Serum DHEAS Research Articles

6891 Exclusive Normetanephrine Secreting Pheochromocytoma In A Young Male

Abstract Disclosure: E. Askar: None. H. Moran: None. IntroductionPheochromocytomas and paragangliomas arise from chromaffin cells and produce excessive catecholamines. Hypertension is their primary clinical symptom. they differ in their catecholamine secretory phenotype; paragangliomas typically secrete norepinephrine, while pheochromocytomas typically secrete epinephrine. Here, we present a case 21-year-old male with pheochromocytoma with elevated norepinephrine but normal epinephrine levels.Case presentationA 21 -year-old male with no past medical history presented with episodes of palpitations, sweating, and elevated blood pressure. He also reported abdominal pain. On admission, his blood pressure was 143/92 mmHg, pulse was 71/min, respiration was 16/min, and oxygen saturation was 100% in room air. The rest of physical exam was not significant. His electrolyte panel was normal. Computed tomography (CT) abdomen and pelvis with contrast was performed and showed a right adrenal mass measuring 4.9 x 4.0 x 6.5 cm which is predominantly hypoattenuating (approximately 30 Hounsfield units) with thick nodular rim of enhancement. Hormonal workup showed normal serum testosterone, DHEA-S, AM cortisol, ACTH, aldosterone, plasma metanephrine, and urine metanephrine, but profoundly high plasma normetanephrine 3641.6 (0.0-210.1) pg/mL. His 24-hour urinary normetanephrine was elevated at 14874 (80-440) ug/24hr, confirming a pheochromocytoma. The high norepinephrine level in the setting of normal epinephrine raised suspicion for Von Hippel Lindau (VHL). He was started on alpha and beta blockage and had laparoscopic removal of the right adrenal gland. The pathology report confirmed the diagnosis of pheochromocytoma confined to right adrenal. The patient was then referred for genetic testing. Conclusion: Pheochromocytoma can be a part of familial disorders, although being sporadic in nature most of the time. As demonstrated in our case, the hallmark of pheochromocytoma associated with VHL is nearly exclusive normetanephrine secretion and a high ratio of normetanephrine to metanephrine. Confirmation and testing of genes aid in proper monitoring and follow-up. The preferred course of treatment is radical resection. Presentation: 6/2/2024

Acrylamide exposure, sex hormones, and pubertal status in Japanese adolescents

ABSTRACT Acrylamide may affect sex hormone levels and the timing of sexual maturation. The present study cross-sectionally examined interrelationship between the urinary metabolite of acrylamide exposure, serum sex hormone levels, and pubertal status in 408 Japanese adolescents aged 13–14 years. Their caregivers completed a questionnaire concerning the health status of their children, including pubertal maturation, and the lifestyles of children and parents. Pubertal status was queried by the Pubertal Development Scale. A major metabolite of acrylamide, N-acetyl-S-(2-carbamoylethyl)-cysteine (AAMA) in first-void urine samples. In male students, urinary AAMA was significantly inversely associated with testosterone, puberty stage, and facial hair growth after controlling for covariates. Serum testosterone and DHEAS were significantly positively associated with puberty stage. In female students, urinary AAMA was not associated with puberty stage, the indices, or any measured hormones. The data suggest that exposure to acrylamide may impact the pubertal development of boys through the effects on testosterone level.

Iraqi Women with Hirsutism, Clinical and Biochemical Characteristics: Retrospective Study

This clinical research aimed to assess the frequency of different some clinical and biochemical features of hirsitusm among Iraqi women retrospectively. Methods: This study is a descriptive cohort study included 100 Hirsutism -affected females. A retrospective analysis of patient assessed using the recently approved diagnostic guidelines for hyper androgenic women with hirsutism Clinical features, family history and hormone levels results were analyzed. Results: At our presentation, the mean age of the 100 Hirsitusm-affected females was 26.9 years ranged of (13-42) years. The mean of BMI (kg/m2) for all patients was 27.38 (Overweight), 55% of women had oligomenorrhea ,3 % had amenorrhea and 42% had none. Associated features were highly Significant (P≤0.01), highly percentage was 39% acne, the low percentage was 6% Alopecia and Acne while 47% of them were none. About 90% of all patients had TSH>0.5(U/mL) while 10 % had TSH <=0.5(U/mL). The mean total serum testosterone level and free testosterone were 0.598 in 72%, 27.69 in 83% of the patients respectively. The mean serum prolactin level was 24.82 but the mean serum DHEA-S (µg/dL) were 328.62 in all patients. A family history was found in 40% of the patients. conclusion: In the current study the clinical characteristics of Hirsitusm was more common in women with a high Body Mass Index nearly a half of them. The most Associated features in hirsute women was Acne and Alopecia. Also more than half of them had oligomenorrhea. While a Biochemical Characteristics study revealed that 90% of hirsute women had hypothyroidism, There is a 37% increase in DHEAS levels, a 72% increase in total testosterone, and a 35% increase in prolactin. The prolactin and total serum testosterone level elevation were not severe. About 40% of the patients had a family history.

