Dehydroepiandrosterone Sulphate Ratio Research Articles

Early menarche and other endocrine disrupting effects of per- and polyfluoroalkyl substances (PFAS) in adolescents from Northern Norway. The Fit Futures study

BackgroundPer- and polyfluoroalkyl substances (PFAS) comprise a large group of chemicals that are ubiquitous in the environment and include recognized persistent organic pollutants. The aim of this cross-sectional study was to investigate possible endocrine disrupting effects of different PFAS in adolescents. MethodsSerum concentrations of PFAS, thyroid, parathyroid and steroid hormones were measured in 921 adolescents aged 15–19 years in the Fit Futures study, Northern Norway. The questionnaire included data on self-reported age at menarche and puberty development score (PDS). Multiple linear and logistic regression analyses and principle component analyses (PCA) were used to assess associations of PFAS with hormones concentrations and puberty indices. ResultsIn girls, total PFAS (∑PFAS), perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), perfluorodecanoate (PFDA) were positively associated with dehydroepiandrosterone sulfate (DHEAS) and negatively associated with 11-deoxycorticosterone (11-DOC)/DHEAS ratio. In boys, the associations with 11-DOC/DHEAS ratio were positive for ∑PFAS, perfluoroheptanoate (PFHpA), perfluoroheptane sulfonate (PFHpS), PFOA, and PFOS. Perfluoroundecanoate (PFUnDA) was negatively associated with free thyroxine (fT4) and free triiodothyronine (fT3) in boys. PFNA and PFDA were also negatively associated with fT3 in boys. Serum parathyroid hormone concentration (PTH) was negatively associated with ∑PFAS and perfluorohexane sulfonate (PFHxS) in girls, and with PFOS in boys. PFDA and PFUnDA were positively associated with early menarche, while ∑PFAS and PFOA were positively associated with PDS in boys.No associations of PFAS with serum testosterone, follicle-stimulating hormone, or luteinizing hormone were found in either sex. In girls, PFOA was positively associated with free testosterone index (FTI). In boys, PFOA was positively associated with androstendione and 17-OH-progesterone, while PFHpA was positively associated with estradiol. ConclusionsSerum concentrations of several PFAS were associated with parathyroid and steroid hormones in both sexes, and with thyroid hormones in boys, as well as with early menarche in girls and higher PDS in boys.

Utilizing dehydroepiandrosterone sulfate and its ratio for detecting mild autonomous cortisol excess in patients with adrenal incidentaloma.

Subclinical Cushing syndrome is a condition of mild autonomous cortisol excess (MACE) that lacks typical features of Cushing syndrome but is associated with many complications. It represents a common hormonal dysfunction among patients with adrenal incidentaloma (AI), defined as unexpected masses or lesions found in the adrenal glands during radiological examinations of the chest or abdomen unrelated to adrenal gland assessment. The study evaluated the accuracy of dehydroepiandrosterone sulfate (DHEA-S) and dehydroepiandrosterone sulfate ratio (calculated by dividing the DHEA-S value by the age and sex-adjusted normal range of DHEA-S) in detecting MACE in AI patients. A cross-sectional study was conducted from April 2021 to July 2022 at the Faiha Specialized Diabetes, Endocrine, and Metabolism Centre (FDEMC) in Basrah, southern Iraq, involving 38 AI patients. Comprehensive laboratory and radiological evaluations were performed, including tests for adrenocorticotropic hormone (ACTH), renin, aldosterone, aldosterone/renin ratio (ARR), metanephrine, normetanephrine, cortisol, DHEA-S, and the 1-mg overnight dexamethasone suppression test (1-mg ONDST). Among the AI patients, 14% had MACE. Both DHEA-S ≤75 µg/dL and a DHEA-S ratio ≤1.7 exhibited a sensitivity of 80% each, with specificities of 73.3% and 76.6%, respectively, in diagnosing MACE in individuals aged ≤65 years. The negative predictive values were 95.7% and 95.8%, respectively. Low DHEA-S and DHEA-S ratio had high sensitivity and specificity in predicting MACE among AI patients aged ≤65 years, with strong negative predictive value.

