Dehydroepiandrosterone Sulfate Levels Research Articles

Integrated omics profiling reveals systemic dysregulation and potential biomarkers in the blood of patients with neuromyelitis optica spectrum disorders

BackgroundNeuromyelitis optica spectrum disorders (NMOSD) are autoimmune conditions that affect the central nervous system. The contribution of peripheral abnormalities to the disease's pathogenesis is not well understood.MethodsTo investigate this, we employed a multi-omics approach analyzing blood samples from 52 NMOSD patients and 46 healthy controls (HC). This included mass cytometry, cytokine arrays, and targeted metabolomics. We then analyzed the peripheral changes of NMOSD, and features related to NMOSD's disease severity. Furthermore, an integrative analysis was conducted to identify the distinguishing characteristics of NMOSD from HC. Additionally, we unveiled the variations in peripheral features among different clinical subgroups within NMOSD. An independent cohort of 40 individuals with NMOSD was utilized to assess the serum levels of fibroblast activation protein alpha (FAP).ResultsOur analysis revealed a distinct peripheral immune and metabolic signature in NMOSD patients. This signature is characterized by an increase in monocytes and a decrease in regulatory T cells, dendritic cells, natural killer cells, and various T cell subsets. Additionally, we found elevated levels of inflammatory cytokines and reduced levels of tissue-repair cytokines. Metabolic changes were also evident, with higher levels of bile acids, lactates, triglycerides, and lower levels of dehydroepiandrosterone sulfate, homoarginine, octadecadienoic acid (FA[18:2]), and sphingolipids. We identified distinctive biomarkers differentiating NMOSD from HC and found blood factors correlating with disease severity. Among these, fibroblast activation protein alpha (FAP) was a notable marker of disease progression.ConclusionsOur comprehensive blood profile analysis offers new insights into NMOSD pathophysiology, revealing significant peripheral immune and metabolic alterations. This work lays the groundwork for future biomarker identification and mechanistic studies in NMOSD, highlighting the potential of FAP as a marker of disease progression.

Effect of Endogenous Hormone Levels on Basal Metabolic Rate in Men With Obesity.

Basal metabolic rate (BMR) is an important factor in weight management and is influenced by fat-free mass (FFM), fat mass (FM) and age. Current knowledge of the influence of hormonal levels on BMR is based on studies with small populations, studies that investigate exogenous administration and studies frequently lacking correction for body composition. Cross-sectional study. All men (n = 457) who were referred to our centre for a metabolic work-up were eligible for inclusion. Median age was 47 (18-78) years and the vast majority had obesity (BMI ≥ 30 kg/m², 90.9%). All men had a measurement of BMR, body composition and measurement of testosterone, sex hormone binding globulin (SHBG), dehydroepiandrosterone sulphate (DHEAS), insulin-like growth factor 1 (IGF-1), thyroid-stimulating hormone (TSH) and free thyroxine (fT4). Men with low, normal and/or high levels of each of these hormones were compared. The association between hormone levels and BMR was assessed through linear regression models. All analyses were controlled for FFM, FM and age. In men with obesity, testosterone (total or free) was not associated with BMR. Linear regression analysis showed that DHEAS was positively associated with BMR in a sample of men with obesity and normal endogenous DHEAS levels, with the following equation: BMR (adjusted R² = 0.72): (BMR [kcal/d] = 513.402 + 18.940 × FFM [kg] + 9.507 × FM [kg] - 3.362 × age [years] + 0.307 × DHEAS [µg/dL]) (p < 0.01). TSH, fT4 and IGF-1 were not associated with BMR. In men with obesity, endogenous DHEAS is positively associated with BMR. Testosterone, TSH, fT4 and IGF-1 were not associated with BMR in men with obesity. Since we examined the specific population of men with obesity and only examined endogenous hormone levels, no extrapolation of results to other populations or the overall population can be made.

Enhancing Sleep and Reducing Occupational Stress Through Forest Therapy: A Comparative Study Across Job Groups.

The coronavirus disease-2019 (COVID-19) pandemic radically shifted occupational patterns, leading to increased telecommuting and related stressors. Healthcare providers, among the most impacted group, faced heightened risks and workplace changes. Our study examined the efficacy of forest therapy in alleviating work-induced stress across various professions, exploring the need for profession-specific stress-relief strategies in the post-pandemic workplace. To examine the impact of COVID-19 on professionals, 62 participants were recruited, consisting of 20 healthcare providers, 21 information technology (IT) specialists, and 21 teachers. Instruments such as Pittsburgh Sleep Quality Index and Hospital Anxiety and Depression Scale, along with salivary tests for cortisol and melatonin, were used to assess the participants' sleep and stress levels. A specialized forest healing program was implemented among these participants. Data analysis was conducted using SPSS Win Ver. 22.0, utilizing paired t-tests and a repeated measures analysis of variance. Significant improvements were observed in the participants' sleep metrics, depression scales, and stress levels after the forest healing program. Physiological measures indicated an increase in melatonin and a decline in cortisol and dehydroepiandrosterone sulfate levels, with only cortisol changes being statistically significant. Teachers, participating during school vacations, exhibited minimal stress-related physiological changes. Overall, the program demonstrated widespread health benefits regardless of occupation or gender. This study showed that forest therapy reduced stress equally across professions, including healthcare providers, IT specialists, and teachers. Individual physiological responses may play a greater role in stress relief than the specific occupation.