Protein-enriched soup and weekly exercise improve muscle health: A randomized trial in mid-to-old age with inadequate protein intake.

Prior research has highlighted the synergistic impact of protein supplementation on muscle function post-exercise in adults; however, evidence supporting the combined effects were less robust and inconsistent on those with protein insufficiency. This investigation aims to explore efficacy of protein-enriched soup coupled with exercise on muscle health and metabolism in middle-aged and older adults with suboptimal protein intake. An open-label, 12-week, randomized controlled trial involving participants with insufficient protein intake (<1.0g/kg/day) was done. The intervention group consumed protein-enriched soup (24-30g protein daily) and 1-h weekly exercise, while controls received health education. Assessments included laboratory tests, functional assessments, and body composition. In this trial, 97 out of 100 randomized participants (mean age: 64.65±4.84years, 81.8% female) completed the study (47 in intervention group and 50 in control group). Compared results of baselines, at 1 and 3months of intervention, significant improvements in waist circumference (83.48±10.22 vs. 82.5±9.88 vs. 82.37±9.42cm, P for trend=0.046), 6-min walking distance (525.65±58.46 vs. 534.47±51.87 vs. 552.02±57.66m, P for trend=0.001), five-time sit-to-stand time (7.63±1.63 vs. 6.81±1.8 vs. 6.4±1.42s, P for trend <0.001), grip strength (26.74±6.54 vs. 27.53±6.99 vs. 28.52±7.09kg, P for trend <0.001), and MNA score (26.8±2.14 vs. 27.73±1.74 vs. 27.55±1.72, P for trend <0.001) were discerned within the intervention group. The intervention demonstrated a significant reduction in serum triglyceride (105.32±49.84 vs. 101.36±42.58 vs. 93.43±41.49mg/dL, P for trend=0.023), increased HDL-C (60.04±16.21 vs. 60±17.37 vs. 62.55±18.27mg/dL, P for trend=0.02), and DHEA-S levels (97.11±54.39 vs. 103.39±56.75 vs. 106.83±60.56μg/dL, P for trend=0.002). Serum myostatin did not differ in both groups, but serum leptin levels significantly increased (9118.88±5811.68 vs. 11508.97±7151.08 vs. 11220.80±7190.71pg/mL, P for trend=0.016) in controls. The intervention group showed greater improvements in 6min walking distance (β=0.71, 95% CI: 6.88 to 40.79, P=0.006), five-time sit-to-stand test (β=-0.87, 95% CI: -1.59 to -0.15, P=0.017), MNA score (β=0.96, 95% CI: 0.20 to 1.71, P=0.013), serum triglycerides (β=-15.01, 95% CI: -27.83 to -2.20, P=0.022), LDL-C (β=-9.23, 95% CI: -16.98 to -1.47, P=0.020), and DHEA-S levels (β=9.98, 95% CI: 0.45 to 19.51, P=0.04) than controls. Protein-enriched soup with weekly exercise over 12weeks significantly improved physical performance, lipid profile, and DHEA-S levels among middle-aged and older adults with inadequate protein intake, while studies assessing long-term benefits of the intervention are needed.

IL-18BP Therapy Ameliorates Reproductive and Metabolic Phenotypes in a PCOS Mouse Model by Relieving Inflammation, Fibrosis and Endoplasmic Reticulum Stress.

There is a chronic inflammation in PCOS patients, which is correlated with the pathogenesis of PCOS. IL-18 and IL-18BP are related with some inflammatory diseases, while less explored in PCOS. Whether IL-18BP could be a potential drug of PCOS remains unknown.IL-18 and testosterone levels were evaluated in serum of 10 non-PCOS control patients and 20 PCOS patients. Female C57/BL6 mice were gavaged with letrozole to induce PCOS mouse model and IL-18 level was evaluated in the serum of PCOS mouse model, and IL-18 is intraperitoneally injected in female mice, IL-18BP is intraperitoneally injected in the PCOS mice models. Then the body weights, estrous cycles, reproductive hormones and morphology of ovaries were analyzed. The level of ovarian chronic inflammation, fibrosis and endoplasmic reticulum (ER) stress are evaluated.IL-18 levels are increased in the serum of PCOS patients and PCOS mice models respectively. The serum DHEAS, iWAT weight and adipocyte size were increased in IL-18 group compared to the control group (P < 0.05). In the PCOS mouse model treated with IL-18BP, the body weight and serum LH/FSH ratio was decreased compared to the PCOS group (P < 0.05). The expression levels of inflammatory factors and fibrosis-related genes, the expression level of endoplasmic reticulum stress-related genes, and the ROS positive area of ovarian tissue was decreased (P < 0.05).IL-18 is involved in inducing PCOS phenotypes, while IL-18BP relieves PCOS phenotypes by alleviating ovarian chronic inflammation, fibrosis and ER stress in PCOS mice.

