Adrenocorticotropic Hormone Levels Research Articles

Impact of Exposure to a Mixture of Organophosphate Esters on the Adrenal Glands of Sprague Dawley Rats.

There is growing evidence that organophosphate esters (OPEs) can act as endocrine-disrupting chemicals. However, only a few studies have assessed the effects of OPE exposure on one of the most important endocrine glands in the body, the adrenal gland. Our aim was to test the effects of a mixture of OPEs detected in Canadian house dust on adrenal function in Sprague Dawley rats. Adult male and female rats (n = 15 per treatment group) were administered either a vehicle or an OPE mixture (0.048, 1.6, or 48 mg/kg bw/day) for 70-72 days via their diet. With OPE exposure, adrenal glands from male adult rats were reduced in weight, while those of female rats showed an increase in weight. This led us to investigate whether OPEs induce sex-specific effects on adrenal gland function and the mechanisms involved. Serum levels of two adrenal hormones, aldosterone and corticosterone, were decreased only in male serum samples. Serum levels of renin and adrenocorticotropic hormone (ACTH), which regulate aldosterone and corticosterone synthesis, respectively, were assessed. Exposure to the OPE mixture decreased renin levels only in males. Serum biochemistry analysis revealed that triglycerides and LDL cholesterol levels were increased in males. Transcriptomic analysis revealed that the top affected pathways in male adrenal glands from all three treatment groups were related to potassium channels, which play a role in regulating aldosterone and corticosterone levels. The most affected pathways in female adrenal glands were related to cholesterol biosynthesis and immune functions. These results show that an environmentally relevant mixture of OPEs affects adrenal function and that these effects are sex specific.

Dysregulated HPA axis during postnatal developmental stages in the BTBR T+ Itpr3tf/J mouse: A model of autism spectrum disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder. Some children with ASD show enhanced cortisol response to stress. BTBR T+ Itpr3tf/J (BTBR) mice, an ASD model, display behavior consistent with the three diagnostic categories of ASD and exhibit an exaggerated response to stress in adulthood. However, it remains unclear how basal corticosterone levels change and how the hypothalamic-pituitary-adrenal axis responds to stress during the early life stages in BTBR mice. In this study, we found that basal corticosterone levels showed characteristic changes, peaking at weaning during postnatal development in both BTBR and control C57BL/6J (B6J) mice. Furthermore, we observed higher corticosterone and corticotropin-releasing hormone levels in BTBR mice than in B6J mice following acute stress exposure during weaning; however, adrenocorticotropic hormone levels were lower in BTBR mice. Glucocorticoid receptor mRNA expression levels in the hippocampus and lateral septum after stress were higher in BTBR mice than in B6J mice. This study documented changes in corticosterone levels at baseline during postnatal development in mice and showed that BTBR mice exhibited disrupted stress responses at weaning.

Adrenal Cortical Carcinoma Presenting as CSCR.

We describe a case of bilateral chronic central serous chorioretinopathy (CSCR) secondary to adrenal cortical carcinoma. Case report of a 70-year-old Hispanic man presenting with bilateral multifocal CSCR. Clinical findings of bilateral chronic CSCR along with 160 µm of subretinal fluid (SRF) and choroidal thickness greater than 400 µm without enhanced depth optical coherence tomography was noted in a patient presenting with distortion in vision in both eyes and weight gain of 15 pounds, weakness, and fatigue starting 8 months prior. Further endocrine testing showed an elevated 24-hour urinary free cortisol level of 137 µg with no change in serum cortisol levels following low-dose dexamethasone suppression test and undetectable serum adrenocorticotropic hormone (ACTH) levels consistent with ACTH-independent Cushing's syndrome. Imaging of the abdomen revealed heterogeneously enhancing masses, and biopsy of the adrenal tumor led to the diagnosis of adrenal cortical carcinoma. He died 3 weeks after starting hospice care, and only completed one round of chemotherapy. Adrenal tumors including adrenal cortical carcinoma may present as bilateral chronic central serous chorioretinopathy.

