprague-Dawley (SD) rats and 16 female SD rats were selected and caged at 1:2. The pregnant rats were randomly divided into the olive oil control group (OOG) and testosterone intervention group (TG), with 8 rats in each group. Olive oil and testosterone were injected from the 15th day of pregnancy, for a total of 4 injections (15th, 17th, 19th, 21st day). After the onset of puberty, the male offspring rats were anesthetized with 2% pentobarbital sodium to collect blood by ventral aorta puncture and decapitated to peel off the hypothalamus and abdominal fat. Serum testosterone (T), free testosterone (FT), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), sex hormone binding globulin (SHBG), and leptin were detected by ELISA, and then the free androgen index (FAI) was calculated. The mRNA levels of androgen receptor (AR), estrogen receptor α (ERα), NPY, leptinR, and NPY2R in the hypothalamus and abdominal fat were detected by RT-PCR. Protein expression levels of AR, ERα, NPY, leptinR, and NPY2R in the arcuate nucleus (ARC) of the hypothalamus were detected by immunohistochemistry. The time of onset of puberty was significantly earlier in the TG than in the OOG (P< 0.05) and was positively correlated with body weight, body length, abdominal fat, and leptinR mRNA levels in adipose tissue in the OOG (P< 0.05), while it was positively correlated with serum DHT and DHEA concentrations and FAI and AR mRNA levels in the hypothalamus in the TG (P< 0.05). The NPY2R mRNA level and protein expression levels of ERα, NPY2R, and leptinR in the TG were significantly higher than those in the OOG, while the protein expression levels of AR and NPY in the TG were significantly lower than those in the OOG (P< 0.05). Testosterone intervention during pregnancy led to an earlier onset of puberty in male offspring rats, which may render the male offspring rats more sensitive to androgens, leptin, and NPY at the onset of puberty.

Multiple exposures to heavy metals and changes in steroid hormones production in 4-year-old children.

Prenatal exposure to multiple heavy metals can interfere with early neurodevelopment, lead to changes in sex hormone concentrations in children, and affect female reproductive health. To date, the influence of prenatal exposure to heavy metals on the endocrine system of children in Chinese electronic waste (e-waste) recycling areas has not been elucidated. Four weeks after delivery, 10 mL of human milk was collected for analysis of three heavy metals (lead (Pb), cadmium (Cd), and mercury (Hg)) via inductively coupled plasma mass spectrometry (ICP-MS). Four serum steroid hormones, including progesterone, testosterone, androstenedione (A-dione), and dehydroepiandrosterone (DHEA), were analyzed in 4-year-old children (25 boys and 17 girls). A multiple linear regression (MLR) model was implemented to investigate the association between each individual metal and serum steroid hormone. The exposure-response relationships were explored by generalized additive models (GAMs). Additionally, a Bayesian kernel machine regression (BKMR) model was used to assess the effects of multiple heavy metal exposures on each steroid hormone. The MLR results show a significant positive association between a natural log unit increase in Hg and DHEA levels after adjusting for confounders (β = 65.50, 95% confidence interval (CI) = 4.37, 126.62). According to the GAM, the univariate exposure-response relationship of Hg on DHEA was almost linear. However, this association was attenuated based on the multiple metal MLR and BKMR results after accounting for multiple heavy metal exposures. Prenatal Hg exposure may affect sex hormones in children by affecting DHEA levels. Prenatal maternal exposure to Hg may have long-term effects on the next generation. Hence, regulatory measures to reduce Hg exposure and long-term monitoring of children's health in e-waste areas are needed.

VALIDATION OF ENZYME-LINKED IMMUNOSORBENT ASSAY TECHNIQUES TO MEASURE SERUM DEHYDROEPIANDROSTERONE (DHEA) AND DHEA-S IN NARWHALS (MONODON MONOCEROS).

