Adrenal Damage Research Articles

C5a Induces Inflammatory Signaling and Apoptosis in PC12 Cells through C5aR-Dependent Signaling: A Potential Mechanism for Adrenal Damage in Sepsis.

The complement system is critically involved in the pathogenesis of sepsis. In particular, complement anaphylatoxin C5a is generated in excess during sepsis, leading to cellular dysfunction. Recent studies have shown that excessive C5a impairs adrenomedullary catecholamine production release and induces apoptosis in adrenomedullary cells. Currently, the mechanisms by which C5a impacts adrenal cell function are poorly understood. The PC12 cell model was used to examine the cellular effects following treatment with recombinant rat C5a. The levels of caspase activation and cell death, protein kinase signaling pathway activation, and changes in inflammatory protein expression were examined following treatment with C5a. There was an increase in apoptosis of PC12 cells following treatment with high-dose C5a. Ten inflammatory proteins, primarily involved in apoptosis, cell survival, and cell proliferation, were upregulated following treatment with high-dose C5a. Five inflammatory proteins, involved primarily in chemotaxis and anti-inflammatory functions, were downregulated. The ERK/MAPK, p38/MAPK, JNK/MAPK, and AKT protein kinase signaling pathways were upregulated in a C5aR-dependent manner. These results demonstrate an apoptotic effect and cellular signaling effect of high-dose C5a. Taken together, the overall data suggest that high levels of C5a may play a role in C5aR-dependent apoptosis of adrenal medullary cells in sepsis.

Dexmedetomidine on the interplay of IL-6 and STAT3 pathways in adrenal gland damage-induced scalding burns in rats.

Scalding burns are a common form of thermal injury that often leads to systemic complications. Pro-inflammatory cytokines like interleukin-6 (IL-6) and the activation of signal transducer and activator of transcription 3 (STAT3) pathways have been linked to the pathophysiology of organ damage caused by burns. This study aimed to investigate the potential therapeutic effects of dexmedetomidine, an α2-adrenergic receptor agonist with anti-inflammatory properties, on the interplay of IL-6 and STAT3 pathways in adrenal gland damage following scalding burns in rats. Twenty-eight rats were divided randomly into four groups. Rats in group 1 (n=7, control) were given only 0.9% intraperitoneal (i.p.) NaCl. Rats in group 2 (n=7, DEX) were exposed to 25°C water for 17 s on day 1 and received 100 mcg/kg/day dexmedetomidine i.p. for 3 days; for rats in group 3 (n=7, Burn), boiling water of 94°C was applied inside for 17 s. Rats in group 4 (n=7, Burn+DEX) were exposed to 94°C water for 17 s and received 100 mcg/kg/day dexmedetomidine i.p. for 3 days. Adrenal gland tissues were histopathological examined, and STAT3, IL-6, and TUNEL staining were performed using immunohistochemically. Our results revealed that scalding burns increased IL-6 and STAT3 expression in the adrenal glands of rats. Histological analysis demonstrated that dexmedetomidine administration ameliorated adrenal gland damage and reduced inflammatory cell infiltration. Our findings suggest that dexmedetomidine protects the adrenal glands in scalding burns. This protection appears to be mediated, at least in part, by its modulation of IL-6 and STAT3 pathways.

Immune checkpoint inhibitors-related endocrinopathies exhibit increased severity in breast cancer patients: a real-world study.

This study aims to systematically evaluate the incidence of immune checkpoint inhibitors (ICIs)-related endocrinopathies and their onset time in patients with breast cancer (BC) in a real-world setting. An analysis was conducted on the medical records of 122 BC patients who underwent ICIs therapy at the Department of Breast Surgery, Guangdong Provincial People's Hospital, from April 2019 to September 2021. Follow-up data continued until October 2022. The research indicated that 60.66% of BC patients experienced ICI-related endocrinopathies. The endocrinopathies included pituitary injury (7.38%), primary thyroid dysfunction (34.43%), supranormal fasting blood glucose or glycohemoglobin levels (16.39%), and adrenal injury (2.46%). Subgroup analyses were further performed based on clinical characteristics, demonstrated variability in the incidence of ICI-related endocrinopathies. Notably, subpopulations harboring genetic mutations exhibited a markedly higher prevalence of hypophysitis, as evidenced by a statistically significant association (P = 0.022). Similarly, individuals with HER2 positivity were found to have a significantly increased incidence of pancreatic islet injury (P = 0.023). Moreover, the study documented that the median onset times of ICIs-related endocrinopathies in pituitary, thyroid, pancreatic, and adrenal damage were 264, 184, 99 and 141 days, respectively, which were substantially longer compared to previous reports involving other tumors. Remarkably, even after 500 days of initiating ICI therapy, new cases of ICI-related endocrine disorders continue to emerge, suggesting a situation of delayed onset of ICI-related endocrinopathies in BC patients. The retrospective analysis confirmed a higher incidence and longer median onset time of ICI-related endocrinopathies in BC patients compared to other cancers. These outcomes underscore the critical need for regular and extended monitoring of endocrine functions in BC patients receiving ICI therapy, advocating for personalized monitoring approaches based on individual clinical profiles.

