The effects of cortisol and adrenal androgen on bone mass in Asians with and without subclinical hypercortisolism.

Analyses using the largest Korean cohort of adrenal incidentaloma (AI) revealed that subtle cortisol excess in premenopausal women and reduced dehydroepiandrosterone-sulfate (DHEA-S) in postmenopausal women and men are associated with bone mineral density (BMD) reduction in Asian patients with subclinical hypercortisolism (SH). INTRODUCTION: Few studies evaluated bone metabolism in Asians with SH. We investigated associations of cortisol and DHEA-S, an adrenal androgen, with BMD in Asians with AI, with or without SH. METHODS: We used cross-sectional data of a prospective multicenter study from Korea. We measured BMD, bone turnover markers, cortisol levels after 1-mg dexamethasone suppression test (1-mg DST), DHEA-S, and baseline cortisol to DHEA-S ratio (cort/DHEA-S) in 109 AI patients with SH (18 premenopausal, 38 postmenopausal women, and 53 men) and 686 with non-functional AI (NFAI; 59 premenopausal, 199 postmenopausal women, and 428 men). RESULTS: Pre- and postmenopausal women, but not men, with SH had lower BMDs at lumbar spine (LS) than those with NFAI (P = 0.008~0.016). Premenopausal women with SH also had lower BMDs at the hip than those with NFAI (P = 0.009~0.012). After adjusting for confounders, cortisol levels after 1-mg DST demonstrated inverse associations with BMDs at all skeletal sites only in premenopausal women (ß = - 0.042~- 0.033, P = 0.019~0.040). DHEA-S had positive associations with LS BMD in postmenopausal women (ß = 0.096, P = 0.001) and men (ß = 0.029, P = 0.038). The cort/DHEA-S had inverse associations with LS BMD in postmenopausal women (ß = - 0.081, P = 0.004) and men (ß = - 0.029, P = 0.011). These inverse associations of cort/DHEA-S remained significant after adjusting for cortisol levels after 1-mg DST (ß = - 0.079~- 0.026, P = 0.006~0.029). In postmenopausal women, the odds ratios of lower BMD by DHEA-S and cort/DHEA-S was 0.26 (95% CI, 0.08-0.82) and 3.40 (95% CI, 1.12-10.33), respectively. CONCLUSION: Subtle cortisol excess in premenopausal women and reduced DHEA-S in postmenopausal women and men may contribute to BMD reduction in Asians with SH.

Plasma dehydroepiandrosterone sulfate levels in patients with major depressive disorder correlate with remission during treatment with antidepressants.

OBJECTIVE: We attempted to investigate whether dehydroepiandrosterone sulfate (DHEA-S) levels are associated with remission of major depressive disorder by assessing scores on the 17-Item Structured Interview Guide for the Hamilton Depression before and after antidepressant treatment. METHODS: Plasma DHEA-S levels in 24 patients diagnosed with major depressive disorder on the basis of Diagnostic and Statistical Manual of Mental Disorders, fourth edition (text revision) before and after antidepressant treatment, and 24 healthy, gender-matched, and age-matched controls were measured using a radioimmunoassay kit. RESULTS: Plasma DHEA-S levels in patients were significantly higher than those in healthy controls. In patients who achieved remission after antidepressant treatment, plasma DHEA-S levels significantly declined compared with the levels before treatment. A significant correlation was observed between changes in DHEA-S levels and Absence of Depressive and Anxious Mood scores, which are calculated from the 2-Item Structured Interview Guide for the Hamilton Depression rating as follows: severity of depressive mood and anxiety in patients before and after antidepressant treatment. CONCLUSIONS: These findings suggest that plasma DHEA-S levels can be used as a putative indicator of the state of remission in patients with major depressive disorder. Copyright © 2014 John Wiley & Sons, Ltd.

The Androgen Dehydroepiandrosterone Sulfate Shows a Greater Relationship with Impulsivity than Testosterone in a Healthy Male Sample.

