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14 pages, 720 KB  
Article
Both Season and Equid Type Affect Endogenous Adrenocorticotropic Hormone Concentrations in Healthy Donkeys, Mules and Hinnies in the United States
by Erin L. Goodrich, Sebastián Gonzalo Llanos-Soto, Renata Ivanek, Toby Pinn-Woodcock, Elisha Frye, Amy Wells, Stephen R. Purdy, Emily Berryhill and Ned J. Place
Animals 2026, 16(2), 290; https://doi.org/10.3390/ani16020290 (registering DOI) - 16 Jan 2026
Viewed by 33
Abstract
Baseline plasma ACTH concentrations are frequently utilized as part of the diagnostic evaluation of equids when PPID is suspected. Baseline ACTH can be impacted by many factors including time of year, i.e., ACTH has generally been found to be elevated during late summer [...] Read more.
Baseline plasma ACTH concentrations are frequently utilized as part of the diagnostic evaluation of equids when PPID is suspected. Baseline ACTH can be impacted by many factors including time of year, i.e., ACTH has generally been found to be elevated during late summer through early autumn in the northern hemisphere. An understanding of ACTH concentrations in healthy equids over the course of a year is useful for the proper interpretation of concentrations in PPID-suspect animals. Previous studies assessing ACTH concentrations in healthy donkeys (Equus asinus) and hybrids (E. asinus x E. caballus) are limited, often utilizing very small numbers, equids from specific and limited geographical regions, limited timeframes or unspecified donkey types (miniature, standard, or mammoth). We aimed to characterize the seasonal variation in baseline ACTH concentrations in healthy miniature donkeys, standard donkeys and hybrids in the United States (US) and to compare those concentrations across these groups. Following outlier removal, 19 standard donkeys (from California (CA), Massachusetts (MA), New York (NY)), 14 miniature donkeys (CA and NY), and 28 hybrids (Texas (TX) and NY) were utilized for analysis. Samples were collected from each equid twice per month from June to November 2019 and once per month from December 2019 through May 2020. The mean ACTH concentration of all equids was higher from mid-August through the end of October compared to the rest of the year (being the highest in the second half of September with the mean (standard deviation) values of 109.6 (52.6), 134.6 (67.4), and 100.8 (189.6) in standard donkeys, miniature donkeys, and hybrids, respectively). Additionally, ACTH concentrations in hybrids were 23% (95% Confidence Interval (CI): 4–38%) and 51% (95% CI: 36–63%) lower than in standard and miniature donkeys, respectively, from mid-August through October. During the rest of the year, hybrids similarly showed 31% (95% CI: 16–43%) and 30% (95% CI: 15–42%) lower ACTH concentrations compared with standard and miniature donkeys, respectively. Full article
(This article belongs to the Special Issue Current Research on Donkeys and Mules: Second Edition)
24 pages, 1256 KB  
Article
Non-Invasive Assessment of Adrenal Activity in the Subterranean Rodent Ctenomys talarum in Field and Laboratory Conditions
by Roxana Zenuto, Valentina Brachetta, María Celina Carrizo, María Sol Fanjul and Cristian Eric Schleich
Animals 2026, 16(2), 234; https://doi.org/10.3390/ani16020234 - 13 Jan 2026
Viewed by 202
Abstract
The endocrine stress response is a valuable tool for evaluating how organisms cope with environmental challenges. However, selecting an appropriate matrix for measuring glucocorticoids (GCs) requires careful consideration of sample quality and accessibility. This study reveals that blood sampling affects plasma cortisol levels [...] Read more.
The endocrine stress response is a valuable tool for evaluating how organisms cope with environmental challenges. However, selecting an appropriate matrix for measuring glucocorticoids (GCs) requires careful consideration of sample quality and accessibility. This study reveals that blood sampling affects plasma cortisol levels in the subterranean rodent Ctenomys talarum, with the effect being reversed shortly thereafter. To facilitate a non-invasive approach, an enzyme-linked immunosorbent assay (EIA) that had previously been validated for measuring plasma cortisol in C. talarum was evaluated to measure adrenocortical activity by analyzing fecal glucocorticoid metabolites (FGCs). Using this assay, we monitored the stress response during wild capture, transport to captivity, adrenocorticotropic hormone (ACTH) stimulation, and immobilization. This showed that FGC levels accurately reflect adrenal activation in these contexts. We also documented a relationship between reproductive seasonality and FGCs. Finally, we provide evidence for a relationship between adrenal activity and behavior. Our results suggest that when considering plasma GCs for the assessment of acute stress, it is crucial to understand the magnitude and timing of the effects of blood sampling on the stress state of organisms. The validation of FGC measurement in C. talarum provides a new option for advancing ecophysiological studies in both the wild and captivity. Full article
(This article belongs to the Special Issue Wild Animal Welfare: Science, Ethics and Law)
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20 pages, 3883 KB  
Article
Physiological Responses of Kalibaus (Labeo calbasu) to Temperature Changes: Metabolic, Haemato-Biochemical, Hormonal and Immune Effects
by Masuda Sultana Mimi, Simon Kumar Das, Mohammad Lutfar Rahman, Mohammad Abdus Salam, Md. Nushur Islam, Tamanna Rahman, Sumi Rani Das, Mohammad Nazmol Hasan and Sabuj Kanti Mazumder
Fishes 2026, 11(1), 46; https://doi.org/10.3390/fishes11010046 - 10 Jan 2026
Viewed by 244
Abstract
A global interest in the cultivation of Kalibaus (Labeo calbasu) has emerged due to decreasing natural stocks and a consistent rise in market value and demand. Given these concerns, understanding the species’ physiological responses to environmental changes is crucial. The present [...] Read more.