Immune-endocrine biomarkers associated with mental health: a 9-year longitudinal investigation from the Hertfordshire Ageing Study

IntroductionAgeing is accompanied by the development of low-grade systemic inflammation which may promote changes in the neural systems predisposing to geriatric depression via the hypothalamic-pituitary-adrenal (HPA) axis.ObjectivesThe aim of this study was to investigate the longitudinal associations between baseline values and conditional changes in immune-endocrine biomarkers and mental health status in a population-based cohort of older adults.MethodsData from 347 subjects(200 men, 147 women) who participated in the Hertfordshire Ageing Study at baseline(mean age 67.3 years) and at 9-year follow-up were analysed. Serum samples for analysis of inflammatory and endocrinological measures were collected at baseline and follow-up. At follow-up, depression (Hospital Anxiety and Depression Scale) and mental health(Short Form-36 questionnaire) were assessed. Baseline values and changes in biomarkers in relation to risk of high depression scores and low mental health scores were examined using logistic regression.ResultsLower baseline cortisol was related to greater risk of high depression scores; higher baseline cortisol: Dehydroepiandrosterone Sulphate ratio(men only) and higher baseline CRP(women only) were related to greater risk of poor mental health scores. In addition, greater decline in cortisol was related to increased risk of high depression scores among men. These relationships were robust(p<0.05) after controlling for sex, age, BMI, smoking, alcohol consumption and number of systems medicated.ConclusionsThis study provides further evidence of the role of the HPA and inflammation in older adults with poor mental health. In addition, the findings highlight sex differences where increased inflammation in women and declines in cortisol in men was linked to poorer mental health.DisclosureNo significant relationships.

Applying machine learning to explore the association between biological stress and near misses in emergency medicine residents.

Physician stress is associated with near misses and adverse medical events. However, little is known about physiological mechanisms linking stress to such events. We explored the utility of machine learning to determine whether the catabolic stress hormone cortisol and the anabolic, anti-stress hormone dehydroepiandrosterone sulfate (DHEA-S), as well as the cortisol to DHEA-S ratio relate to near misses in emergency medicine residents during active duty in a trauma 1 emergency department. Compared to statistical models better suited for inference, machine learning models allow for prediction in situations that have not yet occurred, and thus better suited for clinical applications. This exploratory study used multiple machine learning models to determine possible relationships between biomarkers and near misses. Of the various models tested, support vector machine with radial bias function kernels and support vector machine with linear kernels performed the best, with training accuracies of 85% and 79% respectively. When evaluated on a test dataset, both models had prediction accuracies of around 80%. The pre-shift cortisol to DHEA-S ratio was shown to be the most important predictor in interpretable models tested. Results suggest that interventions that help emergency room physicians relax before they begin their shift could reduce risk of errors and improve patient and physician outcomes. This pilot demonstrates promising results regarding using machine learning to better understand the stress biology of near misses. Future studies should use larger groups and relate these variables to information in electronic medical records, such as objective and patient-reported quality measures.

The Role of the Environment and Type of Exercise on Acute Adrenal Modulation and Perceived Distress of Breast Cancer Survivors Practising Light-Intensity Physical Exercise

Background: Distress and adrenal balance of breast cancer survivors (BCS) are key elements of their psychophysical health, and increasing evidence has shown both physical exercise and the natural environment are effective for their modulation. The aim of the study was to evaluate the acute effects of the environment and type of light intensity workouts, on distress, salivary cortisol and dehydroepiandrosterone sulfate (DHEA-S) in BCS.Methods: Twenty-four BCS participated in six different workouts, each with the same duration and intensity. Three of them were conducted in natural environments – walking (Wnature), canoeing with assistance (Cnature) and a mix of myofascial and yoga exercises (MYnature). The others were conducted in an urban environment, namely walking (Wurban), or an indoor environment, namely mobilisation and light upper body exercises (MCgym) and a mix of myofascial and yoga exercises (MYgym). Before and after each workout, the Distress Thermometer was completed and saliva was collected.Results: Workouts practised in natural environments elicited a higher reduction in cortisol and the cortisol to DHEA-S ratio and a greater DHEA-S increase compared with workouts practised in urban and indoor environments. Overall, Cnature and MYnature were the best activities; among those practised in urban and indoor environments, MYgym elicited the best results. Distress was not acutely reduced after Wurban and MCgym. Conclusion: Natural environments seem to provide the best management of distress, cortisol, DHEA-S and their balance when working out at light intensities. The simultaneous presence of forests and rivers seems to be the key element of the observed results.

Performance of DHEAS as a Screening Test for Autonomous Cortisol Secretion in Adrenal Incidentalomas: A Prospective Study.

