Adrenocortical hypertrophy: establishing cause and toxicological significance

Harvey, Philip W.; Sutcliffe, Catherine G.

doi:10.1002/jat.1569

Cited by 52 publications

(46 citation statements)

References 37 publications

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“…Our bone data also suggested adrenal involvement because the effect of under-nutrition on bone is an indirect endocrine effect, including increased cortisol [33-35]. Finally, we observed adrenal hypertrophy in the inhalant group following exposure, a common outcome of adrenal insufficiency [36]. Utilising a diagnostic flowchart (Fig.…”

Section: Discussionmentioning

confidence: 99%

Adolescent Inhalant Abuse Results in Adrenal Dysfunction and a Hypermetabolic Phenotype with Persistent Growth Impairments

et al. 2018

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Background/Aims: Abuse of toluene products (e.g., glue-sniffing) primarily occurs during adolescence and has been associated with appetite suppression and weight impairments. However, the metabolic phenotype arising from adolescent inhalant abuse has never been fully characterised, and its persistence during abstinence and underlying mechanisms remain unknown. Methods: Adolescent male Wistar rats (post-natal day 27) were exposed to inhaled toluene (10,000 ppm) (n = 32) or air (n = 48) for 1 h/day, 3 days/week for 4 weeks, followed by 4 weeks of abstinence. Twenty air rats were pair-fed to the toluene group, to differentiate the direct effects of toluene from under-nutrition. Food intake, weight, and growth were monitored. Metabolic hormones were measured after exposure and abstinence periods. Energy expenditure was measured using indirect calorimetry. Adrenal function was assessed using adrenal histology and hormone testing. Results: Inhalant abuse suppressed appetite and increased energy expenditure. Reduced weight gain and growth were observed in both the toluene and pair-fed groups. Compared to the pair-fed group, and despite normalisation of food intake, the suppression of weight and growth for toluene-exposed rats persisted during abstinence. After exposure, toluene-exposed rats had low fasting blood glucose and insulin compared to the air and pair-fed groups. Consistent with adrenal insufficiency, adrenal hypertrophy and increased basal adrenocorticotropic hormone were observed in the toluene-exposed rats, despite normal basal corticosterone levels. Conclusions: Inhalant abuse results in negative energy balance, persistent growth impairment, and endocrine changes suggestive of adrenal insufficiency. We conclude that adrenal insufficiency contributes to the negative energy balance phenotype, potentially presenting a significant additional health risk for inhalant users.

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Section: Discussionmentioning

confidence: 99%

Adolescent Inhalant Abuse Results in Adrenal Dysfunction and a Hypermetabolic Phenotype with Persistent Growth Impairments

et al. 2018

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“…Adrenal cortical changes of hyperplasia and hypertrophy associated with stress are diffuse and bilateral, in contrast to focal adrenal cortical hypertrophy which is an incidental or background finding in many species (Harvey and Sutcliffe 2010;Kaspareit 2009;Rohr et al 1978;Soldani et al 1999).…”

Section: Chronic Stressmentioning

confidence: 99%

Interpreting Stress Responses during Routine Toxicity Studies

et al. 2013

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Stress often occurs during toxicity studies. The perception of sensory stimuli as stressful primarily results in catecholamine release and activation of the hypothalamic-pituitary-adrenal (HPA) axis to increase serum glucocorticoid concentrations. Downstream effects of these neuroendocrine signals may include decreased total body weights or body weight gain; food consumption and activity; altered organ weights (e.g., thymus, spleen, adrenal); lymphocyte depletion in thymus and spleen; altered circulating leukocyte counts (e.g., increased neutrophils with decreased lymphocytes and eosinophils); and altered reproductive functions. Typically, only some of these findings occur in a given study. Stress responses should be interpreted as secondary (indirect) rather than primary (direct) test article-related findings. Determining whether effects are the result of stress requires a weight-of-evidence approach. The evaluation and interpretation of routinely collected data (standard in-life, clinical pathology, and anatomic pathology endpoints) are appropriate and generally sufficient to assess whether or not changes are secondary to stress. The impact of possible stress-induced effects on data interpretation can partially be mitigated by toxicity study designs that use appropriate control groups (e.g., cohorts treated with vehicle and subjected to the same procedures as those dosed with test article), housing that minimizes isolation and offers environmental enrichment, and experimental procedures that minimize stress and sampling and analytical bias.This article is a comprehensive overview of the biological aspects of the stress response, beginning with a Summary (Section 1) and an Introduction (Section 2) that describes the historical and conventional methods used to characterize acute and chronic stress responses. These sections are followed by reviews of the primary systems and parameters that regulate and/or are influenced by stress, with an emphasis on parameters evaluated in toxicity studies:

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“…Adrenal glands are known to have a higher volume in septic patients [22], which reflects the stress severity due to sepsis which is associated with a poor prognosis [23], and it is also known to be an independent predictor of mortality in humans [24]. The adrenocortical hypertrophy serves as evidence of increased adrenocortical function [25,26]. As sepsis activates the hypothalamopituitary axis, corticosterone production increases very early in response to the stress of critical illness.…”

Section: Discussionmentioning

confidence: 99%

The MRI Sepsis Score: An Innovative Tool for the Evaluation of Septic Peritonitis in Mice Using 7-Tesla Small Animal MRI

et al. 2018

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Background: Magnetic resonance imaging (MRI) techniques are rarely used in the context of abdominal sepsis and in sepsis research. This study investigates the impact of MRI for monitoring septic peritonitis in an animal model (colon ascendens stent-induced peritonitis, CASP). The CASP model closely mimics that of human disease and is highly standardized. The most frequently employed readout parameter in mouse CASP studies is prolonged or decreased rate of survival. Monitoring the progression of peritonitis via MRI could provide a helpful tool in the evaluation of severity. The use of alternative readout systems could very well reduce the number of research animals. Perspectively, clinical improvement after certain treatment could be classified. Methods: This study describes for the first time MRI findings following the induction of septic peritonitis in mice using the CASP model. Two sublethal groups of mice with septic peritonitis were investigated. Each had received one of two differing stent diameters in order to control the leakage of feces into the abdominal cavity. Each mouse served as its own control. Imaging and analyses were performed blinded. Gut diameters, stomach volume, abdominal organ wall diameters, and volume of the adrenal glands were measured. Serum corticosterone levels were detected using ELISA. Serum IL-6, TNF-α, IL-1β, and IL-10 levels were screened by cytometric bead array. Statistical analysis was performed using the Mann-Whitney U test for nonparametric probes and the Kruskal-Wallis and t tests. Results: Using a 7-tesla MRI scanner 24 and 48 h after induction of septic peritonitis, interenteric fluid, organ swelling of spleen and adrenal glands, as well as dilatation of the stomach were compared to nonseptic conditions. Swelling of adrenal glands resulted in an increased serum corticosterone level. In addition, the wall of the intestine bowel was thickened. Based upon these findings, an MRI score (MRI sepsis score, MSS) for abdominal sepsis in mice was established. Reduced stent sizes led to reduced severity of the abdominal sepsis, which could be reproduced in the MSS, which is described here for the first time. Conclusions: Intraabdominal variations during septic peritonitis are detectable by MRI techniques. MRI methods should become a more important tool for the evaluation of abdominal peritonitis. MSS could provide an interesting tool for the evaluation of therapeutic strategies.

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Adrenocortical hypertrophy: establishing cause and toxicological significance

Cited by 52 publications

References 37 publications

Adolescent Inhalant Abuse Results in Adrenal Dysfunction and a Hypermetabolic Phenotype with Persistent Growth Impairments

Adolescent Inhalant Abuse Results in Adrenal Dysfunction and a Hypermetabolic Phenotype with Persistent Growth Impairments

Interpreting Stress Responses during Routine Toxicity Studies

The MRI Sepsis Score: An Innovative Tool for the Evaluation of Septic Peritonitis in Mice Using 7-Tesla Small Animal MRI

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