A global interest in the cultivation of Kalibaus (Labeo calbasu) has emerged due to decreasing natural stocks and a consistent rise in market value and demand. Given these concerns, understanding the species’ physiological responses to environmental changes is crucial. The present research aimed to assess the effect of varying environmental temperatures on metabolism, haemato-biochemical indices, hormonal concentrations and immune responses in L. calbasu. This study was conducted in triplicate using 100 L glass aquariums at four different temperatures: 22, 26, 30, and 34 °C. The highest weight and length gain were observed at 30 °C, while the lowest occurred at 22 °C. Notably, the best feed conversion ratio (FCR) of 1.51 ± 0.03 was also recorded at 30 °C. Although haematological and biochemical parameters remained within normal ranges, they varied with temperature changes. Indicators of cold and heat stress were evident through lower hematocrit levels and higher white blood cell (WBC) counts. Biochemical indicators such as serum albumin (1.84 ± 0.05 g dL−1), serum globulin (1.64 ± 0.06 gdL−1), HCO3 (30.93 ± 0.62), Na+ (115.60 ± 3.72 mmolL−1), alkaline phosphatase (93.33 ± 9.39 AP, IUL−1), and AST/SGOT (21.00 ± 4.55 UL−1) were significantly higher at 30 °C. Regarding hormonal responses, peak levels of growth hormone (GH), triiodothyronine (T3) (1.44 ± 0.07 ngmL−1), and thyroxine (T4) were recorded at 30 °C. Meanwhile, serum cortisol (1.62 ± 0.06 µgdL−1) and adrenocorticotropic hormone (ACTH) (18.01 ± 3.26 pgmL−1) were highest at 34 °C. Immune responses were strongest between 26 and 30 °C. In conclusion, the results suggest that L. calbasu should ideally be cultured between 26 and 30 °C for optimum growth and health, making it ideal for commercial farming. Full article
(This article belongs to the Special Issue Advancing Fish Nutrition Research for Sustainable Aquaculture)
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15 pages, 704 KB  
Article
Dual-Strain Psychobiotics Combining Live Lactiplantibacillus plantarum PS128 and Heat-Treated Lacticaseibacillus paracasei PS23 Improve Psychological and Neuroendocrine Outcomes in Stressed Adults: A Randomized, Placebo-Controlled Trial
by Mon-Chien Lee, Ting-An Lin and Chi-Chang Huang
Foods 2025, 14(24), 4190; https://doi.org/10.3390/foods14244190 - 6 Dec 2025
Viewed by 1041
Abstract
Chronic psychological stress impairs neuroendocrine balance and increases the risk of mental health disturbances, including anxiety, sleep disruption, and low mood. The gut–brain axis has emerged as a promising target for stress modulation, particularly through psychobiotic interventions. This randomized, double-blind, placebo-controlled trial evaluated [...] Read more.
Chronic psychological stress impairs neuroendocrine balance and increases the risk of mental health disturbances, including anxiety, sleep disruption, and low mood. The gut–brain axis has emerged as a promising target for stress modulation, particularly through psychobiotic interventions. This randomized, double-blind, placebo-controlled trial evaluated the effects of a combined psychobiotic formulation (Neuralli Mood), comprising live Lactiplantibacillus plantarum PS128 (PS128) and heat-treated Lacticaseibacillus paracasei PS23 (HT-PS23), on the psychological and physiological stress responses in a high-stress occupational population. A total of 116 healthy participants with elevated perceived stress (PSS ≥ 14), primarily firefighters, were randomly assigned to receive the dual-strain supplement or placebo for 8 weeks. Stress-related outcomes were assessed by using validated psychological scales and serum biomarkers. Compared with placebo, the psychobiotics group showed significantly greater reductions in overall job stress perception (JSS), state anxiety (STAI), and insomnia severity (ISI) (all p < 0.05). Additionally, serum adrenocorticotropic hormone (ACTH) and norepinephrine levels were significantly reduced post-intervention, whereas cortisol levels remained unchanged. These findings suggested that combining live and heat-treated psychobiotic strains may provide a safe and effective strategy for alleviating psychological stress and regulating neuroendocrine function in high-risk populations. Full article
(This article belongs to the Special Issue Probiotics and Prebiotics in Food: Advances and Latest Trends)
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10 pages, 3316 KB  
Case Report
Role of 68Ga-DOTATOC Positron Emission Tomography in Locating Pulmonary Neuroendocrine Tumor Presenting with ACTH-Dependent Cushing’s Syndrome: A Case Report
by Misako Tanaka, Masakazu Uejima, Kuniaki Ozaki, Maiko Nishigori, Yukako Kurematsu, Kosuke Kaji, Kei Moriya, Tadashi Namisaki, Akira Mitoro, Fumihiko Nishimura, Motoaki Yasukawa and Hitoshi Yoshiji
J. Clin. Med. 2025, 14(24), 8634; https://doi.org/10.3390/jcm14248634 - 5 Dec 2025
Viewed by 332
Abstract
Background: In ectopic adrenocorticotropic hormone (ACTH) syndrome, locating the responsible lesion is often challenging. Case Presentation: A 68-year-old woman was transferred to Nara Medical University hospital for a detailed investigation of her ACTH-dependent Cushing’s syndrome. Because of hypercortisolism-induced immunosuppression, she subsequently developed [...] Read more.
