ACTH Research Articles

Predicting iatrogenic adrenal insufficiency in neonates exposed to prolonged steroid courses: do cortisol levels help?

ObjectiveTo determine whether random cortisol levels obtained in neonates to assess for secondary adrenal insufficiency (AI) after prolonged steroid exposure are predictive of central AI.Study designData were collected on neonates born 2017–2022 who received ≥10 consecutive days of systemic steroids and had cortisol measured thereafter. Data were then collected on whether those neonates developed signs of AI or had a failed adrenocorticotropic hormone (ACTH) stimulation test.ResultsOf the 71 cortisol levels (in 67 neonates) that were analyzed, there was no difference in cortisol levels between neonates who developed AI (median cortisol level of 6.5 mcg/dl) and those who did not (median of 9.2 mcg/dl), or between those who failed their ACTH stimulation test or passed it, using Wilcoxon ranked sum tests.ConclusionThese findings demonstrate that cortisol levels may not be helpful in identifying AI in neonates exposed to prolonged steroids.

Hypopituitarism with secondary adrenocortical insufficiency and arginine vasopressin deficiency due to hypophysitis after COVID-19 vaccination: a case report

BackgroundAlthough vaccination against coronavirus disease (COVID-19) has several side effects, hypopituitarism due to hypophysitis has rarely been reported.Case presentationAn 83-year-old healthy woman, who had received her fourth COVID-19 vaccine dose 2 days before admission, presented to the emergency department with difficulty moving. On examination, impaired consciousness (Glasgow Coma Scale: 14) and fever were observed. Computed tomography and magnetic resonance imaging of the head revealed swelling from the sella turcica to the suprasellar region. Her morning serum cortisol level was low (4.4 μg/dL) and adrenocorticotropic hormone level was normal (21.6 pg/mL). Central hypothyroidism was also suspected (thyroid stimulating hormone, 0.46 μIU/mL; free triiodothyronine, 1.86 pg/mL; free thyroxine, 0.48 ng/dL). Secondary adrenocortical insufficiency, growth hormone deficiency, delayed gonadotropin response, and elevated prolactin levels were also observed. After administration of prednisolone and levothyroxine, her consciousness recovered. On the 7th day of admission, the patient developed polyuria, and arginine vasopressin deficiency was diagnosed using a hypertonic saline test. On the 15th day, the posterior pituitary gland showed a loss of high signal intensity and the polyuria resolved spontaneously. On the 134th day, the corticotropin-releasing hormone loading test showed a normal response; however, the thyrotropin-releasing hormone stimulation test showed a low response. The patient’s disease course was stable with continued thyroid and adrenal corticosteroid supplementation.ConclusionsHerein, we report a rare case of anterior hypopituitarism and arginine vasopressin deficiency secondary to hypophysitis following COVID-19 vaccination.

A Narrative Review of Chondrocalcinosis: Clinical Presentation, Diagnosis, and Therapies.

Calcium pyrophosphate deposition disease is categorized into radiographic chondrocalcinosis, acute calcium pyrophosphate arthritis, chronic calcium pyrophosphate arthritis, and osteoarthritis with calcium pyrophosphate deposition. These entities collectively are characterized by the deposition of calcium into joints, which then may cause localized and systemic inflammation, resulting in pain and swelling in the affected joints. Patients with the ANKH gene are more susceptible to the development of CPP arthritis as are those with primary hyperparathyroidism, hypomagnesemia, and hemochromatosis. Radiographic chondrocalcinosis is asymptomatic. Acute calcium pyrophosphate arthritis results in self-limited periods of joint pain and swelling in the affected joint. Along with localized inflammation, there may also be systemic inflammation characterized by fever and elevated inflammatory markers. Chronic calcium pyrophosphate arthritis results in periods of quiescence interrupted by flares that are identical to acute periods of disease. Osteoarthritis associated calcium pyrophosphate arthritis presents with chronic pain well described in osteoarthritis with periods of acute flares. In 2023, a joint effort by the American College of Rheumatology and the European League Against Rheumatism developed guidelines meant to aid in the recognition of calcium pyrophosphate deposition diseases. The diagnosis is made if there is proof of either crowned dens syndrome or synovial fluid analysis demonstrating calcium pyrophosphate crystals or when more than 56 points are summed utilizing the criteria described in the guidelines. Radiographic chondrocalcinosis requires no therapy. Acute calcium pyrophosphate arthritis is treated with the goal of aborting the flare. Treatment options include nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, oral corticosteroids, parenteral corticosteroids, intraarticular corticosteroids, IL-1 inhibitors, or parenteral adrenocorticotropic hormone (ACTH). The goal in treatment for chronic calcium pyrophosphate arthritis is the suppression of acute flares. The drugs used for acute flare treatment may be given as maintenance therapy with the additional options of methotrexate and hydroxychloroquine.