Effects of Black Rice Anthocyanin Extract on Depression-Like Behavior in Chronic Unpredictable Mild Stress Model Mice

Objective: To investigate the effects of black rice anthocyanins extract (BSE) on depression-like behavior in mice with chronic unpredictable mild stress (CUMS). Methods: A total of 30 male Kunming mice were randomly divided into Control group, model group (CUMS) and black rice anthocyanin extract group (300 mg/kg). Except the blank group, all mice were treated with CUMS to induce depression. After 21 days of intragastric administration, the behavioral changes of the mice were analyzed by body weight, sucrose preference test, open field test, and water maze test. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT). Hematoxylin-eosin staining (HE) was used to observe the pathological changes of neurons in hippocampal CA1 and CA3 regions. Cell apoptosis in hippocampus was detected by terminal deoxynucleotidyl transferase-mediated dutP Nick end labeling (TUNEL) staining. Results: Compared with the model group, the brown-rice anthocyanin treatment group showed significantly increased sucrose preference, increased horizontal movement distance and vertical standing times in the open field test, decreased escape latency in the water maze test, increased residence time in the target quadrant and the number of crossing the platform, and alleviated the damage of hippocampal neurons. Plasma ACTH, CORT, and CRH levels were decreased, and apoptosis rates in the hippocampus were decreased. Conclusion: Black rice anthocyanins have a significant antidepressant effect possibly by regulating the function of HPA axis.

Physiological and Psychological Stress Reactivity in Narcolepsy Type 1.

Narcolepsy type 1 (NT1) is a chronic sleep-wake disorder, characterized by a loss of hypocretin production. Unexpectedly, in post-mortem tissue of people with NT1 there is a loss of corticotrophin-releasing hormone (CRH) in the paraventricular nucleus. CRH is known as activator of the hypothalamic-pituitary-adrenal (HPA) axis in response to stress. This activation results in the release of the stress hormones adrenocorticotropic hormone (ACTH) and cortisol. We hypothesize an altered physiological and psychological stress response in NT1. Participants were people with NT1 (n=14) and matched healthy controls (n=12). The Trier Social Stress Test for Groups (TSST-G), a validated socially evaluated stress test in controlled settings, induced acute stress. We measured ACTH and cortisol levels in blood before and at three timepoints after the TSST-G. We also measured subjective stress and heart rate levels. In both groups, acute stress led to increases in ACTH (p=0.006), cortisol (p<0.001), heart rate (p<0.001) and subjective stress (p<0.001). Subjectively, people with NT1 experienced more stress than controls (p<0.001). No differences were found in heart rate, cortisol, and ACTH between people with NT1 and controls at any timepoint. Secondary analyses showed that men with NT1 had lower cortisol levels immediately after stress induction than men in the control group (p=0.002). People with NT1 show an increased subjective stress response, but no changes in their endocrine or cardiovascular stress reactivity. Further research is required to determine the impact of reduced CRH production and gender in NT1.

Antidepressant and anxiolytic effects of Wuling Capsule in CSDS mice: Alleviating HPA axis hyperactivity via the Nesfatin-1/NF-κB signaling pathway

Ethnopharmacological relevanceWuling capsule, composed of the traditional Chinese medicine Wuling mycelia powder, is made by fermenting and processing Xylaria nigripes (Kl.) Sacc. Clinically, it is commonly used to alleviate depression and anxiety. However, the mechanisms through which Wuling capsule exerts its therapeutic benefits have not been clearly defined. Aim of the studyThis study aims to elucidate the mechanisms by which Wuling capsule alleviates depression and anxiety like behaviors induced by chronic social defeat stress (CSDS) in mice. Materials and methodsHigh-performance liquid chromatography-tandem mass spectrometry system was used to identify the components of the Wuling capsule. Mice were subjected to CSDS to induce depression and anxiety-like behaviors. The expression of hypothalamic corticotropin-releasing hormone (CRH) and Nesfatin-1, as well as serum levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were quantified. Behavioral assessments included the open field test, elevated plus maze, sucrose preference test, and forced swim test to evaluate depression and anxiety levels. Specific manipulation of Nesfatin-1 in the paraventricular nucleus of the hypothalamus (PVN) or cells was achieved through stereotaxic virus injection or plasmid transfection. Intracerebral cannula implantation was used for PVN-specific drug administration. ResultsA total of 123 different components were identified in Wuling capsule. CSDS induced depression and anxiety-like behaviors in mice, along with hyperactivation of the HPA axis, increased hypothalamic Nesfatin-1 levels, and elevated nuclear factor kappa-B (NF-κB) phosphorylation. Overexpression of Nesfatin-1 in the hypothalamus mimicked the effects of CSDS. Conversely, knockdown of hypothalamic Nesfatin-1 or PVN-specific administration of Nesfatin-1 antibody or NF-κB antagonist mitigated CSDS-induced depression and anxiety-like behaviors and hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. In neuroblastoma-2a (N2a) cells, overexpression of Nesfatin-1 led to increased NF-κB phosphorylation and CRH levels, whereas knockdown of Nesfatin-1 produced the opposite effects. Treatment with Wuling capsule alleviated CSDS-induced depression and anxiety-like behaviors, HPA axis hyperactivity, and activation of the hypothalamic Nesfatin-1/NF-κB pathway. ConclusionsThe hypothalamic Nesfatin-1/NF-κB pathway plays a significant role in depression by modulating the HPA axis and is involved in the antidepressant and anxiolytic effects of Wuling capsule.