Background: In ectopic adrenocorticotropic hormone (ACTH) syndrome, locating the responsible lesion is often challenging. Case Presentation: A 68-year-old woman was transferred to Nara Medical University hospital for a detailed investigation of her ACTH-dependent Cushing’s syndrome. Because of hypercortisolism-induced immunosuppression, she subsequently developed severe Nocardia pneumonia and was forced to temporarily depend on noninvasive positive pressure ventilation (NIPPV). Intravenous antifungal agents and antibiotics were administered, resulting in significant symptomatic improvement. Metyrapone was administered to suppress excessive cortisol. Contrast-enhanced magnetic resonance imaging of the pituitary revealed a 4 mm sized poorly enhanced area, and microadenoma was suspected. Although cavernous venous sampling was indispensable prior to trans-spheroidal surgery (TSS), this examination could not be performed because of the presence of deep vein thrombosis. TSS was performed for both diagnostic and therapeutic purposes, but hypercortisolism did not improve. Moreover, immunohistochemical findings of the specimen revealed nonfunctional pituitary tumor. Methods: We re-evaluated the responsible lesion causing ACTH-dependent Cushing’s syndrome. Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) revealed weak and abnormal FDG uptake in the right pericardium, but the possibility of nonspecific uptake could not be ruled out. However, gallium-68 1,4,7,10-tetraazacyclododecane-N,N′,N′′,N′′′-tetraacetic-acid-D-Phe1-Tyr3-octreotide (68Ga-DOTATOC)-PET demonstrated the same degree of abnormal uptake; therefore, a functional pulmonary tumor was strongly suspected. Results: Video-Assisted Thoracic Surgery (VATS) was performed, and histopathological findings of the specimen revealed a neuroendocrine tumor with positive ACTH staining. After VATS, ACTH and cortisol levels were normalized. Conclusions: Here, we report a case of ACTH-dependent Cushing’s syndrome caused by a lung neuroendocrine tumor, in which 68Ga-DOTATOC PET was helpful in detecting the functional tumors. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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18 pages, 6919 KB  
Article
Serum Starvation Affects the Transcriptomic and Proliferative Response to ACTH in Primary Cultures of Rat Adrenocortical Cells
by Małgorzata Blatkiewicz, Emilia Cicha, Marta Szyszka, Karol Jopek, Marianna Tyczewska, Izabela Pieścikowska, Ludwik K. Malendowicz and Marcin Rucinski
Cells 2025, 14(23), 1844; https://doi.org/10.3390/cells14231844 - 22 Nov 2025
Viewed by 742
Abstract
The adrenocorticotropic hormone (ACTH) is a key regulator of adrenal cortex function, promoting glucocorticoid synthesis and modulating cell proliferation. However, the role of extracellular steroid availability in shaping ACTH responses is still not fully defined. In this study, the functional and transcriptomic effects [...] Read more.
The adrenocorticotropic hormone (ACTH) is a key regulator of adrenal cortex function, promoting glucocorticoid synthesis and modulating cell proliferation. However, the role of extracellular steroid availability in shaping ACTH responses is still not fully defined. In this study, the functional and transcriptomic effects of ACTH were investigated in primary rat adrenocortical cells cultured under standard conditions and under simulating serum starvation (charcoal-stripped serum). The cells were treated with ACTH (10 nM), and proliferation was monitored using xCELLigence RTCA, while corticosterone secretion was assessed via ELISA. The RNA extracted from these samples was then utilised for the purpose of microarray-based gene expression profiling. The present study revealed that charcoal-stripped serum markedly improved ACTH-induced corticosterone output, suggesting that the absence of endogenous steroids sensitises cells to ACTH stimulation possibly by removing negative feedback constraints. This enhanced steroidogenic response was accompanied by a significant suppression of proliferation, confirming that the stimulation of specialised functions (such as steroid secretion) reduces proliferative capacity of adrenocortical cells. Transcriptomic data revealed that the steroids stimulating effect on corticosterone output was mainly mediated via steroid biosynthetic and lipid metabolic processes while inhibitory effect on proliferation rate was mediated mainly by cell adhesion molecules. These results suggest that, in primary culture of rat adrenocortical cells, the stimulatory effect of ACTH on their specialised function (corticosteroid secretion) simultaneously reduces their basal function, which is their proliferation process. Changes in this type are also observed in cells cultured in steroid-depleted conditions. Full article
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19 pages, 563 KB  
Review
Gonadal Function and Reproductive Health Challenges in Triple a Syndrome: A Narrative Review
by Ana Gheorghe-Milea and Carmen Emanuela Georgescu
Medicina 2025, 61(11), 2073; https://doi.org/10.3390/medicina61112073 - 20 Nov 2025
Viewed by 481
Abstract
Background and Objectives: Triple A syndrome (TAS) is a rare autosomal recessive disorder characterized by the triad of adrenocorticotropic hormone (ACTH)-resistant adrenal insufficiency, alacrimia (absence of tear production), and achalasia. This article aims to provide a better understanding of gonadal function and reproductive [...] Read more.