This study was designed to examine the relationships among the impulsivity construct as a personality trait, the dehydroepiandrosterone sulfate (DHEA-S), and testosterone in a sample of 120 healthy middle-aged males (Mage = 44.39; SD = 12.88). The sum of the three BIS-11 scales, the SR, and the five UPPS-P scales correlated with DHEA-S 0.23 (p < 0.006) and testosterone 0.19 (p < 0.04), controlling for age. Partial correlations showed that DHEA-S was significantly related to motor impulsivity (0.24; p < 0.008), Sensitivity to Reward (0.29; p < 0.002), Lack of Premeditation (0.26; p < 0.05), and, to a lesser extent, Sensation Seeking (0.19; p < 0.04) and Positive Urgency (0.19; p < 0.04). Testosterone correlated with attention impulsivity (0.18; p < 0.04), Sensation Seeking (0.18; p < 0.04), and Positive Urgency (0.22; p < 0.01). Sensitivity to Reward, Negative Urgency, and Positive Urgency were significant predictors of DHEA-S (R2 = 0.28), and Positive Urgency for testosterone (R2 = 0.09). Non-parametric LOESS graphical analyses for local regression allowed us to visualize the non-linear relationships between the impulsivity scales with the two androgens, including non-significant trends. We discuss the implications of these results for impulsive biological personality traits, the limitations of our analyses, and the possible development of future research.

Distinct serum steroid profiles between adrenal Cushing syndrome and Cushing disease.

Background: Differentiating between adrenal Cushing syndrome (adrenal CS) and Cushing disease (CD) can be challenging if there are equivocal or falsely elevated adrenocorticotropic hormone (ACTH) values. We aim to investigate the diagnostic value of serum steroid profiles in differentiating adrenal CS from CD. Method: A total of 11 serum steroids in adrenal CS (n = 13) and CD (n = 15) were analyzed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Age- and gender-specific steroid ratios were generated by dividing the actual steroid concentration by the upper limit of the relevant reference range. A principal component analysis (PCA) and an orthogonal partial least squares discriminant analysis (OPLS-DA) were performed. Results: The PCA and OPLS-DA analyses showed distinct serum steroid profiles between adrenal CS and CD. Dehydroepiandrosterone sulfate (DHEA-S), dehydroepiandrosterone (DHEA), and androstenedione ratios were identified as biomarkers for discrimination by variable importance in projection (VIP) in combination with t-tests. The sensitivity and specificity of DHEA-S ratios <0.40 were 92.31% (95% CI 64.0%-99.8%) and 93.33% (95% CI 68.1%-99.8%), respectively, in identifying adrenal CS. The sensitivity and specificity of DHEA ratios <0.18 were 100% (95% CI 75.3%-100.0%) and 100% (95% CI 78.2%-100.0%), respectively, in identifying adrenal CS. Conclusion: Our data support the clinical use of the DHEA-S and DHEA ratios in the differential diagnosis of adrenal CS and CD, especially when falsely elevated ACTH is suspected.

An attempt to create a treatment algorithm of central adrenal insufficiency using CRH test, DHEA-S and clinical evaluation.

Objective : To examine diagnostic performance of corticotropin-releasing hormone (CRH) test combined with baseline dehydroepiandrosterone sulfate (DHEA-S) in patients with a suspect of central adrenal insufficiency. Methods : Patients (n=215) requiring daily or intermittent hydrocortisone replacement, or no replacement were retrospectively checked with their peak cortisol after CRH test and baseline DHEA-S. Results :  None of 106 patients with the peak cortisol ≥ 17.5 µg / dL after CRH test required replacement, and all 64 patients with the peak cortisol < 10.0 µg / dL required daily replacement. Among 8 patients with 10.0 µg / dL ≤ the peak cortisol < 17.5 µg / dL and baseline DHEA-S below the reference range, 6 patients required daily replacement and 1 patient was under intermittent replacement. Among 37 patients with 10.0 µg / dL ≤ the peak cortisol < 17.5 µg / dL and baseline DHEA-S within the reference range, 10 and 6 patients were under intermittent and daily replacement, respectively. Conclusions : No patients with the peak cortisol ≥ 17.5 µg / dL required hydrocortisone replacement, and all patients with the peak cortisol below 10.0 µg / dL required daily replacement. Careful clinical evaluation was required to determine requirement for replacement in patients with 10.0 µg / dL ≤ the peak cortisol < 17.5 µg / dL even in combination with baseline DHEA-S. J. Med. Invest. 69 : 287-293, August, 2022.