Systemic absorption of triamcinolone acetonide is increased from intrasynovial versus extrasynovial sites and induces hyperglycemia, hyperinsulinemia, and suppression of the hypothalamic-pituitary-adrenal axis.

Steroid-associated laminitis remains a major concern with use of corticosteroids in horses. Individual case factors such as joint pathology, pre-existing endocrinopathies, or corticosteroid type, dose, and timing influencing steroid-induced laminitis risk have not been investigated. This study aimed to determine if systemic absorption of triamcinolone acetonide (TA) varies between intrasynovial (antebrachiocarpal) and extrasynovial (sacroiliac) injection sites, and to determine the effects of TA absorption on glucose, insulin, cortisol, and adrenocorticotropic hormone (ACTH). Twenty adult horses were randomized into antebrachiocarpal or sacroiliac joint injection groups, and each horse received bilateral injections with a total dose of 18 mg triamcinolone. Blood was collected prior to injection and at 1, 2, 4, 6, 8, 10, 12, 16, 20, 24, 36, 48, 60, and 72 h post-injection. Peak TA absorption occurred at 8 h in both groups, and was significantly higher in the intrasynovial group compared to the extrasynovial group (1.397 ng/mL, 0.672 ng/mL, p < 0.05). Plasma TA levels were significantly higher in the intrasynovial group from 8 to 36 h post-injection (p < 0.05). There was no difference in glucose, insulin, cortisol, or ACTH between groups at any time point. Insulin and glucose were significantly increased from baseline at all timepoints from 10-72 h and 1-72 h post-injection, respectively. Horses with elevated baseline insulin values (>20 μU/mL) from both groups experienced a more marked hyperinsulinemia, reaching a mean peak insulin of 197.5 μU/mL as compared to 90.06 μU/mL in those with normal baseline insulin. Cortisol and ACTH were significantly decreased from baseline at timepoints from 4-72 h post-injection in both groups. This study is the first to evaluate drug absorption from the sacroiliac site and demonstrates that drug absorption varies between intrasynovial and extrasynovial injection sites. TA absorption causes metabolic derangements, most notably a marked hyperinsulinemia that is more severe in horses with elevated baseline insulin values. The influence of baseline endocrinopathies on response to corticosteroid administration as well as the effect of corticosteroid-induced metabolic derangements warrant further investigation as risk factors for corticosteroid-associated laminitis.

A study on the early metabolic effects of salt and fructose consumption: the protective role of water