Narwhals (Monodon monoceros) are increasingly exposed to anthropogenic disturbances that may increase their stress levels with unknown consequences for the overall population dynamics. The validation and measurement of chronic stress biomarkers could contribute toward improved understanding and conservation efforts for this species. Dehydroepiandrosterone (DHEA) and its sulfated metabolite DHEA-S are collectively referred to as DHEA(S). Serum DHEA(S) concentrations combined in ratios with cortisol [cortisol/DHEA(S)] have been shown to be promising indicators of chronic stress in humans, domestic animals, and wildlife. During field tagging in 2017 and 2018 in Baffin Bay, Nunavut, Canada, 14 wild narwhals were sampled at the beginning and end of the capture-tagging procedures. Serum DHEA(S) were measured with commercially available competitive enzyme-linked immunosorbent assays (ELISA) developed for humans. A partial validation of the ELISA assays was performed by the determination of the intra-assay coefficient of variation, confirmation of the DHEA(S) dilutional linearity, and the calculation of the percentage of recovery. Mean values (nanograms per milliliter ± standard error of the mean) of narwhal serum cortisol, DHEA(S), and cortisol/DHEA(S) ratios, at the beginning and at the end of handling, respectively, are reported (cortisol = 30.74 ± 4.87 and 41.83 ± 4.83; DHEA = 1.01 ± 0.52 and 0.99 ± 0.50; DHEA-S = 8.72 ± 1.68 and 7.70 ± 1.02; cortisol/DHEA = 75.43 ± 24.35 and 84.41 ± 11.76, and cortisol/DHEA-S = 4.16 ± 1.07 and 6.14 ± 1.00). Serum cortisol and cortisol/DHEA-S were statistically higher at the end of the capture (P= 0.024 and P= 0.035, respectively). Moreover, serum cortisol at the end of handling was positively correlated to total body length (P = 0.042) and tended to be higher in males (P = 0.086). These assays proved easy to perform, rapid, and suitable for measuring serum DHEA(S) of narwhals and that calculated cortisol/DHEA(S) are potential biomarkers for chronic stress in narwhals and possibly other cetaceans.

Serum and hair steroid profiles in patients with nonfunctioning pituitary adenoma undergoing surgery: A prospective observational study

Patients who undergo transsphenoidal surgery (TSS) experience perioperative hormonal changes, but there are few studies on the perioperative changes of serum and hair steroid profiles. This study investigated the perioperative changes in steroid metabolic signatures in patients with nonfunctioning pituitary adenoma (NFPA) who underwent transsphenoidal surgery (TSS). A total of 55 participants who underwent TSS for NFPA at a single center between July 2017 and October 2018 were enrolled. Fifteen serum steroids and their metabolic ratios were profiled using gas chromatography-mass spectrometry (GC-MS) before and 1 day, 1 week, and 3 months after TSS. Five steroids from hair samples collected 1 day and 3 months after TSS were also quantitatively compared. Serum cortisol and its A-ring reductive metabolites, as well as 6β-hydroxycortisol, increased dramatically 1 day after TSS and then gradually decreased. Seven serum steroids, including adrenal androgens and mineralocorticoids, and hair cortisone levels were significantly lower in patients with preoperative adrenocorticotropic hormone (ACTH) deficiency (N = 7) than in those without ACTH deficiency (N = 48). Serum levels of dehydroepiandrosterone (DHEA) levels 1 week after TSS predicted ACTH deficiency 3 months after TSS, with 100 % sensitivity and 86 % specificity. A significant positive correlation between the preoperative serum and hair DHEA levels (r = 0.356, P = 0.008) was observed. These findings suggest that the levels of DHEA in both the serum and hair could be an early marker of ACTH deficiency after TSS. In addition, hair cortisone may be a useful preoperative indicator of chronic ACTH deficiency.

Low serum dehydroepiandrosterone levels are associated with diabetic retinopathy in patients with type 2 diabetes mellitus.