Folliculogenesis and steroidogenesis alterations after chronic exposure to a human-relevant mixture of environmental toxicants spare the ovarian reserve in the rabbit model

BackgroundIndustrial progress has led to the omnipresence of chemicals in the environment of the general population, including reproductive-aged and pregnant women. The reproductive function of females is a well-known target of endocrine-disrupting chemicals. This function holds biological processes that are decisive for the fertility of women themselves and for the health of future generations. However, insufficient research has evaluated the risk of combined mixtures on this function. This study aimed to assess the direct impacts of a realistic exposure to eight combined environmental toxicants on the critical process of folliculogenesis.MethodsFemale rabbits were exposed daily and orally to either a mixture of eight environmental toxicants (F group) or the solvent mixture (NE group, control) from 2 to 19 weeks of age. The doses were computed from previous toxicokinetic data to reproduce steady-state serum concentrations in rabbits in the range of those encountered in pregnant women. Ovarian function was evaluated through macroscopic and histological analysis of the ovaries, serum hormonal assays and analysis of the expression of steroidogenic enzymes. Cellular dynamics in the ovary were further investigated with Ki67 staining and TUNEL assays.ResultsF rabbits grew similarly as NE rabbits but exhibited higher total and high-density lipoprotein (HDL) cholesterol levels in adulthood. They also presented a significantly elevated serum testosterone concentrations, while estradiol, progesterone, AMH and DHEA levels remained unaffected. The measurement of gonadotropins, androstenedione, pregnenolone and estrone levels yielded values below the limit of quantification. Among the 7 steroidogenic enzymes tested, an isolated higher expression of Cyp19a1 was measured in F rabbits ovaries. Those ovaries presented a significantly greater density/number of antral and atretic follicles and larger antral follicles without any changes in cellular proliferation or DNA fragmentation. No difference was found regarding the count of other follicle stages notably the primordial stage, the corpora lutea or AMH serum levels.ConclusionFolliculogenesis and steroidogenesis seem to be subtly altered by exposure to a human-like mixture of environmental toxicants. The antral follicle growth appears promoted by the mixture of chemicals both in their number and size, potentially explaining the increase in atretic antral follicles. Reassuringly, the ovarian reserve estimated through primordial follicles number/density and AMH is spared from any alteration. The consequences of these changes on fertility and progeny health have yet to be investigated.

The association between female sexual function and metabolic features of the polycystic ovary syndrome in Turkish women of reproductive age

Objective To investigate the association between female sexual function and metabolic features among women with polycystic ovary syndrome (PCOS) during reproductive age. Method This was a cross-sectional study in which 288 women with PCOS and 180 women without PCOS between the ages of 20 and 40 years were evaluated. All women had serum total testosterone, androstenedione, DHEA-S, fasting glucose, total cholesterol, HDL-C, LDL-C, and triglyceride levels analyzed. The McCoy Female Sexual Questionnaire (MFSQ) was applied to all studied women. Exploratory factor analysis and reliability analysis were done after data collection. The factor loadings of MFSQ domains were compared between women with PCOS and controls. Results Average factor loadings of the MFSQ sexuality domain and MFSQ sexual partner domain were significantly lower in the PCOS group when compared to controls. There was no correlation between the two sexual function domains of the MFSQ and the PCOS features either in the PCOS group or the controls. Conclusion PCOS is a heterogeneous disease with different metabolic components, such as insulin resistance, obesity, and hyperandrogenism. Although sexual function among women with PCOS was lower than controls, no differences were found in metabolic features of the PCOS and non-PCOS groups with relation to sexual function determined by the MFSQ.

Predictors of bone mineral density in patients receiving glucocorticoid replacement for Addison's disease.

Patients receiving long-term glucocorticoid (GC) treatment are at risk of osteoporosis, while bone effects of substitution doses in Addison's disease (AD) remain equivocal. The project was aimed to evaluate serum bone turnover markers (BTMs): osteocalcin, type I procollagen N-terminal propeptide (PINP), collagen C-terminal telopeptide (CTX), sclerostin, DKK-1 protein, and alkaline phosphatase (ALP) in relation to bone mineral density (BMD) during GC replacement. Serum BTMs and hormones were assessed in 80 patients with AD (22 males, 25 pre- and 33 postmenopausal females) on hydrocortisone (HC) substitution for ≥3 years. Densitometry with dual-energy X-ray absorptiometry covered the lumbar spine (LS) and femoral neck (FN). Among BTMs, only PINP levels were altered in AD. BMD Z-scores remained negative except for FN in males. Considering T-scores, osteopenia was found in LS in 45.5% males, 24% young and 42.4% postmenopausal females, while osteoporosis in 9.0%, 4.0% and 21.1%, respectively. Lumbar BMD correlated positively with body mass (p = 0.0001) and serum DHEA-S (p = 9.899 × 10-6). Negative correlation was detected with HC dose/day/kg (p = 0.0320), cumulative HC dose (p = 0.0030), patient's age (p = 1.038 × 10-5), disease duration (p = 0.0004), ALP activity (p = 0.0041) and CTX level (p = 0.0105). However, only age, body mass, ALP, serum CTX, and sclerostin remained independent predictors of LS BMD. Standard HC substitution does not considerably accelerate BMD loss in AD patients and their serum BTMs: CTX, osteocalcin, sclerostin, DKK-1, and ALP activity remain within the reference ranges. Independent predictors of low lumbar spine BMD, especially ALP activity, serum CTX and sclerostin, might be monitored during GC substitution.

