Serum Adrenocorticotropic Hormone Research Articles

Melatonin counteracts polyethylene microplastics induced adreno-cortical damage in male albino rats

There are various substances that can disrupt the homeostatic mechanisms of the body, defined as endocrine-disrupting chemicals (EDCs). The persistent nature of microplastics (MPs) is a cause for concern due to their ability to accumulate in food chains and widespread use, making their toxic effects particularly alarming. The potential of MPs for disrupting the endocrine system was observed in multiple tissues. Moreover, the adrenal gland is known to be extremely sensitive to EDCs, while with the effect of MPs on the adrenal gland has not previously been studied. This study aimed to highlight the potential polyethylene microplastics (PE-MPs) induced adreno-toxic effects rather than exploring the implicated mechanisms and concluding if melatonin (Mel) can afford protection against PE-MPs induced adreno-toxicity. To fulfill the goal, six groups of rats were used; control, Mel, PE-MPs (3.75 mg/kg), PE-MPs (15 mg/kg), PE-MPs (3.75 mg/kg) +Mel, and PE-MPs (15 mg/kg) +Mel. PE-MPs induced toxic changes in the adrenal cortex, which was evident by increased adrenal weight, histopathological examination, and ultrastructural changes detected by electron microscope. A reduction in serum cortisol and an increase in serum adrenocorticotropic hormone resulted from the adreno-toxic effects of PE-MPs. Mechanisms may include the reduction of steroidogenesis-related genes, as PE-MPs drastically reduce mRNA levels of StAR, Nr0b1, Cyp11A1, as well as Cyp11B1. Also, oxidative stress that results from PE-MPs is associated with higher rates of lipid peroxidation and decreased superoxide dismutase and glutathione. PE-MPs inflammatory effect was illustrated by elevated expression of IL-1β and NF-ķB, detected by immunohistochemical staining, in addition to increased expression of caspase-3 and mRNA of Bax, markers of proapoptotic activity. The impacts of PE-MPs were relatively dose-related, with the higher dose showing more significant toxicity than the lower one. Mel treatment was associated with a substantial amelioration of PE-MPs-induced toxic changes. Collectively, this study fills the knowledge gap about the MPs-induced adrenal cortex and elucidates various related toxic mechanisms. It also supports Mel’s potential protective activity through antioxidant, anti-inflammatory, anti-apoptotic, and gene transcription regulatory effects.

Effects of noise exposure on stress hormone changes during task performance in young Korean men: quasi-experimental study

ABSTRACT Numerous studies have suggested that noise exposure might be associated with changes in stress hormone levels. However, quantitative evidence for these effects in humans is rare and remains controversial. This study aimed to investigate the acute effects of exposure to noise and its different levels on stress hormone changes in task performance. Quasi-experimental noise exposure environment was established for 90 male university student volunteers in their twenties, and each was exposed to different noise levels during task performance. The stress hormones tested included cortisol, adrenocorticotropic hormone (ACTH), adrenaline, and noradrenaline. A one-way ANOVA was performed to investigate differences in hormone levels measured in the three groups according to the noise exposure levels (35, 45, or 75 dB). Analysis of covariance (ANCOVA) was used to adjust for confounding factors that might affect hormone levels. After adjusting for confounders, significant exposure-dependent differences were found in hormone levels in salivary cortisol, serum cortisol, serum ACTH, and serum adrenaline. The amount of hormonal increase in 75 dB exposure group compared to 35 or 45 dB groups was detected. Similar results were also seen in the rate of change analysis. Our findings indicate that short-term noise exposure during task performance elevates stress hormone levels. Further, the extent of stress hormone alterations varies with noise exposure levels. Changes in hormone levels are an objective measure that may be used to identify health effects and stress responses in various noise environments.

Tao-Hong-Si-Wu-Tang Improves the Depressive-like Behaviors in Mice Experiencing Perimenopausal Depression Through Modulating Activity of the Hypothalamic-Pituitary-Adrenal-Ovary Axis and Activating the BDNF-TrkB-CREB Signaling Pathway.