This cross-sectional study assessed the association of serum dehydroepiandrosterone levels with the risk of diabetic retinopathy in patients with type 2 diabetes mellitus in China. Patients with type 2 diabetes mellitus were included in a multivariate logistic regression analysis to assess the association of dehydroepiandrosterone with diabetic retinopathy after adjusting for confounding factors. A restricted cubic spline was also used to model the association of serum dehydroepiandrosterone level with the risk of diabetic retinopathy and to describe the overall dose-response correlation. Additionally, an interaction test was conducted in the multivariate logistic regression analysis to compare the effects of dehydroepiandrosterone on diabetic retinopathy among age, sex, obesity status, hypertension, dyslipidemia, and glycosylated hemoglobin level subgroups. In total, 1,519 patients were included in the final analysis. Low serum dehydroepiandrosterone was significantly associated with diabetic retinopathy in patients with type 2 diabetes mellitus after adjustment for confounding factors (odds ratio [quartile 4 vs quartile 1]: 0.51; 95% confidence interval: 0.32-0.81; P=0.012 for the trend). Additionally, the restricted cubic spline indicated that the odds of diabetic retinopathy decreased linearly as the dehydroepiandrosterone concentration increased (P-overall=0.044; P-nonlinear=0.364). Finally, the subgroup analyses showed that the dehydroepiandrosterone level stably affected diabetic retinopathy (all P for interaction >0.05). Low serum dehydroepiandrosterone levels were significantly associated with diabetic retinopathy in patients with type 2 diabetes mellitus, suggesting that dehydroepiandrosterone contributes to the pathogenesis of diabetic retinopathy.

CORRELATIONS OF ENDOGENOUS TESTOSTERONE AND DHEA-S IN PERIPHERAL ARTERIAL DISEASE

Background: Peripheral arterial disease is Occlusive disease of the arteries of the extremity. Common causes are Atherosclerosis (most common), Buerger's disease, vasculitis and other arteritis, thromboembolism etc. Peripheral arterial disease (PAD) is a treacherous disease as it remains asymptomatic for so long. As PAD progresses, it may lead to classical intermittent claudication and critical limb ischemia. DHEAS has been demonstrated to have an antiatherosclerotic effect by prevention of platelet aggregation, uptake of cholesterol and a decrease in the proliferation of vascular smooth muscle cells. Testosterone causes vasodilation of the peripheral arteries by acting on the endothelium of the vessels and in turn results in release of nitric oxide (NO) which is a vasodilator and helps in vasodilation. Testosterone suppresses expression of vascular cell adhesion molecule-1 (proinammatory cytokines), anti-inammatory factors by its derivative 5-dihydrotestosterone which is the earliest step in atherosclerosis. Interestingly Testosterone and DHEAS also has benecial effects on cardiac ischemia, angina and chronic heart failure. The aim of this study is to look for any relationship of Testosterone and DHEAS in Peripheral Arterial Disease. Total 50 patients both inpatients and out Methods: patients were studied. The period of study was from September 2016 to June 2018. Patients who were proven to have peripheral arterial disease on colour doppler were taken for study. The study was done to look if any relationship is present between serum testosterone and dehydroepiandrosterone sulfate (DHEA-S) in a peripheral arterial disease patients. Data were documented and stored in a proper database format. At the end of data collection from the samples, data analysis was done using SPSS 16 software and appropriate tests of signicance were applied. For categorical variables Chi-square test and Fischer's Exact test was used. For comparing two groups of mean student's t-test was used. To correlate more than two continuous data Pearson and Spearman Correlation Coefcient was used. P value &lt;0.05 considered as statistically signicant. Our results showed that total serum testosterone Results: and DHEA-S were not signicantly decreased in PAD patients in comparison to the control group. We could not observe any signicant correlation. These results express that there is no signicant correlation Conclusion: of Serum Testosterone and Dehydroepiandosterone with Peripheral arterial Disease. In our study there are signicant correlations with inammatory markers (C reactive protein, Interleukin6, Homocysteine) Lipid prole (cholesterol, Triglyceride, HDL, VLDL) and HbA1C with serum Testosterone and Dehydroepiandosterone in Peripheral Arterial Disease

Endometrial Heparin-Binding Epidermal Growth Factor Gene Expression and Hormone Level Changes in Implantation Window of Obese Women with Polycystic Ovarian Syndrome