The effects of methimazole combined with propranolol on heart rate, bone metabolism, and thyroid hormone levels in patients with hyperthyroidism: A systematic review and a meta-analysis of case-control studies.

The combination of methimazole and propranolol is considered an effective treatment regimen for hyperthyroidism in clinical practice; however, detrimental effects on the heart rate, bone metabolism and thyroid hormone levels have been reported. Therefore, the present study aimed to systematically review the efficacy and safety differences in patients with hyperthyroidism and the effects of treatment on heart rate, bone metabolism, cortisol, and adrenocorticotropic hormone levels using case-control studies. Clinical case-control trials of methimazole combined with propranolol for the treatment of hyperthyroidism were selected from Chinese and English databases, and data were collected from the establishment of the database until August 2024. Two independent researchers evaluated the quality of the literature using the Newcastle-Ottawa Scale (NOS). Meta-analysis of each effect index was performed using RevMan software (version 5.3), and the quality of the results was evaluated using the GRADE profiler system letter description method. Sixteen clinical case-control trials were included in this study. Of these, 2 trials exhibited NOS scores of 7, 6 trials exhibited NOS scores of 6, and 8 trials exhibited NOS scores of 5. These accounted for 12.5% of the high-quality literatures, and included 772 patients treated with methimazole combined with propranolol (observation group) and 771 patients treated with methimazole alone (control group). The results of the meta-analysis demonstrated that methimazole combined with propranolol improved the cure rate, the total effective rate, and heart rate, compared with the control group (P < .05). In addition, calcification, bone glutamate protein, free triiodothyronine, free tetraiodothyronine, thyroid-stimulating hormone, cortisol, and adrenocorticotropic hormone were significantly different between the 2 groups (P < .05). There were no significant differences in leukemia, headache, dizziness, skin pruritus, bone pain, arthralgia, or in improving parathyroid hormone or reducing gastrointestinal reactions between the 2 groups. The present study demonstrated that methimazole combined with propranolol may significantly improve the heart rate, bone metabolism and associated hormone levels in patients with hyperthyroidism, without significantly increasing the risk of adverse reactions. However, due to the impact of primary literature type, quality or research methods high-quality, multicenter, rigorously designed clinical trials are required for further verification.

Apple Polyphenol Extracts Attenuated Depressive-Like Behaviors of High-Sucrose Diet Feeding Mice by Farnesoid X Receptor-Mediated Modulation of Bile Acid Circulation within the Liver-Gut-Brain Axis.

