Osilodrostat is an oral steroidogenesis inhibitor used in the treatment of hypercortisolism. It works by inhibiting 11-beta-hydroxylase, a key enzyme in cortisol synthesis. As a consequence of drug action, adrenal insufficiency can be observed in about 40% of patients. Although this effect has been accepted as a consequence of therapy, recent reports suggest adrenal insufficiency can persist even after discontinuation of osilodrostat. We present the case of a 74-year-old female patient who developed prolonged adrenal insufficiency after withdrawal of osilodrostat. The patient was diagnosed with ectopic ACTH-dependent Cushing's syndrome and underwent radiotherapy for a primary lesion located in the anterior mediastinum. During treatment, osilodrostat was introduced (2 to 4 mg/d), and adrenal insufficiency developed within four weeks. Hydrocortisone (intermittently dexamethasone) replacement therapy was initiated, and over time, undetectable morning cortisol levels continued. After de-escalating the osilodrostat dose, the drug was withdrawn 15 months after initiation. Despite being off the drug for 11 months, the patient with adrenal insufficiency (morning serum cortisol: 37.2 nmol/L), still requires hydrocortisone substitution. The underlying mechanism of prolonged adrenal insufficiency after osilodrostat discontinuation remains unclear. It is unknown whether this is due to permanent inhibition of 11-beta-hydroxylase or interference at another step in steroidogenesis. Factors such as treatment duration, dose, or individual sensitivity may play a role, but other mechanisms, such as an adrenolytic effect, should also be considered. We expect an increase of similar cases, which we believe will lead to further research to better understand the mechanisms behind prolonged adrenocortical blockade after osilodrostat discontinuation.

We report the case of a 50-year-old female diagnosed with primary aldosteronism (PA) complicated with mild autonomous cortisol secretion (MACS). The patient had a 5-year history of hypertension, and screening revealed an elevated aldosterone-to-renin ratio (ARR). Although she demonstrated no clinical features of Cushing's syndrome, her serum potassium level was at the lower end of the normal range. The baseline plasma renin activity was <0.2 ng/mL/h, and the plasma aldosterone concentration was 165 pg/mL. Confirmatory tests supported the diagnosis of PA, and computed tomography (CT) revealed a 19-mm tumor in the left adrenal gland. Following a 1-mg dexamethasone suppression test, her serum cortisol level measured 9.0 μg/dL, and the diurnal rhythm of cortisol secretion was absent. Plasma adrenocorticotropic hormone (ACTH) was suppressed. Adrenal venous sampling (AVS) revealed right-sided dominance before and after ACTH stimulation, with lateralization indices of 43.8 and 5.0, respectively. Considering the findings, we prioritized treatment for MACS and performed left adrenalectomy. Hypertension and elevated ARR persisted postoperatively. Histopathological examination revealed a 26-mm CYP11B-positive and CYP11B2-negative adenoma. The surrounding adrenal cortex contained multiple CYP11B1-negative and CYP11B2-positive nodules and micronodules. This case was retrospectively considered to represent bilateral PA. The AVS interpretation was misleading owing to cortisol imbalance between the adrenal veins due to cortisol producing adenoma. Treatment strategies for patients with PA and concurrent MACS should encompass a comprehensive assessment of AVS and CT findings.

Effects of chronic salinity stress on growth performance, physiological response and intestinal microbiota of largemouth bass (Micropterus salmoides).

Traditional coca chewing and cortisol modulation in Andean miners: A pilot quasi-experimental repeated-measures study on stress physiology at high altitude.