Polycystic ovarian syndrome (PCOS) is a common endocrine disorder amongst reproductive-age women, and 61% to 76% of women with PCOS are obese. Obese women with PCOS are usually burdened with infertility problems due to implantation failure. Thus, progesterone treatment is usually used to improve implantation rates. Although Hb-EGF expression is actively involved in endometrial receptivity and implantation, the data on heparin-binding epidermal growth factor (Hb-EGF) expression following progesterone therapy in obese women with PCOS are still lacking. To investigate the changes in serum follicle-stimulating hormone (FSH), luteinising hormone (LH), dehydroepiandrosterone sulphate (DHEA), progesterone and oestradiol levels and Hb-EGF expression in obese women with PCOS during the implantation window following progesterone therapy. A total of 40 participants aged 18-40 years old were recruited following the provision of written consent. The participants were divided into the obese PCOS, normal-weight PCOS, obese fertile and normal-weight fertile groups. First blood collection was done before ovulation. Then, daily oral micronised progesterone (Utrogestan 200 mg) was given to the PCOS group for 10 days. The treatment was followed by a second blood collection and endometrial tissue sampling by using a Pipelle de Cornier catheter. In the fertile group, ovulation was confirmed by using ultrasound, and a second blood sample was collected on days 7 to 9 postovulation. The serum levels of FSH, LH, DHEA, progesterone and oestradiol were measured in all participants. Wilcoxon signed-rank test was used to compare FSH, LH, DHEA, progesterone and oestradiol levels during pre- and postovulation. Mann-Whitney test was performed to compare FSH, LH, DHEA, progesterone and oestradiol levels between two groups: (1) the PCOS group and the fertile group, (2) the obese PCOS group and the non-obese PCOS group and (3) the obese group and the non-obese fertile group. Serum FSH levels were lower in obese women in their follicular phase than in women with normal weight regardless of their PCOS status, whereas serum LH/FSH ratios and DHEA levels were higher in women with PCOS than in women without PCOS. However, endometrial Hb-EGF expression was lower in the obese PCOS group than in the normal-weight PCOS group. Different patterns of hormonal levels and Hb-EGF expression levels were seen between the studied groups. However, further in vitro and in vivo studies are needed to investigate the mechanism underlying the changes in FSH, LH/FSH ratio, DHEA and Hb-EGF expression in PCOS after progesterone treatment.

Serum testosterone level correlates with left ventricular hypertrophy in older women.

Sex hormones may play an important role in age-related cardiac remodeling. However, their impact on cardiac structure and function in females of advanced age still remains unclear. The aim of this study is to evaluate the relationship between sex hormones level and echocardiographic parameters in older women with concomitant cardiovascular diseases. The study group included 52 community-dwelling women with mean age 79.5 ± 2.8 years, consecutive patients of an outpatient geriatric clinic. In all the subjects, a transthoracic echocardiogram was performed and serum testosterone, estradiol, follicle-stimulating hormone, luteinising hormone, dehydroepiandrosterone sulphate, and cortisol levels were determined. Testosterone level correlated positively with interventricular septum diastolic dimension (IVSd) (rS=0.293, p<0.05), left ventricular mass index (rS=0.285, p<0.05), E/E' ratio (rS=0.301, p<0.05), and negatively with E' (rS=-0.301, p<0.05). Estradiol level showed a positive correlation with the posterior wall dimension (rS=0.28, p<0.05). Besides, no significant correlations between clinical or echocardiographic parameters and other hormones were observed. Female subjects with diagnosed left ventricular hypertrophy (LVH) (n=34) were characterized by a significantly higher rate of hypertension (p=0.011), higher waist-to-height ratio (p=0.009), higher testosterone level (0.82 vs. 0.48 nmol/L, p=0.024), higher testosterone/estradiol ratio (16.4 vs. 9.9, p=0.021), and received more anti-hypertensive drugs (p=0.030). In a multiple stepwise logistic regression, the best determinants of LVH were the presence of hypertension (OR=6.51; 95% CI 1.62-26.1), and testosterone level (OR= 6.6; 95% CI 1.19-36.6). Higher serum testosterone levels may contribute to pathological cardiac remodeling, especially in hypertensive women. Estradiol, gonadotropins, DHEAS, and cortisol were not related to echocardiographic parameters.

Low serum dehydroepiandrosterone is associated with diabetic dyslipidemia risk in males with type 2 diabetes.