Although the association between high-sugar diets and depression has been verified, few studies have explored the antidepressant mechanisms of apple polyphenol extracts (APE). Therefore, fifty-four C57BL/6 male mice aged 5 weeks were randomly assigned into five groups: the control group with the standard diet (CON), the constant high-sucrose diet group (HSD), the "2 + 5" alternate diet group (A-HSD), and the 500 mg/(kg·bw) APE treatment for the HSD group (APE) and the A-HSD group (A-APE), respectively. The data of hypothalamic-pituitary-adrenal (HPA) axis function and behavioral experiments confirmed the success in the establishment of depression-like mouse models in both HSD and A-HSD groups, which were significantly alleviated after APE treatment. Meanwhile, APE reduced serum levels of corticosterone and adrenocorticotrophic hormone, alleviated histopathological damage of the liver, colon, and brain, respectively, elevated the protein expressions of Occludin, ZO-1, and MUC-2, and decreased Firmicutes/Bacteroidota ratio and Dubosiella abundance with the increased microbiota of Tannerellaceae_unclassified, Muribaculum, and Lachnospiraceae_unclassified. Moreover, APE treatment reduced Farnesoid X receptor (FXR) protein levels along with the increased expressions of CYP7A1 and TGR5, lowered the contents of serum and fecal total bile acids, and modulated fecal BA compositions, particularly glycocholic acid (GCA) and isolithocholic acid (ILCA). Thus, both the constant and alternate high-sucrose diets successfully induced depression-like behaviors in mice, and APE might be a potential nutraceutical to attenuate high-sucrose diet-induced depression by regulating BAs circulation within the liver-gut-brain axis mediated by FXR.

Stress-induced coronary spasms: evaluating the role of serum cortisol in variant angina

Abstract Background and purpose Variant angina is a type of angina pectoralis caused by vasospasm, and the patients were recommended to take lifelong medication to suppress spasms. In addition to risk factors, mental stress can be a precipitating factor in vasospasm. We can analyze whether mental stress can affect vasospasm by analyzing the relationship between serum cortisol levels, the major stress hormone, and coronary artery vasospasm. Methods We prospectively enrolled patients who were admitted for coronary angiography from October 2022 to August 2023. We divided them into 2 groups: variant angina and those who had other angiographic findings such as insignificant, stable angina, unstable angina, or non ST segment elevation myocardial infarction. The primary endpoint was the norepinephrine, cortisol, and adrenocorticotropic hormone (ACTH) level at admission, cortisol and ACTH level at Day 1 after admission, and after discharge when visiting the outpatient clinic. We used students' t-tests to examine the differences between groups. Results A total of 196 patients were enrolled, and 23 patients were diagnosed with variant angina. The variant angina group showed significantly higher serum cortisol levels on Day1 than the other diagnosis group (10.1±3.4 µg/dL vs. 8.4±4.1 µg/dL, p-value 0.044). There were no significant differences between baseline norepinephrine, ACTH, cortisol levels, Day 1 ACTH, and serum ACTH, cortisol levels after discharge. However, the serum cortisol levels showed an increased trend than other diagnosis group (baseline cortisol 9.7±3.5 vs. 8.3±4.1, p-value 0.082; after discharge cortisol 9.3±2.7 vs. 8.6±3.6, p-value0.294). Conclusions The variant angina group had a higher level of serum cortisol level than other diagnosis groups. Also, this trend was sustained at baseline and after discharge. Further research with a large cohort is warranted.

Lindera aggregata improves intestinal function and alleviates depressive behaviors through the BDNF/TrkB/CREB signaling pathway induced by CUMS in mice

Depression is a common mental illness, which is highly related to intestinal motor dysfunction and causes a global burden of disease. Lindera aggregata (LA), a traditional medicinal herb, has been used to treat gastrointestinal disorders; however, the effect of LA on depression remains unclear. Here, we assessed the impact of LA on chronic unpredictable mild stress (CUMS)-induced depression in mice and explored the related mechanisms. The results showed that LA ameliorated depressive behaviors in mice exposed to CUMS, as evidenced by improved performance in the sucrose preference test, force swimming test, and open field test, as well as increased serum levels of adrenocorticotropic hormone and 5-hydroxytryptamine. In addition, LA increased the serum levels of D-xylose and ghrelin, indicating that LA can promote gastrointestinal motility. Additional studies revealed that LA relieved CUMS-induced hippocampal tissue damage, as shown by hematoxylin and eosin and Nissl staining. LA increased the expression levels of brain-derived neurotrophic factor (BDNF) and promoted the activation of tropomyosin receptor kinase B (TrkB) and cAMP response element-binding (CREB) in the hippocampus of CUMS-exposed mice or in corticosterone-injured HT22 cells. In conclusion, LA can improve CUMS-induced depressive behavior in mice, potentially through hippocampal neuroprotection mediated by the BDNF/TrkB/CREB signaling pathway, which also contributes to improved intestinal function.

