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Relative adrenal insufficiency (RAI) is common in critically ill patients with cirrhosis, but it has been also documented in non-critically ill patients. Its pathophysiology is complex and not well understood yet. In this review, we aimed to present potential mechanisms and causal pathways implicated in the pathogenesis of RAI in cirrhosis. There is accumulating evidence supporting a suboptimal baseline adrenal function in cirrhosis mainly due to decreased cortisol synthesis and metabolism rates from the adrenal gland. Apart from this peripheral impairment, more recent studies suggest that there is a greater defect in the central stimulation of the hypothalamic-pituitary-adrenal (HPA) axis (hypothalamus/pituitary gland). Pro-inflammatory mediators, which are elevated in cirrhosis, have been also implicated through suppression of the HPA axis, decrease in cortisol synthesis and tissue glucocorticoid resistance. All abovementioned support the hepatoadrenal syndrome hypothesis that during episodes of acute decompensation there is suboptimal adrenocortical response that leads to worse outcomes. In conclusion, the complex pathophysiology of adrenal dysfunction in cirrhosis has not been fully elucidated yet and further research is needed in order to better understand this rather common entity in cirrhosis. [ABSTRACT FROM AUTHOR]

Background: Adverse events of secondary adrenal insufficiency caused by anti-PD-1 immune agents are relatively rare in clinical practice, so in this article, we retrospectively analyzed three patients who suffered secondary adrenal cortex dysfunction caused by tislelizumab immunotherapy for Non-Small Cell Lung Cancer (NSCLC)and reviewed the literature. This rare immune-related adverse event was investigated by summarizing the clinical features of the patients. Case presentation: We reported three NSCLC patients who suffered secondary adrenal cortex dysfunction induced by tislelizumab immunotherapy at our hospital from July 2021 to October 2023. We analyzed and summarized the clinical characteristic, laboratory examination, pathological staging, etc. We also reviewed related literature of pituitary inflammation and adrenal cortex dysfunction caused by immunotherapy. Results: The median age of the three patients was 56 years. All the patients had a history of smoking. After receiving tislelizumab treatment (median cycle: 7), laboratory examination showed a decrease in morning cortisol and adrenocorticotropic hormone (ACTH), both were diagnosed with secondary adrenal insufficiency. Only one patient had symptoms of fatigue, vomiting, and weight loss. One of these patients also had simultaneous subclinical hypothyroidism. All three patients discontinued immunotherapy and received replacement therapy with glucocorticoids. At the last follow-up, none of the three patients restarted immunotherapy, because cortisol did not return to normal. This is similar to that of previous reports. Conclusion: Based on previous reports and our three cases, when laboratory tests of NSCLC patients receiving immunotherapy showed a decrease in morning cortisol and ACTH levels, especially when clinical symptoms were obvious, the possibility of immunotherapy-related pituitary inflammation causing secondary adrenal cortex dysfunction should be considered. Prompt monitoring and hormone replacement therapy should be provided to prevent adrenal crises. [ABSTRACT FROM AUTHOR]

The aim of this study was to reveal the effects of obesity and phytotherapy with 20-hydroxyecdysone (20E) on the nuclei of adrenal zona fasciculata (ZF) in the gerbil Gerbillus tarabuli by analyzing nuclear shape and gray-level co-occurrence matrix (GLCM) texture characteristics and by quantifying heterochromatin. Twelve gerbils were divided into three groups: control (C), HC and HC-20E (animals receiving a high-calorie-diet without or with a supplement of 20E, respectively). The adrenals were removed and fixed for histological and statistical analysis. Principal component analysis showed a positive correlation of area, perimeter and textural correlation in C. Nevertheless, a negative correlation was recorded for contrast and entropy. The obesity caused a disorder in nuclear texture; negative correlation was noted with heterochromatin fraction, which may be related to increased ZF activity. However, administration of 20E seems to improve the nuclear state by preserving circularity, uniformity and homogeneity of nuclei as well as the proportion of heterochromatin, which could be a sign of a downregulation of cell activity.Our results suggest that new techniques of image processing could contribute to the understanding of nuclear changes associated with obesity and its possible therapy in this gerbil model for metabolic syndrome. [ABSTRACT FROM AUTHOR]

Bacterial sepsis is a serious threat to the body homeostasis and is often associated with high mortality in non-coronary intensive stations. In order to survive sepsis, rapid activation of the hypothalamus-pituitary-adrenal gland axis and sympathomedullary system is necessary. In many patients with sepsis, the function of those two arms of the stress system is dysregulated with underlying mechanisms remaining unknown. In our previous experimental studies, we have demonstrated that LPS-induced systemic inflammation and CLP-induced peritonitis can result in adrenal gland damage. Histological and transcriptomic analysis revealed a potential involvement of the adrenal microvascular endothelium in this process. However, our knowledge about the function of adrenal microvascular cells during sepsis is scarce. In the present study, we have characterized transcriptomic alterations in isolated mouse adrenal microvascular endothelial cells induced by systemic administration of bacterial LPS. Our results revealed that LPS induced a distinct transcriptomic profile in the adrenal microvascular cells, including multiple genes regulating inflammation, activation of the coagulation cascade and vascular permeability. Activation of those genes may be potentially involved in the damage to the microvascular endothelium and altogether contribute to the sepsis-mediated adrenal dysregulation. [ABSTRACT FROM AUTHOR]