Background and Objectives: Triple A syndrome (TAS) is a rare autosomal recessive disorder characterized by the triad of adrenocorticotropic hormone (ACTH)-resistant adrenal insufficiency, alacrimia (absence of tear production), and achalasia. This article aims to provide a better understanding of gonadal function and reproductive health in TAS by summarizing existing data from the literature regarding this topic. Materials and Methods: A comprehensive literature review was carried out until September 2025, using four electronic databases (PubMed, Embase, Web of Science and Scopus). Results: The review included a total of 25 articles. The most frequent findings in the articles included in the review were erectile dysfunction, ejaculatory dysfunction, delayed puberty, hypogonadism and fertility issues. Furthermore, several studies revealed reduced adrenal androgen levels in male patients, while other case reports documented the presence of osteoporosis in individuals with TAS. Conclusions: Gonadal dysfunction and reproductive health challenges in TAS remain underexplored aspects. The multisystemic nature of TAS requires a comprehensive approach to patient care for optimizing quality of life, and this review underscores the importance of evaluating reproductive function in individuals with this rare syndrome. Full article
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47 pages, 1674 KB  
Review
The Influence of Different Light Spectra on Broiler Chicken Endocrine Systems and Productivity
by Lenuța Galan, Gheorghe Solcan and Carmen Solcan
Animals 2025, 15(21), 3209; https://doi.org/10.3390/ani15213209 - 4 Nov 2025
Viewed by 1709
Abstract
In birds, light can penetrate the cranial bones and reach deep brain regions, where non-visual photoreceptors, especially in the hypothalamus, detect spectral and photoperiodic cues. Alongside retinal photoreception, deep-brain light sensing contributes to circadian entrainment and regulates melatonin secretion by the pineal gland. [...] Read more.
In birds, light can penetrate the cranial bones and reach deep brain regions, where non-visual photoreceptors, especially in the hypothalamus, detect spectral and photoperiodic cues. Alongside retinal photoreception, deep-brain light sensing contributes to circadian entrainment and regulates melatonin secretion by the pineal gland. These light-driven pathways modulate endocrine activity, playing a key role in muscle development. This review explores how monochromatic light-emitting diode (LED) illumination, particularly green and blue wavelengths, affects the somatotropic axis (growth hormone-releasing hormone [GHRH]-growth hormone [GH]-insulin-like growth factor 1 [IGF-1]), the gonadal axis (gonadotropin-releasing hormone [GnRH]-luteinizing hormone [LH]/follicle-stimulating hormone [FSH]-sex steroids [testosterone, estrogen, progesterone]), the thyroid axis (thyrotropin-releasing hormone [TRH]-thyroid-stimulating hormone [TSH]-thyroxine [T4]/triiodothyronine [T3]), and the hypothalamic-pituitary-adrenal (HPA) axis (corticotropin-releasing hormone [CRH]-adrenocorticotropic hormone [ACTH]-corticosterone). Green light enhances early-stage muscle growth via GHRH and IGF-1 upregulation, while blue light supports later myogenic activity and oxidative balance. Light schedules also influence melatonin dynamics, which in turn modulate endocrine axis responsiveness to photic cues. Furthermore, variations in photoperiod and exposure to artificial lights at night (ALAN) affect thyroid activity and HPA axis reactivity, influencing metabolism, thermoregulation, and stress resilience. Together, ocular and intracranial photoreception form a complex network that links environmental light to hormonal regulation and muscle growth. These insights support the strategic use of LED lighting to optimize broiler performance and welfare. Full article
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9 pages, 400 KB  
Article
Repository Corticotropin Therapy for Refractory Noninfectious Inflammatory Ocular Diseases
by Christian Nieves-Ríos, Ricardo A. Murati Calderon and Armando L. Oliver
J. Clin. Med. 2025, 14(21), 7785; https://doi.org/10.3390/jcm14217785 - 2 Nov 2025
Viewed by 504
Abstract
Objectives: To describe the outcomes of patients with refractory noninfectious ocular inflammatory diseases who underwent treatment with repository corticotropin injection (RCI). Methods: A retrospective cohort study was conducted. Patients who failed treatment with corticosteroids and were subsequently treated with RCI were [...] Read more.