Maternal Obesity and Differences in Child Urine Metabolome

Background/objective: Approximately one-third of pregnant individuals in the U.S. are affected by obesity, which can adversely impact the in utero environment and offspring. This study aimed to investigate the differences in urine metabolomics between children exposed and unexposed to maternal obesity. Methods: In a study nested within a larger pregnancy cohort of women–offspring pairs, we measured untargeted metabolomics using liquid chromatography–mass spectrometry in urine samples from 68 children at 4–8 years of age. We compared metabolite levels between offspring exposed to maternal obesity (body mass index [BMI] ≥ 30.0 kg/m2) vs. unexposed (maternal BMI 18.5–24.9 kg/m2) and matched them on covariates, using two-sample t-tests, with additional sensitivity analyses based on children’s BMI. This study reports statistically significant results (p ≤ 0.05) and potentially noteworthy findings (fold change &gt; 1 or 0.05 &lt; p &lt; 0.15), considering compounds’ involvement in common pathways or similar biochemical families. Results: The mean (SD) maternal age at study enrollment was 28.0 (6.3) years, the mean child age was 6.6 (0.8) years, 56% of children were male, and 38% of children had a BMI in the overweight/obese range (BMI ≥ 85th percentile). Children exposed to maternal obesity had lower levels of 5-hydroxyindole sulfate and 7-hydroxyindole sulfate and higher levels of secondary bile acids. Phenylacetic acid derivatives were lower in offspring exposed to obesity and in offspring who had a current BMI in the overweight/obese range. Exposure to maternal obesity was associated with lower levels of androgenic steroid dehydroepiandrosterone sulfate (DHEA-S). Conclusions: In this preliminary study, children exposed to maternal obesity in utero had differences in microbiome-related metabolites in urine suggestive of altered microbial catabolism of tryptophan and acetylated peptides. Some of these differences were partially attributable to the offspring’s current BMI status. This study highlights the potential of urine metabolomics to identify biomarkers and pathways impacted by in utero exposure to maternal obesity.

Serotonin, cortisol, and DHEA-S levels in anxious and depressive pregnant women living with HIV

Pregnancy in women living with human immunodeficiency virus (WLWH) represents an important challenge for maternal-fetal health. Besides, they can also present anxiety (Anx) and depression (Dep). Imbalances in serotonin (5-HT), dehydroepiandrosterone sulfate (DHEA-S), and cortisol (CORT) levels can contribute to Anx and Dep manifestations. Currently, there is not enough data about the neuroendocrine and neurochemical changes in pregnant WLWH with affective disorders. This study aimed to characterize 5-HT, DHEA-S, and CORT plasma levels in Mexican pregnant WLWH presenting Anx/Dep. Forty-two adult pregnant women were recruited during the third trimester of gestation at the National Institute of Perinatology in Mexico during 2019–2022. These patients were divided into three groups: (1) pregnant WLWH with Anx/Dep (n = 16), (2) pregnant without HIV but with Anx/Dep (n = 12), and (3) healthy pregnant women without Anx/Dep (n = 14). WLWH presented a marked reduction in 5-HT (41.33 ± 39.37 ng/dL) compared to non-infected pregnant women with Anx/Dep (220.2 ± 151.8 ng/dL) and the healthy group (370.0 ± 145.3 ng/dL). Anx/Dep infected and uninfected pregnant women showed a significant reduction in DHEA-S levels (86.58 ± 30.59 and 76.9 ± 36.7 µg/dL, respectively) compared to healthy subjects (149.7 ± 44.6 µg/dL). Anx and Dep symptoms were inversely correlated with 5-HT and DHEA-S levels. No significant differences were observed in CORT levels among the three groups (p = 0.094). Our results suggest the presence of a disbalance in 5-HT and DHEA-S levels in pregnant WLWH with affective symptoms.

The state of the hypothalamic-pituitary-adrenal system in workers exposed to electric and magnetic fields of industrial frequenc

Introduction. Electric and magnetic fields of industrial frequency are an integral part of production processes, and their effect on the human body is of increasing interest both among scientists and among specialists in the field of medicine and occupational safety. In recent decades, there has been growing concern about the potential impact of these areas on the health of workers, especially those who are exposed to prolonged exposure in the course of their professional activities. In this context, we pay special attention to the neuroendocrine system, which plays a key role in regulating many physiological processes, including metabolism, stress reactions and maintaining homeostasis. The study of the fundamentals of the neuroendocrine system and the mechanisms of the effect of electromagnetic fields on the body not only contributes to the deepening of scientific knowledge in the field of biomedical research, but also has practical significance in ensuring occupational safety and improving working conditions in industrial enterprises, allowing to identify possible health consequences and develop effective measures to protect workers from negative bioeffects. The study aims to research the effects of electric and magnetic fields of industrial frequency on the functional state of the hypothalamic-pituitary-adrenal system of employees of electric grid facilities. Materials and methods. Specialists examined 144 employees of the main group engaged in the repair and operation of electric grid facilities and 40 employees of the control group who were not exposed to electromagnetic fields of industrial frequency. We determined the concentration of adrenocorticotropic hormone, cortisol and dehydroepiandrosterone sulfate in blood serum samples and calculated the ratio of dehydroepiandrosterone sulfate to cortisol. Results. Workers exposed to the combined effects of electric and magnetic fields of industrial frequency had a lower (p&lt;0.05) level of adrenocorticotropic hormone (1.9 [0.5; 3.9] pg/ml) and dehydroepiandrosterone sulfate (5.8 [3.7; 8.4] mmol/l) in the blood compared with the group of workers exposed to magnetic fields industrial frequency fields (4.4 [2.1; 12.9] pg/ml; 9.8 [6.3; 14.5] mmol/l) and to the control group (6.4 [4.0; 19.8] pg/ml; 7.8 [4.7; 13.3] mmol/l), respectively. The scientists also revealed in the group of workers exposed to combined exposure in the field, the association of a low ratio of dehydroepiandrosterone sulfate and cortisol with the development of cardiovascular diseases and feedback from work experience (p&lt;0.05). Limitations. The study is limited by the number of people surveyed (144 employees). Conclusion. The results of the study indicate the hypoactivity of the hypothalamic-pituitary-adrenal system induced by exposure to electric and magnetic fields of industrial frequency, manifested by a decrease in the level of adrenocorticotropic hormone, dehydroepiandrosterone sulfate and its relationship to cortisol in workers exposed to combined effects of electric and magnetic fields of industrial frequency. Ethics. The work complies with ethical standards developed in accordance with the Helsinki Declaration of the World Medical Association "Ethical Principles of conducting Scientific medical research with human participation" as amended in 2000 and the "Rules of Clinical Practice in the Russian Federation" approved by Order of the Ministry of Health of the Russian Federation dated 04/01/2016 No. 200n. We received informed consent from each examined person to participate in the study, approved in accordance with the established procedure by the local Ethics Committee of Izmerov Research Institute of Occupational Health (minutes of the meeting of the Ethics Committee No. 17 dated 12/16/2015).