Increasing serum osmolality has recently been linked with acute stress responses, which over time can lead to increased risk for obesity, hypertension, and other chronic diseases. Salt and fructose are two major stimuli that can induce acute changes in serum osmolality. Here we investigate the early metabolic effects of sodium and fructose consumption and determine whether the effects of sodium or fructose loading can be mitigated by blocking the change in osmolality with hydration. Forty-four healthy subjects without disease and medication were recruited into four groups. After overnight fasting, subjects in Group 1 drank 500 mL of salty soup, while those in Group 2 drank 500 mL of soup without salt for 15 min. Subjects in Group 3 drank 500 mL of 100% apple juice in 5 min, while subjects in Group 4 drank 500 mL of 100% apple juice and 500 mL of water in 5 min. Blood pressure (BP), plasma sodium, and glucose levels were measured every 15 min in the first 2 h. Serum and urine osmolarity, serum uric acid, cortisol, fibroblast growth factor 21 (FGF21), aldosterone, adrenocorticotropic hormone (ACTH) level, and plasma renin activity (PRA) were measured at the baseline and 2 h. Both acute intake of salt or fructose increased serum osmolality (maximum ∼4 mOsm/L peaking at 75 min) associated with a rise in systolic and diastolic BP, PRA, aldosterone, ACTH, cortisol, plasma glucose, uric acid, and FGF21. Salt tended to cause greater activation of the renin-angiotensin-system (RAS), while fructose caused a greater rise in glucose and FGF21. In both cases, hydration could prevent the osmolality and largely block the acute stress response. Acute changes in serum osmolality can induce remarkable activation of the ACTH-cortisol, RAS, glucose metabolism, and uric acid axis that is responsive to hydration. In addition to classic dehydration, salt, and fructose-containing sugars can activate these responses. Staying well hydrated may provide benefits despite exposure to sugar and salt. More studies are needed to investigate whether hydration can block the chronic effects of sugar and salt on disease.

Effects of chronic exposure to a high fat diet, nutritive or non-nutritive sweeteners on hypothalamic-pituitary-adrenal (HPA) and -gonadal (HPG) axes of male Sprague-Dawley rats.

Diet-related factors are of great significance in the regulation of hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonad (HPG) axes. In this study, we aimed to investigate the effects of chronic exposure to a high fat diet (HFD), fructose or sucralose on the endocrine functions. Male, Sprague-Dawley rats received a normal chow diet, HFD, 10% fructose or 0.02% sucralose for 10 weeks. Behavioral changes were assessed by open field (OFT) and elevated plus-maze (EPM) tests at week 8. H&E staining was used to observe pathological changes in adrenal cortex, testis and perirenal adipose tissue. Serum hormone concentrations were quantified via enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of genes along the HPA and HPG axes were determined using real-time PCR. All types of dietary interventions increased body weight and disturbed metabolic homeostasis, with anxiogenic phenotype in behavioral tests and damage to cell morphology of adrenal cortex and testis being observed. Along the HPA axis, significantly increased corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) concentrations were observed in the HFD or 0.02% sucralose group. For HPG axis, gonadotropin-releasing hormone (GnRH) and estradiol (E2) concentrations were significantly increased in all dietary intervention groups, while decreased concentrations of follicle-stimulating hormone (FSH) and testosterone (T) were also detected. Moreover, transcriptional profiles of genes involved in the synthesis of hormones and corresponding hormone receptors were significantly altered. Long-term consumption of HFD, fructose or sucralose manifested deleterious effects on endocrine system and resulted in the dysregulation of HPA and HPG axes.

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.

The Influence of Dietary Synbiotic on Agonistic Behavior, Stress, and Brain Monoamines via Modulation of the Microbiota–Gut–Brain Axis in Laying Hens

A complex system of neural pathways, collectively known as the microbiota–gut–brain (MGB) axis, interconnects the gut microbiota, the gastrointestinal system, and the brain along with its periphery. Previous studies have demonstrated that modulation of the MGB axis can influence stress-related behaviors such as anxiety. This connection becomes apparent in scenarios like agonistic behavior in laying hens, which is characterized by aggressive head and feather pecks, that can ultimately result in cannibalism and death. The objective was to examine the effects of a dietary synbiotic on agonistic behavior, plasma and brain monoamines, stress parameters, and cecal microbiota counts via modulation of the MGB axis. A total of 396 W36 Hy-Line laying hens were provided at random with a control (CON: basal diet) or treatment (SYN: basal diet supplemented with synbiotic) diet from 50 to 60 weeks old (nine pens/treatment, 22 birds/pen). Blood samples and video recordings (three consecutive days/week) were taken at 50 and 60 weeks. At 60 weeks, three hens/pen were euthanized for brain and cecal microbiota collection. Threatening, fighting, head, body, and feather pecking all occurred less frequently at 60 weeks in the SYN group (p &lt; 0.05). Plasma corticosterone, adrenocorticotropic hormone, dopamine, and serotonin were significantly lower while tryptophan and 5-hydroxyindoleacetic acid were significantly higher in birds from the SYN group (p &lt; 0.05). Significant differences in serotonin, 5-hydroxyindoleacetic acid, dopamine, homovanillic acid, and 3,4-dihydroxyphenylacetic acid were observed in the hypothalamus, hippocampus, and amygdala of the brain. Serotonin and dopamine turnover rates were significantly different in all three regions of the brain (p &lt; 0.05). Cecal counts of Lactobacillus and Bifidobacterium were significantly higher in the SYN group (p &lt; 0.05). Synbiotic supplementation resulted in many significant differences, indicating activation of the serotonergic systems and modulation of both the MGB axis and HPA axis with positive effects on welfare and stress.