Tao-Hong-Si-Wu-Tang (THSWT), a traditional Chinese herbal remedy, is commonly utilized for the treatment of female perimenopausal depression through regulating menstruation, but the mechanism remains unknown. In this study, ICR mice were randomly divided into six groups: low, medium, and high dose of THSWT (0.5, 1.5, and 4.5 g/kg), soy isoflavone (250 mg/kg), ovariectomy group, and control group. All mice, except the control group, had ovaries removed and were exposed to hypoxic stimulation for 28 days to establish a perimenopausal depression mice model. The mice, having unrestricted access to food and water, were administered THSWT treatment for a duration of 14 days. The Western blotting and Enzyme linked immunosorbent assay kits were used to determine protein and hormone levels, respectively. Experimental results showed that THSWT reduced the immobility time of mice from 150.8 s to 104.9 s in the tail suspension test, and it decreased the immobility time of mice from 165.7 s to 119.0 s in the forced swimming test, outperforming the results obtained with soy isoflavones. In addition, THSWT upregulated the protein expression of follicle-stimulating hormone receptor and downregulated the protein expression of corticotropin-releasing hormone-receptor 1 in the hippocampus. Compared with the oophorectomized group, treatment with THSWT decreased the levels of corticosterone and adrenocorticotropic hormone in serum by 173.7 and 23.4 ng/mL, respectively. These findings showed that THSWT could stimulate the perimenopausal nerve tissue and regulate the level of serum hormones in mice. THSWT exhibited promising potential as a viable alternative drug for hormone treatment of perimenopause in clinical use.

Intracerebroventricular injection of kisspeptin in male rats activates hypothalamo-pituitary-gonadal axis, but not hypothalamo-pituitary-adrenal axis

Kisspeptin is an important hormone involved in the stimulation of the hypothalamo-pituitary gonadal (HPG) axis. The HPG axis can be suppressed in certain conditions such as stress, which gives rise to the activation of the hypothalamo-pituitary-adrenal (HPA) axis. However, the physiological role of kisspeptin in the interaction of HPG and HPA axis is not fully understood yet. This study was conducted to investigate the possible effects of central kisspeptin injection on HPG axis as well as HPA axis activity. Adult male Wistar rats were randomly divided into seven groups as followed: sham (control), kisspeptin (50 pmol), P234 (1 nmol), kisspeptin + p234, kisspeptin + antalarmin (0.1 μg), kisspeptin + astressin 2B (1 μg), and kisspeptin + atosiban (300 ng/rat) (n = 10 each group). At the end of the experiments, the hypothalamus, pituitary, and serum samples of the rats were collected. There was no significant difference in corticotropic-releasing hormone immunoreactivity in the paraventricular nucleus of the hypothalamus, serum adrenocorticotropic hormone, and corticosterone levels among all groups. Moreover, no significant difference was detected in pituitary oxytocin level. Serum follicle-stimulating hormone and luteinizing hormone levels of the kisspeptin, kisspeptin + antalarmin, and kisspeptin + astressin 2B groups were significantly higher than the control group. Serum testosterone levels were significantly higher in the kisspeptin kisspeptin + antalarmin, kisspeptin + astressin 2B, and kisspeptin + atosiban groups compared to the control group. Our findings suggest that central kisspeptin injection causes activation in the HPG axis, but not the HPA axis in male rats.

Electroacupuncture can Modify Stress, Low-Grade Inflammation in the Duodenum, and Damage to the Intestinal Barrier in Rats with Functional Dyspepsia through the CRF Signaling Pathway

In the domain of functional gastrointestinal disorders, Functional Dyspepsia (FD) stands out due to its widespread occurrence internationally. Historically, electroacupuncture (EA) has been employed as a therapeutic modality for FD, demonstrating notable clinical efficacy. This research aimed to delve into the impact of EA on stress responses, minor duodenal inflammatory processes, and the integrity of the intestinal barrier within FD-affected rodent models while also elucidating the underlying mechanisms. Thirty-six male Wistar rats were evenly distributed into three cohorts: a normal, a modeled FD, and an EA treatment group. The FD condition in the rats, barring those in the normal, was induced through a series of multifactorial procedures. For the EA cohort, the rats received electroacupuncture at the acupoints RN12 (Zhongwan) and ST36 (Zusanli) for 20 minutes daily over a span of one week. The gastric residue rate (GRR), intestinal propulsion rate (IPR), and changes in emotional state were measured in each group of rats. Additionally, serum levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) were detected, and the duodenal inflammatory condition and intestinal mucosal barrier status were observed through staining and fluorescence. The expression levels of Claudin-1, Junctional Adhesion Molecule 1 (JAM-1), Corticotropin-Releasing Factor (CRF), and Corticotropin-Releasing Factor Receptor 1 (CRF-R1) were also detected. The study demonstrated that EA had a positive effect on body weight and food intake, GRR, and IPR in FD rats. Additionally, the EA group showed a decrease in serum levels of CRH, ACTH, and CORT, as well as a decrease in the number of duodenal mast cells and tryptase content. Furthermore, the expression of tight junction proteins Claudin-1 and JAM-1 was increased in the EA group compared to the model group. EA also reduced the levels of CRF and CRF-R1 in the hypothalamus and duodenum. EA has been shown to improve the stress state of FD rats, inhibit the activation of mast cells in the duodenum, and reduce low-grade inflammatory response and damage to the intestinal mucosal barrier. It is believed that EA achieves these effects by modulating the expression of CRF and its receptors in the brain-gut interaction pathway through the CRF signaling pathway. This provides a new approach to treating FD.