Effects of circuit weight training by intensity on stress hormones and antioxidant capacity in high-school wrestlers.

We aimed to investigate the effects of 8-week circuit weight training by intensity on blood stress hormones and antioxidant capacity in high-school wrestlers. This study involved 27 male wrestlers with >2 years of wrestling experience who were randomly assigned to either a low intensity (n=13) or a high-intensity circuit weight training group (n=14). The participants performed circuit weight training for 60 min per session, 3 times per week for 8 weeks. The low- and high-intensity circuit weight training exercises were performed at 50%-60% and 70%-80% of one-repetition maximum for 10 stations, respectively, and 8-15 repeated sessions per station were performed in order. No changes were observed in adrenocorticotropic hormone (ACTH), cortisol, epinephrine, and norepinephrine levels between the two training groups. When compared to levels before the training, ACTH and epinephrine levels decreased, whereas cortisol levels increased. However, no difference was observed in norepinephrine levels. Further, no differences were observed in malondialdehyde (MDA) and glutathione peroxidase (GPX) levels between the two groups. However, MDA and GPX levels were increased from those before training. Changes in superoxide dismutase levels were observed between the two groups, but the change was significant only in the high-intensity circuit weight training group. Long-term training did not increase lipid peroxidation, but increased the activity of antioxidant enzymes that defend against oxidative stress. The antioxidant defense system in tissues can be regulated by exercise intensity as well as physical training status.

Evaluation of anterior pituitary hormone levels in patients with atrial fibrillation

Aim: The risk of ischemic stroke is increased 5-fold in patients with atrial fibrillation (the most common reason for cardiac arrhythmia). The aim is to investigate whether insufficiency in anterior pituitary hormones develops in patients diagnosed with atrial fibrillation and no history of cerebrovascular accident. Method: A group of 65 patients with chronic /paroxysmal atrial fibrillation without a history of cerebrovascular accident and a group of 65 healthy controls without arrhythmia were included in this study. Atrial fibrillation was diagnosed by electrocardiography or 24-hour rhythm holter. Demographic data, biochemical tests, echocardiography findings were compared between the groups. P&lt;0.05 was considered statistically significant. Results: There was no statistical difference in gender and age distribution between groups (p&lt;0.05). (Patient group: Mean age 68 ± 7 years (16 (24.6%) male and 49 (75.4%) female) / Control group: Mean age 67 ± 6 years (18 (27.7%) male and 47 (72.3%) female). Serum insulin-like growth factor-1, adrenocorticotropic hormone and cortisol levels were significantly lower in the patient group compared to the control group (p=0.048, p=0.005, p=0.023). There was no significant difference in serum thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, and prolactin levels between groups. Left atrial diameter and left ventricular end-diastolic diameter were higher in the patient group (p&lt;0.0001). The left ventricular ejection fraction value was lower in the patient group (p&lt;0.0001). Conclusion: It was thought that the reason for the low level of insulin-like growth factor-1 in the setting of normal liver and kidney functions and simultaneous cortisol and adrenocorticotropic hormone deficiency, in patients with atrial fibrillation with no history of cerebrovascular accident might be due to silent cerebral ischemia leading to pituitary dysfunction.

Endocrine dysregulation in COVID-19: molecular mechanisms and insights.

This review describes the impact of COVID-19 on the endocrine system, focusing on cortisol signaling and growth factor-induced endocrine resistance. As expected, SARS-CoV-2 infection induces systemic inflammation, resulting in stimulation of the adrenal glands leading to elevated cortisol levels with normal adrenocorticotropic hormone (ACTH) levels. The cytokine storm could also stimulate cortisol production. However, in some instances, cortisol levels rise independently of ACTH due to a phenomenon known as "pseudo-Cushing's syndrome," where adrenal glands become less responsive to ACTH. Plasma proteomic analyses showed that this pattern was variably observed among COVID-19 patients, potentially involving calcium dysregulation and GNAS-regulated activities, ultimately impacting the regulation of microvascular permeability. COVID-19 also exhibited a syndrome resembling endocrine resistance, governed by receptor tyrosine kinase signaling pathways. Mild cases displayed elevated activity of EGFR and MMP9, along with increased expression of survival factors like Bax and Bcl2. In contrast, more severe cases involved IGFR-I and enhanced NOTCH signaling, with altered expression of Bcl2, AKT1, and MAPK8. In summary, these findings describe the complex interplay between COVID-19 and endocrine pathology, particularly endocrine resistance. These insights suggest potential endocrine targets for therapeutic interventions to improve short- and long-term outcomes for COVID-19 patients.