Early Response, Long-Term Seizure Outcome, and Very-Low-Dose Adrenocorticotrophic Hormone Therapy for Infantile Epileptic Spasms Syndrome With Down Syndrome

BackgroundInfantile epileptic spasms syndrome (IESS) with Down syndrome has good treatment response and good seizure outcomes with high-dose adrenocorticotrophic hormone (ACTH) therapy. We investigated the early treatment response of epileptic spasms (ES), long-term seizure outcome, and efficacy of very-low-dose ACTH therapy for IESS with Down syndrome. MethodsWe retrospectively investigated patients with Down syndrome and IESS between April 1983 and January 2023. We defined response to treatment as clinical remission and electrographic resolution of hypsarrhythmia after treatment for more than one month and early treatment as any treatment for ES within three months of initiation of treatment. Long-term seizure outcomes were determined by the presence of any type of seizure within one year of the last visit. We investigated the dosage and efficacy of very-low-dose ACTH therapy. ResultsThirty patients were enrolled with a median follow-up period of 7.7 years (range: 1.3 to 19.1). The response and relapse rates in the early treatment were 83.3% and 16.0%, respectively. The seizure-free rate of long-term seizure outcomes was 80.0%. Long-term seizure outcomes correlated with early treatment response to ES. The response rate of very-low-dose ACTH therapy was 59.3%. The efficacy of ACTH therapy tended to be dose-dependent (P = 0.055). ConclusionsEarly treatment response to ES may be useful in predicting long-term seizure outcomes of IESS with Down syndrome. Very-low-dose ACTH therapy was the most effective treatment for ES and could exhibit dose-dependent efficacy. Depending on the IESS etiology, the ACTH dose could be reduced to minimize its side effects.

Patient with type 1 diabetes mellitus with poor glycemic control with adrenocorticotropic hormone (ACTH)-secreting pituitary macroadenoma

Patient with type 1 diabetes mellitus with poor glycemic control with adrenocorticotropic hormone (ACTH)-secreting pituitary macroadenoma

Effect of Maternal High Fat Diet on the Hypothalamus-Pituitary-Adrenal Gland (HPA) Axis of the Offspring in Sheep