Intrinsic and extrinsic physiological stressors (physical, metabolic, or psychological) are constantly challenging the body's homeostatic mechanisms. Regardless of their nature, the body will initiate a series of autonomic responses in an effort to maintain homeostasis. For example, to cope with a perceived threat, cardiac output and respiration are increased, the availability of glucose is increased, and blood flow to the heart, brain, and muscles is increased. Conversely, once the threat subsides, counter-regulatory mechanisms act to down-regulate these responses. The adaptive stress response is essential for a patient's well-being. An altered adaptive stress response may lead to illness, and, at times, even to death. Oral healthcare providers must develop preventive and therapeutic strategies compatible with the functional capacity of a patient's adaptive stress response. [ABSTRACT FROM AUTHOR]

Objective: To correlate between cortisol precursors in neonates with vasopressor resistant hypotension and demographic characteristics.Methods: We investigated 48 neonates with vasopressor-resistant hypotension. Gestation at birth ranged from 34 to 42 weeks and postnatal age from 4 to 14 days. Cortisol and precursor steroids were measured soon after the onset of volume expansion and inotropes for treatment of shock. Their concentrations were determined using liquid chromatography/mass spectrometry.Results: In neonates with vasopressor-resistant hypotension, the serum levels of cortisol were within normal nonstress range. There was a strong negative linear association between postnatal age and dehydroepiandrosterone level (r = -0.50, p < .01), which decreased with neonatal age. In addition, there was a significant positive association between gestational age at birth and 17-hydroxy-pregnenolone (r = 0.33, p = .02). No further significant associations were evident between the neonatal weight, duration of gestation or gender and of the levels of cortisol or the other steroids (p > .05). The cause of therapy-resistant hypotension did not appear to influence the steroid levels.Conclusions: Cortisol stress response is absent in these severely ill late preterm and term infants. This may be due to inhibition of the distal pathway of cortisol synthesis. [ABSTRACT FROM AUTHOR]

Inflammatory markers and adrenocorticotropic hormone (ACTH) stimulation test results may help us recognise critically ill dogs with poor disease outcome. Systemic inflammatory response syndrome (SIRS) criteria, the fast version of the Acute Patient Physiologic and Laboratory Evaluation Score (APPLEfast), complete blood count, albumin and C-reactive protein (CRP) levels, baseline and stimulated cortisol levels and Δcortisol value were recorded in 50 client-owned dogs admitted to the Small Animal Hospital of the University of Veterinary Medicine Budapest with various inflammatory or neoplastic conditions. Increasing APPLEfast score was associated with a decreasing chance of survival (P = 0.0420). The Δcortisol value was significantly higher in SIRS dogs than in non-SIRS dogs (mean ± SD ΔcortisolSIRS: 342.5 ± 273.96; mean ± SD Δcortisolnon-SIRS: 175.3 ± 150.35; P = 0.0443). Elevated baseline or stimulated cortisol levels were associated with a higher chance of non-survival (P = 0.0135 and P = 0.0311, respectively). These data indicate that pathologically higher baseline and stimulated cortisol levels represent an exaggerated stress response in critically ill dogs, which is negatively associated with survival. [ABSTRACT FROM AUTHOR]

Objective: Therapy-resistant hypotension complicates diseases in neonates. Our objective was to investigate whether lack of therapeutic response to plasma expanders and inotropes associates with serum levels of cortisol and its precursors.Methods: We investigated 96 infants with hypotension and critical neonatal disease for cortisol metabolism and are divided into responders and non-responders to plasma expanders and inotropes. Serum concentrations of steroids were analysed soon after the onset of volume expansion and inotrope treatment for shock. The 48 non-responders were treated with intravenous hydrocortisone (HC) and serum cortisol concentrations were monitored a week later.Results: The mean cortisol concentrations did not differ between the responders and non-responders: 13.6 ± 2.5 and 12.5 ± 4.5 μg/dL, respectively. Dehydroepiandrosterone (37.3 ± 19.5 versus 324.0 ± 106.3; p < 0.0001) and 17-hydroxy-pregnenolone concentrations were lower in responders than in non-responders. Dehydroepiandrosterone levels in non-responders were inversely associated with postnatal age (r = 0.50, p < 0.0001). There were no differences in 17-hydroxy-progesterone, 11-deoxy-cortisol and cortisone between the responders and non-responders. Hydrocortisone administration acutely increased blood pressure. Six non-responders who died despite HC administration had low levels of cortisol. The responders had normal serum cortisol after HC treatment.Conclusion: Precursors of cortisol, proximal to the 3β-hydroxysteroid dehydrogenase activity, accumulated in neonates with hypotension, responding to HC treatment. [ABSTRACT FROM AUTHOR]