Autonomous cortisol secretion (ACS) affects up to 30% of patients with adrenal incidentalomas (AIs). The current guidelines for ACS diagnosis are not decisive. A lower dehydroepiandrosterone sulfate (DHEAS) level is a potential biomarker, but the evidence is conflicting. This prospective study aimed to evaluate and validate the ACS screening and diagnostic accuracy of DHEAS. Recruited patients with AI were screened for adrenal medullary and cortisol hypersecretion. The diagnosis of ACS was based on a serum cortisol level ≥ 50 nmol/L following a 1-mg dexamethasone suppression test (DST) and a low-dose DST. Age- and sex-specific DHEAS ratios were also calculated. In the development cohort (45 ACS and 242 non-ACS patients), the areas under the receiver operator characteristic curves (AUCs) of DHEAS and the DHEAS ratio were 0.869 (95% CI 0.824-0.906) and 0.799 (95% CI 0.748-0.844), respectively. The optimal DHEAS cutoff for diagnosing ACS was 60 μg/dL, with a sensitivity of 75.6% (95% CI 60.5-87.1) and a specificity of 81.4% (95% CI 76.4-86.5). The midnight serum cortisol level had moderate diagnostic accuracy [AUC 0.875 (95% CI 0.831-0.911)]. Suppressed adrenocorticotropic hormone (≤2.2 pmol/L) had a lower sensitivity (55.6%), and the 24-hour urinary free cortisol lacked sensitivity and specificity [AUC 0.633 (95% CI 0.603-0.721)]. In the validation cohort (14 ACS and 45 non-ACS patients), the sensitivity and specificity of the optimized DHEAS cutoff were 71.4% (95% CI 41.9-91.6) and 82.2% (95% CI 68.0-92.0), respectively. A single basal measurement of DHEAS is valuable for identifying ACS. Because of its stability and ease of use, the DHEAS level could be used as an ACS screening test.

Immune-endocrine biomarkers associated with mental health: A 9-year longitudinal investigation from the Hertfordshire Ageing Study

BackgroundThe study of neural-endocrine-immune system interactions has led to substantial advances in our understanding of neuropsychiatric disorders. Growing evidence reveals the pivotal roles of inflammatory cytokines signalling the brain to produce neurochemical, neuroendocrine, and neuroimmune changes which affect mood and behaviour. Ageing is accompanied by the development of low-grade systemic inflammation which may promote changes in the neural systems predisposing to geriatric depression via the hypothalamic-pituitary-adrenal (HPA) axis. The aim of this study was to investigate the longitudinal associations between baseline values and conditional changes (independent of baseline) in immune-endocrine biomarkers and mental health status in a population-based cohort of older adults. MethodsData from 347 subjects (200 men, 147 women) who participated in the Hertfordshire Ageing Study at baseline (1994/5, mean age 67.3 years) and at 9-year follow-up were analysed. Serum samples for analysis of inflammatory and endocrinological measures were collected at baseline and follow-up. At follow-up, depression (Hospital Anxiety and Depression Scale) and mental health (Short Form-36 questionnaire) were assessed. Baseline values and changes in biomarkers in relation to risk of high depression scores (top sex-specific third) and low mental health scores (bottom sex-specific third) were examined using logistic regression. ResultsLower baseline cortisol was related to greater risk of high depression scores; higher baseline cortisol: dehydroepiandrosterone sulphate ratio (men only) and higher baseline C-reactive protein (CRP) (women only) were related to greater risk of poor mental health scores. In addition, greater decline in cortisol was related to increased risk of high depression scores among men. These relationships were robust (p < 0.05) after controlling for sex, age, BMI, smoking, alcohol consumption and number of systems medicated. ConclusionThis study provides further evidence of the role of the HPA axis and inflammation in older adults with poor mental health. In addition, the findings highlight sex differences where increased inflammation in women and declines in cortisol in men were linked to poorer mental health. Further research is warranted to confirm these findings. This could lead to the search for potential biomarkers to stratify medications as well as developing novel intervention targets to improve mental health at older age.

Role of insulin-like growth factor 1, sex and corticosteroid hormones in male major depressive disorder

BackgroundHormones of the hypothalamic–pituitary–gonadal (HPG), hypothalamic–pituitary–adrenal (HPA), and hypothalamic–pituitary–somatotropic (HPS) axes are potentially involved in major depressive disorder (MDD), but these hormones have not been simultaneously investigated in male patients with MDD. We investigated the association between male MDD symptoms and estradiol, testosterone, cortisol, dehydroepiandrosterone sulfate (DHEAS), and insulin-like growth factor 1 (IGF1).MethodsSerum estradiol, testosterone, cortisol, DHEAS, and IGF1 levels were measured in 54 male patients with MDD and 37 male controls and were compared with clinical factors. We investigated the associations between hormone levels and Hamilton Depression Rating Scale (HAM-D) scores. The correlations among hormones were also investigated.ResultsPatients had significantly lower estradiol levels than controls (22.4 ± 8.4 pg/mL vs. 26.1 ± 8.5 pg/mL, P = 0.040). Serum estradiol levels were negatively correlated with HAM-D scores (P = 0.000094) and positively correlated with Global Assessment of Functioning scores (P = 0.000299). IGF1 levels and the cortisol:DHEAS ratio were higher in patients than in controls (IGF1: 171.5 ± 61.8 ng/mL vs. 144.1 ± 39.2 ng/mL, P = 0.011; cortisol:DHEAS ratio: 0.07 ± 0.05 vs. 0.04 ± 0.02, P = 0.001). DHEAS levels were lower in patients than in controls (227.9 ± 108.4 μg/dL vs. 307.4 ± 131.2 μg/dL, P = 0.002). IGF1, cortisol:DHEAS ratio, and DHEAS were not significantly correlated with HAM-D scores. Cortisol and testosterone levels were not significantly different between patients and controls. Serum estradiol levels were positively correlated with DHEAS levels (P = 0.00062) in patients, but were not significantly correlated with DHEAS levels in controls.ConclusionEstradiol may affect the pathogenesis and severity of patients with MDD in men, and other hormones, such as those in the HPA and HPS axes, may also be involved in male MDD. Additionally, a correlation between estradiol and DHEAS may affect the pathology of MDD in men.