Maternal consumption of a high fat diet (HFD) during pregnancy is associated with metabolic dysfunction and altered HPA axis function in the offspring. These effects are well established in species with short gestation length (e.g., rodents), but less established in species with longer gestation periods more comparable with humans. The objective of the study was to determine the effect of maternal HFD on basal and stimulated cortisol secretion in the offspring at 16 weeks of age in sheep. All experiments were approved by the Institutional Animal Care and Use Committee at Cal Poly Pomona. Pregnant ewes were assigned to control (n=3) and HFD (n=3) groups. The control group was fed farmers best complete ewe and ram pellets. The HFD group was fed the same diet with an additional 30% rumen protected fat (Megalac, Volac Wilmar Feed Ingredients Ltd). After birth lambs were weaned at 12 weeks of age and given free access to control pellet diet with grains. To assess adrenal cortisol secretion at 16 weeks, lambs were infused intravenously with adrenocorticotropic hormone (ACTH; 2 ug/kg cortrosyn in 1 mL saline). Blood samples (1 mL) were taken through the jugular catheter at −30, −15, and 0 min (immediately before) and 5, 15, 30, 60, 90, and 120 min after ACTH administration for measurement of plasma cortisol by ELISA. Data were analyzed by two-way repeated measures ANOVA with a Tukey posthoc test. Basal plasma cortisol tended to be higher in HFD (32±8 ng/mL) than control (13±3 ng/mL) lambs, but this did not reach statistical significance. Plasma cortisol was higher than baseline from 15 to 90 minutes after ACTH administration in all lambs (p&lt;0.05). The increment in plasma cortisol was higher in HFD than control lambs from 15-90 minutes (p&lt;0.05). Accordingly, the maximum increase in plasma cortisol at 60 minutes and was higher in HFD (245±8 ng/mL) than control lambs (121±50 ng/mL p&lt;0.05). These preliminary data suggest that maternal consumption of a high fat diet during pregnancy may increase basal and stimulated activity of the HPA axis in sheep. The study was funded by a Strategic Interdisciplinary Research Grant (SIRG) at California State Polytechnic University, Pomona. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Pituitary Neuroendocrine Tumor Organoids Generated from Induced Pluripotent Stem Cells Reveal the Dysregulation of Cell Lineage Differentiation in Cushing’s Disease

Background: Cushing’s Disease (CD) is an endocrine disease typically caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary neuroendocrine tumor (PitNET). Corticotroph subtype PitNETs subsequently stimulate the adrenal glands to overproduce causing a wide range of detrimental effects on health, including increased stroke rates, diabetes, obesity, depression, anxiety, and a threefold increase in the risk of death from cardiovascular disease. In some instances, CD is a manifestation of genetic mutation syndromes that include MEN1, FIPA, CDH23 and Carney complex. In other cases, somatic mutations underlie the development of CD including mutations in the deubiquitinase gene USP8, identified in 35-62 % of sporadic corticotroph PitNETs and USP48 as a driver mutation in USP8 wild-type tumors. There are currently no in vitro models to study the impact of genetic mutations on the pathways leading to PitNET development in humans. Objective: To define the cellular complexity of corticotroph subtype PitNETs at a spatial single-cell resolution. Methodology: Organoids were generated from a CD patient expressing a CDH23 mutation (hPitNETO iPSCDH23) as reported by our group (Mallick et al., 2023, Translational Research). CRISPR-Cas9 gene editing of iPSCs was also used to model the development of corticotroph PitNETs expressing USP48 and USP8 mutations. Human PitNET organoids (PitNETOs) were generated from tumor tissue harvested during transsphenoidal surgery. Cell lineage trajectory analysis was performed on scRNA-seq data collected during the iPSC differentiation program. ScRNA-seq was used to compare the transcriptomic profile and cell composition of CD patient PitNETOs to the patient’s own tissue using the NanoString CosMxTM spatial transcriptomic analysis. Results: Organoids generated from a CD patient expressing a CDH23 mutation (hPitNETO iPSCDH23) exhibited tumor behavior consistent with the expected pathology and function of sparsely granulated corticotroph PitNETs. Cell lineage trajectories of hPitNETO iPCCtrl control cultures revealed multiple branching paths from the stem-like (SOX2/PAX7+) base cluster leading to clusters enriched for markers of pituitary cell lineages (lactotroph, somatotroph, thyrotroph, gonadotroph and corticotroph). Trajectory analysis for hPitNETO iPSCDH23 showed dysregulation in the normal pituitary cell lineage differentiation leading to the development of poorly differentiated corticotrophs (PAX7+/TPit+) and PAX7+/stem cells. CosMxTM spatial gene mapping revealed a cell population co-expressing PAX7 and stem cell markers SOX2 and CD44 that was abundant in Crooke cell and sparsely granulated TPit+ PitNET subtypes. An increase in the PAX7/SOX2/CD44 PitNET cell population correlated with a higher Knosp grade, tumor size and invasiveness, when compared to densely granulated PitNETs. Conclusions: Defining the complexity of the PitNET microenvironment will provide insights into the pathogenesis of CD and potentially lead to the stratification of high-risk patients for disease recurrence. 1R01DK133325. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Infertility in POMC-deficient mice