Pre-Conception Androgen Levels and Obstetric Outcomes in Polycystic Ovary Syndrome: A Single-Center Retrospective Study

Hyperandrogenism is a determining diagnostic factor for PCOS. If pregnancy is conceived, it is considered high-risk due to several potential complications, but the correlation between pre-pregnancy androgen levels and obstetric outcomes is poorly characterized. Objective: To determine if pre-pregnancy serum androgen concentrations and androgen indexes differed when certain obstetric and neonatal outcomes appeared in PCOS. Methods: A single-center, retrospective study was carried out. All patients were treated between 2012 and 2019. A total of 73 patients had all the endocrine and obstetric data available. Pre-pregnancy hormone levels (total testosterone-T, androstenedione-AD, DHEAS (dehydroepiandrosterone sulfate), SHBG (sex-hormone-binding globulin), and TSH (thyroid-stimulating hormone) were collected, and T/SHBG, AD/SHBG, DHEAS/SHBG, T/AD indexes were calculated and compared. Results: When miscarriage was present in the history, significantly elevated pre-pregnancy AD levels were observed. Higher pre-pregnancy AD level was noted in PCOS patients delivering female newborns as compared to males. Additionally, a higher T/AD ratio was associated with subsequent preterm delivery, but significance was lost after age adjustment. Maternal age at delivery had a significant negative correlation with pre-pregnancy DHEAS levels and DHEAS/SHBG ratio. Pre-pregnancy SHBG displayed a significant negative correlation, while pre-pregnancy androgen/SHBG ratios exhibited positive correlations with both birth weight and birth weight percentile. Conclusions: Based on our data, AD and the T/AD ratio emerge as distinctive factors in certain outcomes, implying a potential specific role of altered 17-β-HSD (17β-hydroxysteroid dehydrogenase) enzyme activity, possibly influencing offspring outcomes. The pre-pregnancy T/SHBG ratio exhibits a potentially stronger correlation with fetal growth potential compared to SHBG alone. DHEAS and maternal age at delivery are strongly correlated in PCOS patients.

7135 Changes in 11-oxygenated androgens in healthy prepubertal children from ages 4, 6, to 8 years: a prospective cohort study

Abstract Disclosure: Y. Lee: None. K. Lee: None. J. Kim: None. Y. Lim: None. J.I. Kim: None. B. Kim: None. Y. Hong: None. J. Song: None. C. Shin: None. Y. Lee: None. Background: 11-oxygenated androgens (11-oxyandrogens) have been recognized for their important role in adrenarche or androgen excess conditions. However, the trajectory during childhood remains understudied. Herein, we examined the longitudinal changes in 11-oxyandrogens among healthy prepubertal children. Methods: In an ongoing prospective cohort study, 172 prepubertal children with available blood samples at the ages of 4, 6, and 8 years were included. Serum concentrations of 14 adrenal androgens and precursors, including dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEAS), androstenedione (A4), testosterone (T), 11β-hydroxyandrostenedione (11OHA4), 11-ketoandrostenedione (11KA4), 11β-hydroxytestosterone (11OHT), and 11-ketotestosterone (11KT) were assessed using liquid chromatography-tandem mass spectrometry. Repeated measures ANOVA was used to analyze the changes in adrenal androgens across age groups. Linear mixed model analysis was used to evaluate factors associated with adrenal hormone levels during 4 to 8 years of age. Results: Among 172 prepubertal children (107 boys, 65 girls), 11OHA4 was the predominant 11-oxyandrogen, exceeding concentrations of DHEA or A4. Serum 11KT level was higher than testosterone level from 6 years of age. Across age 4, 6, and 8 years, 11-oxyandrogens showed an increasing trend. Trajectories of 11OHA4, 11KA4, and 11KT significantly differed by sex (p for interaction &amp;lt; 0.05). Serum levels of 11OHA4 and 11KT consistently increased from 4, 6, to 8 years in both sexes, while 11OHT increased during 6-8 years (p &amp;lt; 0.05 for all). Serum 11KA4 levels increased during 4-6 years in boys and 6-8 years in girls (p &amp;lt; 0.05 for all). Girls showed higher levels of 11OHA4, 11KA4 at 4 years, 11OHT at 6 years, and 11KT at 4 and 6 years. Regarding classic adrenal androgens, DHEA, DHEAS, and A4 also exhibited increases in different patterns between sexes (p for interaction &amp;lt; 0.05) during 4-8 years. Girls had higher serum DHEA and A4 levels at 4 and 6 years, and DHEAS levels at 4 years (p &amp;lt; 0.05 for all). In boys, lower gestational age, lower birth weight z-score, and higher body mass index (BMI) z-score were correlated with elevated levels of DHEA and DHEA-S. Additionally, a higher BMI z-score was associated with increased levels of A4, 11OHT, and 11KT (p &amp;lt; 0.05 for all, multivariable models). In girls, a higher BMI z-score was linked to elevated DHEA levels, while a higher birth weight z-score was associated with increased A4 levels (p &amp;lt; 0.05 for all, multivariable models). Conclusion: In prepubertal children, 11-oxyandrogens showed increasing patterns similar to classic androgens, with sex-differences. Some 11-oxyandrogens were more predominant than classic androgens. This study suggests the importance of 11-oxyandrogens as biomarkers for zona reticularis development and adrenarche in prepubertal children. Presentation: 6/3/2024