Dopamine as a potential diagnostic biomarker in women's sexual dysfunction.

Dopamine and prolactin are the key mediators involved in sexual function in both males and females, but the role of dopamine in female sexual dysfunction (FSD) is still unclear. The aim was to investigate the possible role of dopamine and their relationship with sex steroid hormones (estrogen, progesterone and dehydroepiandrosterone; DHEA) and prolactin levels in Egyptian women suffering from sexual dysfunction. This study included 84 women having sexual dysfunction (FSD group) and 84 normal sexual function (control group). All women were subjected to the questionnaire to assess their demographic and gynecological data as well as female sexual function index (FSFI). Blood samples were collected from all women for measuring serum estradiol, progesterone, DHEA, prolactin and dopamine levels. FSD patients had significantly higher serum progesterone and DHEA and prolactin levels; while significantly lower dopamine and estradiol levels versus controls (p < 0.001). In all women, dopamine level appeared as a predictor of FSD at cut-off point ≤8.8 ng/mL with sensitivity (75%), specificity (92%) and accuracy (83%) (p < 0.001). The low levels of dopamine were associated with significantly higher prevalence in patients with low estradiol (p < 0.001) and high progesterone (p < 0.001), DHEA (p < 0.001) and prolactin (p = 0.004). Also, dopamine was significantly positive correlation with arousal score (r = 0.16, p = 0.04), and negative correlation with age (r = -0.31, p < 0.001), pain score (r = -0.19, p = 0.01), DHEA (r = -0.45, p < 0.001) and prolactin (r = -0.28, p < 0.001). Low serum dopamine level is a potential diagnostic biomarker in women's sexual dysfunction and their association with high prolactin and sex steroid hormones dysfunction.

High level of psychological stress in COVID-19 recovered individuals: role of copeptin as a potential biomarker.

Study aimed to assess stress in COVID-19 recovered individuals using a validated questionnaire PSS-10 score and stress biomarkers - salivary cortisol and serum copeptin. A total of 83 subjects of which 54 subjects (66.3%) who were hospitalized were recruited 8-20 weeks following recovery from COVID-19. Stress was assessed by PSS-10 stress-scale after a mean duration of 14.5 weeks after recovery. Sixty-eight subjects (81.9%) had new or persistent symptoms after recovery. Subjects were divided into two groups on the basis of PSS score; mild stress (PSS:0-13) and moderate to severe stress (PSS:>14) and levels of biomarkers (serum copeptin, DHEAS and salivary cortisol) were compared in the two groups. Forty-four subjects (53%) had moderate to severe stress and 39 subjects (47%) had mild stress. Subjects with post COVID symptoms had significantly higher stress levels as compared to subjects who were asymptomatic [15 vs. 9; p = 0.003]. Serum copeptin levels were significantly higher among subjects with moderate to severe stress as compared to those with mild stress [0.41 vs. 0.67 ng/mL; p = 0.031]. Subjects with moderate to severe stress had higher median salivary cortisol compared to subjects with mild stress [1.03 vs. 1.44 nmol/L; p = 0.448]. Our study demonstrated moderate to severe stress in over half and some level of stress in nearly all COVID recovered individuals even after 3 months. Serum copeptin was found to be a useful biomarker to objectively measure stress in these subjects.

The impact of menopause and serum DHEA-S level on the severity of Covid-19

ObjectivesWe aimed to demonstrate the difference between premenopausal and postmenopausal women in respect of the clinical course and outcomes of Covid-19. We investigated the epidemiological and hormonal factors which influence the severity of the disease. Study designThis observational cross-sectional study included the female patients admitted to a Covid-19 outpatient clinic between July 2020 and June 2021 and diagnosed with a positive polymerase chain reaction test. Blood samples were obtained to determine the serum levels of follicle stimulating hormone, luteinizing hormone, estradiol, total testosterone and dehydroepiandrosterone sulfate. Main outcome measureOur primary outcome was the poor clinical course of the disease in postmenopausal women. Our secondary outcome was the contribution of hormonal status to the clinical course of the disease. ResultsOur cohort consisted of 253 female patients (85 with mild, 125 with moderate and 43 with severe disease; 101 at the premenopausal and 152 at the postmenopausal stage). There was a statistically significant difference between the patients in different severity groups regarding clinical data and serum levels of luteinizing hormone, follicle stimulating hormone, estradiol and dehydroepiandrosterone sulfate. Being one year younger decreased the odds of having severe Covid-19 0.338-fold relative to the group with mild disease. A decrease in the serum dehydroepiandrosterone sulfate level was associated with a 2.604-fold increase in the odds of having severe Covid-19 relative to the group with mild disease. Being postmenopausal increased the odds of having severe disease compared with mild disease by 2.687-fold. ConclusionsThe prognosis of Covid-19 is more favorable in premenopausal women compared with postmenopausal women. Age, postmenopausal status and serum levels of dehydroepiandrosterone sulfate are important predictors of the severity of Covid-19 for women.