Background: Metabolic syndrome is a multifactorial condition characterized by central obesity, insulin resistance, dyslipidemia, and hypertension, leading to increased cardiometabolic risk. Conventional therapies often show limited long-term success due to poor compliance. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, is emerging as a potential adjunct in managing obesity-related metabolic disorders by modulating neural circuits responsible for appetite and impulse control. Aims and Objectives: To evaluate the effect of high-frequency rTMS on anthropometric, behavioral, and biochemical parameters in obese individuals with metabolic syndrome. Materials and Methods: This randomized, single-blind, sham-controlled trial included 30 obese adults divided equally into intervention (real rTMS) and control (sham) groups. The intervention group received 12 sessions of 10 Hz rTMS over the left dorsolateral prefrontal cortex for 4 weeks. Assessments were conducted at baseline, post-therapy, 15 days, and 30 days. Outcomes included body mass index (BMI), waist circumference (WC), body weight, food craving questionnaire-trait (FCQ-T) scores, fasting blood sugar, hemoglobin, lipid profile, high-sensitivity C-reactive protein (hs-CRP), and serum cortisol. Data were analyzed using the Statistical Package for the Social Sciences v21, with P&lt;0.05 considered significant. Results: rTMS produced significant reductions in BMI (−1.06±0.684 kg/m2), WC (−1.59±1.140 cm), body weight (−2.98±1.731 kg), and FCQ-T scores (−14.13±8.927) over 30 days (P=0.001). Triglycerides and hs-CRP decreased significantly, while high-density lipoprotein cholesterol showed mild improvement. Glycemic parameters showed marginal, non-significant changes. Conclusion: High-frequency rTMS is a safe and effective non-pharmacological adjunct that improves obesity-related anthropometric and behavioral outcomes and exerts favorable metabolic effects in patients with metabolic syndrome.

Blood sampling by venipuncture is a routine procedure used in animal experiments and veterinary diagnostics. It can cause stress due to restraint and pain associated with penetration of the skin by a needle. When stressful procedures are repeated, stress can increase through anticipation after negative experiences or decrease due to habituation and/or positive reinforcement. The aim of this study was to describe the reaction to repeated blood sampling on the affective state of the animals. We wanted to observe how repeated blood sampling would affect stress parameters in goats that underwent an intensive cooperative vet care training protocol and were managed with a focus on gentle handling. Eight dairy goats underwent weekly blood sampling over a four-month period as part of a transfer study. Stress parameters were assessed using serum cortisol concentration, temperature changes in the inner corner of the eye measured by infrared thermography, and an ethogram showing voluntary and aversive behavior. Neither the serum cortisol concentration nor the eye temperature changed significantly over time during blood sampling. However, the ethogram showed that the goats approached the blood sampling position significantly faster and more voluntarily. In this study, we did not observe changes within the measured physiological stress parameters due to repeated blood sampling over three months. However, the voluntary behavior of the trained goats increased over time as a result of positive reinforcement training and habituation.

The intensive mariculture of S. aurata can promote aquaculture development, although it can also pose challenges because of predatory behavior and environmental stressors caused by intensification. The objective of this study is to alleviate stress and prevent cannibalism, thereby improving the fish’s performance and welfare. A 90-day growth experiment investigated the dietary inclusion of melatonin (ML) on Sparus aurata performance, physiology, immunity, histopathology, and welfare when grown in saline groundwater (36 ppt) at stocking densities (SD) of 50 fish/500 L‒tank (SD50) and 100 fish/500 L‒tank (SD100). Six fish groups in triplicate were fed three increasing levels of ML (0, 25, and 50 mg/kg− 1 diet) expressed as T1, T2 and T3 under SD50, and T4, T5, and T6 under SD100. Fish (n = 1350) weighing 16.46 ± 0.18 g/fish were grown using a flow-through system and a daily feeding rate of 4%. The results revealed significant declines in nitrogen by-product (NH3 and NO2) levels of fish fed ML in a dose density-dependent manner. Fish fed ML under both densities showed significantly improved growth indices, FCR, growth hormone, and crude protein content compared with those fed the control diet, with T2 and T6 groups achieving the highest values. ML augmentation enhanced serum lipase, protease, immunoglobulin, albumin, globulin, antioxidants, and proinflammatory cytokine interleukin-1β and lowered serum cortisol, glucose, ALT, AST, and ALP. Under both densities, the ML-fish presented healthier livers and intestines than those fed the control diet, which showed marked liver vacuoles and steatotic changes. The ML-SD interaction showed superior fish performance, particularly in groups T2 and T6; thus, it is recommended to administer dietary melatonin at 25 mg/kg for seabream reared at 50 fish per 500-liter tank and 50 mg/kg for those cultivated at 100 fish per 500-liter tank using groundwater.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11259-025-10992-6.