Objectives: To describe the outcomes of patients with refractory noninfectious ocular inflammatory diseases who underwent treatment with repository corticotropin injection (RCI). Methods: A retrospective cohort study was conducted. Patients who failed treatment with corticosteroids and were subsequently treated with RCI were included. Primary outcome measures were intraocular inflammatory activity, intraocular pressure (IOP), and the development of complications. Results: A total of 19 eyes from 10 patients were included. Most of the patients were women (70.0%) and the median age at presentation was 49.0 years (30.0–84.0 years). The ocular diagnoses were anterior/intermediate uveitis, intermediate/posterior uveitis, panuveitis, ocular cicatricial pemphigoid, and anterior scleritis. Seventeen (89.5%) eyes had active disease. The median duration of RCI treatment was 16.0 months (6.0–28.0 months). Nine (90.0%) patients, representing 17 (89.5%) eyes, achieved disease inactivity and remained quiescent at the last visit. No patient was on systemic corticosteroids at the last evaluation. The mean IOP was lower under RCI than corticosteroid at one month (16.0 mmHg ± 6.1 vs. 20.8 mmHg ± 9.5, p = 0.033) and four months (15.6 mmHg ± 2.9 vs. 17.8 mmHg ± 3.7, p = 0.046); however, the overall difference was not significant (16.2 mmHg ± 1.1 vs. 17.3 mmHg ± 1.8, p = 0.057). Incidence rates were the highest for posterior subcapsular cataracts (44.4% per eye-year). Relative risk analysis (RR) showed a 40.0% risk reduction for cystoid macular edema (RR = 0.60, p = 0.054). Conclusions: RCI may be an alternative treatment for refractory noninfectious ocular inflammatory diseases in patients who have failed treatment with corticosteroids. Full article
(This article belongs to the Special Issue Progress in Clinical Diagnosis and Therapy in Ophthalmology)
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20 pages, 994 KB  
Perspective
Endocrinology and the Lung: Exploring the Bidirectional Axis and Future Directions
by Pedro Iglesias
J. Clin. Med. 2025, 14(19), 6985; https://doi.org/10.3390/jcm14196985 - 2 Oct 2025
Cited by 1 | Viewed by 2200
Abstract
The lung is increasingly recognized as an organ with dual endocrine and respiratory roles, participating in a complex bidirectional crosstalk with systemic hormones and local/paracrine activity. Endocrine and paracrine pathways regulate lung development, ventilation, immunity, and repair, while pulmonary cells express hormone receptors [...] Read more.
The lung is increasingly recognized as an organ with dual endocrine and respiratory roles, participating in a complex bidirectional crosstalk with systemic hormones and local/paracrine activity. Endocrine and paracrine pathways regulate lung development, ventilation, immunity, and repair, while pulmonary cells express hormone receptors and secrete mediators with both local and systemic effects, defining the concept of the “endocrine lung”. This narrative review summarizes current evidence on the endocrine–pulmonary axis. Thyroid hormones, glucocorticoids, sex steroids, and metabolic hormones (e.g., insulin, leptin, adiponectin) critically influence alveologenesis, surfactant production, ventilatory drive, airway mechanics, and immune responses. Conversely, the lung produces mediators such as serotonin, calcitonin gene-related peptide, endothelin-1, leptin, and keratinocyte growth factor, which regulate vascular tone, alveolar homeostasis, and immune modulation. We also describe the respiratory manifestations of major endocrine diseases, including obstructive sleep apnea and lung volume alterations in acromegaly, immunosuppression and myopathy in Cushing’s syndrome, hypoventilation in hypothyroidism, restrictive “diabetic lung”, and obesity-related phenotypes. In parallel, chronic pulmonary diseases such as chronic obstructive pulmonary disease, interstitial lung disease, and sleep apnea profoundly affect endocrine axes, promoting insulin resistance, hypogonadism, GH/IGF-1 suppression, and bone metabolism alterations. Pulmonary neuroendocrine tumors further highlight the interface, frequently presenting with paraneoplastic endocrine syndromes. Finally, therapeutic interactions are discussed, including the risks of hypothalamic–pituitary–adrenal axis suppression with inhaled corticosteroids, immunotherapy-induced endocrinopathies, and inhaled insulin. Future perspectives emphasize mapping pulmonary hormone networks, endocrine phenotyping of chronic respiratory diseases, and developing hormone-based interventions. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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24 pages, 603 KB  
Review
Dexamethasone Suppression Testing in Patients with Adrenal Incidentalomas with/Without Mild Autonomous Cortisol Secretion: Spectrum of Cortisol Cutoffs and Additional Assays (An Updated Analysis)
by Alexandra-Ioana Trandafir and Mara Carsote
Biomedicines 2025, 13(9), 2169; https://doi.org/10.3390/biomedicines13092169 - 5 Sep 2025
Viewed by 3583
Abstract
Background/Objective: The overnight 1-mg dexamethasone suppression test (DST) represents the conventional/standard tool for endogenous hypercortisolemia screening, typically in relationship with adrenal and pituitary masses. Nevertheless, an associated spectrum of challenges and pitfalls is found in daily practice. This analysis aimed to evaluate: [...] Read more.