Yeast Extract Peptides Alleviate Depression in Chronic Restraint Stress Rats by Alleviating Hippocampal Neuronal Apoptosis and Dysbiosis of the Gut Microbiota.

Depression as a global neurological disorder, and hippocampal neuronal apoptosis and disorders of the gut microbiota are closely related to it. This study aims to expose the ameliorative effect of enzyme peptides (AP) from brewer's yeast on depressive behavior caused by chronic restraint stress (CRS) in rats. After 4 weeks of AP intervention, a significant alleviation of depressive behavior in the sucrose preference test (SPT), forced swim test (FST), and light-dark test (LDT) is observed in depressed rats. AP ameliorates neuronal damage with increased the expression of the key CREB/BDNF/TrkB/Akt signaling pathway, which increases the levels of the monoamine neurotransmitters 5-hydroxytryptamine (5-HT) and norepinephrine (NE) in the hippocampus, buffering hyperactivity of the hypothalamo-pituitary-adrenal axis (HPA), and decreasing the serum cortisol (CORT) and adrenocorticotropic hormone (ACTH) levels in rats. In addition, AP modulates the disruption of the rat gut microbiota by chronic restraint stress (CRS), and the changes in the abundance of Lactobacillus animalis and Lactobacillus johnsonii are probably the key for AP performing antidepressant benefits. A strong correlation is found between gut microbiota and biochemical markers of depression. AP, as a natural and safe active substance, has a positive effect in the treatment of depression.

Targeted long-read sequencing identifies missing pathogenic variant in unsolved 11β-hydroxylase deficiency

Background11β-hydroxylase deficiency (11β-OHD), caused by homozygosity or compound heterozygosity CYP11B1 variants, is the second most common cause of congenital adrenal hyperplasia (CAH). Due to the high degree of sequence identity between CYP11B1 and CYP11B2, chimeric genes, and complex structural variants (SVs), the conventional approach to gene testing for 11β-OHD is facing challenges. The study aimed to clarify the underlying genetic causes of two siblings of a Chinese family with 11β-OHD.MethodsPeripheral blood samples and clinical information were collected from subjects and their family members. Sex steroid concentrations were measured using LC-MS/MS. Long-range PCR-based next-generation sequencing (NGS), PCR assay and target long-read sequencing were used to detect the pathogenic variants.ResultsEarly onset hypertension, increased serum levels of adrenocorticotropin (ACTH), progesterone, testosterone, and decreased cortisol and potassium were detected in both affected siblings. Long-range PCR-based NGS identified a heterozygous missense variant (NM_000497.4:c.281 C > T, p.P94> L) in CYP11B1 gene in the two siblings. PCR detected no chimeric CYP11B2/CYP11B1 gene. We finally identified a second pathogenic variant in CYP11B1 gene via target long-read sequencing (T-LRS). This novel variant was a deletion-insertion variant and located chr8:143957269–143,957,579 (hg19) with the insertion of ‘ACAG’ (NM_000497.4:c.954 + 78_980delinsACAG), which was in trans with CYP11B1: c.281 C > T.ConclusionsOur study suggests that the integrated long-range PCR-based NGS and T-LRS seem to be the most reliable and accurate method for 11β-OHD genetic diagnosis and carrier sequencing.