Biochemical Study of The Ameliorative Influences of Fennel Oil against Cyproconazole-Induced Adrenal Gland Damage in Albino Rats

Biochemical Study of The Ameliorative Influences of Fennel Oil against Cyproconazole-Induced Adrenal Gland Damage in Albino Rats

COVID-19 infection: from stress-related cortisol levels to adrenal glands infarction.

Cortisol is a key element in acute stress including a severe infection. However, in coronavirus-associated disease, 20% of subjects experience hypocortisolemia due to direct or immune damage of pituitary and adrenal glands. One extreme form of adrenal insufficiency is found in 2∕3 of cases with viral and post-viral adrenal infarction (AI) (with∕without adrenal hemorrhage) that is mostly associated with a severe coronavirus disease 2019 (COVID-19) infection; it requires prompt glucocorticoid intervention. Some reports are incidental findings at computed tomography (CT)∕magnetic resonance imaging (MRI) scans for non-adrenal complications like pulmonary spreading and others are seen on post-mortem analysis. This is a review of PubMed-accessible, English papers focusing on AI in addition to the infection, between March 1, 2020 and November 1, 2021. Exclusion criteria were acute adrenal insufficiency without the histopathological (HP) and∕or imaging report of adrenal enlargement, necrosis, etc., respective adrenal failure due to pituitary causes, or non-COVID-19-related adrenal events. We identified a total of 84 patients (different levels of statistical evidence), as follows: a retrospective study on 51 individuals, two post-mortem studies comprising nine, respectively 12 patients, a case series of five subjects, seven single-case reports. HP aspects include necrosis associated with ischemia, cortical lipid degeneration (+/- focal adrenalitis), and infarcts at the level of adrenal cortex, blood clot into vessels, acute fibrinoid necrosis in arterioles and capsules, as well as subendothelial vacuolization. Collateral potential contributors to adrenal damage are thrombotic events, coagulation anomalies, antiphospholipid syndrome, endothelial dysfunction, severe COVID-19 infection with multiorgan failure, etc. Clinical picture is variable from acute primary adrenal insufficiency to asymptomatic or mild evolution, even a retrospective diagnostic; it may be a part of long COVID-19 syndrome; glucocorticoid therapy for non-adrenal considerations might mask cortisol deficient status due to AI∕hemorrhage. Despite its rarity, the COVID-19-associated AI/hemorrhage represents a challenging new chapter, a condition that is essential to be recognized due to its gravity since prompt intervention with glucocorticoid replacement is lifesaving.

The Role of Oxidative Stress and Inflammation in X-Link Adrenoleukodystrophy.

X-linked adrenoleukodystrophy (X-ALD) is an inherited disease caused by a mutation in the ABCD1 gene encoding a peroxisomal transmembrane protein. It is characterized by the accumulation of very-long-chain fatty acids (VLCFAs) in body fluids and tissues, leading to progressive demyelination and adrenal insufficiency. ALD has various phenotypes, among which the most common and severe is childhood cerebral adrenoleukodystrophy (CCALD). The pathophysiological mechanisms of ALD remain unclear, but some in vitro/in vivo research showed that VLCFA could induce oxidative stress and inflammation, leading to damage. In addition, the evidence that oxidative stress and inflammation are increased in patients with X-ALD also proves that it is a potential mechanism of brain and adrenal damage. Therefore, normalizing the redox balance becomes a critical therapeutic target. This study focuses on the possible predictors of the severity and progression of X-ALD, the potential mechanisms of pathogenesis, and the promising targeted drugs involved in oxidative stress and inflammation.