Paeoniflorin Alleviates Anxiety and Visceral Hypersensitivity via HPA Axis and BDNF/TrkB/PLCγ1 Pathway in Maternal Separation-induced IBS-like Rats.

Irritable Bowel Syndrome (IBS) is a prevalent gastrointestinal disorder that significantly diminishes the quality of life for affected individuals. The pathophysiology of IBS remains poorly understood, and available therapeutic options for IBS are limited. The crucial roles of brain-gut interaction, which is mediated by the Hypothalamic-Pituitary-Adrenocortical (HPA) axis and the autonomic nervous system in IBS, have attracted increasing attention. The objective of this study was to examine the impact of paeoniflorin (PF) on anxiety and visceral hypersensitivity in maternal separation-induced IBS-like rats. The IBS-like rat model was established through the implementation of Maternal Separation (MS) and subsequently subjected to various doses of PF administered via oral gavage for 14 days. Anxiety-like behavior was evaluated using the Open Field Test (OFT) and Elevated Plus Maze (EPM) test. The assessment of visceral sensitivity involved the utilization of the Abdominal Withdrawal Reflex (AWR) score and electromyographic (EMG) responses of the external oblique muscle in response to colorectal distention. The levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT), and corticotrophin-releasing hormone (CRH) were examined by ELISA. Quantitative real-time PCR (qRT-PCR) and immunofluorescence were employed to detect the expressions of CRH receptors 1 (CRHR1) and 2 (CRHR2). Glucocorticoid receptors (GR), mineralocorticoid receptor (MR), brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB), and phospholipase C γ1 (PLCγ1) were examined by Western blot. The results showed that MS induced anxiety-like behavior and visceral hypersensitivity, while PF treatment attenuated these changes. Furthermore, the HPA axis hyperactivity in MS rats was attenuated by PF treatment, indicated by reduced serum ACTH, CORT, and CRH levels and recovered hippocampal CRHR1 and GR expressions. In addition, PF inhibited BDNF/TrkB signaling by downregulating the protein levels of BDNF, TrkB, and phospho-PLCγ1 in the colon. These findings suggest that PF alleviated anxiety and visceral hypersensitivity in MS-induced IBS-like rats, which may be the modulation of HPA axis activity and BDNF/TrkB/PLCγ1 signaling pathway.

Coated sodium butyrate and vitamin D3 supplementation improve gut health through influencing intestinal immunity, barrier, and microflora in early-stage broilers.

Intestinal development and function are critical to maintaining sustained broiler growth. The present study aimed to evaluate the effects of coated sodium butyrate (CSB) and vitamin D3 (VD3) on the intestinal immunity, barrier, oxidative stress and microflora in early-stage broilers. In total, 192 one-day-old broilers were assigned to a 2 × 2 factorial design including two dietary supplements at two different levels, in which the main effects were VD3 (3000 or 5000 IU kg-1) and CSB (0 or 1 g kg-1). The results showed that CSB supplementation increased ileal goblet cells (GCs) numbers, villus height and decreased crypt depth in broilers. CSB increased ileal proliferating cell nuclear antigen expression and high-level VD3 decreased cluster of differentiation 3 expression. CSB reduced serum d-lactate, endotoxin (ET), adrenocorticotropic hormone, corticosterone and malondialdehyde (MDA) concentrations and increased total antioxidant capacity (T-AOC) level. Meanwhile, high-level VD3 decreased serum ET concentration. Furthermore, CSB increased ileal T-AOC, lysozyme (LYZ) and transforming growth factor (TGF)-β and decreased MDA, whereas high-level VD3 decreased ileal MDA and increased secretory immunoglobulin A. CSB up-regulated ileal claudin1, superoxide dismutase 1, TGF-β and LYZ mRNA expression and down-regulated interleukin-1β mRNA expression. CSB combined with high-level VD3 increased ileal Faecalibaculum abundance. Spearman correlation analysis showed that Faecalibaculum was related to the immune and barrier function. Dietary supplementation with CSB and high-level VD3 improved early gut health in broilers by promoting intestinal development, enhancing antioxidant capacity, strengthening barrier function and enhancing the favorable composition of the gut bacterial flora. © 2024 Society of Chemical Industry.