Correlation between salivary dehydroepiandrosterone sulfate (DHEA-S) levels and cervical vertebral maturation in Saudi individuals.

Background: Growth incidents usually progress in a fairly expected sequence; however, their timing and pattern vary across individual subjects. Biochemical biomarkers have an association with bone metabolism and produce signals which stimulate the growth and development of various craniofacial structures. Steroid dehydroepiandrosterone sulfate (DHEA-S) plays a major role in the initiation of growth hormone actions which has a significant role in promoting and accelerating skeletal maturation during puberty. The aim of this study was to investigate the correlation between salivary DHEA-S levels and cervical vertebral maturation (CVM) stages throughout the circumpubertal developmental period. Methods: One hundred forty-one participants (70 males and 71 females), between 7 and 23years of age, were categorized into six cervical stages (CS) based on lateral cephalograms. Using a passive drooling technique, unstimulated whole saliva samples were collected from all enrolled subjects. DHEA-S levels were analyzed using the enzyme-linked immunosorbent assay (ELISA) and correlated with the six CVM stages. Results: One-way analysis of variance ANOVA showed that the mean salivary DHEA-S levels at CS 3 and CS 4 were significantly different from the values recorded at other stages, and the two stages were statistically significant from each other. Pearson linear correlation of mean salivary DHEA-S levels from CS 1 to CS 6 showed a significant positive correlation. Conclusion: Salivary DHEA-S can be used as a non-invasive indicator for detecting the pubertal growth spurt.

Investigation of early puberty prevalence and time of addition thelarche to pubarche in girls with premature pubarche: two-year follow-up results.

We aimed to determine the prevalence of early puberty in girls with premature pubarche and analyze the time interval between their pubarche and succeeding thelarche. This study included 60 female children with premature pubarche. We retrospectively collected clinical, laboratory, and radiological findings from all participants. We investigated the time interval between pubarche and thelarche in cases wherein premature pubarche was followed by thelarche. The mean age at onset of pubarche was 6.93 ± 0.79 yr old. Among the participants, 16.7% were preterm, 20% were small for gestational age (SGA), and 55% were overweight or obese. The mean time interval between pubarche and thelarche was 11.20 ± 7.41 mo. The mean serum DHEA-S level was higher in the preterm group (p = 0.016), and DHEA-S levels were generally higher in the SGA group (p = 0.004). This study documented the presence of being overweight or obese and having more advanced growth than their genetic potential in half of the patients who had premature pubarche. In addition to these identified risk factors, obesity-independent DHEA-S levels were observed to be higher in patients who had early puberty with the first six months of their follow-up considered to be the most critical time in predicting early puberty.

"The Competitive Season and Off-Season": Preliminary Research concerning the Sport-Specific Performance, Stress, and Sleep in Elite Male Adolescent Basketball Athletes.

BACKGROUND: Through scholastic sports programs, adolescent athletes compete to represent their communities. However, few studies investigate the changes in physiological and mental profiles during varied sport periodization among this population. Therefore, the purpose of this study was to compare the changes in sports performance and stress-related biomarkers between the competitive season (CS) and off-season (OS) in elite adolescent basketball players. METHOD: Nine elite Division I male basketball players (age: 15-18 years. old) participated in this study. Basketball-specific performance, salivary dehydroepiandrosterone sulfate (DHEA-S)/cortisol levels, mood state, and sleep quality were all accessed during the CS and OS periods. RESULTS: The training load during OS was 26.0% lower than CS (p = 0.001). Muscle mass, aerobic capacity, 10 m sprint, and Abalakov jump (AJ) power during OS were greater than that during CS (+2.2-9.8%, p < 0.05), but planned agility was greater during CS (p = 0.003). The salivary DHEA-S/cortisol was greater during CS than during OS (p = 0.039). The overall mood state and sleep quality did not differ between periods, but the POMS-tension was higher during CS (p = 0.005). CONCLUSION: The present study demonstrates that muscle mass, aerobic capacity, peak AJ power, and 10 m sprint performance, but not planned agility, were greater during OS compared to CS among elite adolescent basketball players. Furthermore, the stress-related responses reflected by the D/C ratio and mood tension were relatively lower during the OS in these athletes. Thus, this study suggests that coaches and sport science professionals should closely monitor athletes' training states across varied training/competition periods to better react to modifying training or recovery plans.