Sex steroid hormones are associated with the advancement of metabolic diseases such as dyslipidemia. This cross-sectional study aimed to investigate the relationship between dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, and testosterone levels and the risk of dyslipidemia in people with type 2 diabetes mellitus. The analysis included 1,927 patients with type 2 diabetes mellitus. Serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, and testosterone levels were determined using lipid chromatography-tandem mass spectrometry. Multivariable analyses were performed to investigate the association between the variables and dyslipidemia. The multivariable-adjusted odds ratio (OR) and 95% confidence interval (CI) of dyslipidemia across DHEA tertiles were 0.39 and 0.24-0.64, respectively (p trend = 0.001). This relationship was still maintained when analyzed as a continuous variable (odds ratio, 0.96; 95% confidence interval, 0.92-0.99; P < 0.01). However, in males with type 2 diabetes mellitus, no significant correlations were found between rising levels of dehydroepiandrosterone sulfate, androstenedione, and total testosterone and the risk of dyslipidemia (all P > 0.05). Furthermore, there was no significant association between androgen precursors and total testosterone with regard to the risk of developing dyslipidemia (all P > 0.05). Serum dehydroepiandrosterone levels were substantially and adversely correlated with dyslipidemia in adult men with T2DM. These results indicated that dehydroepiandrosterone may have an essential role in the development of dyslipidemia. More prospective research is required to validate this link.

Sex Steroid Hormone Analysis in Human Tear Fluid Using a Liquid Chromatography—Mass Spectrometry Method

The marked sexual dimorphism prevalent in inflammatory/autoimmune diseases is mostly due to sex hormone actions. One common eye disease that disproportionately affects women is dry eye. Thus, our aim was to optimise our highly sensitive liquid chromatography-tandem mass spectrometry method for steroid hormone quantification in tear fluid (TF). We used tears and matched serum samples from 10 heathy individuals. Estrone, estradiol testosterone, progesterone, androstenedione, and dehydroepiandrosterone, were quantified with an HPLC coupled with a Triple Quad 5500 MS. Estrone was measured in 80% of female and 20% of male TF samples (mean ± SD, 68.9 ± 62.2 pmol/L), whereas estradiol was undetectable in tears. Progesterone was identified in half of the female tear samples (2.91 ± 3.47 nmol/L) but in none of the male samples, whereas testosterone was quantifiable only in male tears (0.24 ± 0.1 nmol/L). TF hormone levels were, on average, from 1.4% to 55% of systemic values. Estrone, progesterone, and testosterone levels in tears correlated with the matching serum samples (r = 0.82, 0.79, and 0.85, respectively), but androstenedione and dehydroepiandrosterone showed no correlations. Our LC-MS/MS method could detect five out of the six steroid hormones studied in individual human TF samples and could therefore be used to analyse the role of sex steroids in eye diseases.

A high serum dehydroepiandrosterone concentration is a predictor of candidates for active surveillance in men with serum prostate-specific antigen < 10 ng/mL

BackgroundThere is no consensus on the role of serum dehydroepiandrosterone (DHEA) concentrations in the detection of prostate cancer. This study examined the effectiveness of serum DHEA in predicting candidate patients for active surveillance (AS) prior to prostate biopsy.MethodsA systematic prostate needle biopsy was performed in 203 men with serum PSA levels of < 10 ng/mL to detect prostate cancer. Serum DHEA concentrations were measured with liquid chromatography-tandem mass spectrometry (LC–MS/MS) just before biopsy. Patient’s age, serum prostate-specific antigen (PSA) levels, prostate volume, and serum DHEA concentrations were compared with pathological findings in multivariate analyses.ResultsThe median patient’s age, PSA, serum DHEA concentration and prostate volume were 68 years, 5.5 ng/mL, 1654.7 pg/mL, and 31.2 mL, respectively. In a multivariate analysis, low PSA values, high serum DHEA concentrations, and large prostate volume were significant predictors of the patients with benign prostatic hyperplasia (BPH) or prostate cancer with a Gleason score of ≤ 3 + 4 who are candidate for AS. The DHEA cut-off point for predicting BPH or prostate cancer with a Gleason score of ≤ 3 + 4 was 2188 pg/mL, with a sensitivity, specificity, positive predictive value, and negative predictive value of 33.7%, 96.0%, 98.4%, and 16.9%, respectively.ConclusionThe study indicated that higher serum DHEA concentrations prior to prostate biopsy might predict the patients with BPH or prostate cancer with a Gleason score ≤ 3 + 4 who are candidate for AS, in men with PSA of < 10 ng/mL.