This study investigated the effects of dietary Hydrilla verticillata extract (HVE) on growth performance, physiological responses, and disease resistance in Labeo rohita fingerlings subjected to Aeromonas hydrophila challenge. Following acclimatization, the fish were divided into 15 tanks at random (30 fish per tank) and given five different diets that contained 0, 75, 150, 300, or 600mg/kg HVE for 60 days. Growth was significantly (P < 0.05) boosted by dietary HVE, with 300mg/kg showing the maximum weight gain and protein efficiency ratio, however, higher dose (600mg/kg) reduced the growth performance. In HVE-fed groups, malondialdehyde levels dropped and antioxidant enzyme activity (SOD, CAT, and GPx) significantly increased, suggesting improved oxidative state. Elevated ALP, decreased AST and ALT activity, and decreased serum glucose and cortisol levels all indicated enhanced hepatic function and less stress. At 300mg/kg, nonspecific immunological responses, such as lysozyme activity and total immunoglobulins, were markedly increased. Cumulative mortality decreased dramatically in HVE-supplemented groups after the A. hydrophila challenge, with fish fed 300mg/kg exhibiting the lowest cumulative mortality. The optimal dietary HVE level was calculated as 252.46mg/kg based on weight gain%. These results show that dietary HVE, especially 300mg/kg, significantly enhances Labeo rohita growth, antioxidant defence, immunological function, and resistance to A. hydrophila.

Background This cross-sectional study assessed the impact of long-term use of skin-whitening products containing corticosteroids on the function of the adrenal glands. Objectives To assess the impact of extended use of corticosteroid-based whitening creams on serum cortisol levels and to examine the prevalence of adrenal suppression among habitual users. Methods This research, executed at the Hawija Technical Institute from January to April 2025, included 57 participants aged 20 to 40. Before enrolling, all participants gave their written consent. Individuals with chronic endocrine disorders or those receiving systemic corticosteroids were excluded. They were split into two groups: 38 regular (14 male and 24 female) users of skin-whitening creams (≥3 months) as the experimental group and 19 (7 male and 12 female) non-users as the control group. The Mindray CL-900i, a fully automated chemiluminescence immunoassay analyzer, was used to measure the levels of cortisol in the serum. Results In comparison to controls (7.85 ± 3.54 μg/dL; p = 0.0004), users had a significantly lower mean cortisol level (4.25 ± 2.23 μg/dL), with 42% of users exhibiting cortisol &lt;5 μg/dL, indicating adrenal suppression. There were no discernible variations in BMI between the groups or between male and female users. These results show that extended exposure to corticosteroids suppresses the hypothalamic-pituitary-adrenal axis. Conclusions Using skin-whitening creams that contain corticosteroids too often can make the adrenal glands work less well. It is suggested that public health measures be used to inform users about endocrine risks and to control these products.

ABSTRACTThis study investigated the effect of monophasic oral contraceptive (OC) use on self‐paced cycling performance, thermoregulation, and skeletal muscle strength and contractile properties in healthy women. Eight physically active women performed 30 min fixed intensity cycling at 50% Wmax, followed by a 30 min self‐paced time trial (TT) with each section interspersed with a 30 s maximal sprint at 9, 19, and 29 min. The tests were conducted in different ambient conditions corresponding to either baseline day 1 (20°C, BASE), day 8 (20°C COOL), or day 18 (32°C WARM) of 1 month pill cycle. Core (Tc) and skin (Tsk) temperatures, heart rate, perceptual, neuromuscular responses, and serum cortisol (CORT) were measured multiple times throughout the trials and postexercise. Time trial performance remained unchanged across conditions (range 10.9–11.1 km) although Tc was elevated in WARM in the final 15 min of self‐paced exercise, reaching 38.5°C (p < 0.05). CORT was increased from preexercise, whereas lactate increased in all conditions (p < 0.05). Peak force was significantly reduced from pre (439 ± 95 and 429 ± 121 N) to postexercise (345 ± 91 and 361 ± 94 N) for BASE and WARM, respectively, (p < 0.05). Twitch contractile duration declined (∼14%; p < 0.05) in all conditions along with time to peak force (∼17%, p < 0.05) in BASE and WARM. We conclude that OC use does not affect self‐paced cycling performance across ambient conditions with no detrimental alteration in neuromuscular performance across the menstrual cycle.