The effect of pilates training on hormonal and psychophysical function in older women.

DHEA-S and cortisol and their ratio are important determinants of some physiological and psychological function during aging. The present study aimed to determine the effect of eight weeks of pilates training on diurnal salivary cortisol, dehydroepiandrosterone sulfate (DHEA-S), and cortisol to DHEA-S ratio, cardiorespiratory fitness (CF), and psychological function in older women. Twenty-seven healthy older women (aged 60-65 years) participated in the study voluntarily and were divided into two groups of pilates training (N.=15) and control (N.=12), randomly. Before and after the experiment, salivary samples (at wake up and 30-min postawakening, midday, 5 p.m., and 9 p.m.) were taken and the participants completed the questionnaires. Cognitive function was assessed by the MMSE questionnaire. Pilates training was performed three times weekly, in non-consecutive days. Pilates training increased V̇O2<inf>max</inf> (48%, P<0.001) and cognitive function (73%, P<0.001) and decreased BMI (16%, P=0.042), anxiety (53%, P<0.001) and depression (67%, P<0.001) compared to the control group. Also, in pilates training group, mean cortisol (16%, P=0.039), CAR (24%, P=0.010), fall after peak of cortisol (15%, P=0.50), morning DHEA-S (43%, P<0.001) and mean DHEA-S (34%, P=0.002) increased compared to the control group. This study suggests that pilates training could improve mental and physical function which was accompanied by changes of diurnal cortisol and DHEA as one of the possible effective factors.

Cortisol to Dehydroepiandrosterone Sulphate Ratio and Executive Function in Bipolar Disorder

Introduction: Bipolar disorder (BD) is associated with impairment in cognitive domains such as verbal memory and executive functions. Very few studies have assessed dehydroepiandrosterone sulphate (DHEA-S) in BD and its relation to cognitive functioning despite evidence showing its regulatory effects on glucocorticoid action. The aim of our study was to explore the association of cortisol, DHEA-S, and cortisol to DHEA-S ratio with visuospatial memory and executive functioning in BD. Methods: Cognitive performance of 60 bipolar I patients and 30 healthy subjects was evaluated by using Cambridge Neuropsychological Test Automated Battery tasks targeting visuospatial memory (spatial recognition memory) and executive functions (planning [Stockings of Cambridge; SOC] and attentional set shifting [ID/ED]). Morning serum cortisol and DHEA-S levels were measured in patients. Main effects of cortisol, DHEA-S, and cortisol/DHEA-S ratio for each neurocognitive task were explored in multiple regression analyses correcting for demographic and clinical parameters as well as treatment-related factors (current use of antipsychotic and mood stabilizer medication). Results: Bipolar patients showed poorer performance than healthy subjects in planning and attentional set shifting but not in visuospatial memory. Cortisol to DHEA-S ratio predicted worse performance in planning (SOC). Conclusions: This is the first study to assess memory and executive function in BD in relation to DHEA-S and cortisol to DHEA-S ratio. We report an association of cortisol to DHEA-S ratio with worse performance in planning in bipolar I patients, which warrants further investigation.