The pro-opiomelanocortin (POMC) gene is expressed in the hypothalamus and pituitary and its product is cleaved into several peptides including the melanocyte stimulating hormones (α, β, or γ-MSH), adrenocorticotropic hormone (ACTH), and beta-endorphin. Alpha-MSH is involved in regulating appetite, sexual behavior, and melanin, while ACTH regulates secretion of glucocorticoids from the adrenal cortex. Humans who have a POMC mutation either produce an abnormally short version of POMC or are missing the protein completely and therefore lack these hormones. This has biological consequences including red hair and fair skin, early-onset obesity (due to severe hyperphagia), and potentially hypothyroidism, hypogonadism, and infertility. Many of these same effects are seen with mice containing this deficiency. We are interested in studying infertility through a mouse model of hypothalamic-specific POMC-deficiency. These mice also experience early-onset obesity and infertility. Estradiol is a key reproductive hormone that is essential for fertility. POMC deficiency may lead to hypogonadism, which can cause low levels of estrogen so we hypothesize that POMC-deficient mice have reduced estrogen levels, which may contribute to their infertility. To test this hypothesis, we will measure estrogen levels in POMC-deficient mice at different stages of the estrus cycle using an estradiol ELISA kit. We expect the POMC-deficient mice to have lower estrogen levels than control mice. We also plan to use liquid chromatography mass spectrometry (LC-MS) to measure estrogen levels. Before collecting the blood samples, vaginal cell samples are obtained and viewed under a microscope to analyze the ratio of cells and determine which stage the females were in—proestrus, estrus, metestrus, or diestrus. Blood samples are then collected into 1.5 mL microcentrifuge tubes with 10 microliters of 0.5 M EDTA to prevent blood clotting. After blood is collected, it is centrifuged at 2,000 g for 20 minutes at 4 degrees Celsius. The plasma is then stored at -80 degrees Celsius until analysis. Based on preliminary results we expect the POMC deficient mice to have reduced estrogen and/or altered levels throughout the cycle. So far, our results have indicated that POMC-deficient female mice have abnormal estrus cycles and also reduced uterine weights. The conclusions from this study will help us understand more about the causes of infertility in POMC-deficient mice, which may also lead to greater understanding on how to treat humans with infertility due to a POMC mutation. Support for this research was provided by IRACDA grant NIHK12GM111725 to Z.T. and UVU Scholarly Activities Grant to A.G. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Cardiovascular Risk Factors in Sheehan's Syndrome: A Case-Control Study.

Obesity, dyslipidaemia and insulin resistance are associated with hypopituitarism. The association between these conditions and Sheehan's syndrome (SS) caused by post-partum pituitary gland necrosis is poorly understood. This study aimed to assess cardiovascular risk surrogate markers in SS patients, and we compared clinical, biochemical and radiological testing with healthy controls. In this cross-sectional study, we studied 45 patients with SS on standard replacement therapy and compared them with healthy controls. All subjects underwent anthropometric, inflammatory marker and hormonal measurement (adrenocorticotropic hormone (ACTH), stimulated cortisol, insulin-like growth factor-1 (IGF-1), thyroxine (T4), follicle-stimulating hormone (FSH), luteinising hormone (LH), oestradiol (E2), prolactin (Prl), insulin, interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP)). Carotid intima-media thickness (CIMT), flow-mediated dilation (FMD) and echocardiography were also performed. The mean age and body mass index (BMI) of SS patients were 48.1 ± 10.0 years and 24.3 ± 4.3 kg/m2, respectively, while those of controls were 44.6 ± 12.0 years and 24.6 ± 3.2 kg/m2, respectively. Systolic blood pressure was significantly higher in SS (124.6 ± 20.8 vs. 117.0 ± 18.6 mm of Hg, P < 0.05). All SS patients were hypothyroid, and all except one were hypocortisolaemic. Triglyceride (TG) levels were significantly higher in SS patients (165.6 ± 83.3 vs. 117.2 ± 56.1, P < 0.01), but no difference in the prevalence of metabolic syndrome (MetS) was found. hs-CRP (9.1 (5.2-18.5) vs. 1.5 (0.6-2.8), P < 0.001) and IL-6 (4.9 (3.7-7.3) vs. 3.1 (2.0-4.2), P < 0.001) were significantly higher in SS patients. CIMT was significantly increased in SS patients, but no difference in FMD was found. Echocardiography revealed no significant difference in left ventricular (LV) dimensions, interventricular thickness, posterior wall thickness, ejection fraction, LV mass and diastolic function. SS patients show increased cardiovascular risk with hypertension, dyslipidaemia and increased atherosclerotic and inflammatory markers.