ODP026 An Incidental Giant Normotensive Pheochromcytoma with Elevated Metanephrines demonstrated no evidence of hypertensive crisis during a major surgery

Abstract A 48-year-old Caucasian male with no known past medical history admitted to our hospital following MVA resulting in acute severely comminuted displaced fracture of the left femur and tibia. On admission, the patient was in severe pain. His vitals were significant for elevated blood pressure (BP) of 137/100 and pulse rate of 161 per minute, which resolved soon after pain medications and splint placement. On review of systems, he denied episodic spells of headaches, palpitations, pallor, tremors, anxiety, abdominal pain, or diaphoresis. He denied any family history of endocrine disorders. Physical exam was unremarkable, except for the left femur traction splint. He had multiple CT imaging performed for evaluation of his injuries. On CT scan of the abdomen, he was found to have a 7.2cm adrenal incidentaloma with imaging characteristics consistent with pheochromocytoma. He was admitted to the intensive care unit for one day for closer monitoring where he remained hemodynamically stable without any BP lowering medications. Laboratory work up for a pheochromocytoma was pending. However, due to concern of compartment syndrome of left lower extremity, patient underwent two emergent procedures of open reduction and internal fixation of left femur and tibial fracture repair. Robust monitoring of hemodynamics was performed during both surgeries but patient did not require any antihypertensive medications during the procedures. Eventually, serum total metanephrines drawn on admission day two, resulted as 7848 pg/ml (normal &amp;lt;205pg/ml), normetanephrines 3626 pg/ml (normal &amp;lt;148pg/ml), and metanephrines 4224 pg/ml (normal&amp;lt;57pg/ml). Serum cortisol, aldosterone, renin, dehydroepiandrosterone sulfate, and glucose were within normal limits. On day 3 of admission, repeated serum metanephrines were persistently elevated in 4000s. 24-hour (hr) urine studies showed total metanephrines 7353 mg/24hr (normal &amp;lt;832 mg/24hr), metanephrines 4934 mg/24hr (normal &amp;lt;315 mg/24hr), normetanephrines 2419 mg/24hr (normal &amp;lt;676 mg/24hr) and creatinine2.3g/24 hr (normal &amp;lt;2. 0g/24hr) . MRI abdomen confirmed pheochromocytoma abutting the pancreas and left upper pole of kidney. Interestingly, patient remained hemodynamically stable with highest BP measurement of 120/90 throughout the hospital course. He was eventually discharged on Prazosin 1 mg twice daily which was gradually increased to 5 mg daily in divided doses; increase fluid intake and high salt diet. Beta-blocker was not added due to borderline blood pressure. The patient underwent robotic left radical adrenalectomy without any intraoperative hemodynamic instability. Pathology was consistent with pheochromocytoma, confined to the adrenal gland without no capsular invasion. The patient refused genetic testing. Presentation: No date and time listed

RF03 | PMON300 Sex Hormones, Sex Hormone Binding Globulin, and Gonadotropins in Men with Inguinal Hernias

Abstract Background More than 1 in 4 men will undergo inguinal hernia repair during their lifetime. Age is a significant risk factor for inguinal hernias in men with increased incidence in older age. Sex steroid hormone changes are observed with a higher ratio of serum estradiol (E2) to testosterone (T) as men age. We previously demonstrated that a shift from androgen to estrogen action caused inguinal hernia formation in a transgenic male mouse model with increased estrogen action in lower abdominal muscle tissues. However, age-related changes in serum E2 levels in men are conflicting, as some studies have reported increases but others have noted unchanged or even decreased E2 levels with advancing age. Method: This study was performed on 212 men with inguinal hernias, aged 20 to 90 years, stratified at 10-year intervals of age (20-30, 31-40, 41-50, 51-60, 61-70, 71-80, 81-90 years). We assessed total T (TT), total E2 (TE2), dehydroepiandrosterone (DHEA), sex hormone-binding globulin (SHBG), and gonadotropins (FSH and LH). Body mass index (BMI) was calculated using height and weight. Results The BMI distribution was balanced for men with inguinal hernias among all age groups. TE2 was low in 23.7%, normal in 65.8%, and high in 10.5% of men 50 years or younger. In contrast, the percentage of patients with high TE2 was increased 2.6-fold in men over the age of 50 (20.1% in low, 52.3% in normal, and 27.6% in high). TT was normal in all men 50 years and younger but was low in 3.5% and normal in 96.5% of men over the age of 50. We found that serum TE2 levels and the ratio of TE2/TT positively correlated with age (p=0.001). In addition, serum TE2 levels were significantly higher in the advanced age groups (71-80 and 81-90 years) than in the young age group (20-40 years). Serum TT levels decreased but did not reach significance in the advanced age groups compared to the young age group. Remarkably the ratio of E2/T was higher in the advanced age groups than in the young age group (20-30 years). Serum DHEA levels in men over the age of 50 were significantly higher than in men 50 years or younger. SHBG levels were higher in men over 70 years than men 50 years or younger (p&amp;lt; 0.01). Serum levels of FSH and LH in men over 60 years were 3-fold greater than in men 50 or younger (p&amp;lt;0.01). Conclusions Our findings suggest a correlation of increased estrogen action in the formation of inguinal hernias at an advanced age. This points to a potential utilization of inhibitors of estrogen synthetase or estrogen antagonists in a subset of elderly inguinal hernia patients with increased circulating estrogen as a non-surgical intervention. Presentation: Saturday, June 11, 2022 1:42 p.m. - 1:47 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Lokaal gebruik van dehydro-epiandrosteron voor de behandeling van vaginale atrofie na borstkanker