Background/Objective: The overnight 1-mg dexamethasone suppression test (DST) represents the conventional/standard tool for endogenous hypercortisolemia screening, typically in relationship with adrenal and pituitary masses. Nevertheless, an associated spectrum of challenges and pitfalls is found in daily practice. This analysis aimed to evaluate: (I.) the diagnosis relevance of 1-mg DST in patients with adrenal incidentalomas (AIs) with/without mild autonomous cortisol secretion (MACS) exploring different cutoffs of the second-day plasma cortisol after dexamethasone administration (cs-DST) with respect to cardio-metabolic outcomes; (II.) the potential utility of adding other biomarkers to DST [plasma morning adrenocorticotropic hormone (ACTH), 24-h urinary free cortisol (UFC), late-night salivary cortisol (LNSC), dehydroepiandrosterone sulfate (DHEAS)]; and (III.) DST variability in time. Methods: This narrative analysis was based on searching full-text, English articles in PubMed (between January 2023 and April 2025) via using different term combinations: “dexamethasone suppression test” (n = 239), “diagnosis test for autonomous cortisol secretion” (n = 22), “diagnosis test for mild autonomous cortisol secretion” (n = 13) and “diagnosis test for Cushing Syndrome” (n = 61). We manually checked the title and abstract and finally included only the studies that provided hormonal testing results in adults with non-functional adenomas (NFAs) ± MACS. We excluded: reviews, meta-analyses, editorials, conference abstracts, case reports, and case series; non-human research; studies that did not provide clear criteria for distinguishing between Cushing syndrome and MACS; primary aldosteronism. Results: The sample-focused analysis (n = 13 studies) involved various designs: cross-sectional (n = 4), prospective (n = 1), retrospective (n = 7), and cohort (n = 1); a total of 4203 patients (female-to-male ratio = 1.45), mean age of 59.92 years. I. Cs-DST cutoffs varied among the studies (n = 6), specifically, 0.87, 0.9, 1.2, and 1.4 µg/dL in relationship with the cardio-metabolic outcomes. After adjusting for age (n = 1), only the prevalence of cardiovascular disease remained significantly higher in >0.9 µg/dL vs. ≤0.9 group (OR = 2.23). Multivariate analysis (n = 1) found cs-DST between 1.2 and 1.79 µg/dL was independently associated with hypertension (OR = 1.55, 95%CI: 1.08–2.23, p = 0.018), diabetes (OR = 1.60, 95%CI: 1.01–2.57, p = 0.045), and their combination (OR = 1.96, 95%CI:1.12–3.41, p = 0.018) after adjusting for age, gender, obesity, and dyslipidemia. A higher cs-DST was associated with a lower estimated glomerular filtration rate (eGFR), independently of traditional cardiovascular risk factors. Post-adrenalectomy eGFR improvement was more pronounced in younger individuals, those with lower eGFR before surgery, and with a longer post-operative follow-up. Cs-DST (n = 1) was strongly associated with AIs size and weakly associated with age, body mass index and eGFR. Cortisol level increased by 9% (95% CI: 6–11%) for each 10 mL/min/1.73 m2 decrease in eGFR. A lower cs-DST was associated with a faster post-adrenalectomy function recovery; the co-diagnosis of diabetes reduced the likelihood of this recovery (OR = 24.55, p = 0.036). II. Additional biomarkers assays (n = 5) showed effectiveness only for lower DHEAS to pinpoint MACS amid AIs (n = 2, cutoffs of <49.31 µg/dL, respectively, <75 µg/dL), and lower ACTH (n = 1, <12.6 pmol/L). III. Longitudinal analysis of DST’s results (n = 3): 22% of NFAS switch to MACS after a median of 35.7 months (n = 1), respectively, 29% (n = 1) after 48.6 ± 12.5 months, 11.8% (n = 1) after 40.4 ± 51.17 months. A multifactorial model of prediction showed the lowest risk of switch (2.4%) in individuals < 50 years with unilateral tumor and cs-DST < 0.45 µg/dL. In the subgroup of subjects without cardio-metabolic comorbidities at presentation, 25.6% developed ≥1 comorbidities during surveillance. Conclusions: The importance of exploring the domain of AIs/NFAs/MACS relates to an increasing detection in aging population, hence, the importance of their optimum hormonal characterization and identifying/forestalling cardio-metabolic consequences. The spectrum of additional biomarkers in MACS (other than DST) remains heterogeneous and still controversial, noting the importance of their cost-effectiveness, and availability in daily practice. Cs-DST serves as an independent predictor of cardio-metabolic outcomes, kidney dysfunction, while adrenalectomy may correct them in both MACS and NFAs, especially in younger population. Moreover, it serves as a predictor of switching the NFA into MACS category during surveillance. Changing the hormonal behavior over time implies awareness, since it increases the overall disease burden. Full article
(This article belongs to the Section Neurobiology and Clinical Neuroscience)
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9 pages, 588 KB  
Communication
Differential Neuroendocrine Responses and Dysregulation of the Hypothalamic–Pituitary–Adrenal Axis Following Repeated Mild Concussive Impacts and Blast Exposures in a Rat Model
by Rex Jeya Rajkumar Samdavid Thanapaul, Jishnu K. S. Krishnan, Manoj Y. Govindarajulu, Chetan Y. Pundkar, Gaurav Phuyal, Joseph B. Long and Peethambaran Arun
Brain Sci. 2025, 15(8), 847; https://doi.org/10.3390/brainsci15080847 - 8 Aug 2025
Cited by 1 | Viewed by 1091
Abstract
Traumatic brain injury (TBI) remains a significant public health concern, particularly among military personnel and contact sport athletes who are frequently exposed to repeated blast overpressure waves and mild concussive impacts, respectively. While moderate and severe TBIs have been extensively studied, the long-term [...] Read more.