Weaning stress impairs calf health by causing growth retardation and immune dysfunction, underscoring the need for targeted interventions. Maternal bovine appeasing substance (MBAS) has been proposed as a novel therapy for stress in cattle, but its efficacy against weaning stress remains unclear. This study assessed the health impacts of weaning and evaluated MBAS as a potential intervention. Health impacts were first evaluated in 60 weaned Holstein calves. Then, another 60 healthy calves of similar age were randomly divided into two groups (n=30/group). Control calves received a single 2.5 mL saline spray one day pre-weaning, while the MBAS group received a single 2.5 mL spray of MBAS (100 mg/mL). Weaning stress increased diarrhea (56.52% to 78.26%) and respiratory disease incidence (10.17% to 15.88%), elevated exercise steps (32196±1267 vs 38226±1132, p=0.0043), and reduced dry matter intake (2.78±0.03 vs 2.59±0.06 kg/d at D4, p=0.0041) and average daily gain (ADG, 0.89±0.05 vs 0.71±0.04 kg/d, p=0.0230) within 15 days post-weaning. MBAS improved ADG (0.92±0.15 vs 1.25±0.14 kg/d at D7, p=0.0120), lowered respiratory disease (23.07% to 17.42%) and diarrhea incidence (83.70% to 52.70%), and shortened diarrhea duration (4.32±0.47d vs 3.15±0.32d, p=0.0090). It also reduced serum interleukin-1 (49.39±2.40 vs 43.51±1.64 pg/mL, p=0.0350), haptoglobin (58.29±3.3 vs 49.40±3.65 μg/mL, p=0.0050), and cortisol (37.42±1.67 vs 33.05±2.24 nmol/L, p=0.0310), while increasing immunoglobulin G (10.30±1.46 vs 13.50±1.58 μg/mL, p=0.0131) and interferon-γ (6.89±0.47 vs 7.94±0.63 ng/L, p=0.0330) on D5. MBAS alleviates weaning stress by inhibiting inflammation, enhancing immunity, and reducing anxiety, providing an effective strategy to improve calf health.

BackgroundFractures of the limbs are a common health problem among school-aged children and can cause severe pain as well as emotional issues. Traditional care may not fully meet the comprehensive needs of these children. Therefore, exploring more comprehensive intervention measures is of significant clinical importance.ObjectiveThis research aimed to evaluate the clinical effect of Child Life intervention combined with a comprehensive nutrition intervention on pain management, nutritional status, and treatment compliance of school-age children with limb fractures.MethodsA total of 100 school-age children with limb fractures treated in our hospital from March 2024 to September 2024 were selected and randomly divided into a control group (CG) and an observation group (OG) using the random number table method, with 50 cases in each group. The CG received conventional nursing intervention, while the OG received Child Life intervention and comprehensive nutrition intervention on the basis of the CG. The pain scores, serum cortisol levels, treatment compliance, and nutritional status in both groups before and after surgery were compared.ResultsAt 12 h and 24 h after surgery, the FLACC scores in the OG were lower than those in the CG (p < 0.001, t = 5.042; p < 0.001, t = 4.836). At 12 h and 24 h after surgery, serum cortisol level in the OG exhibited depletion relative to that in the CG (p < 0.001, t = 6.049; p < 0.001, t = 11.662). After intervention, treatment compliance in the OG was higher than that in the CG, indicating statistical significance (p = 0.037, χ2 = 4.332; p = 0.017, χ2 = 5.741; p = 0.025, χ2 = 5.005). At 24 h after surgery, Lc, HGB, PA, and ALB levels in the OG were higher than those in the CG, indicating statistical significance (p < 0.01, t = 2.717; p < 0.001, t = 3.433; p < 0.001, t = 5.023; p < 0.001, t = 4.230).ConclusionA combination of Child Life intervention and comprehensive nutrition intervention can enhance the pain management effect in school-age children with limb fractures, attenuate their pain level, ameliorate their perioperative stress status, and improve their postoperative nutritional status, accelerating their recovery.