Protective effect of functional food containing Dendrobium officinale via mediation of the FSHR/PI3K/AKT signaling pathway on menopausal syndrome in rats

Menopausal symptoms are age-related disorders related to the deficiency of estrogen that can be influenced by emotional and dietary habits. Guocaoyin superior-national-functional food (GSNF), a traditional Chinese medicine primarily containing Dendrobium officinale, offers notable benefits for mitigating metabolic disorders caused by unhealthy diet. Currently, there is limited research on the impact of GSNF on menopausal syndrome, and its underlying pharmacological mechanisms remain poorly understood. The aim of this study was to evaluate the ameliorative effect of GSNF on menopausal syndrome and to investigate its effect on endocrine metabolic disorders induced by ovarian failure. The findings demonstrate that GSNF raised levels of serum estradiol (E2), anti-mullerian hormone (AMH), and inhibin B (INHB), reduced levels of serum gonadotropin-releasing hormone (GnRH) and follicle-stimulating hormone (FSH), and ameliorated ovarian pathological damage in rats experiencing menopausal syndrome. It was discovered that GSNF enhanced ovarian FSHR and ERα protein expression, stimulated follicular development by activating the PI3K/AKT pathway, and hindered ovarian follicular apoptosis while improving ovarian function through the regulation of apoptosis-related proteins Bcl-2, BAX, and Caspase-3 expression. Furthermore, GSNF augmented the expression of hippocampal FSHR protein and upregulated the expression of hippocampal PI3K and AKT proteins. Additionally, it reduced serum corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, facilitated the release of 5-hydroxytryptamine (5-HT), dopamine (DA), and norepinephrine (NE), and boosted hippocampal tissue neuron count, thereby ameliorating depression-like symptoms during menopause. Moreover, GSNF supplementation improved glucose-lipid metabolism disorders and mitigated hepatic steatosis in model rats. Overall, our research revealed a new function for GSNF in mitigating the adverse impact of negative emotion and unhealthy dietary habits on menopausal symptoms. These findings indicate that GSNF may be a viable option for treating menopausal syndrome.

Perfluorotetradecanoic acid exposure to adult male rats stimulates corticosterone biosynthesis but inhibits aldosterone production.

Perfluorotetradecanoic acid (PFTeDA) is a novel perfluoroalkyl substance that ubiquitously exists in the environment. However, whether PFTeDA affects adrenal cortex function remains unclear. Male Sprague-Dawley rats (age of 60 days) were daily administered with PFTeDA (0, 1, 5, and 10 mg/kg body weight) through gavage for 28 days. PFTeDA did not change body and adrenal gland weights. PFTeDA markedly elevated serum corticosterone level at 10 mg/kg but lowering serum aldosterone level at this dosage without influencing serum adrenocorticotropic hormone level. PFTeDA thickened zona fasciculata without affecting zona glomerulosa. PFTeDA remarkably upregulated the expression of corticosterone biosynthetic genes (Mc2r, Scarb1, Star, Cyp21, Cyp11b1, and Hsd11b1) and their proteins, whereas downregulating aldosterone biosynthetic enzyme Cyp11b2 and its protein, thereby distinctly altering their serum levels. PFTeDA markedly downregulated the expression of antioxidant genes (Sod1 and Sod2) and their proteins at 10 mg/kg. PFTeDA significantly decreased SIRT1/PGC1α and AMPK signaling while stimulating AKT1/mTOR signaling. Corticosterone significantly inhibited testosterone production by adult Leydig cells at >0.1 μM in vitro; however aldosterone significantly stimulated testosterone production at 0.1 nM. In conclusion, exposure to PFTeDA at male rat adulthood causes corticosterone excess and aldosterone deficiency via SIRT1/PGC1α, AMPK, and AKT1/mTOR signals, which in turn additively leads to testosterone deficiency.

Serum ACTH and Cortisol Level is Associated with the Acute Gastrointestinal Injury Grade in ICU Patients.