478. Elevated Plasma Adrenocorticotropic Hormone (ACTH) Levels Correlate With Reduced Suicidal Thoughts in Psychiatric Patients Relative to Control Groups, Regardless of Depression Intensity

478. Elevated Plasma Adrenocorticotropic Hormone (ACTH) Levels Correlate With Reduced Suicidal Thoughts in Psychiatric Patients Relative to Control Groups, Regardless of Depression Intensity

The influence of cortisol co-secretion on clinical characteristics and postoperative outcomes in unilateral primary aldosteronism.

The prevalence of unilateral primary aldosteronism (UPA) with cortisol co-secretion varies geographically. To investigate the prevalence and clinical characteristics of UPA with cortisol co-secretion in a Chinese population. Retrospective cohort study. We recruited 580 patients with UPA who underwent cosyntropin stimulation test (CST) after the 1-mg dexamethasone suppression test (DST) and retrospectively analyzed the clinical characteristics and postoperative outcomes of UPA with and without cortisol co-secretion. UPA with cortisol co-secretion (1 mg DST>1.8 ug/dL) was identified in 65 of 580 (11.2%) patients. These patients were characterized by older age, longer duration of hypertension, higher concentration of plasma aldosterone and midnight cortisol, lower adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEAS), larger tumor diameter, and more history of diabetes mellitus. Cortisol and aldosterone levels were higher and DHEAS level was lower in UPA with cortisol co-secretion at 0-120 min after CST. Among 342 UPA patients with KCNJ5 gene sequencing and follow-up results, the complete clinical success rate was lower in UPA with cortisol co-secretion (33.3% vs. 56.4%, P<0.05); the complete biochemical success rate and KCNJ5 mutation did not differ between the two groups. Age, tumor size, and ACTH were independent predictors of UPA with cortisol co-secretion. Sex, BMI, duration of hypertension, KCNJ5 mutation, and cortisol co-secretion were independent predictors for complete clinical success in UPA after surgery. UPA with cortisol co-secretion is not uncommon in China, but the clinical features were distinctly different from those without co-secretion. Cortisol co-secretion is an independent risk factor for incomplete clinical success after surgery in UPA.