7291 From Vaginal Bleeding to Genetic Complexity: McCune Albright Syndrome in a Toddler; Emphasizing Atypical Manifestations, Diagnostic Challenges, and Comprehensive Management

Abstract Disclosure: A.G. Martinez Sanchez: None. N. Fernandez: None. C.L. Bustamante Escobar: None. Background: McCune Albright Syndrome (MAS) is a rare genetic disorder characterized by a triad of peripheral precocious puberty, irregular café-au-lait spots, and bone fibrous dysplasia. It is often caused by post-zygotic somatic mutations in the GNAS1 gene. We present a case of a patient initially presenting with precocious puberty, whose diagnostic journey revealed MAS with atypical manifestations. Presentation: A 23-month-old girl was brought to the emergency department after her mother noticed vaginal bleeding during a diaper change; denied any trauma, fever, rash, or dysuria. Patient developed accelerated growth about six months earlier, followed by pubic hair three months prior and bilateral thelarche two weeks before presentation. The patient had no exposure to endocrine disruptors. The physical examination revealed a well-developed child, in the 92nd percentile for weight and 97th for height. Additionally, breast buds, fine hair on the labia, and minimal blood at the vaginal introitus, with no apparent signs of trauma. Initial laboratory findings showed prepubertal LH and FSH levels, elevated estradiol 120 pg/ml (prepubertal range &amp;lt;10) and advanced bone age (4.2 years). Normal levels of testosterone, 17-hydroxyprogesterone, and DHEA sulfate. Pelvic ultrasound demonstrated an enlarged uterus (5.6 x 1.8 x 2.4 cm) and a large cystic lesion (4.4 cm) on the right ovary. During a follow-up at the endocrinology department one week later, a meticulous examination identified an irregular café-au-lait spot measuring about 2cm over the occipital right side of her scalp. Further tests, including GnRH stimulation test, tumor markers (LDH, b-HCG, CEA, and Ca19-9), brain MRI and bone scan, yielded normal findings. Given the presentation consistent with Peripheral precocious puberty, Letrozole was initiated at 1.25 mg daily. Three months later, her growth velocity remained accelerated. However, there was a decrease in both breast tissue and uterus size (4.2 x 1.2 x 1.7 cm), and the ovarian cyst was resolved. Genetic testing in blood indicated no mutations. To conduct a thorough assessment, the insulin-like growth factor (IGF-1) level was measured and found to be 200 ng/mL (normal range 56-144 ng/mL). Unfortunately, obtaining prolactin levels was challenging due to difficult intravenous (IV) access. Conclusion: This case reveals the complexity of MAS in precocious puberty, emphasizing atypical features that add complexity to the diagnosis. Identifying an irregular café-au-lait spot served as a diagnostic indicator, revealing the diverse clinical presentations. The challenges of relying solely on genetic testing for diagnosis are evident due to the mosaic nature and tissue-specific distribution of the mutation, as highlighted by the absence of mutations in this patient. Long-term management requires ongoing monitoring and a multidisciplinary approach for optimal patient outcomes. Presentation: 6/1/2024