The value of serum dehydroepiandrosterone sulfate in differential diagnosis of Cushing's syndrome

Objective: To evaluate the changes and diagnostic value of serum dehydroepiandrosterone sulfate (DHEAS) in Cushing's syndrome (CS) with different etiologies. Methods: The study retrospectively recruited patients diagnosed as CS in Drum Tower Hospital affiliated to Nanjing University Medical School between January 2012 and June 2019, including 36 patients (8 males, 28 females, with an average age of 44 years) with Cushing disease (CD) and 64 patients (6 males, 58 females, with an average age of 39 years) with adrenal CS (ACS). Meanwhile, 97 patients diagnosed as nonfunctional adrenal adenoma (NFA) were also included as controls. Clinical characteristics, laboratory data, adrenocorticotropic hormone (ACTH), serum DHEAS level and sex-and age-adjusted DHEAS ratio of the three groups were collected. The sensitivity and specificity of DHEAS and its ratio in differential etiology diagnosis of CS were compared using receiver operating characteristic (ROC) curve analysis. Results: Compared to NFA group, ACS patients had lower DHEAS levels [0.39 (0.39, 0.63) μmol/L vs 2.96 (1.92, 4.60) μmol/L, P<0.01] and lower DHEAS ratio [0.58 (0.27, 0.98) vs 3.95 (3.08, 6.83), P<0.01]. DHEAS [6.49 (4.32, 11.63) μmol/L] and DHEAS ratio [9.17 (4.49, 15.41)] in CD patients were significantly higher compared to those in NFA and ACS patients (all P<0.01). There were 53 ACS patients (82.8%) with suppressed ACTH level (<2.2 pmol/L) and 11 patients (17.2%) with normal/high ACTH level (≥2.2 pmol/L). The level of 24 hour urine free cortisol in normal/high ACTH level group was lower than the suppressed ACTH group [(1 299±511) nmol/24 h vs (1 972±876) nmol/24 h, P=0.04]. No significant differences were found in the DHEAS and DHEAS ratio between the two groups. ROC analysis showed that the area under the curve of serum DHEAS and DHEAS ratio in diagnosing ACS from CD was 0.997 and 0.990, respectively. The optimal cut-off values for DHEAS and its ratio were 2.06 μmol/L and 2.10, respectively. The diagnostic sensitivity and specificity of DHEAS were 97.5% and 100%, and those of DHEAS ratio were 95.0% and 100%, respectively. Conclusion: There are significant differences in serum DHEAS level and DHEAS ratio between ACS and CD patients, which might be used as indicators for the identification of the two main CS etiologies, especially in the identification of ACS patients without plasma ACTH suppression from CD patients.

MON-188 The Diagnostic Value of DHEAS in Subtyping Patients with Cushing Syndrome

Objective: Serum dehydroepiandrosterone sulfate (DHEAS) can be used to assess the integrity of the hypothalamic-pituitary-adrenal (HPA) axis. The aim of this study was to evaluate the clinical value of DHEAS in differentiating adrenal Cushing syndrome (ACS) from Cushing’ disease (CD). Methods: We recruited 100 patients with Cushing syndrome, 36 with CD and 64 with ACS. 72 sex-, age- and BMI-matched nonfunctional adrenal adenomas (NFAAs) were served as controls. Clinical and laboratory data were collected. DHEAS levels were measured and DHEAS ratio was calculated by dividing the measured DHEAS by the lower limit of the respective reference range (age- and sex-matched). Results: 1) No significant differences in age, sex, or BMI were detected among the NFAAs, ACS and CD groups. Compared to NFAAs group, ACS patients had lower plasma ACTH levels [1.11(1.11,1.74) vs 5.0 ± 2.9 pmol/L, P<0.01], lower DHEAS levels (24.00 ± 20.72 vs 189.05 ± 82.03 ug/dL, P < 0.01) and lower DHEAS ratio [0.58(0.27,0.98) vs 5.34 ± 3.0]; Plasma ACTH (22.12 ± 14.22 pmol/L), DHEAS (309.4 ± 201.1 ug/dL) and DHEAS ratio (10.51 ± 7.65) in CD patients were significantly higher compared to those in NFAAs and ACS patients (all P<0.01). 2) In ACS patients, there were 53 patients with suppressed ACTH level of <2.0 pmol/L, 11 patients without plasma ACTH suppression (≥2.0pmol/L). Compared to NFAAs, lower DHEAS and DHEAS ratio were detected in these two groups, and no significant differences were found in the DHEAS [15(15, 23.5) vs 23.8 ± 14.4 ug/dL, P=0.86] and DHEAS ratio [0.58(0.27, 0.80) vs 1.0(0.25,2.09) ug/dL, P=0.40] between the two groups. 3) ROC analysis showed that the area under the curve (AUC) of plasma ACTH, serum DHEAS and DHEAS ratio in diagnosing 0.954, 0.997 and 0.990 respectively. The optimal cut-off values for DHEAS and its ratio were 79.1ug/dL, and 2.09, respectively. The diagnostic sensitivity and specificity of plasma ACTH (<2.0pmol/L) were 84.1 and 100%, those of DHEAS were 97.5% and 100%, and those of DHEAS ratio were 95% and 100%, respectively. Conclusions: Patients with different subtype of Cushing syndrome showed distinctive DHEAS levels and DHEAS ratio. DHEAS and DHEAS ratio are useful in differential diagnosis of Cushing syndrome. Especially, when the plasma ACTH level is not conclusive. The measurement of DHEAS may offer a supplementary test to diagnosis ACS from CD. Keywords: Adrenal Cushing syndrome; Cushing disease; Adrenocorticotropic hormone; Dehydroepiandrosterone sulfate

Hypoglycemia and Glucocorticoid-free Immunosuppression are Related With Low Dehydroepiandrosterone Sulfate Level.