The relationship between acute gastrointestinal symptoms and cortisol or adrenocorticotropic hormone (ACTH) levels has rarely been reported. We hypothesized that the elevation of serum cortisol or ACTH levels may be correlated with the severity of the acute gastrointestinal injury grade (AGI). This study was an observational study. All patients were admitted to the ICU between 2019.1.1 and 2020.1.1.. Serum ACTH and cortisol levels and clinical data were collected from the electronic medication records. The highest AGI grade during the ICU stay was the major endpoint to observe. The patient was treated in a standard procedure in the ICU. A total of 235 patients were included in our study, 132 of whom developed AGI. In univariate regression, cortisol level was found to be a risk factor for 28-day mortality. Serum cortisol and ACTH levels correlated with APACHE II, AGI grade, PCT, and CRP levels. Spearman analysis and partial correlation analysis indicated that cortisol and ACTH levels were correlated with AGI grade. The ACTH and cortisol levels were positively correlated with the higher severity of AGI grade. The cortisol level may be a useful way to access the GI injury.

Depression and hyponatraemia unmasking hypopituitarism

Abstract Hyponatraemia is a common clinical problem encountered in clinical practice and has multifactorial aetiology. The presentation of hyponatremia due to hypopituitarism secondary to pituitary apoplexy is rarely seen and sometimes missed. We report the case of a 34-year-old male with a history of reduced social interaction, decreased sexual drive, fatigue, vomiting, hiccoughs and presented to the hospital with altered sensorium. Laboratory testing revealed hyponatraemia (107 mEq/L); there was reduced serum cortisol (8 AM), decrease in serum adrenocorticotropic hormone (8 AM) and pituitary hormone assay suggestive of hypopituitarism. Magnetic resonance imaging of the brain with dynamic pituitary contrast suggestive of pitutary apoplexy. The patient was managed with 3% sodium chloride infusion, hydrocortisone and thyroid supplementation.

Serum Levels of Cortisol and Adrenocorticotropic Hormone and their Association with Depression in Environmentally Exposed Populations in Kazakhstan.

This study aimed to investigate the serum levels of cortisol and adrenocorticotropic hormone (ACTH) and the prevalence of depression in the environmentally exposed population of Kazakhstan compared to the environmentally unexposed populations. Additionally, the study aimed to evaluate the capacity of cortisol and ACTH to predict moderate and severe depression in populations exposed to environmental risk factors. This cross-sectional study included 1881 nominally healthy individuals aged between 18-52years who were lifelong residents of Abay, Borodulikha, Ust-Kamenogorsk, Aksay, and Berezovka settlements, which are characterized by exposure to various types of environmental pollutants. Comparisons were made with residents of control sites with no known industrial or radioactive pollution (Uralsk and Kurchum). The Russian version of the PHQ-9 questionnaire was used to evaluate the presence and severity of depression. Serum cortisol levels were measured using solid-phase chemiluminescent immunoassay, while serum ACTH levels were tested with chemiluminescent assays. Populations exposed to environmental pollution from condensate gas extraction (Berezovka and Aksay) had higher median serum cortisol concentrations. However, the populations of the two controls had the highest median serum levels of ACTH. The median total PHQ-9 scores were the lowest in residents of control sites, which also had the highest proportion of individuals with no or minimal depression. Both serum cortisol and ACTH identified moderate, moderately severe, and severe depression. The findings highlight the potential impact of environmental pollution on stress hormone levels and depression, calling for further research and public health interventions to address this issue.

Sargassum horneri Extract Attenuates Depressive-like Behaviors in Mice Treated with Stress Hormone.

Sargassum horneri, a brown seaweed, is known for its various health benefits; however, there are no reports on its effects on depression. This study aimed to investigate the antidepressant effects of S. horneri ethanol extract (SHE) in mice injected with corticosterone (CORT) and to elucidate the underlying molecular mechanisms. Behavioral tests were conducted, and corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and CORT levels were measured. A fluorometric monoamine oxidase (MAO) enzyme inhibition assay was performed. Neurotransmitters like serotonin, dopamine, and norepinephrine levels were determined. Moreover, the ERK-CREB-BDNF signaling pathway in the prefrontal cortex and hippocampus was evaluated. Behavioral tests revealed that SHE has antidepressant effects by reducing immobility time and increasing time spent in open arms. Serum CRH, ACTH, and CORT levels decreased in the mice treated with SHE, as did the glucocorticoid-receptor expression in their brain tissues. SHE inhibited MAO-A and MAO-B activities. In addition, SHE increased levels of neurotransmitters. Furthermore, SHE activated the ERK-CREB-BDNF pathway in the prefrontal cortex and hippocampus. These findings suggest that SHE has antidepressant effects in CORT-injected mice, via the regulation of the hypothalamic-pituitary-adrenal axis and monoaminergic pathway, and through activation of the ERK-CREB-BDNF signaling pathway. Thus, our study suggests that SHE may act as a natural antidepressant.