Adrenoleukodystrophy in Adults: About a Case

Background: the goal is to think about leukodystrophy which can mimic a progressive picture of multiple sclerosisMaterial(s) and Method(s): We report the observation of a man with adreno-leukodystrophy whose neurological manifestations were late.Result(s): The diagnosis of adrenoleukodystrophy is made on a bundle of clinical and radiological arguments (male, presence of adrenal damage, appearance of radiological lesions, encephalic and medullary damage), the diagnosis is confirmed by the determination of very long chain fatty acids.Conclusion(s): Adrenoleukodytrophy can mimic certain pathologies, in particular multiple sclerosis in its progressive form, hence the interest of certain paraclinical examinations and a good analysis of the imagery.Lorenzo's oil normalizes C26 levels within 4 weeks but has no effect on neurological progression patients already affected. However, this therapeutic management seems to be interesting in patients asymptomatic and not having cerebral involvement. Background: the goal is to think about leukodystrophy which can mimic a progressive picture of multiple sclerosis Material(s) and Method(s): We report the observation of a man with adreno-leukodystrophy whose neurological manifestations were late. Result(s): The diagnosis of adrenoleukodystrophy is made on a bundle of clinical and radiological arguments (male, presence of adrenal damage, appearance of radiological lesions, encephalic and medullary damage), the diagnosis is confirmed by the determination of very long chain fatty acids. Conclusion(s): Adrenoleukodytrophy can mimic certain pathologies, in particular multiple sclerosis in its progressive form, hence the interest of certain paraclinical examinations and a good analysis of the imagery. Lorenzo's oil normalizes C26 levels within 4 weeks but has no effect on neurological progression patients already affected. However, this therapeutic management seems to be interesting in patients asymptomatic and not having cerebral involvement.

Histopathological Analysis of Adrenal Glands after Simian Varicella Virus Infection.

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.

Extracellular vesicles derived from bone marrow mesenchymal stem cells repair functional and structural rat adrenal gland damage induced by fluoride

The adrenal glands have striking morpho-biochemical features that render them vulnerable to the effects of toxins. Aims: This study was conducted to explore the therapeutic utility of extracellular vesicles derived from bone marrow mesenchymal stem cells (BMSC-EVs) against fluoride-induced adrenal toxicity. Materials and methods: The work included isolation and further identification of BMSC-EVs by transmission electron microscopy and flow cytometric analysis. Adrenal toxicity in rats was induced by oral administration of 300 ppm of sodium fluoride (NaF) in drinking water for 60 days followed by a single dose injection of BMSC-EVs. The effects of BMSC-EVs against NaF was evaluated by adrenal oxidant/antioxidant biomarkers, hormonal assay of plasma adrenocorticotrophic hormone (ACTH) and corticosterone (CORT) and mRNA gene expression quantitation for adrenal cortical steroidogenic pathway-encoding genes. Histopathological examination of the adrenal tissue was performed. Key findings: BMSC-EVs were effectively isolated and characterized. NaF exposure decreased adrenal superoxide dismutase and catalase activities, increased adrenal malondialdehyde levels, elevated plasma ACTH, diminished CORT concentrations and downregulated the adrenal cortical steroidogenic pathway-encoding genes. In addition, NaF-induced marked adrenal histopathological lesions. Significance: BMSC-EVs treatment repaired damaged adrenal tissue and recovered its function greatly following NaF consumption. BMSC-EVs reversed the toxic effects of NaF and reprogramed injured adrenal cells by activating regenerative processes.

Influenza A (H1N1) and COVID-19: features of adrenal lesions

Stressors are one of the causes of adrenal damage in influenza A (H1N1) and COVID-19. When they act, the same type of morphofunctional changes develop in the cortical layer of the adrenal glands. To a greater extent such processes are expressed in adrenocorticocytes of a reticular zone. This does not negate the existence of other mechanisms of adrenal damage by viruses, in particular the mechanism of mimicry of viral peptides to human adrenocorticotropic hormone (ACTH), as a result of which, after the production of antibodies, the latter affect both the pathogen and ACTH, causing hypocorticism. This paper reviews the histological and immuno­histochemical study of the influenza A (H1N1) (3 clinical cases) and COVID-19 (1 clinical case) influence on adrenal glands. The study showed that both influenza A (Н1N1) and COVID-19 cause adrenal damage. Histo­logical changes in these diseases are characterized by edema and partial destruction of endocrine cells in both the medulla and adrenal cortex. However, COVID-19 caused more significant damage to the medulla with reducing of Chromogranin A substrates levels of endocrine cells. In COVID-19 case signs of ischemia in the medulla and adrenal cortex were found, although in influenza A (H1N1) cases the plethora and vasodilatation of microcirculatory vessels were obser­ved. Hypoxic damage in the COVID-19 clinical case was accompanied by accumulation in the cytoplasm of endocrine cells of lipofuscin granules — a marker of activation of free radical oxidation of lipids.