Low dehydroepiandrosterone sulfate (DHEAS) levels and a high cortisol/ DHEAS ratio are associated with higher mortality in elderly, dialyzed, and immunocompromised patients. The role of these hormones in patients with hypoglycemia unawareness (hypo) or in pancreas or islet recipients treated by glucocorticoid-free immunosuppressive regimen (IS) has not been studied. The aim of this study was to determine the effects of IS and of recurrent hypoglycemia on DHEAS and adrenocorticotropic hormone (ACTH) levels in patients with type-1 diabetes (T1DM). A case control, cross-sectional analysis of patients in a prospective database enrolled 84 patients with T1DM. They were divided into 4 groups of 21 subjects each: 1) islet or pancreas recipients with hypoglycemia who are IS (hypo +, IS +); 2) pancreas and kidney transplant recipients without insulin or hypoglycemia (hypo -, IS +); 3) T1DM patients with hypoglycemia (hypo +, IS -); and 4) T1DM patients without hypoglycemia (hypo -, IS -). DHEAS and ACTH levels were significantly decreased in patients with hypoglycemia (P = 0.0002 and P = 0.0001, respectively) as well as in those with IS (P = 0.0497 and P &lt; 0.001, respectively) compared to those without hypoglycemia or IS. The influence of hypoglycemia unawareness on DHEAS levels was stronger than that of immunosuppression (P &lt; 0.10). Low DHEAS and ACTH levels represent an additional component of hypoglycemia unawareness syndrome and they remain low in patients receiving glucocorticoid-free immunosuppression. DHEAS may serve as a marker, the importance of which remains unclear, but deserves attention.

Androsterone glucuronide to dehydroepiandrosterone sulphate ratio is discriminatory for obese Caucasian women with polycystic ovary syndrome

BackgroundAndrosterone glucuronide (ADTG) concentrations have been suggested as a marker of the effects of androgens at the target tissue level. As the mechanism for hyperandrogenemia in obese and nonobese polycystic ovary syndrome (PCOS) may differ, this study compared the different androgen parameters in non-obese compared to obese women with PCOS, and in normal subjects.MethodsEleven non-obese and 14 obese women with PCOS were recruited and compared to 11 control women without PCOS. Total testosterone, dehydroepiandrosterone sulphate (DHEAS), ADTG, and androstenedione were analysed using gold standard tandem mass spectrometry, and the free androgen index (FAI) was calculated.ResultsTotal testosterone, ADTG and androstendione levels did not differ between non-obese (body mass index (BMI) ≤25 kg/m2) and obese PCOS (BMI >25 kg/m2) but all were significantly higher than for controls (p < 0.01). The ADTG to DHEAS ratio was significantly elevated 39 ± 6 (p < 0.01) in obese PCOS in comparison to non-obese PCOS and controls (28 ± 5 and 29 ± 4, respectively). The free androgen index (FAI) and insulin resistance (HOMA-IR) were significantly higher in obese PCOS compared to non-obese PCOS and controls (p < 0.01). DHEAS was significantly higher in the non-obese versus obese PCOS (p < 0.01). All androgen parameters were significantly lower and sex hormone binding globulin (SHBG) significantly higher in normal subjects compared to those with obese and non-obese PCOS.ConclusionsThe ADTG:DHEAS ratio was significantly elevated in obese PCOS compared to non-obese PCOS and controls suggesting that this may be a novel biomarker discriminatory for obese PCOS subjects, perhaps being driven by higher hepatic 5α reductase activity increasing ADTG formation in these women.

Serum dehydroepiandrosterone sulfate in assessing the integrity of the hypothalamic-pituitary-adrenal axis