THE EFFECT OF N-STEAROYLETHANOLAMINE ON THE STRESS HORMONES LEVELS IN OLD RATS WITH INDUCED CHRONIC INFLAMMATION

Numerous studies aimed at elucidating the evolutionary acquisition of the endocannabinoid system gradually expand our understanding of the development and functioning of living organisms. It is now well-known the indispensable role of endocannabinoids in higher nervous activity and other signaling high-activity compounds. Among the representatives of this system are saturated long-chain N-acyl ethanolamines, including N-stearoylethanolamine. Previous studies have illuminated a range of important functional features of NSE on various biochemical processes, including anti-inflammatory, neuroprotective, and antidyslipidemic properties. Aim. Considering the involvement of the endocannabinoid system in neurotransmission processes and the influence of NAE on steroidogenesis, hypotheses have been formed and, accordingly, the goal of determining the involvement of NSE as an adaptogen of the sympathoadrenal and hypothalamo-pituitary-adrenal systems, including its influence on their functional state in rats during aging under conditions of low-grade chronic inflammatory processes. Methods. To achieve this goal, an experimental group of animals with "pathological" aging was formed, to which NSE was administered for some time. At the end of the experiment, blood plasma was collected from the animals, and the concentration of circulating adrenaline, corticosterone, and adrenocorticotropic hormones was analyzed using immunoassay and spectrophotometric methods. Results. During the analysis of the obtained results, geroprotective properties of NSE were identified, which likely result from an indirect pathway of its influence on humoral regulation systems. Conclusions. Analysis of the obtained results suggests that saturated N-acylethanolamines (NAEs), including NSE, may act as direct modulators of endocannabinoid system activity or indirect regulators by regulating steroidogenesis, integrating into the system of humoral regulation.

West Syndrome due to ALG13 mutation presenting vigabatrin-associated reversible MRI signal changes and drug-induced dyskinesia

Heterozygous mutations in the asparagine-linked glycosylation 13 (ALG13) gene cause a rare genetic disorder that severely affects neurological development. Symptoms associated with ALG13 mutations include severe epilepsy and/or West syndrome (WS). Most cases reported in the literature describe typical characteristics of patients within whom de novo mutations have been identified. A 5-month-old girl with developmental delay and epileptic spasms, without dysmorphic features, is described. Electroencephalography (EEG) showed hypsarrhythmia, compatible with WS, but complementary examinations did not find an underlying etiology. Vigabatrin therapy was started, and then adrenocorticotropic hormone (ACTH) therapy was added. On follow-up, brain magnetic resonance imaging (MRI) revealed restricted diffusions compatible with vigabatrin-associated reversible MRI signal changes. As the spasms and hypsarrhythmia on EEG persisted, a second cycle of ACTH was performed, and then, the patient manifested a hyperkinetic movement, characteristic of drug-induced dyskinesia. Further investigation was carried out, and whole-exome sequencing revealed a de novo pathogenic variant in ALG13 gene. The current case report expands our knowledge of WS by considering a female patient with unspecific clinical features arising from an undefined subjacent etiology. This case also emphasizes the importance of a thorough work-up to determine the underlying genetic etiology and presents the challenges in the diagnostic investigation in clinical practice.

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.

Increased Adrenocorticotropic Hormone Levels Predict Recovery of Consciousness in Patients With Disorders of Consciousness.

The potential influence of pituitary-related hormones (including both pituitary gland and target gland hormones) on functional recovery after traumatic brain injury has been observed. However, the relationship between these hormones and the recovery of consciousness in patients with disorders of consciousness (DOC) remains unclear. In this retrospective and observational study, 208 patients with DOC were recruited. According to the Glasgow Outcome Scale (GOS) scores after 6 months, patients with DOC were categorized into two subgroups: a favorable prognosis subgroup (n = 38) comprising those who regained consciousness (GOS score ≥3), and a poor prognosis subgroup (n = 156) comprising those who remained in DOC (GOS score <3). Comparative analyses of pituitary-related hormone levels between the two subgroups were conducted. Further, a binary logistic regression analysis was conducted to assess the predictive value of pituitary-related hormones for the patients' prognosis. The favorable prognosis subgroup showed a significant increase in adrenocorticotropic hormone (ACTH) levels (p = 0.036). Moreover, higher ACTH levels and shorter days since injury were significantly associated with a better prognosis, with odds ratios (ORs) of 0.928 (95% confidence interval [CI] = 0.873-0.985, p = 0.014) and 1.015 (95% CI = 1.005-1.026, p = 0.005), respectively. A subsequent receiver operating characteristic (ROC) analysis demonstrated the potential to predict patients' prognosis with an area under the curve value of 0.78, an overall accuracy of 75.5%, a sensitivity of 77.5%, and a specificity of 66.7%. Our findings indicate that ACTH levels could serve as a clinically valuable and convenient predictor for patients' prognosis.