Determination of serum cortisol levels as a stress marker in hospitalized dogs

Abstract Background Diagnosing central adrenal insufficiency (CAI) is challenging in patients with inconclusive morning cortisol (4-18 µg/dL). Dynamic tests like the short Synacthen test (SST) are imperfect, necessitating reliable tools to stratify CAI risk and reduce diagnostic delays. Objective To develop and validate a predictive scoring system integrating clinical, biochemical, and imaging variables for CAI diagnosis in patients with indeterminate morning cortisol levels. Methods A retrospective study of 341 adults with suspected CAI and indeterminate morning cortisol. CAI was confirmed via SST (peak cortisol &amp;lt;18 µg/dL). Multivariate analysis identified key predictors for the CAI-Score, including morning cortisol, pituitary hormone deficits, tumor size, and treatment history. A machine learning model was also developed to enhance the prediction accuracy. Results Lower morning cortisol (6.27 vs. 10.29 µg/dL, p&amp;lt;0.0001), male sex (OR 1.77, p=0.011), larger pituitary tumors (2.46 vs. 1.89 cm, p=0.044), and ≥3 pituitary hormone deficits (OR 35.38, p=0.001) independently predicted CAI. The CAI-score (range 0–12.5 points) stratified risk, with scores ≥4.5 indicating high CAI likelihood (70.1% vs. 10.5% at 0 points). Combining serum cortisol and pituitary hormone deficits improved diagnostic accuracy (AUC of 0.745) over cortisol alone (AUC 0.680). A web-based tool (https://cai-predictor.streamlit.app/) was created for convenient clinical application. Conclusion The CAI-score improves diagnostic accuracy in ambiguous cases of suspected CAI by integrating morning serum cortisol with key clinical parameters. As morning serum cortisol and SST have limitations in CAI, the CAI score may act as a supportive rather than a standalone tool in the evaluation of patients for CAI.

To explore the early clinical manifestations, random cortisol levels, and management of late-onset circulatory collapse (LCC) in preterm infants. Preterm infants with LCC from October to December 2023 at the Affiliated Suzhou Hospital of Nanjing Medical University were included. Maternal perinatal factors and infants' early clinical symptoms, signs, random serum cortisol levels, treatment, and outcomes were retrospectively analyzed. Seven preterm infants with LCC were included, with gestational ages of 25 weeks + 2 days to 29 weeks and birth weights of 800-1 150 g. At 3 weeks of age, abnormal weight gain [gain rate: 21-28.5 g/(kg·d)], generalized edema, low serum sodium (129.5-135.2 mmol/L), and decreased random serum cortisol concentrations (13.6-44.6 nmol/L) were observed. After 1-2 weeks of hydrocortisone treatment, edema subsided and serum sodium increased. In clinically stable preterm infants, early manifestations of LCC include abnormal weight gain, generalized edema, recurrent hyponatremia, and decreased random serum cortisol concentrations. Hydrocortisone treatment effectively improves symptoms.

Despite extensive research, the interplay between hormonal stress markers and pregnancy-specific anxiety in the pathogenesis of preeclampsia remains insufficiently understood. This study aimed to analyze the simultaneous relationships between serum cortisol levels, pregnancy-related anxiety, and the occurrence of preeclampsia among third-trimester pregnant women. A case–control study was conducted at three hospitals in Banda Aceh, Indonesia, involving third-trimester pregnant women. Serum cortisol concentrations were measured using an immunoassay, and anxiety levels were assessed with the validated Pregnancy Related Anxiety Questionnaire (PRAQ). Preeclampsia diagnosis followed standard clinical and laboratory criteria. Associations between cortisol levels (categorized into high and normal) and PRAQ scores (classified as high and low–moderate) with preeclampsia were evaluated using the Chi-squared test, and crude odds ratios (OR) with 95% confidence intervals (95%CI). The Spearman’s correlation was used to determine the correlation between cortisol levels and PRAG scores. A total of 66 pregnant women were included in the final analysis (33 with preeclampsia and 33 with normal pregnancy). Women with high serum cortisol levels had a markedly greater likelihood of developing preeclampsia compared with those with normal cortisol levels (odds ratio (OR)=34.00; 95% confidence interval (95%CI): 4.93–234.46). Similarly, women with high pregnancy-related anxiety exhibited a significantly elevated risk of preeclampsia (OR=16.71; 95%CI: 4.95–56.39). No significant correlation was observed between cortisol levels and PRAQ scores in both groups (preeclampsia: r=-0.041, p=0.821; normal pregnancy: r=0.278, p=0.117). In conclusion, elevated serum cortisol and high pregnancy-related anxiety are independently associated with preeclampsia, although not directly correlated with each other. These findings highlight the potential of dual screening for cortisol and pregnancy-specific anxiety as an innovative approach for early identification of women at high risk of preeclampsia.