Background Hepatopulmonary syndrome (HPS) is a relatively common complication in patients with decompensated cirrhosis. Our aim was to evaluate the prevalence of HPS, its clinical impact, and the possible association between HPS and characteristics of patients with decompensated cirrhosis. Methods Patients with stable decompensated cirrhosis admitted to our department and assessed for HPS were included. For each patient, several clinical, laboratory and echocardiographic parameters as well as renal function were recorded. The severity of liver disease was evaluated according to the Model for End-stage Liver Disease and Child-Pugh scores, and renal function was assessed using 51chromium complexed wiThethylene diamine tetracetic acid. In addition, the short synacthen test was performed in each patient to evaluate the adrenal function. Results Sixty-three patients were enrolled, 26 (41.3%) of whom diagnosed with HPS. In multivariate analysis, the presence of hepatocellular carcinoma [odds ratio (OR) 8.1, 95% confidence interval (CI) 5.3-27.9, P=0.045] and salivary cortisol at T60 (60 min aft er the intravenous injection of 250 µg corticotropin) (OR 0.88, 95%CI 0.71-0.98, P=0.045) were the factors independently associated with HPS. T60 salivary cortisol had relatively good discriminative ability for the presence of HPS (area under the curve=0.73). The presence of HPS was not associated with the outcome (P=0.22). Conclusion In our cohort of patients with decompensated cirrhosis, the presence of hepatocellular carcinoma and T60 salivary cortisol were the only factors independently associated with HPS. [ABSTRACT FROM AUTHOR]

To review the effects of critical illness on hypothalamic–pituitary–adrenal (HPA) function in human and veterinary medicine. Data from human and veterinary literature was reviewed. Relative adrenal insufficiency (RAI) appears to be common in critically ill human patients with sepsis or septic shock. Hypotension that is refractory to fluid therapy and requires vasopressors is the most common presentation of RAI in the human intensive care unit (ICU). Many investigators now advocate the use of a low-dose adrenocorticotropin hormone stimulation test to diagnose RAI. It is important to evaluate for the presence of adrenal dysfunction, because current data suggest that treatment with ‘stress’ or low doses of glucocorticoids (200–300 mg hydrocortisone daily) may improve patient outcome in humans. There is a paucity of controlled studies in the veterinary literature regarding the effects of critical illness on HPA function. The results of these studies are varied. However, research models of sepsis and hemorrhagic shock suggest the existence of RAI in animals. Prospective clinical studies are needed to further examine pituitary–adrenal response to severe illness in veterinary patients, and to determine if there are therapeutic options, including glucocorticoid administration, which will improve patient outcome in animals. RAI is well documented in critically ill human patients, yet little is known about adrenal dysfunction in veterinary critically ill patients. A small number of studies suggest that RAI may exist in certain subpopulations of veterinary patients. The syndrome of RAI could be considered as a differential diagnosis in seriously ill veterinary patients that fail to respond to appropriate therapy, especially when hypotension refractory to fluid and vasopressor therapy is encountered. This disorder may represent a previously unidentified syndrome in critically ill veterinary patients with important therapeutic implications. [ABSTRACT FROM AUTHOR]

Latent varicella zoster virus (VZV) has been detected in human adrenal glands, raising the possibility of virus-induced adrenal damage and dysfunction during primary infection or reactivation. Rare cases of bilateral adrenal hemorrhage and insufficiency associated with VZV reactivation have been reported. Since there is no animal model for VZV infection of adrenal glands, we obtained adrenal glands from two non-human primates (NHPs) that spontaneously developed varicella from primary simian varicella virus (SVV) infection, the NHP VZV homolog. Histological and immunohistochemical analysis revealed SVV antigen and DNA in the adrenal medulla and cortex of both animals. Adrenal glands were observed to have Cowdry A inclusion bodies, cellular necrosis, multiple areas of hemorrhage, and varying amounts of polymorphonuclear cells. No specific association of SVV antigen with βIII-tubulin-positive nerve fibers was found. Overall, we found that SVV can productively infect NHP adrenal glands, and is associated with inflammation, hemorrhage, and cell death. These findings suggest that further studies are warranted to examine the contribution of VZV infection to human adrenal disease. This study also suggests that VZV infection may present itself as acute adrenal dysfunction with "long-hauler" symptoms of fatigue, weakness, myalgias/arthralgias, and hypotension. [ABSTRACT FROM AUTHOR]