6450 Leydig Cell Tumor: A Rare Cause of Post-menopausal Hyperandrogenism

Abstract Disclosure: R. Nakdali: None. S. Athimulam: None. Introduction: Ovarian steroid cell tumors are a rare subtype of sex-cord stromal tumors. Leydig cell tumors is a subtype of sex-stromal tumors that is found in &amp;lt; 1% of all ovarian tumors. They are typically benign, unilateral, and secrete androgens which causes virilization. Below we present the case of a postmenopausal woman who presented with signs of virilization and was diagnosed with an ovarian Leydig cell tumor. Case: A 62-year-old postmenopausal woman, with a history of partial hysterectomy with right oophorectomy presented to Endocrinology clinic for evaluation of thyroid nodules. However, clinically she had signs of virilization noted by the provider on examination. She reported progressive androgenic alopecia, cystic acne, oily skin, hoarseness of voice and hirsutism, with increase hair growth over upper lip, chin and jaw line requiring daily shaving. She denied taking any supplements. She reported embarrassment of these physical changes and prior providers had attributed this to aging, therefore not prompting further testing. This caused significant emotional distress to the patient, leading to isolation. Biochemical testing confirmed elevated bioavailable testosterone (193.1 ng/dL) and total testosterone levels (579 ng/dL), with no evidence of hypercortisolemia. Magnetic resonance imaging (MRI) revealed a heterogenous soft tissue mass (2.9 x 2.1 x 2.1 cm) in the left ovary. She underwent a left salpingo-oophorectomy and pathology confirmed a well-differentiated 2.4 cm Leydig cell tumor. Post-operatively, she reported improvement in facial and body hirsutism, reduced shaving frequency decrease in androgenic hair loss, with noticeable hair growth in her frontal scalp, and her skin became less oily with reduced acne. Post-operative labs confirmed cure of hyperandrogenism (Bioavailable testosterone &amp;lt; 2.6 ng/dL; Total testosterone: &amp;lt; 10ng/dL; and Free androgen index &amp;lt; 0.5%). She has been referred to genetics for evaluation. Discussion: Post-menopausal hyperandrogenism poses a diagnostic challenge as it can be mistaken for hormonal imbalances seen with aging. Often times, patients do not report symptoms due to embarrassment unless specifically addressed by provider. Initial testing consists of total and free testosterone and dehydroepiandrosterone sulfate (DHEAS) levels to assess the source of hyperandrogenism. Ruling out hypercortisolemia and assessment for ingestion of testosterone or DHEA supplements is vital. Pelvic ultrasound or cross-sectional imaging (CT or MRI) of abdomen and pelvis can identify structural abnormalities in the ovaries or adrenal glands. Prompt evaluation and management can alleviate significant distress to the patient. Leydig cell tumors represent a rare but important consideration in the differential diagnosis of postmenopausal hyperandrogenism, such as in our patient. Presentation: 6/2/2024

8661 A case of post-menopausal female with virilization due to Sertoli-Leydig cell ovarian tumor recurring in contralateral ovary 8 years later

Abstract Disclosure: M.S. Maharaul: None. J.L. Miller: None. Introduction: Sertoli-Leydig cell tumors (SLCTs) are rare androgen-secreting tumors of the ovaries, accounting for less than 0.5% of all ovarian tumors. Their incidence peaks in the second to third decade of life. New onset of severe hyperandrogenism with virilization in postmenopausal women is exceedingly rare, and the three most frequent causes are ovarian tumors, ovarian hyperthecosis and adrenal androgen producing tumors. We report one such case of ovarian androgen producing tumor which was further complicated by recurrence in the contralateral ovary. Case: A 66-year-old woman presented for evaluation of hyperandrogenism. Physical examination revealed evidence of virilization and clitoromegaly. Laboratory workup was remarkable for total serum testosterone level of 367 ng/dL with normal dehydroepiandrosterone sulfate and cortisol levels. A computerized scan of abdomen did not show any adrenal masses. Transvaginal ultrasound revealed uterine myomas but did not show any ovarian pathology. She underwent selective vein catheterization of her adrenal glands as well as ovaries and was noted to have right ovary secreting 3,982 ng/dL of testosterone whereas all other samples had total testosterone levels &amp;lt; 200 ng/dL. She underwent right salpingo-oophorectomy. Histopathologic examination revealed a 2.2 cm well differentiated Sertoli-Leydig cell tumor confined to the ovary; the fallopian tube was negative for tumor. Six weeks later, her serum total testosterone level was 18 ng/dL. 8 years later, she returns with recurrent symptoms of hyperandrogenism. Repeat workup revealed a total testosterone level of 662 ng/dL. A computerized scan of abdomen and transvaginal ultrasound revealed an unremarkable uterus and left ovary. Magnetic resonance imaging of the pelvis was done that showed a 1.2 cm enhancing mass in the left ovary. She then underwent left salpingo-oophorectomy and supracervical hysterectomy. Histopathologic examination revealed a 1.5 cm Sertoli-Leydig-cell tumor of the left ovary, the fallopian tube was negative for tumor. Six weeks later, her serum total testosterone level was 24 ng/dL and she felt significant improvement in her symptoms. Conclusion: We present an interesting case of virilization in a post-menopausal female due to Sertoli-Leydig cell tumor that resolved after unilateral oophorectomy but recurred 8 years later in the contralateral ovary with resolution after completion oophorectomy. Presentation: 6/2/2024