Effects of morroniside isolated from Cornus officinalis fruits on functional gastrointestinal disorders and gastric ulcer in mice

The dried fruits of Cornus officinalis (Cornaceae) are used in Kampo medicine (e.g. Hachimigan and Goshajinkigan) to treat senile osteoporosis, diabetes, gastric atony, frequent urination, and diarrhea/constipation associated with aging. The present study investigated the effects of a C. officinalis fruit extract and morroniside, an iridoid compound from isolated these fruits, on the reduction in gastric emptying small intestinal motility caused by 5-hydroxytryptamine (5-HT) and 1-(3-chlorophenyl) biguanide (5-HT3 receptor agonist), and gastric ulcers induced by 150 or 75 mM HCl/90 % EtOH (HCl-EtOH) and/or 5-HT in mice. C. officinalis extract (500 mg/kg) and morroniside (20 and 50 mg/kg) suppressed the reduction in gastric emptying induced by 5-HT- and 5-HT3 agonist. C. officinalis extract, morroniside and 5-HT3 receptor antagonist (ramosetron) attenuated 5-HT-induced diarrhea. Furthermore, morroniside (20 and 50 mg/kg) prevented EtOH/HCl-induced gastric ulcers and those caused by 5-HT. Morroniside (20 and 50 mg/kg) attenuated elevations in the plasma levels of corticosterone, corticotropin-releasing factor (CRF), and adrenocorticotropic hormone (ACTH) in 75 mM HCl/90 % EtOH- and 5-HT-treated mice. The results obtained herein suggest the potential of morroniside as an effective treatment for irritable bowel syndrome, such as diarrhea and functional dyspepsia (reductions in gastric emptying and small intestinal motility), caused by 5-HT. The present study suggests a role for morroniside in the regulation of elevations in CRF, ACTH, and corticosterone levels through hypothalamic-pituitary-adrenal axis activity induced by stress loading, such as a 5-HT treatment and/or HCl/EtOH stimulation.

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).

Long-term outcome of unilateral adrenalectomy for primary bilateral macronodular adrenal hyperplasia.

Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a form of Cushing's syndrome (CS) characterized by heterogeneous cortisol secretion and clinical comorbidities. Previously, bilateral adrenalectomy was the standard treatment for PBMAH, but this approach carried a high risk of primary adrenocortical insufficiency. In recent decades, unilateral adrenalectomy (U-Adx) has emerged as an effective alternative. However, limited research exists on its postoperative efficacy and prognostic predictors. Therefore, the present study aimed to investigate the long-term effectiveness and prognostic predictors of U-Adx in treating PBMAH. A total of 61 patients with PBMAH diagnosis who underwent U-Adx at a single center between 2004 and 2022 were retrospectively evaluated. Patients were categorized into persistent hypercortisolism and remission groups based on postoperative biochemical outcomes at the last follow-up (>12 months after U-Adx). Clinical characteristics, comorbidities, plasma adrenocorticotropic hormone (ACTH), serum cortisol, and 24-h urinary-free cortisol (24-h UFC) levels were analyzed pre- and postoperatively. We further examined whether baseline plasma ACTH, serum cortisol, 24-h UFC levels, and the inhibition of cortisol and 24-h UFC after a low-dose dexamethasone suppression test (LDDST) could predict non-remission following U-Adx. Additionally, we explored the improvements in hypertension, abnormal glucose metabolism, osteoporosis, and other complications in patients with PBMAH post-U-Adx. After U-Adx, 22 of the 45 patients (48.89%) achieved initial remission within 6 months. At the last follow-up, 25 of the 45 patients underwent all required biochemical tests and cortisol assessment tests, among which eight of 25 (32.00%) were in remission and 17 of 25 (68.00%) were experiencing persistent hypercortisolism. Moreover, five of those 25 patients exhibited recurrence after initial remission. Baseline 24-h UFC level > 2 times the upper limit of normal (2ULN) and unsuppressed 24-h UFC after LDDST may predict persistent hypercortisolism postoperatively. Lastly, long-term postoperative follow-up revealed that hypertension decreased with hypercortisolism remission, whereas osteoporosis worsened with persistent hypercortisolism. The short-term remission rate of hypercortisolism was 48.89% in patients with PBMAH treated with U-Adx, while a long-term remission rate of 32.00% was achieved after a median follow-up of 38.58 months. Furthermore, this finding suggests that baseline 24-h UFC level > 2ULN and unsuppressed 24-h UFC after LDDST predict persistent hypercortisolism in the long-term post-U-Adx. Finally, U-Adx improved cortisol circadian rhythm alterations and ACTH suppression in the patients in the remission group, thereby substantially alleviating hypertension and delaying the development of osteoporosis linked to PBMAH.