Vaginal dehydroepiandrosterone for the treatment of vaginal atrophy in breast cancer survivors Vaginal atrophy is a common problem in breast cancer survivors, but often remains undiscussed with the health care professional. Vaginal oestrogens are the standard treatment, yet this treatment remains quite controversial in breast cancer survivors. Vaginal dehydroepiandrosterone (DHEA) appears to be a promising alternative. PubMed was screened for clinical trials on offering local DHEA for the treatment of vaginal atrophy in breast cancer survivors. Only 2 published articles, both covering 1 randomized double-blind controlled trial, were found. In that study, 443 participants were equally randomized into 3 arms: each participant receiving daily vaginal administration during 12 weeks of 3.25 mg DHEA, 6.5 mg DHEA and a plain moisturizer. All arms showed improvement in both vaginal dryness and dyspareunia, yet no dose of DHEA administration led to a statistically significant difference on both parameters compared to the plain moisturizer. Some significant self-reported side effects were observed. Serum DHEA sulphate and testosterone increased significantly depending on the DHEA dose in comparison to a plain moisturizer, yet still remaining within the normal postmenopausal range. Oestradiol amounts also increased in the 6.5 mg DHEA group, but not in the 3.25 mg DHEA group and, remarkably, not in women taking an aromatase inhibitor. Vaginal DHEA improves the symptoms of vaginal atrophy, especially in terms of sexual experience. However, further research is needed on the efficacy and safety of long-term use of vaginal DHEA in breast cancer survivors, especially in case of hormone-sensitive breast cancer.

Low Dehydroepiandrosterone (DHEA) Level Is Associated with Poor Immunologic Response among People Living with HIV/AIDS.

Dehydroepiandrosterone (DHEA) is an adrenal steroid converted to potent androgens. This study aimed to discover the association between serum DHEA levels and immunologic response in people with HIV/AIDS (PLWHA). We enrolled patients aged ≥ 18 years who were treated with combination antiretroviral therapy (cART). We measured CD4+ and CD8+ T-cell counts, HIV-RNA titres, and serum DHEA levels. We assigned each patient to a good- or poor-responder group depending on their CD4+ T-cell counts at study enrolment. Participants with CD4+ T-cell counts > 200/µL were assigned to the good-responder group, whilst those with CD4+ T-cell counts < 200/µL were assigned to the poor-responder group. The participants were followed up for 2 years. The poor-responder group showed lower CD4+ T-cell counts and higher HIV PCR titres at their initial HIV diagnosis and in their 2-year follow-up data. Serum DHEA level was lower in the poor-responder group. Multivariable logistic analysis showed that BMI, initial CD4+ T-cell counts, and serum DHEA level were clinical factors associated with poor immunologic responsiveness to cART in PLWHA. Therefore, DHEA may be used as an indicator of the immunological recovery of PLWHA.