THU015 Unilateral Adrenal Hyperplasia Causing ACTH-independent Hypercortisolism

Abstract Disclosure: N. Mogar: None. M.A. McConnell : None. R. Yu: None. J.E. Weinreb: None. Background: Adrenal cortical hyperplasia is defined radiographically as a non-malignant growth or enlargement of the adrenal glands. Adrenal hyperplasia is most commonly bilateral, with unilateral adrenal hyperplasia occurring less frequently. Unilateral adrenal hyperplasia has been associated with primary hyperaldosteronism, and there are only a few case reports describing unilateral adrenal hyperplasia associated with ACTH-independent hypercortisolism. Clinical Case: A 56-year-old man with sleep apnea was incidentally found to have a 4.6 cm left adrenal nodule found on computed tomography (CT) chest imaging. Adrenal CT revealed a heterogeneous 4.6 x 3.3 x3.7 cm left adrenal mass with internal calcifications and a portion of the mass measuring 38 Houndsfield units (HU). His 8AM serum cortisol level was 19.80 mcg/dL (5-23 mcg/dL). No ACTH level was collected; however, a serum DHEA-S level was 55 mcg/dL (32-240 mcg/dL). After low dose dexamethasone suppression test (LDDS), the serum cortisol level was elevated at 2.3 mcg/dL (&amp;lt;1.8 mcg/dL). Repeat LDDS revealed a cortisol level of 2.9 mcg/dL. A 24-hour urine free cortisol level was 27.2 mcg/24h (4-50 mcg/24h). Testing for pheochromocytoma and hyperaldosteronism was negative. The patient had no historical or physical signs of Cushing’s syndrome and no signs of malignancy. Due to concerning features on adrenal CT imaging (tumor size &amp;gt;4 cm, internal calcifications, and HU &amp;gt;10), the patient underwent unilateral adrenalectomy. The patient did not receive intraoperative corticosteroids and remained normotensive post-operatively. However, his post-operative 8AM cortisol level was &amp;lt;0.2 mcg/dL (5-23 mcg/dL) on two separate occasions. He was discharged on a short course of hydrocortisone, with eventual recovery of his hypothalamic-pituitary-adrenal (HPA) axis. Pathology revealed a diagnosis of cortical adrenal hyperplasia. Conclusion: The presence of postoperative hypocortisolemia demonstrates that this patient had ACTH-independent hypercortisolism. This case report would be one of few describing the rare diagnosis of unilateral adrenal hyperplasia associated with ACTH-independent hypercortisolism and would add to the sparse literature currently available on this condition. Additionally, this case report highlights the clinical significance of mild autonomous cortisol secretion (MACS); despite only having an unsuppressed cortisol level following LDDS, this patient was found to have a suppressed HPA axis after unilateral adrenalectomy requiring corticosteroids. Early identification and treatment of MACS and treatment of adrenal insufficiency following adrenalectomy is essential to prevent adverse events. Presentation: Thursday, June 15, 2023

FRI402 “An Unusual Presentation Of Polycystic Ovary Syndrome” - Isolated DHEA-S Elevation In A Patient With Difficulty Conceiving And Recent Onset of Hirsutism