Comparison of Anthropometric Measures for Evaluating the Association Between Hypogonadism and Hypothalamic-Pituitary-Gonadal Hormones in a Taiwanese Population.

To investigate the degree of association between levels of sex hormones and anthropometric indices in male population. A cross-sectional survey was conducted between July 2014 and July, 2016, in a men's health polyclinic in Taiwan. Body mass index, waist circumference, waist-to-height ratio (WHtR), and conicity index were tested. Serum total testosterone, free testosterone, and dehydroepiandrosterone sulfate (DHEA-S) were measured. Decreased testosterone levels were correlated with the four indices (r = -0.09 to -0.27, p < 0.01). In hypogonadism group, DHEA-S deficiency was associated with older age, higher anthropometric indices, and chronic illness. The areas under the receiver operating characteristic curves of hypogonadism and DHEA-S deficiency by the four anthropometric indices ranged from 52.5% to 65.9%. Logistic regression analysis revealed that obesity, defined by the four indices, was associated with increased risk of hypogonadism. Moreover, obesity was also associated with increased risk and DHEA-S deficiency. Anthropometric indices analyzed are associated with lower testosterone and DEAH-S deficiency. A WHtR of 0.5 is suggested to be a simple and reliable indicator of hypogonadism and DHEA-S deficiency.

Assessment of hormonal alterations in major depressive disorder: A clinical study.

Major depressive disorder (MDD) is a severe mood disorder that may lead to use of drugs, alcohol, and even suicide in acute cases. It has been shown that neurotransmitters and hormones have the same receptors and pathways in the mood area of the brain. Therefore, metabolic and biochemical changes are expected in MDD and, in such diseases, understanding the hormonal alterations would be extremely helpful in the management or treatment with hormone replacement therapy. We evaluated levels of cortisol, adrenocorticotropic hormone (ACTH), testosterone, thyroid-stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3), free thyroxine index (FT4I), T3 resin uptake (T3RU), and dehydroepiandrosterone sulfate (DHEA-S) in 79 patients suffering from MDD and 71 healthy controls. The existence of MDD was confirmed by a face-to-face structured clinical interview. We started the investigation by taking a blood sample from the study population. Then, hormone levels were measured by enzyme-linked immunosorbent assay. Significant differences were found between TSH, FT4I, DHEA-S, ACTH, testosterone, and cortisol/DHEA-S ratio in MDD patients compared to the healthy controls. We also demonstrated a correlation between MDD recurrence and FT4I index and TSH, respectively. Regarding some hormonal changes in patients with MDD, hormonal shifts should be considered in the treatment or management of MDD patients.

An aptameric graphene nanosensor for label-free detection of small-molecule biomarkers.

This paper presents an aptameric graphene nanosensor for detection of small-molecule biomarkers. To address difficulties in direct detection of small molecules associated with their low molecular weight and electrical charge, we incorporate an aptamer-based competitive affinity assay in a graphene field effect transistor (FET), and demonstrate the utility of the nanosensor with dehydroepiandrosterone sulfate (DHEA-S), a small-molecule steroid hormone, as the target analyte. In the competitive affinity assay, DHEA-S specifically binds to aptamer molecules pre-hybridized to their complementary DNA anchor molecules immobilized on the graphene surface. This results in the competitive release of the strongly charged aptamer from the DNA anchor and hence a change in electrical properties of the graphene, which can be measured to achieve the detection of DHEA-S. We present experimental data on the label-free, specific and quantitative detection of DHEA-S at clinically appropriate concentrations with an estimated detection limit of 44.7 nM, and analyze the trend observed in the experiments using molecular binding kinetics theory. These results demonstrate the potential of our nanosensor in the detection of DHEA-S and other small molecules in biomedical applications.