THU647 Patient With Successful Conception During Treatment For Cushing Disease: Case Report

Abstract Disclosure: C. Iweha: None. E.K. Babler: None. M. Castillo: None. Introduction Cushing Disease (CD) is an endocrine disorder that predominantly affects women of childbearing age and is characterized by excess secretion of adrenocorticotropic hormone (ACTH) with hypercortisolism. We report a case of a woman with ACTH-dependent hypercortisolism treated with pasireotide who had a successful pregnancy while on treatment. Clinical Case A 27-year-old woman presented to the initial consult on 9/01/2011 with a 4-year history of ongoing symptoms of hirsutism, diaphoresis, oligomenorrhea, myalgia, and acne. A physical exam revealed an overweight female with mild facial acne and hirsutism. Family history included autoimmune disease in mother (lupus and multiple sclerosis). She was frustrated by the lack of a definitive diagnosis over 4 years; she was anxious and using multiple medications, including anxiolytics and analgesics, without relief of symptoms. Patient did not use alcohol and never smoked. Labs revealed initial morning (AM) cortisol = 26.9 µg/dL (normal range: 5-23 µg/dL) and ACTH = 14 pg/mL (normal: 6-58 pg/mL); 24-hour urinary cortisol was 110.6 µg/24 h (normal:<100 µg/dL) and serum ACTH =8 pg/mL. Low-dose (1 mg) dexamethasone suppression test reduced AM cortisol to 1.7 µg/dL and ACTH of 8 pg/mL. No evidence of adrenal adenoma on abdominal CT or pituitary adenoma on brain MRI, and IPSS confirmed diagnosis. Based on hypercortisolism and normal ACTH level, diagnosis was ACTH-dependent CD. We advised the patient to join a clinical trial for pasireotide, and she began treatment on 1/3/2013. She presented for follow-up on 6/17/2014 and reported improvement of some symptoms on 0.6 mg pasireotide twice daily, the highest dose she could tolerate. She reported experiencing chronic pain; medications included prescription analgesics, muscle relaxants, and anxiolytics. On 6/23/2015, our patient returned for a follow-up when she was 5.5 months pregnant. While on pasireotide, she became pregnant and subsequently left the study and discontinued treatment. She reported recurrence of hirsutism, acne, fatigue, and hyperemesis with discontinuation of pasireotide. Patient returned twice more during pregnancy and had a successful delivery and healthy infant. Clinical Conclusions Successful conception and pregnancy are unusual with CD due to fertility-inhibiting hormonal effects of excess cortisol. Some medications for CD impede pregnancy through their mechanism (eg, mifepristone). Our patient conceiving while on treatment is promising for women with CD. Although her CD symptoms returned when pasireotide was discontinued, she delivered a healthy infant; limited pasireotide data in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. Our case underscores the potential for successful conception for women with CD when cortisol levels are normalized with treatment that avoids suppressing menstruation. Presentation: Thursday, June 15, 2023

SAT328 Severe Exogenous Cushing Syndrome Caused By A Potent Steroid Concealed In Arthritis Supplement