Abstract Disclosure: C. Musurakis: None. J.L. Gilden: None. Background: Isolated DHEA-S levels and worsening hirsutism often prompt the clinician to investigate more serious causes for the elevation, such as an adrenal mass. Clinical Case: A 29-year-old female G0P0 with Norwegian and English heritage and familial hypertriglyceridemia, was referred for elevated DHEA-S levels, and difficulty conceiving for past three years. She had hirsutism of face, chest, and abdomen, worsening over the last two years. Acne had also progressively worsened to cystic type. Menarche was at age 12, and menses were regular. She had never used contraception. Medications: docosahexanoic acid, eicosapentanoic acid, topical azelaic acid, benzoyl peroxide, clindamycin, pantoprazole, prenatal vitamins, and cholecalciferol. There was a family history of acne, but not for hirsutism or menstrual irregularities. Vitals: BP 137/73, HR 81, Ht 165.10 cm, Wt 86.18 Kg, BMI 31.68. Ferriman-Gallwey score was 10 with normal genitalia. Labs (luteal phase): DHEA-S 756 mcg/dL with repeat of 596 mcg/dl(n=35-430), total testosterone 25 ng/dL(n=2-45), free testosterone 4.3 pg/mL(n=0.1-6.4), prolactin 6.6 ng/mL(n=2.2-30.3), LH 5.1 mIU/mL(n=0.6-16.6), FSH 4.7 mIU/mL(n=1.7-12.9), 17-OH progesterone 74 ng/dL(n=139-431), androstenedione 163 ng/dL(n=73-184), estradiol 59.79 pg/mL(n=55.8-214.2), AMH 1.38 ng/mL(n=0.69-13.39), midnight salivary cortisol &amp;lt;0.03 and 0.05 mcg/dL(n&amp;lt;5), IGF-1 258 ng/mL(n=63-373), ACTH 31 pg/mL(n=0-47), AM cortisol 12.58 ug/dL(n=5.3-22.5), TSH 1.27 uIU/mL(n=0.358-3.74), Free T4 0.88 ng/dL (n=0.76-1.46), peroxidase antibodies 49.8 U/m (n=0-60), thyroglobulin antibodies &amp;lt;15(n=0-60), HbA1c 5.5% (n&amp;lt;=5.6%), 25-OH vitamin D 42.7 ng/mL(n=30-100) and negative pregnancy urine test. US pelvis: small follicles in ovaries and normal size. MRI abdomen w/wo contrast: normal bilateral adrenal glands. Cosyntropin stimulation test: baseline cortisol 15.03 ug/dL,17-OH progesterone 168 ng/dL. 30 mins: Cortisol 30.39ug/dL(n&amp;gt;18),17-OH progesterone 130ng/dL(n&amp;lt;200). 60 mins: cortisol 38.95ug/dL(n&amp;gt;18), 17-OH progesterone 153ng/dL(n&amp;lt;200). Non-Classical Congenital Adrenal Hyperplasia was excluded. Polycystic Ovary Syndrome (PCOS) was diagnosed based on clinical and biochemical hyperandrogenism, lack of adrenal mass, and clinical signs of anovulation. Conclusion: As reported by Carmina et al, few patients with PCOS exhibit isolated increase of serum DHEA-S. It is important to recognize that non-classic forms of PCOS (normal ovaries or normal ovulatory cycles) can present with a higher prevalence of adrenal hyperandrogenism than the common classical forms of PCOS. Reference: Carmina E, Longo RA. Increased Prevalence of Elevated DHEAS in PCOS Women with Non-Classic (B or C) Phenotypes: A Retrospective Analysis in Patients Aged 20 to 29 Years. Cells. 2022 Oct 17;11(20):3255. doi: 10.3390/cells11203255. PMID: 36291122; PMCID: PMC9601254. Presentation: Friday, June 16, 2023

The Hormonal Status Comparison of Unilateral and Bilateral Adrenal Adenomas: Are They the Same?

Objective: It is not yet clear whether unilateral/bilateral adenomas are different in terms of both functionality and etiology. We investigated whether there were differences in hormonal profiles and evaluate the cortisol secretion profiles of unilateral and bilateral adenomas. Methods: Hormonal secretory profiles and clinical features of patients with adenomas were collected. Detailed evaluation was made in terms of hypercortisolemia. Results: Of the 184 patients examined, 140 had unilateral and 44 had bilateral adenomas. 73% of the patients were female and the mean body mass index was 34±8.1kg/m2. The mean age was 57.1±9.8 years. The average size of the adrenal masses was 23.3±10.5mm. While 83% of the evaluated adenomas were nonfunctional, ACS was found in 11% (n:20), hyperaldosteronism in 4% (n:8), and pheochromocytoma (PCC) in 2% (n:3) of the patients. The prevalence of ACS in bilateral/unilateral adenomas was 20.5%/7.9%, respectively. While serum adrenocorticotropic hormone level (25.6±16.6vs19.3±15µg/dL), urinary free cortisol level (162.3±108.3vs243.3±234.2µg/day), and low-dose-dexamethasone-suppression-test results (1.6±1.9vs1.73±1.7µg/dL) were not statistically different, the only difference between unilateral and bilateral adenomas was in serum DHEA-S level (141.4±85vs77.7±73.8 µg/dL, p:0.003). Conclusion: Although there is no significant difference between the two groups in terms of clinical findings, it is clear that ACS is more prevalent in bilateral adenomas than unilateral. Because of the negative effects of long-term hypercortisolism, precise management of ACS is noteworthy. The evaluation of ACS should be done more carefully in bilateral adenomas considering that ACS is more in bilateral adenomas than unilateral. According to our findings, we also suggest that DHEA-S may be an indicator for ACS.

Association between contralateral adrenal and hypothalamus-pituitary-adrenal axis in benign adrenocortical tumors.

Adrenal incidentaloma (AI) is commonly discovered on cross-sectional imaging. Mild autonomous cortisol secretion is the most common functional disorder detected in AI. To delineate the association between radiological characteristics of benign adrenocortical tumors and hypothalamus-pituitary-adrenal (HPA) axis. In the study, 494 patients diagnosed with benign unilateral adrenocortical tumors were included. Mild autonomous cortisol secretion (MACS) was diagnosed when cortisol after 1mg-dexamethasone suppression test (1-mg DST) was in the range of 1.8-5ug/dl. Non-functional adrenocortical tumor (NFAT) was diagnosed as cortisol following 1-mg DST less than 1.8ug/dL. We performed Logistics regression and causal mediation analyses, looking for associations between radiological characteristics and the HPA axis. Of 494 patients, 352 (71.3%) with NFAT and 142 (28.7%) with MACS were included. Patients with MACS had a higher tumor diameter, thinner contralateral adrenal gland, and lower plasma ACTH and serum DHEAS than those with NFAT. ACTH (OR 0.978, 0.962-0.993) and tumor diameter (OR 1.857, 95%CI, 1.357-2.540) were independent factors associated with decreased serum DHEAS (all P<0.05). ACTH was also associated with decreased contralateral adrenal diameter significantly (OR 0.973, 95%CI, 0.957-0.988, P=0.001). Causal mediation analysis showed ACTH mediated the effect significantly for the association between 1-mg DST results and DHEAS level (Pmediation<0.001, proportion=22.3%). Meanwhile, we found ACTH mediated 39.7% of the effects of 1-mg DST on contralateral adrenal diameter (Pmediation=0.012). Patients with MACS had thinner contralateral adrenal glands and disturbed HPA axes compared with NFAT. ACTH may partially be involved in mediating the mild autonomous cortisol secretion to DHEAS and the contralateral adrenal gland.