6450 Leydig Cell Tumor: A Rare Cause of Post-menopausal Hyperandrogenism

Abstract Disclosure: R. Nakdali: None. S. Athimulam: None. Introduction: Ovarian steroid cell tumors are a rare subtype of sex-cord stromal tumors. Leydig cell tumors is a subtype of sex-stromal tumors that is found in &amp;lt; 1% of all ovarian tumors. They are typically benign, unilateral, and secrete androgens which causes virilization. Below we present the case of a postmenopausal woman who presented with signs of virilization and was diagnosed with an ovarian Leydig cell tumor. Case: A 62-year-old postmenopausal woman, with a history of partial hysterectomy with right oophorectomy presented to Endocrinology clinic for evaluation of thyroid nodules. However, clinically she had signs of virilization noted by the provider on examination. She reported progressive androgenic alopecia, cystic acne, oily skin, hoarseness of voice and hirsutism, with increase hair growth over upper lip, chin and jaw line requiring daily shaving. She denied taking any supplements. She reported embarrassment of these physical changes and prior providers had attributed this to aging, therefore not prompting further testing. This caused significant emotional distress to the patient, leading to isolation. Biochemical testing confirmed elevated bioavailable testosterone (193.1 ng/dL) and total testosterone levels (579 ng/dL), with no evidence of hypercortisolemia. Magnetic resonance imaging (MRI) revealed a heterogenous soft tissue mass (2.9 x 2.1 x 2.1 cm) in the left ovary. She underwent a left salpingo-oophorectomy and pathology confirmed a well-differentiated 2.4 cm Leydig cell tumor. Post-operatively, she reported improvement in facial and body hirsutism, reduced shaving frequency decrease in androgenic hair loss, with noticeable hair growth in her frontal scalp, and her skin became less oily with reduced acne. Post-operative labs confirmed cure of hyperandrogenism (Bioavailable testosterone &amp;lt; 2.6 ng/dL; Total testosterone: &amp;lt; 10ng/dL; and Free androgen index &amp;lt; 0.5%). She has been referred to genetics for evaluation. Discussion: Post-menopausal hyperandrogenism poses a diagnostic challenge as it can be mistaken for hormonal imbalances seen with aging. Often times, patients do not report symptoms due to embarrassment unless specifically addressed by provider. Initial testing consists of total and free testosterone and dehydroepiandrosterone sulfate (DHEAS) levels to assess the source of hyperandrogenism. Ruling out hypercortisolemia and assessment for ingestion of testosterone or DHEA supplements is vital. Pelvic ultrasound or cross-sectional imaging (CT or MRI) of abdomen and pelvis can identify structural abnormalities in the ovaries or adrenal glands. Prompt evaluation and management can alleviate significant distress to the patient. Leydig cell tumors represent a rare but important consideration in the differential diagnosis of postmenopausal hyperandrogenism, such as in our patient. Presentation: 6/2/2024

Clinical characteristics and treatment during preconception and perinatal period of infertile women with non-classical 21-hydroxylase deficiency

ObjectiveA single-center observational study to determine the clinical characteristics and therapeutic dose adjustments in women of reproductive age with infertility and non-classical 21-hydroxylase deficiency (NC-21OHD).DesignA retrospective analysis of 20 women of reproductive age who were diagnosed with NC-21OHD during an infertility evaluation at Shengjing Hospital of China Medical University from January 2013 to May 2024 was performed. The clinical manifestations, auxiliary examinations, adjustment of glucocorticoid (GC) treatment during preconception and perinatal period, and pregnancy outcomes were analyzed.Results14 of 16 patients (87.5%) had inappropriately elevated progesterone levels during the follicular phase. The average levels of 17α-hydroxyprogesterone, testosterone, androstenedione, and dehydroepiandrosterone sulfate in the follicular phase were also significantly increased. All 20 infertile patients received GC treatment before preparing for pregnancy. During the follow-up, six of 20 patients had seven conceptions. three patients had spontaneous abortions in the first trimester and four patients delivered babies (4/20). Three patients had a GC dose that was maintained throughout pregnancy and one had an increase in the GC dose starting in the second trimester. Of the remaining 16 patients, seven are still trying to conceive and nine had discontinued treatment.ConclusionsAn abnormal increase in the follicular phase progesterone level is the most common serologic marker for NC-21OHD among infertile women. Ovulation can be restored after GC treatment, but the proportion of successful conceptions remains low. The dose of GCs in most pregnant women remained unchanged throughout pregnancy.

The effects of opioid tapering on select endocrine measures in men and women with head and neck cancer-a longitudinal 12-month study.

Opioid treatment may affect endocrine measures in humans either through centrally or peripherally mediated mechanisms. There is a general lack of longitudinal studies examining endocrine measures in opioid-treated patients. To longitudinally follow the levels of select endocrine measures in men and women with head and neck cancer for 1 year, who after having completed radiotherapy began tapering opioids. This was a prospective, longitudinal, observational study. Testosterone and estradiol were measured in men and women, respectively. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEAS), and prolactin were measured in both sexes. Women were grouped based on if premenopausal or postmenopausal. Samples were collected when opioid tapering started and at 1, 3, 6, and 12 months after tapering start. Daily opioid doses at the same time points were registered. Twenty-five men and 12 women were followed for 12 months. In men, testosterone levels increased significantly during the first month after opioid tapering started (P < 0.001). Levels of testosterone, FSH, DHEAS, and prolactin changed significantly in men during the study period. A moderate correlation between opioid dose reduction and testosterone level increase in men aged ≤60 years was found (r s = -0.577, 95% CI -0.854 to -0.044, P = 0.039). In postmenopausal women (n = 10), levels of FSH and LH changed significantly during the study period. Previously known effects of opioids on endocrine measures in humans seem to be reversible as select endocrine measures changed significantly in men and postmenopausal women after opioid tapering was initiated.