Traumatic brain injury (TBI) remains a significant public health concern, particularly among military personnel and contact sport athletes who are frequently exposed to repeated blast overpressure waves and mild concussive impacts, respectively. While moderate and severe TBIs have been extensively studied, the long-term neuroendocrine consequences of mild, repetitive brain trauma are poorly understood. In this study, we investigated the temporal dynamics of hypothalamic–pituitary–adrenal (HPA) axis dysregulation following repeated mild concussive head impacts and blast exposures using two clinically relevant rodent models. Male Sprague-Dawley rats were subjected to repeated mild concussive impacts using a modified weight drop model or repeated blast exposures using an advanced blast simulator. Plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone were measured on days 1 and 30 post-injuries. Our findings revealed that repeated blast exposures induced elevation of plasma ACTH and corticosterone on days 1 and 30 post-blasts. After the repeated mild concussive impacts, increased plasma levels of corticosterone were observed on days 1 and 30, but ACTH levels were increased only on day 30. This study is among the first to directly compare neuroendocrine outcomes of repeated mild concussive impacts and blast exposures within a unified experimental framework. Our findings demonstrate distinct temporal trajectories of HPA axis dysregulation depending on injury type and highlight plasma levels of ACTH and corticosterone as potential biomarkers of subclinical brain trauma. These insights may inform early diagnostic approaches and therapeutic strategies aimed at mitigating long-term stress-related complications following mild traumatic brain injuries. Full article
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19 pages, 6101 KB  
Article
A High-Calorie Diet Aggravates Lipopolysaccharide-Induced Pulmonary Inflammation in Juvenile Rats via Hypothalamic-Pituitary-Adrenal Axis-Related Pathways
by Qianqian Li, Hui Liu, Chen Bai, Lin Jiang, Chen Su, Xueying Qin, Tiegang Liu and Xiaohong Gu
Int. J. Mol. Sci. 2025, 26(14), 6554; https://doi.org/10.3390/ijms26146554 - 8 Jul 2025
Viewed by 1034
Abstract
The hypothalamic-pituitary-adrenal (HPA) axis plays an important regulatory role in inflammatory responses to systemic or local infection in the host. A high-calorie diet, which can aggravate pediatric pneumonia and delay recovery, is intimately associated with HPA axis disorder; however, its underlying mechanisms remain [...] Read more.
The hypothalamic-pituitary-adrenal (HPA) axis plays an important regulatory role in inflammatory responses to systemic or local infection in the host. A high-calorie diet, which can aggravate pediatric pneumonia and delay recovery, is intimately associated with HPA axis disorder; however, its underlying mechanisms remain unknown. This study examined whether the mechanism by which a high-calorie diet aggravates pneumonia is related to HPA axis disorder. In this study, juvenile rats were fed a high-calorie diet and/or nebulized with lipopolysaccharide (LPS) for model construction. Our data shows that a high-calorie diet increases interleukin-1 beta(IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels in lung tissues and aggravates LPS-induced inflammatory injury in the lungs of juvenile rats. Additionally, we found that a high-calorie diet decreases the expression level of serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) in juvenile rats with pneumonia, resulting in HPA axis disorder. Hypothalamus proteomics and Western blot results proved that a high-calorie diet upregulated the expression level of hypothalamus hypoxia-inducible factor-1 alpha (HIF-1α) in juvenile rats with pneumonia, and this mechanism is associated with reduced HIF-1α ubiquitination. We further observed that HPA axis disorder was significantly abated and inflammatory damage in rat lung tissues was significantly alleviated after in vivo HIF-1α pathway inhibition. This shows that pneumonia aggravation by a high-calorie diet is associated with interference in the HIF-1α-mediated HPA axis. A high-calorie diet boosts HIF-1α signaling in the hypothalamus and exacerbates LPS-induced pneumonia by disrupting the HPA axis. This sheds light on lung inflammation and strengthens the lung-brain connection. Full article
(This article belongs to the Section Molecular Endocrinology and Metabolism)
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11 pages, 222 KB  
Article
Effects of Rumen-Protected Taurine Supplementation on Ruminal Fermentation, Hematological Profiles, Liver Function, and Immune Responses in Yaks
by Shoupei Zhao, Lianghao Lu, Yuanyuan Chen, Huaming Yang, Bao Zhang, Mingyu Cao, Wenju Chao, Wanchao Xue, Xiaorong Fan, Jianxin Xiao, Rui Hu, Quanhui Peng, Lizhi Wang, Zhisheng Wang and Bai Xue
Animals 2025, 15(13), 1929; https://doi.org/10.3390/ani15131929 - 30 Jun 2025
Viewed by 832
Abstract
The present study evaluated the effects of dietary rumen-protected taurine (RPT) supplementation on ruminal fermentation, hematological parameters, liver function, stress-related hormones, and immune responses in yaks. Eighteen yaks were randomly allocated to three groups: a control group receiving no RPT (CON), a low-dose [...] Read more.