Low serum allopregnanolone levels in children with attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) has increasing evidence for the role of neurohormones in its etiopathogenesis. It has been suggested that the effects of neurosteroids on the brain in the early developmental period may predispose to neurodevelopmental pathologies. In our study, we examined serum dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and allopregnanolone levels in children with ADHD and whether these neurosteroids differ in the presence of specific learning disorder (SLD) and oppositional defiant disorder (ODD) comorbidities (ADHD+SLD and ADHD+ODD). We also investigated the relationship between neurosteroid levels and the severity of ADHD symptoms. Thirty-five prepubertal children with ADHD and 33 prepubertal healthy children, all aged 6–10 years, were included in this study. The severity of ADHD symptoms was assessed with the parent-rated and teacher-rated Turgay DSM-IV Disruptive Behavior Disorders Rating Scale (T-DSM-IV-S). Serum allopregnanolone levels were significantly lower in the ADHD group compared to healthy controls. When analyzed according to comorbidity status, serum allopregnanolone levels were lower in ADHD+SLD and ADHD+ODD groups compared to healthy controls. However, when compared to healthy children, serum DHEA and DHEA-S levels in children with ADHD were not significantly different. Serum allopregnanolone levels were negatively associated with teacher-rated T-DSM-IV-S hyperactivity/impulsivity scores for all participants only. These findings suggest that allopregnanolone may play a role in the pathophysiology of ADHD, especially in the presence of ODD and SLD comorbidities.

COVID-19 patients with altered steroid hormone levels are more likely to have higher disease severity.

PurposeThis study aims to evaluate the correlations between the severity of the disease and serum steroid levels by analyzing the serum steroid levels in COVID-19 patients with different levels of disease progression and the control group.MethodsMorning serum Aldosterone, 11-deoxycortisol, Androstenedione, 17-hydroxyprogesterone, Dihydrotestosterone (DHT), Dehydroepiandrosterone (DHEA), Corticosterone, Dehydroepiandrosterone sulfate (DHEAS), Estrone, Estradiol, Progesterone, 11-deoxycorticosterone, Cortisol, Corticosterone, Androsterone, Pregnenolone, 17-hydroxypregnenolone and 21-deoxycortisol levels were measured in 153 consecutive patients were grouped as mild, moderate, and severe based on the WHO COVID-19 disease severity classification and the control group. Steroid hormone levels were analyzed at once with a liquid chromatography-tandem mass spectrometric method (LC-MS/MS).ResultsIn our study, nearly all steroids were statistically significantly higher in the patients’ group than in the control group (p < 0.001). Also, DHEA was an independent indicator of the disease severity with COVID-19ConclusionsOur study reveals that the alteration in steroid hormone levels was correlated with disease severity. Also, steroid hormone levels should be followed up during COVID-19 disease management.

Correlation of dehydroepiandrosterone with diabetic nephropathy and its clinical value in early detection.

Aims/IntroductionThis study was carried out to assess the association of dehydroepiandrosterone (DHEA) with diabetic nephropathy (DN) in patients with type 2 diabetes mellitus to better predict the progression of diabetic nephropathy.Materials and MethodsA total of 1,082 patients with type 2 diabetes mellitus in the Department of Endocrinology and Metabolism of Tianjin Medical University General Hospital were enrolled in this study, and grouped for comparison. The effect of serum DHEA on DN was evaluated by multivariate logistic regression analysis, and receiver operating characteristic curves were established to explore the optimal concentration of DHEA in patients with DN and non‐DN.ResultsDHEA was significantly decreased in patients with DN (P < 0.001). The prevalence of DN was significantly higher in the low DHEA quartile than in the other quartiles (P < 0.001). Spearman‐related analysis showed that DHEA levels were negatively correlated with patient age, course of diabetes, systolic blood pressure, blood creatinine, uric acid, urine albumin‐to‐creatinine ratio, 24‐h urine microalbumin, 24‐h urine protein quantification and glomerular filtration rate, and positively correlated with body mass index, total cholesterol and low density lipoprotein. Logistic regression analysis showed that the effect of DHEA on DN was statistically significant (P < 0.001). The receiver operating characteristic curve showed that the sensitivity was 81.4%, the specificity was 70% and the area under the curve was 0.812 when the optimal cut‐off value was 1,640 (pg/mL).ConclusionDHEA is significantly associated with DN and might be a protective factor for DN, and is important for the prediction of DN.

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.