Abstract Disclosure: S. Maraqa: None. L. Bushnaq: None. R. Singh, PhD: None. N. Genere: None. Cushing syndrome (CS) is a rare disorder caused by excessive systemic glucocorticoids and associated with increased mortality and worsening quality of life. CS most commonly occurs from exogenous glucocorticoid use, while Cushing disease causes most of endogenous cases. Here, we present a case of a 64-year-old woman with rapidly progressive CS due to an over-the-counter (OTC) arthritis supplement with unlisted dexamethasone. A 64-year-old woman with reported CS who was evaluated in our Endocrinology center after she moved to the United States. She was previously diagnosed with pituitary CS in Mexico following a 6 months history of rapid 50-pound weight gain, profound proximal muscle weakness requiring assistive device, and unprovoked vertebral fractures; laboratory evaluation found elevated 24-hour urinary cortisol 272 mcg/24h, 1mg dexamethasone suppression test total cortisol 5.6 mcg/dl (< 1.8), and adrenocorticotropic hormone (ACTH) 16 pg/mL. Pituitary MRI was unremarkable. Past medical history included primary hypothyroidism and hypertension. Physical exam was notable for blood pressure 160/108 mmHg, heart rate 96, BMI 33 kg/m², moon face, supraclavicular fat pads, central obesity, skin bruises, and proximal muscle weakness. Unexpectedly, re-evaluation showed undetectable serum ACTH and cortisol. A thorough review of medications identified no recent exposure to glucocorticoids. However, a synthetic glucocorticoid screen showed markedly elevated serum dexamethasone concentration. Follow-up discussion revealed that she had started an arthritis supplement “Artri-King” 6 months prior to these symptoms. We collaborated with Mayo Clinic Labs to evaluate dexamethasone contents in this drug; each tablet was found to contain 0.9 mg of dexamethasone, which was unreported in the ingredient list. This supplement was stopped, and the patient was started on physiologic hydrocortisone. Two months later, AM cortisol was 5.6 mcg/dL and ACTH 23 pg/ml. Eight months later, she continues to have adrenal insufficiency but has had a substantial clinical improvement.Exogenous CS is readily diagnosed in patients taking prescribed glucocorticoids; however, diagnosis can be more challenging in cases where the presence of glucocorticoids is concealed. The US Food and Drug Administration follows more limited regulatory guidelines for dietary supplements compared to prescribed drugs. A study by Tucker.et.al. reported that 20% of dietary supplements have unapproved ingredients.1 This is especially concerning, considering that over half of the US population admits to taking dietary supplements.2 On April 2022, the FDA published a public notice for “Artri-King”, declaring the presence of unlisted dexamethasone.3 Should such agents prove to be the culprit of CS, they must be tapered off gradually or in the presence of physiologic hydrocortisone to avoid the risk of adrenal crisis. Presentation: Saturday, June 17, 2023

THU036 68Ga-DOTATOC PET/CT In Localization Of ACTH-producing Pituitary Tumors In Patients With Cushing Disease

Abstract Disclosure: K. Kim: None. Localization of adrenocorticotrophic hormone (ACTH) producing pituitary tumors has paramount importance as definitive management mainly involves surgical resection of tumors. High-resolution functional imaging modalities, such as 68Ga-DOTATOC PET/CT, have been recently introduced in clinical practice for the identification of neuroendocrine tumors. In this study, we focused on the performance of 68Ga-DOTATOC PET/CT as a tool for localizing ACTH secreting pituitary tumors compared to pituitary MRI. In a retrospective cohort study, we identified 44 patients with Cushing disease who underwent both 68Ga-DOTATOC PET/CT and pituitary MRI before TSA in Severance Hospital from 2015 to 2019. 30 of 44 patients with pathologically positive ACTH immunoreactivity confirmed under TSA were included in final analysis. We compared the accuracy of the predicted tumor location on 68Ga-DOTATOC PET/CT and MRI based on the tumor location under TSA.Median age was 34(15-68) years and 25 of 30 patients showed detected tumor in 68Ga-DOTATOC PET/CT. Age (25 vs. 51 years), pre-operative ACTH level (62.21 vs. 26.21 pg/ml). pre-operative cortisol level (20.60 vs. 17.90 pg/ml), and tumor size on MRI (7.75 vs. 5.00 mm) were not differ according to the presence or absence of DOTATOC uptake. The sensitivity of 68Ga-DOTATOC PET/CT was comparable to those of MRI (90.9% vs. 100% in microadenomas, 79.0% vs. 94.7% in macroadenomas, all p >0.05). However, it was inferior to lateralize pituitary adenoma compared to MRI (72.0% vs. 75.9%, p=0.03). The tumors were localized successfully in 18 patients by 68Ga-DOTATOC PET/CT and we divided into two groups depending on successful lateralization. Pre-operative ACTH in successfully lateralized group was significantly higher than that in the failing lateralized group (91.64 vs. 48.54 pg/ml, p=0.010). The area under the curve was measured to be 0.778 with cut-off 96.59pg/ml in ACTH level to determine the successful lateralization. Pre-operative ACTH higher than 96.59 pg/ml showed the best diagnostic accuracy (Sensitivity 50%, specificity 100%).68 Ga-DOTATOC PET/CT showed that successful detection rate was comparable to those of MRI, but success rate of lateralization was inferior. Serum ACTH level determines the successful lateralization of ACTH secreting pituitary tumor in Cushing disease. Presentation: Thursday, June 15, 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.

Effect of classical music on growth performance, stress level, antioxidant index, immune function and meat quality in broilers at different stocking densities.