Is the 1mg-dexamethasone suppression test a precise marker of glucocorticoid excess and cardiometabolic risk in patients with adrenal incidentalomas?

To analyze if the 1mg-dexamethasone suppression test (DST) is a reliable marker of glucocorticoid excess and cardiometabolic risk in patients with adrenal incidentalomas (AIs). Cross-sectional study of patients with nonfunctioning adrenal incidentalomas (NFAIs, defined by cortisol post-DST ≤ 1.8 µg/dL) and patients with autonomous cortisol secretion (ACS, defined by cortisol post-DST > 1.8 µg/Dl). The urinary steroid profile (USP) was determined by gas chromatography coupled to mass spectrometry. Both groups were matched by sex, age and body mass index. Forty-nine patients with AIs (25 with ACS and 24 with NFAI) were included. As a whole, AIs showed a high excretion of β-cortolone, tetrahydro-11-deoxycortisol (THS), α-cortolone, α-cortol, tetrahydrocortisol (THF) and tetrahydrocortisone (THE). A positive yet modest correlation between post-DST cortisol and total excretion of glucocorticoid metabolites (r = 0.401, P = 0.004) was observed, with the stronger being observed with total THS (r = 0.548, P < 0.001) and THF (r = 0.441, P = 0.002). Some of the metabolites that were elevated in patients with AIs, were higher in patients with ACS-related comorbidities than in those without comorbidities. Post-DST cortisol showed a fair diagnostic accuracy for the prediction of ACS-related comorbidities (AUC 0.767 [95% CI 0.634-0.882]). However, post-DST diagnostic accuracy improved when combined with urinary cortisone, α-cortol, THS and serum DHEAS (0.853 [0.712‒0.954]). The DST has a positive, but modest, correlation with urinary glucocorticoid excretion. Similarly, the diagnostic accuracy of the DST for the prediction of ACS-related comorbidities is only fair, but it may be improved if combined with the results of the USP and serum DHEAS. This is the first study aimed to evaluate if 1mg-dexamethasone suppression test (DST) is a reliable marker of glucocorticoid excess and cardiometabolic risk in patients with adrenal incidentalomas (AIs) and if urinary steroid profile was measured by GS-MS could improve such a prediction. We found a positive yet modest correlation between post-DST cortisol and total excretion of glucocorticoid metabolites, with the stronger being observed with total tetrahydro-11-deoxycortisol (THS) and tetrahydrocortisol. Post-DST cortisol showed a fair diagnostic accuracy for the prediction of ACS-related comorbidities (AUC 0.767). However, post-DST diagnostic accuracy improved when combined with urinary cortisone, α-cortol, THS and serum DHEAS (0.853).

Association of Sex Hormones and Androgens with Disease Activity in Premenopausal Females with Rheumatoid Arthritis.

Gonadal sex hormone dysfunction is frequently reported in patients with Rheumatoid arthritis (RA). The relationship of these hormones with disease activity is still not clear and whether the hormone imbalance leads to increased severity of RA is not well studied in this part of the world. The present study aimed to elucidate this fact. It was a cross-sectional observational study performed in 80 premenopausal females with definite RA at a tertiary care hospital in New Delhi, India over one year. Patients were subjected to investigations as per the protocol and a fasting venous blood sample for hormone levels was collected in the follicular phase of their menstrual cycle. A statistically significant correlation by linear logistic regression analysis was found between disease activity (as measured by DAS28) and serum progesterone, FSH, and prolactin, while serum testosterone and DHEAS showed an inverse relationship with disease activity. Low s. prolactin, and s. FSH as well as high s. testosterone and s. DHEAS were found to be associated with target clinical goals in RA (ie, remission and low disease activity). On multivariate logistic regression analysis, serum prolactin showed a direct association. (p=0.016, OR= 1.009. C.I.= 1.0021.017) and serum testosterone were found to have an inverse relationship (p=0.002, OR= 0.017, C.I.=0.001-0.237) with disease activity in this group of individuals. Serum levels of sex hormones may be helpful in predicting disease activity among patients with RA, and in future, may be used to guide treatment of severe refractory disease, unresponsive to conventional treatment with DMARDs, especially in resource-poor settings.