8034 Putting the Pieces Together: Carney Complex, A Hyper-Rare Congenital Neoplastic Syndrome

Abstract Disclosure: G. Fontanazza: None. A.R. Conforti: None. K. Bird: None. M. Caplan: None. Intro: Carney complex (CNC) is an autosomal dominant disorder characterized by multisystem neoplasia that primarily affects the thyroid, pituitary, and adrenal glands. Its prevalence is not well established, as only 750 cases have been reported worldwide. This condition arises when an inactivating PRKAR1A gene mutation results in dysregulated cell proliferation and tumorigenesis. Complications include the potential for malignant transformation and systemic manifestations, necessitating comprehensive management and ongoing surveillance of disease progression. Case: The patient is a 58-year-old woman who initially presented as a teenager with complaints of hirsutism, truncal obesity, and violaceous abdominal striae. Initial workup revealed a low-dose dexamethasone suppression test that resulted in a non-suppressed cortisol levels. She also had undetectable adrenocorticotropic hormone (ACTH) levels. Imaging revealed no pituitary masses and demonstrated slight bilateral adrenal enlargement without adenomas. Despite these results, she was empirically treated for presumed pituitary-dependent Cushing's disease and received external beam radiation. Despite treatment, she continued to have episodes of hypercortisolism that were apparent clinically and biochemically. Over time, she developed a cardiac myxoma with six cerebrovascular accidents and multiple benign tumors. As an adult, she underwent extensive endocrine evaluation, which revealed urine cortisol excretion that paradoxically rose in response to dexamethasone. ACTH levels were always undetectable, even when she was significantly hypercortisolemic. Genetic testing revealed a homozygous mutation in the melanocortin-2 receptor (MC2R). Accordingly, she elected to have a bilateral adrenalectomy and was started on hydrocortisone and fludrocortisone. Discussion: The patient exhibited ACTH-independent micronodular adrenal hyperplasia and its most frequent variant, primary pigmented nodular adrenocortical disease. Bilateral pigmented nodular hyperplasia is a finding which can occur in association with CNC and cause episodic hypercortisolism. These patients have been shown to respond to dexamethasone with a paradoxical increase in glucocorticoid excretion. While management requires ongoing surveillance, this patient had not been diagnosed until later in life and did not have regular screening. When speculating on the late detection, her story reflects the parable of the blind men and the elephant: endocrinology managed Cushing's disease, cardiology managed atrial myxoma, and oncology managed osteochondromyxomas. Limited perspective with specialized management and an inability to see the whole picture led to prolonged diagnosis with unfortunate sequelae. This report encourages physicians to develop perspective awareness and to consider the entire picture when treating patients. Presentation: 6/2/2024

6640 Utility of bilateral inferior petrosal sinus sampling for diagnosis and management of Cushing's disease in children ; a case report

Abstract Disclosure: V. leal: None. L. Socha: None. S.S. Awadalla: None. The causes of adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS) are Cushing's disease (CD) and ectopic ACTH syndrome (EAS). The differential diagnosis of CS and the localization of lesions in CD and EAS are often challenging. The utility of bilateral inferior petrosal sinus sampling (BIPSS), an important test in adults, is less defined in children.A 16-year-old girl was referred for evaluation and treatment of Cushing syndrome she experienced weight gain, secondary amenorrhea, and back pain. 24-hour urinary free cortisol and low-dose dexamethasone suppression tests suggested Cushing syndrome. Adrenocorticotropic hormone (ACTH) level and high-dose dexamethasone suppression test confirmed Cushing disease. Pituitary magnetic resonance reported a microadenoma. To rule ectopic ACTH syndrome, and localize the pituitary tumor, bilateral inferior petrosal sinus sampling (BIPSS) was performed with desmopressin to stimulate ACTH. Finally, the patient was diagnosed with Cushing disease due to right ACTH-secreting pituitary microadenoma and underwent endoscopic endo-nasal transsphenoidal surgery.In conclusion , BIPSS can be a valuable tool not only for discriminating between pituitary origin and ectopic ACTH-secreting Cushing syndrome, but also for providing precise localization of pituitary adenomas, thereby facilitating appropriate treatment. Presentation: 6/1/2024