ObjectiveTo evaluate the relationship between age- and gender-adjusted dehydroepiandrosterone sulfate (DHEA-S) levels and low-dose adrenocorticotropic hormone (ACTH) stimulation in assessing the integrity of the hypothalamic-pituitary-adrenal (HPA) axis, in patients who were at risk of HPA insufficiency, including those currently being treated with glucocorticoids. MethodsForty-six participants with a suspicion of secondary adrenal insufficiency were recruited from the Diabetes and Endocrinology Clinic at Ramathibodi Hospital, Mahidol University, Bangkok. Low-dose (1μg) ACTH stimulation was performed in every participants, and serum DHEA-S was measured at baseline before ACTH injection. ResultsIndividuals with normal age- and gender-specific DHEA-S levels had baseline serum cortisol and peak cortisol levels higher than those with reduced DHEA-S. Normal age- and gender-specific DHEA-S levels predicted intact HPA function with a sensitivity of 87.1%, a specificity of 86.7%, a positive predictive value of 93.1%, and a negative predictive value of 76.5%. To account for the age and gender dependency of DHEA-S, the DHEA-S ratio was calculated by measured DHEA-S divided by the lower limit of the respective reference range for all participants. A DHEA-S ratio of more than 1.78 had 100% sensitivity regarding intact HPA function. Area under the receiver operating characteristic [ROC] curve was 0.920. (95% CI, 0.844–0.997). ConclusionNormal age- and gender-specific DHEA-S level or a DHEA-S ratio of more than 1.78 are valuable markers of HPA integrity. Serum DHEA-S may be a candidate for a less costly approach where ACTH stimulation is unavailable.

Steroid Sulfatase Deficiency and Androgen Activation Before and After Puberty.

Context:Steroid sulfatase (STS) cleaves the sulfate moiety off steroid sulfates, including dehydroepiandrosterone (DHEA) sulfate (DHEAS), the inactive sulfate ester of the adrenal androgen precursor DHEA. Deficient DHEA sulfation, the opposite enzymatic reaction to that catalyzed by STS, results in androgen excess by increased conversion of DHEA to active androgens. STS deficiency (STSD) due to deletions or inactivating mutations in the X-linked STS gene manifests with ichthyosis, but androgen synthesis and metabolism in STSD have not been studied in detail yet.Patients and Methods:We carried out a cross-sectional study in 30 males with STSD (age 6–27 y; 13 prepubertal, 5 peripubertal, and 12 postpubertal) and 38 age-, sex-, and Tanner stage-matched healthy controls. Serum and 24-hour urine steroid metabolome analysis was performed by mass spectrometry and genetic analysis of the STS gene by multiplex ligation-dependent probe amplification and Sanger sequencing.Results:Genetic analysis showed STS mutations in all patients, comprising 27 complete gene deletions, 1 intragenic deletion and 2 missense mutations. STSD patients had apparently normal pubertal development. Serum and 24-hour urinary DHEAS were increased in STSD, whereas serum DHEA and testosterone were decreased. However, total 24-hour urinary androgen excretion was similar to controls, with evidence of increased 5α-reductase activity in STSD. Prepubertal healthy controls showed a marked increase in the serum DHEA to DHEAS ratio that was absent in postpubertal controls and in STSD patients of any pubertal stage.Conclusions:In STSD patients, an increased 5α-reductase activity appears to compensate for a reduced rate of androgen generation by enhancing peripheral androgen activation in affected patients. In healthy controls, we discovered a prepubertal surge in the serum DHEA to DHEAS ratio that was absent in STSD, indicative of physiologically up-regulated STS activity before puberty. This may represent a fine tuning mechanism for tissue-specific androgen activation preparing for the major changes in androgen production during puberty.

Estrogen Regulation of Fetal Adrenal Cortical Zone-Specific Development in the Nonhuman Primate Impacts Adrenal Production of Androgen and Cortisol and Response to ACTH in Females in Adulthood.

We showed that the volume of the fetal zone of the fetal adrenal gland and serum dehydroepiandrosterone sulfate (DHAS) levels at term were increased in baboons in which estradiol levels were suppressed by treatment with aromatase inhibitor 4,4-[1,2,3-triazol-1yl-methylene] bis-benzonitrite (letrozole). The fetal zone remodels postnatally into the reticular zone and DHAS production, and serum levels decline with age. Therefore, we determined whether the trajectory of reticular zone DHAS secretion and response to ACTH were altered in offspring deprived of estrogen in utero. Female offspring were delivered to baboons untreated or treated daily throughout the second half of gestation with letrozole (estradiol reduced >95%) or letrozole plus estradiol and cortisol and DHAS determined in blood samples obtained bimonthly between 4 and 125 months and after iv bolus of ACTH. The slope/rate of decline in serum DHAS with advancing age was greater (P < .01) in letrozole-treated (-0.54 ± 0.005) than untreated (-0.32 ± 0.003) baboons and partially restored by letrozole-estradiol (-0.43 ± 0.004). Serum cortisol was similar and relatively constant in all offspring. Moreover, in letrozole-treated offspring, serum DHAS at 61-66, 67-95, and 96-125 months were lower (P < .05), and cortisol to DHAS ratio was greater (P < .05) than in untreated offspring. ACTH at high level increased cortisol and DHAS in untreated baboons and cortisol but not DHAS in letrozole-treated offspring. We propose that postnatal development of the primate adrenal cortex, including the decline in reticular zone DHAS production, response to ACTH and maintenance of cortisol to DHAS ratio with advancing age is modulated by exposure of the fetal adrenal to estradiol.