Endocrine Dysfunc-Tion Among Patients with Covid-19: A Experience from Tertiary Hospital in Bangladesh

Background: Endocrine systems are vulnerable to destruction and dysfunction by coronavirus disease 2019 (COVID-19). Data regarding the follow-up status of hormones following the recovery are scarce in the literature. The aim of the study to evaluate hormone levels and statuses among noncritically ill patients with COVID-19 during and three months after acute infection. Methods: This longitudinal study was done in a tertiary care hospital from September 2021 to February 2022 among 91 noncritical RT-PCR-confirmed COVID-19 patients. After taking relevant history and performing physical examinations, blood was drawn between 07:00 am to 09:00 am in a fasting state to measure serum TSH, FT4, total testosterone (TT), DHEAS, cortisol, and plasma ACTH during hospitalization and after three months. All the hormones were measured by chemiluminescent microparticle immune assay. Results: During admission,19.8% of participants had adrenal insufficiency (&lt;276 nmol/L) and 28.0% had different types of thyroid function abnormalities. Among 37 males, 8.1% had low TT and 29.7% had low DHEAS. Among 54 females, 27.8% had high TT and 7.4% had low and 3.7% had high DHEAS. Among 91, 8 died, 68 were lost to follow-up, and follow-up hormone levels were available for only 15 participants. The number of participants with adrenal insufficiency increased from 1 to 7. During admission, 7 patients had various types of thyroid function abnormalities which reduced to only three cases including two cases of primary hypothyroidism. While TT and DHEAS status deteriorated in males, increased hyperandrogenemia status was observed in females. Conclusion: Adrenal insufficiency is common during shortterm follow-up periods even in noncritical cases of COVID-19 whereas most of the patients with thyroid function abnormalities recovered. A sex-specific opposite response was observed in androgen status. J Medicine 2023; Vol. 34, No. 2(1) Supplement: 218

Differential methylation pattern in pubertal girls associated with biochemical premature adrenarche

ABSTRACT Biochemical premature adrenarche is defined by elevated serum DHEAS [≥40 μg/dL] before age 8 y in girls. This condition is receiving more attention due to its association with obesity, hyperinsulinemia, dyslipidemia, and polycystic ovary syndrome. Nevertheless, the link between early androgen excess and these risk factors remains unknown. Epigenetic modifications, and specifically DNA methylation, have been associated with the initiation and progression of numerous disorders, including obesity and insulin resistance. The aim of this study was to determine if prepubertal androgen exposure is associated with a different methylation profile in pubertal girls. Eighty-six healthy girls were studied. At age 7 y, anthropometric measurements were begun and DHEAS levels were determined. Girls were classified into Low DHEAS (LD) [<42 μg/dL] and High DHEAS (HD) [≥42 μg/dL] groups. At Tanner stages 2 and 4 a DNA methylation microarray was performed to identify differentially methylated CpG positions (DMPs) between HD and LD groups. We observed a differential methylation pattern between pubertal girls with and without biochemical PA. Moreover, a set of DNA methylation markers, selected by the LASSO method, successfully distinguished between HD and LD girls regardless of Tanner stage. Additionally, a subset of these markers were significantly associated with glucose-related measures such as insulin level, HOMA-IR, and glycaemia. This pilot study provides evidence consistent with the hypothesis that high DHEAS concentration, or its hormonally active metabolites, may induce a unique blood methylation signature in pubertal girls, and that this methylation pattern is associated with altered glucose metabolism.

Changes in hormones, Leukocyte Telomere Length (LTL), and p16INK4a expression in SM-exposed individuals in favor of the cellular senescence

Sulfur mustard (SM) is a chemical warfare agent with well-known severe toxic effects and may cause long-term debilitating injuries. We aimed to evaluate aging and longevity in Iranian SM-exposed survivors using some endocrine and molecular biomarkers for the first time. Dehydroepiandrosterone (DHEA), prolactin (PRL), cortisol, testosterone, and luteinizing hormone (LH) were measured in 289 male SM-veterans and 66 age-matched males using the ELISA method. Leukocyte Telomere Length (LTL) measurement and p16INK4a expression were measured in the peripheral blood leukocytes of 55 males who were exposed to SM. We found a significantly lower serum DHEAS level and higher serum PRL level in SM-exposed groups (without any related to the severity of lung injuries) compared to healthy controls, but no significant difference in serum levels of cortisol, testosterone, and LH. The molar ratio of DHEAS/cortisol was significantly higher in controls compared to the SM-exposed individuals especially those with severe lung damage. Some biological parameters of allostatic load score such as DHEAS and DHEAS/cortisol ratio significantly decreased long-term after the SM exposure. Additionally, we found that LTL was shorter in SM-exposed veterans rather than unexposed controls while p16INK4a gene expression significantly increased in these groups. It seems that DHEAS, DHEAS/cortisol ratio, LTL, and p16INK4a gene expression have changed significantly in favor of cellular senescence in SM-exposed patients. Therefore, it seems that SM exposure increases biological age compared to chronological age in SM-exposed survivors.