The present study evaluated the effects of dietary rumen-protected taurine (RPT) supplementation on ruminal fermentation, hematological parameters, liver function, stress-related hormones, and immune responses in yaks. Eighteen yaks were randomly allocated to three groups: a control group receiving no RPT (CON), a low-dose group receiving 20 g/day (RPT20), and a high-dose group receiving 40 g/day (RPT40). Supplementation with RPT did not significantly affect ruminal pH, microbial protein concentration, ammonia nitrogen, total volatile fatty acids, or the individual volatile fatty acid profiles (p > 0.05). A decreasing trend in red blood cell count was observed (p = 0.050), while no significant changes were detected in white blood cell or platelet indices (p > 0.05). Liver function markers, including albumin, alanine transaminase, aspartate transaminase, and total protein, remained unchanged, although a trend toward altered alkaline phosphatase activity was noted (p = 0.074). No significant effects were observed on acute-phase proteins (serum amyloid A, C-reactive protein) or stress-related hormones (epinephrine, adrenocorticotropic hormone, cortisol) (p > 0.05). Importantly, serum immunoglobulin A and immunoglobulin G levels were significantly increased in response to RPT supplementation (p = 0.029 and p = 0.043, respectively), suggesting enhanced humoral immunity. These findings indicate that RPT may improve immune function in yaks without negatively affecting rumen fermentation or liver health. Full article
20 pages, 4908 KB  
Article
Genes That Associated with Action of ACTH-like Peptides with Neuroprotective Potential in Rat Brain Regions with Different Degrees of Ischemic Damage
by Ivan B. Filippenkov, Yana Yu. Shpetko, Daria A. Ales, Vasily V. Stavchansky, Alina E. Denisova, Vadim V. Yuzhakov, Natalia K. Fomina, Leonid V. Gubsky, Lyudmila A. Andreeva, Nikolay F. Myasoedov, Svetlana A. Limborska and Lyudmila V. Dergunova
Int. J. Mol. Sci. 2025, 26(13), 6256; https://doi.org/10.3390/ijms26136256 - 28 Jun 2025
Viewed by 1592
Abstract
In the treatment of ischemic stroke, an innovative approach is the use of neuroprotective compounds. Natural peptides, including adrenocorticotropic hormone (ACTH), can serve as the basis for such drugs. Previously, a significant effect of non-hormonal ACTH(4-7)PGP (Semax) and ACTH(6-9)PGP peptides on the functions [...] Read more.
In the treatment of ischemic stroke, an innovative approach is the use of neuroprotective compounds. Natural peptides, including adrenocorticotropic hormone (ACTH), can serve as the basis for such drugs. Previously, a significant effect of non-hormonal ACTH(4-7)PGP (Semax) and ACTH(6-9)PGP peptides on the functions of the nervous system was shown. Also, while using RNA-Seq, we firstly revealed differentially expressed genes (DEGs) that associated with peptides in the penumbra-associated region of the frontal cortex (FC) of rats at 24 h after transient middle cerebral artery occlusion (tMCAO) model. Peptides significantly reduced profile disturbances caused by ischemia for almost two-thousand DEGs in FC related to the neurotransmitter and inflammatory response. Here, we studied how peptides affected the expression of genes in the striatum with an ischemic focus, predominantly. The same animals from which we previously acquired FC were used to collect striatum samples. Peptides generated fewer DEGs in the striatum than in the FC. Both peptides tended to normalize the profile of disturbances caused by ischemia for hundreds of DEGs, whereas 152 genes showed an even more affected profile in the striatum under ACTH(6-9)PGP action. These DEGs were associated with inflammation, predominantly. About hundred genes were overlapped between both peptides in both tissues and were associated with neuroactive ligand-receptor interaction, predominantly. Thus, genes that are associated with the ACTH-like peptide action in rat brain regions with varying levels of ischemia injury were identified. Moreover, differential spatial regulation of the ischemia process in the rat brain at the transcriptome levels was discovered under peptides with different ACTH structures. We suppose that our results may be useful for selecting more effective neuroprotective drug structures in accordance with their specific tissue/damage therapeutic impact. Full article
(This article belongs to the Special Issue Nutraceuticals for the Maintenance of Brain Health)
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