High-stocking density is one of the factors that can easily cause oxidative stress and inflammatory reaction of broilers. Currently, music therapy has been proposed to help animals relieve stress to some extent. However, it is still unclear whether classical music can alleviate stress in broilers at high stocking densities. Hence, this study aimed to investigate the effects of classical music on growth performance, stress level, antioxidant index, immune function and meat quality of broilers under different stocking densities. A total of 540 one-day-old broilers with similar body weight were randomly divided into 6 treatment groups, with 6 replicates per group, which included two feeding environments (with/without classical music) and three stocking densities (15.5, 17.9, and 20.3 birds/m2), thereby making a 2 × 3 factorial arrangement. The results showed as follows: increasing stocking density decreased the average daily feed intake and average daily gain (ADG), increased feed-to-gain ratio (F/G) and mortality of broilers. Moreover, increased density resulted in an increase in serum corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels. Increasing stocking density decreased spleen and bursal indices, serum immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) levels. Increasing stocking density elevated serum malondialdehyde (MDA) and decreased catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities. Increasing stocking density decreased serum total protein (TP) levels and increased total cholesterol (TC) and glucose (GLU) levels. Additionally, increasing stocking density decreased the cooking liss of pectoralis and increased the L*24h value of pectoralis. Meanwhile, playing classical music for broilers increased their ADG and decreased F/G, and decreased serum CORT, ACTH, GLU content. In addition, the bursa of Fabricius index, serum IgA and IgG contents as well as the a*24h value of pectoralis was increased under the music therapy. In conclusion, high-stocking density (20.3 birds/m2) harmed the growth performance and health of broilers, and the classical music stimulus ameliorated the negative effects to some extent.

Electroacupuncture in the treatment of IBS in rats: Investigation of the mechanisms of CRH+ neurons in the paraventricular nucleus.

Electroacupuncture (EA) is well documented to treat irritable bowel syndrome (IBS). However, the mechanism of the central nervous system related to IBS and acupuncture stimulation is still not well known. In this study, a rat model of IBS was established by cold-restraint comprehensive stresses for 15 days, and it was found that the levels of corticotropin-releasing hormone (CRH), corticosterone (CORT), and adrenocorticotropic hormone (ACTH) in the peripheral serum were increased; the visceral sensitivity was enhanced; and the intestinal motility was accelerated, specifically, there was an enhancement in the discharge frequency of neurons in the paraventricular nucleus (PVN). EA treatment for 3 days, 20 min/day, alleviated the increase in the levels of CRH, CORT, and ACTH in the peripheral serum of rats, reduced the visceral sensitivity of IBS rats, and inhibited colon movement and discharge frequency of the neurons in the PVN. Additionally, EA could reduce the excitability of CRH neurons and the expression of CRHR1 and CRHR2 in PVN. At the same time, the expression of CRH, CRHR1, and CRHR2 in the peripheral colon was decreased. Taken together, EA appears to regulate intestinal functional activity through the central CRH nervous system, revealing the central regulation mechanism of EA in IBS rats, and providing a scientific research basis for the correlation among the meridians, viscera, and brain.

Associations of Diabetic Retinopathy Severity With High Ambulatory Blood Pressure and Suppressed Serum Renin Levels.

The relationships between serum renin levels, severity of diabetic retinopathy (DR), and 24-hour blood pressure (BP) have not been previously reported. To explore causes for DR and the relationships of 24-hour ambulatory BP, and hormone levels with the severity of DR. The diabetic patients were classified as having no DR, simple DR, or severe DR (preproliferative DR plus proliferative DR) based on funduscopic examination, and we measured 24-hour BP, serum active renin (ARC), aldosterone (SAC), adrenocorticotropic hormone, and cortisol levels in each group. Compared to those with no DR or simple DR, patients with severe DR showed significantly higher 24-hour BPs, including daytime and nighttime systolic and diastolic BP levels, independent of diabetic duration and HbA1c levels. The variability of nighttime systolic BP was greater in patients with severe DR than in those with nonsevere DR, although nocturnal BP reduction was similar between the groups. The ambulatory BPs were significantly inversely associated with ARC. The ARC was significantly lower in severe DR patients than in those with no DR or simple DR (3.2 [1.5-13.6] vs 9.8 [4.6-18.0] pg/mL, P < .05), but there were no differences in SAC in patients taking calcium channel blockers and/or α-blockers. No associations were found between DR severity and other hormone levels. Severe DR was associated with higher 24-hour BPs and suppressed ARC. These findings suggest that mineralocorticoid receptor overactivation may play a role in higher BP levels and severe DR in diabetic patients.