Disease remission and surgical outcomes of endoscopic transsphenoidal surgery for Cushing's Disease: a single centre experience.

Background: Post-traumatic stress disorder (PTSD) is a severe psychiatric condition prevalent among combat veterans. Its diagnosis is challenging due to the heterogeneity of clinical presentations and the complex interplay of pathogenic factors. Objective: This study aimed to develop and validate a diagnostic algorithm for combat-related PTSD by integrating clinical data with a panel of biological markers associated with blood–brain barrier disruption (anti-GFAP and anti-NSE antibodies), HPA axis dysfunction (cortisol), and neuroinflammation (IL-6, IL-8). Methods: A total of 721 male participants were enrolled: 434 veterans with PTSD (F43.1), 147 combat veterans without PTSD, and 140 non-combat military controls. All participants underwent clinical and psychometric assessment (Likert scale, HADS). Serum levels of biomarkers were measured using ELISA. Statistical analysis included non-parametric tests, correlation analysis, and binary logistic regression with Wald’s method to build a predictive model. Results: The binary logistic regression model identified cortisol and IL-6 as the most significant predictors of PTSD. The final algorithm, based on a cortisol level below 199.8 nmol/L and an IL-6 level above 0.002438 pg/mL, correctly classified 78% of patients (AUC = 0.724, 95% CI [0.669, 0.779]). Furthermore, levels of IL-4, IL-8, and cortisol positively correlated with the severity of combat stress factors, independent of physical injuries. Conclusions: We developed a novel diagnostic algorithm for combat-related PTSD based on cortisol and IL-6 levels, demonstrating high accuracy. The correlation between neuroinflammatory markers and the severity of combat exposure suggests their role as primary indicators of stress response, highlighting their utility for early risk identification and targeted interventions.

Weaning represents a major developmental milestone for foals, especially when 4- to 7-month-old foals are abruptly separated from their dams. Studies have shown that the post-weaning period is associated with physiological and psychological stress, which may affect immune function. The present study aimed to describe and analyze the pattern of blood inflammatory biomarkers related to the innate immune system. A gradual foal-dam separation procedure was chosen, which included post-weaning social buffering by a familiar adult horse. Twelve Thoroughbred foals (six fillies, six colts) aged 4-6 months were enrolled and divided into a colt and a filly group, and after weaning, were kept as such. Blood samples were collected before and up to 7 days after weaning. Serum cortisol and cytokines (IL-2, IL-6, IL-10, TNF-α, IFN-γ) were quantified using equine-specific ELISA kits. Routine descriptive statistics were used to present the data, and inferences were drawn using a two-way repeated measures ANOVA. The level of significance was set at p < 0.05. Results showed significant differences in the concentrations of IL-10 (p < 0.001), IFN-γ (p < 0.01), and TNF-α (p < 0.01) on various days post-weaning. An apparent significant sex effect was not shown, but IL-10 peaked on day 3 in fillies. IFN-γ decreased significantly by day 5 in both sexes. Conversely, TNF-α levels increased significantly by day 5. No significant changes were observed for cortisol.

The research was done to explore the influence of quinoa extract on periodontium, and to assess serum YKL-40 level in a depression rat model. An overall number of 30 male albino rats weighing170-180 g were used. Animals were grouped into three categories; group I: control group, group II: depressed group, group III: depressed group treated with 600 mg/kg body weight quinoa extract. The experimental duration extended to a period of 21 days. Blood samples obtained from the heart were transported to biochemistry tubes for ELISA analysis following euthanization. Mandibular molar region specimens were subjected to decalcification for histological evaluation. Quinoa extract ameliorated the degenerative changes of periodontium in the experimental depression model, increased body weight and serum serotonin level, and decreased serum cortisol and YKL-40 levels. Quinoa extract may be utilized as a preventative measure against the periodontal damage brought on by depression.