Age-dependent changes in visceral adiposity are associated with decreased plasma levels of DHEA-S in sigma-1 receptor knockout male mice

The sigma-1 receptor (S1R) is involved in intracellular lipid synthesis and transport. Recent studies have shown that its genetic inactivation impairs adipogenic differentiation in vitro. This study investigated the role of S1R in adipose tissue physiology and metabolic health using adult and old WT and S1R KO mice.Visceral fat mass was increased in adult, but not old S1R-KO male mice compared to that of WT mice, despite having similar body weights, food intake, and energy expenditure. The average adipocyte size was 64 % larger in adult KO mice than in adult WT mice. Adult S1R-KO mice showed reduced plasma dehydroepiandrosterone sulfate (DHEA-S) and elevated fasting plasma leptin concentrations. Lipidomic analysis revealed alterations in plasma metabolite concentrations, particularly reduced levels of sphingomyelins, ceramides, phosphatidylcholines, lysophosphatidylcholines, and cholesteryl esters in adult mice. Decreased expression of Pparγ, Adipoq, and Atgl was detected in visceral white adipose tissue (vWAT) isolated from adult KO mice. Additionally, Fabp4 and Adipoq expression levels were significantly lower in KO adipose-derived stromal cells than in WT adipose-derived stromal cells. A fivefold increase in the mitochondrial fatty acid oxidation rate and a 43 % increase in electron transfer coupling capacity were detected in adult S1R-KO vWAT.In summary, our investigation revealed an age-dependent association between increased visceral adiposity and decreased plasma levels of DHEA-S in S1R-deficient male mice. These findings underscore the potential role of S1R in regulating metabolic processes in adipose tissue and suggest that DHEA-S is a potential mediator of adiposity changes in the absence of S1R.

Clinical and diagnostic evidence of benign endometrial pathology in postmenopausal patients

The objective: to study clinical and diagnostic features of the benign endometrial conditions in the postmenopausal women.Materials and method. 64 postmenopausal patients with various severity of postmenopausal vaginal bleeding were examined. All patients underwent clinical, radiological, laboratory and histological examinations, reproductive history data and body mass index indicators were evaluated. Of them 33 persons were diagnosed with complex endometrial hyperplasia without atypia, 16 women – endometrial polyp and 15 women – hyperplasia with atypia. Routine gynecological examination including abdominal and pelvic examination following transvaginal ultrasound examination for the determination of the uterine and ovarian volume as well, as the endometrial thickness were conducted. Patients included in the study underwent computer tomography and magnetic resonance imaging as indicated. All patients with endometrial pathology underwent endometrial biopsy by standard dilatation and curettage or Pipelle-biopsy with histological examination of the obtained material. The concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEA-S), estradiol, estrone, progesterone, prolactin, and testosterone were determined in blood serum.Results. It was confirmed that in 87,5% of cases endometrial hyperplasia manifested with vaginal bleeding. Endometrial thickness in examined persons ranged from 14.1±1.6 mm in patients with atypical endometrial hyperplasia to 21.3±4.8 mm in patients with complex endometrial hyperplasia without atypia. The study of blood levels of hormones found that postmenopausal patients with endometrial hyperplasia have lower FSH concentration, LH/FSH ratio, estradiol, testosterone levels, with significantly high values of prolactin, DHEA-S and estrone. During the postmenopausal period, hyperplasia was developed in 10% of cases by the presence of bleeding, and 86.2% of cases by the presence of blood spotting. Conclusions. The study suggests that high body mass index, numerous artificial abortions, high blood levels of estrone, DHEA-S and prolactin as well as increased thickness of endometrium influence the frequency of endometrial hyperplasia in postmenopausal women.

Adipose tissue insulin resistance in young Japanese women is associated with metabolic abnormalities and dehydroepiandrosterone-sulfate.

The proportion of young Japanese women who are underweight is exceptionally high. We previously showed that the prevalence of impaired glucose tolerance (IGT) was high in underweight young Japanese women, and that IGT was characterized by high free fatty acid levels and adipose tissue insulin resistance (ATIR). As the next step, this study aimed to explore factors associated with elevated ATIR in this population. Ninety-eight young, healthy, underweight women participated in this study. To investigate the relationship between ATIR and metabolic parameters, participants were divided into three groups (Low, Medium, and High) according to ATIR level. Body composition examination, oral glucose tolerance testing, and blood biochemical analysis were performed; Adipo-IR and the Matsuda index were used as indices of ATIR and systemic insulin sensitivity, respectively. Participants in the High ATIR group had the highest prevalence of IGT (25%), and significantly higher body fat percentage, whole-body insulin resistance, and levels of insulin-like growth factor-1 and dehydroepiandrosterone sulfate (DHEA-S) than the other two groups. They were also significantly younger and had higher systolic blood pressure than the Low ATIR group. Multiple regression analysis showed that DHEA-S, which is known to enhance lipolysis in adipose tissue, was an independent correlate of ATIR. Underweight Japanese women with high ATIR had impaired metabolism, a higher prevalence of IGT, higher systemic insulin resistance, and higher systolic blood pressure. DHEA-S was a determinant of high ATIR levels.

Influence of sex and functional status on the value of serum steroid profiling in discriminating adrenocortical carcinoma from adrenocortical adenoma.