Unemployment is associated with lower cortisol awakening and blunted dehydroepiandrosterone responses

Previous research has investigated the endocrinological consequences of unemployment as a likely pathway behind chronic stress and negative health outcomes. Despite these early attempts at delineating the neuroendocrine consequences of the chronic stress experienced by the unemployed, identifying a consistent and stable effect has remained elusive. Here we sought to strengthen existing knowledge into the effect of the stress of employment status on cortisol by improving on the methodological weaknesses of earlier studies and extend this line of enquiry by measuring the steroid hormone Dehydroepiandrosterone-Sulfate (DHEAS). Saliva samples were collected from unemployed and employed participants at four time points across two days. As expected, unemployed people reported higher stress, lower social support and lower self-esteem. Unexpectedly, the unemployed showed lower overall cortisol output, a likely consequence of a higher cortisol awakening response (CAR) in the employed. However, they also had a higher DHEA output across the day, albeit the diurnal pattern across the day was more dysregulated compared to that seen in those employed with a blunted response evident in the evening; the cortisol:DHEAS ratio was also lower in the unemployed group. Further, these hormone differences were correlated with self-esteem and stress. Taken together these results suggest that the relationship between employment status and endocrine responses is far more complicated than previously thought. We have shown for the first time that unemployed people have a lower CAR, but also show a blunted DHEA response relative to those employed and we suggest that this may be a feature of chronic stress exposure or perhaps dependent on the prevailing socio-economic context.

Bereavement reduces neutrophil oxidative burst only in older adults: role of the HPA axis and immunesenescence.

BackgroundThe effect of the chronic stress of bereavement on immunity is poorly understood. Previous studies have demonstrated negative effects on immunity in older adults, and those who report higher depressive symptoms. The aim of the present study was to compare the effect of bereavement on neutrophil function in healthy young and old adults, also assessing serum levels of the stress hormones, cortisol and dehydroepiandrosterone sulphate (DHEAS). 41 young (mean age 32 years) and 52 older adults (mean age 72 years), bereaved and non-bereaved, took part in the study. They completed questionnaires on socio-demographic and health behaviour characteristics, as well as psychosocial variables, and provided a blood sample for analysis of neutrophil function (phagocytosis and reactive oxygen species (ROS) production) and stress hormone analysis.ResultsBereaved participants in both age groups reported more symptoms of depression and anxiety than controls and scored moderately highly on bereavement-specific questionnaires for these symptoms. Despite this, young bereaved participants showed robust neutrophil function when compared to age-matched non-bereaved controls, and comparable stress hormone levels, while reduced neutrophil ROS production and raised stress hormone levels (cortisol:DHEAS ratio) were seen in the older bereaved group compared to their age-matched controls.ConclusionsReduced neutrophil function among older bereaved participants may be the result of the inability to maintain stress hormone balance, specifically the cortisol:DHEAS ratio.

Depressive symptoms are associated with reduced neutrophil function in hip fracture patients.

Hip fracture is a common trauma in older adults with a high incidence of depression, which relates to poorer prognosis including increased risk of infection. Ageing is accompanied by reduced immunity, termed immunesenescence, resulting in increased susceptibility to infection. We examined whether physical trauma (hip fracture) and psychological distress (depressive symptoms) had additive effects upon the aged immune system that might contribute to poor outcomes after injury. Neutrophil function was assessed in 101 hip fracture patients (81 female) 6 weeks and 6 months after injury and 43 healthy age-matched controls (28 female). Thirty eight fracture patients had depressive symptoms at 6 weeks. No difference in neutrophil phagocytosis of Escherichia coli was observed between controls and hip fracture patients, but superoxide production was significantly reduced in hip fracture patients with depressive symptoms compared with patients without symptoms (p=.001) or controls (p=.004) at 6 weeks. Superoxide production improved 6 months following fracture to the level seen in controls. We detected elevated serum cortisol, reduced dehydroepiandrosterone sulphate (DHEAS) and an increased cortisol:DHEAS ratio in fracture patients with depressive symptoms compared with patients without depressive symptoms or controls at 6 weeks and 6 months after injury. Serum IL6, TNFα and IL10 were higher among patients with depressive symptoms at 6 weeks. The cortisol:DHEAS ratio and IL6 levels related to depressive symptom scores but not to neutrophil function. In conclusion, depressive symptoms related to poorer neutrophil function after hip fracture, but this was not driven by changes in stress hormone or cytokine levels.