It is challenging for clinicians to distinguish adrenocortical carcinoma (ACC) from benign adrenocortical adenomas (ACA) in their early stages. This study explored the value of serum steroid profiling as a complementary biomarker for malignancy diagnosis of ACC other than diameter and explored the influence of sex and functional status. In this retrospective study, a matched cohort of patients diagnosed with either ACC or ACA based on histopathology was meticulously paired in a 1:1 ratio according to sex, age, and functional status. Eight serum steroids including 11-deoxycortisol, 11-deoxycorticosterone, progesterone, androstenedione, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), 17-hydroxyprogesterone, and estradiol, were quantified by liquid chromatography tandem mass spectrometry. We conducted a comparative analysis of the clinical characteristics and serum steroid profiles of patients with ACC and ACA, with further subgroup analysis. The study included 31 patients with ACC and 31 matched patients with ACA. Patients with ACC exhibited significantly larger tumor diameters, lower body mass index (BMI), and higher levels of 11-deoxycortisol, progesterone, and androstenedione than those with ACA. 11-deoxycortisol was the only valuable index for discriminating ACC from ACA, regardless of functional status and sex. Progesterone, DHEA, and DHEAS levels were higher in the functional ACC group than in the non-functional ACC group. Female ACC patients, especially in postmenopausal female exhibited higher levels of androstenedione than male patients. The area under the curve of tumor diameter, 11-deoxycortisol, and BMI was 0.947 (95% CI 0.889-1.000), with a sensitivity of 96.8% and specificity of 90.3%. Serum steroid profiling serves as a helpful discriminative marker for ACC and ACA, with 11-deoxycortisol being the most valuable marker. For other steroid hormones, consideration of sex differences and functional status is crucial.

Short Rest Between Flights Is Associated With Increased Serum Stress Hormone Levels in Airline Pilots: A Cross-Sectional Study.

Work-related stress is a critical area of research in civil aviation, given the potential for severe consequences when airline pilots (APs) are overwhelmed or unable to perform optimally. While pilots are traditionally considered to be exposed to various stressors, the impact of specific occupational characteristics on stress in the aviation industry remains inadequately understood. Considering that biomarkers are increasingly being utilized as objective measures of stress in human research, this cross-sectional study investigated the association between occupational variables and serum levels of cortisol and dehydroepiandrosterone sulfate (DHEAS) as stress biomarkers in commercial APs. A total of 120 male APs completed a survey assessing the following work-related characteristics: position (captain vs. first officer), years of experience, total flight hours, flight hours in the preceding year, inter-flight rest duration, and flight route length. Serum cortisol and DHEAS concentrations were determined from venous blood samples obtained between 08:00 and 09:00 a.m., following a minimum eight-hour fasting period. The biomarker data were analyzed in relation to the aforementioned occupational characteristics. The mean serum cortisol and DHEAS concentrations in the entire cohort were 8.5±2.1 µg/dL and 214.6±96.4 µg/dL, respectively. There were no significant differences in the levels of the two stress hormones in relation to position, years of experience, total flight hours, flight hours in the preceding year, or flight route length. However, an inter-flight rest period of less than one hour was significantly associated with elevated serum cortisol (P<0.01) and reduced DHEAS levels (P<0.001) compared to longer rest durations. Notably, a stepwise decrease in DHEAS concentrations was observed for rest periods of <1 hour, 1-4 hours, 4-24 hours, and >24 hours. After adjustment for potential confounders in multivariable analyses, a rest period of <1 hour remained independently associated with both serum cortisol (odds ratio [OR]=1.09, 95% confidence interval [CI]=1.04-1.13, P<0.01) and DHEAS (OR=0.94, 95% CI=0.92-0.97, P<0.001). Serum stress hormones in APs are associated with short inter-flight rest periods. Optimization of rest durations may contribute to improved pilot well-being and performance. Further research is warranted to determine ideal rest period lengths and develop interventions to mitigate the potential adverse effects of abbreviated rest periods between flights.

The value of serum dehydroepiandrosterone sulfate in the functional evaluation of adrenal space-occupying lesions in adults

Objective: To evaluate the function of serum dehydroepiandrosterone sulfate (DHEAS) in adult adrenal space-occupying lesions. Methods: In this cross-sectional study, 395 patients with adrenal space-occupying lesions who had their DHEAS levels measured were collected from the First Medical Center of Chinese PLA General Hospital from January 2010 to June 2021. They were divided into the adrenal Cushing syndrome (ACS) group (n=100) and non-ACS group (n=295). The former was divided into the cortisol-producing adrenal adenoma (CPA) group (n=67) and primary bilateral macronodular adrenal hyperplasia (PBMAH) group (n=33). Clinical data of each group were collected and compared among groups by independent samples t-test, chi-square test, and Mann-Whitney U test. Serum DHEAS ratio corrected for age and sex was further constructed to identify the receiver operating characteristic curve and the optimal tangent point value for different adrenal occupation. Results: Patients in the ACS group were younger (44.9±13.7 vs. 49.9±12.5, P=0.001); had a larger proportion of women (79/100 vs.139/295, P=0.001); and had higher cortisol levels [8∶00Am, 497.31 (343.52, 606.50) vs. 353.11 (267.50, 487.91) nmol/L, P<0.001] than those in the non-ACS group. The serum DHEAS level and ratio in the ACS group were significantly lower than those in the non-ACS group [0.50 (0.40, 1.21) vs. 2.68 (1.56, 4.32) μmol/L, 1.00 (0.43, 1.68) vs. 3.17 (2.21, 4.54), both P<0.001]. When the serum DHEAS ratio cut-off point was 1.29, the sensitivity and specificity for differential diagnosis of ACS and non-ACS were 72.0% and 91.5% respectively. The ratio of DHEAS in the CPA group was lower [0.58 (0.27, 1.05) vs. 1.14 (1.04, 2.40), P<0.001] than that in the PBMAH group. When the serum DHEAS ratio cut-off point was 0.99, the sensitivity and specificity for differential diagnosis of CPA and PBMAH were 64.2% and 81.2% respectively. Conclusion: Corrected age-sex DHEAS ratio can assist in the functional assessment of adrenal space-occupying lesions.