PHARMACOLOGICAL FEATURES OF MEDICINAL PRODUCTS WITH MINERALCORTICOID ACTIVITY IN NEPHROLOGICAL PRACTICE

Introduction. Mineralocorticoids mainly affect the exchange of electrolytes, promote retention in the body of sodium, chlorides and water, and accelerate the excretion of potassium, calcium and magnesium. Their synthesis and blood supply are regulated mainly by angiotensin-II, which makes it possible to consider aldosterone as a part of renin-angiotensin-aldosteon system, which ensures the proper state of water-salt metabolism and hemodynamics. 
 The purpose. Consider the relationship of dynamic balance of mineralocorticoids in patients with kidney and adrenal lesions.
 Material and methods. Review of contemporary and foreign literary sources; techniques - description, analysis, abstracting. 
 Results. The pathogenesis of the development and progression of adrenal and kidney damage is closely associated with impaired synthesis, absorption of mineralocorticoids. The glucocorticoid activity of aldosterone roughly corresponds to 1/3 of cortisone. Main target organs of the hormone are salivary glands and kidneys. In the kidneys, aldosterone enhances sodium reabsorption. In pathological cases, the prolonged presence of chlorides and water in the body leads to the development of edema, hypernatremia, hypokalemia, hypervolemia, arterial hypertension, and sometimes, to the development of congestive heart failure. It poses particular danger in patients with impaired renal function. Deoxycorticosterone acetate (DOCSA) is a synthetic analogue of the Mineralocorticoids of the adrenal cortex. The drug is indicated for rapid-flowing adrenal hypofunction (addisonism), for myasthenia (increases muscle tone and performance), shock and trauma, for hypocorticism. Spironolactone is effective in swelling associated with increased aldosterone production, congestive heart failure, liver cirrhosis and nephrotic syndrome. Conclusions. Patients with kidney and adrenal lesions may have a violation of mineralocorticoid homeostasis, for the correction of which synthetic mineralocorticoids and their analogues, mineral and glucocorticoid antagonists, are used.

Assessment of autoantibodies against 21-hydroxylase in the diagnosis of primary autoimmune adrenal insufficiency

Primary adrenal insufficiency is manifested by a deficiency of adrenal cortex hormones and can lead to a life-threatening condition. Early diagnosis is key to patient survival. Auto-antibodies to one of the adrenal steroidogenesis enzymes, 21-hydroxylase, are an immunological marker of autoimmune adrenal insufficiency. On the one hand, the study of antibodies to 21-hydroxylase is a method that helps establish the etiology of the disease – the autoimmune genesis of adrenal gland damage. On the other hand, the determination of autoantibodies to 21-hydroxylase is the only prognostic factor of the risk of adrenal insufficiency, which makes it possible to prevent the development of acute adrenal crisis. The article provides a brief literature review on autoantibodies to 21-hydroxylase and the pathogenesis of autoimmune adrenal insufficiency, and a series of clinical cases that illustrates the significant role of autoantibodies to 21-hydroxylase in diagnosis of adrenal insufficiency.

Transcriptional Analysis of Sepsis-Induced Activation and Damage of the Adrenal Endothelial Microvascular Cells

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.

Multiorgan toxicity induced by EtOH extract of Fructus Psoraleae in Wistar rats

BackgroundThe fruits of Psoralea corylifolia L. (Fructus Psoraleae, FP) has a long history and a wide range of applications in the treatment of osteoporosis and leukoderma. Although it is well known that FP could cause hepatotoxicity and reproductive toxicity, less is known about its potential toxicity on multiple organs. PurposeThis study aims to determine the multiorgan toxicity of EtOH extract of FP (EEFP) and to investigate the underlying mechanisms through a systematic evaluation in Wistar rats. Study design and methodsWistar rats were orally administered with the EEFP at doses of 1.5, 1.0 and 0.5 g/kg for 28 days. Histopathologic and clinicopathologic analyses were performed, and the hormone levels in serum and the mRNA levels of enzymes related to the production of steroid hormones in adrenal glands were detected. The area of each band of adrenal glands and the steroid levels in the adrenal glands were also measured. ResultsAfter the treatment, both the histopathologic and clinicopathologic examination showed that EEFP caused liver, prostate, seminal vesicle and adrenal gland damage. Among the enzymes involved in the regulation of adrenal steroid hormone production, NET, VMAT2, and CYP11B1 were upregulated, while CYP17A1 was downregulated. Among the adrenal steroid hormones, COR and NE were upregulated, while levels of DHT and serum ACRH and CRH decreased. ConclusionOur results indicated that adrenal gland, prostate, and seminal vesicles could also be the target organs of FP-induced toxicity. Abnormal enzyme and hormone production related to the hypothalamic pituitary adrenal (HPA) axis caused by the EEFP may be the potential toxic mechanism for changes in the adrenal gland and secondary sex organs of male rats.

Using microwave thermal ablation to develop a subtotal, cortical-sparing approach to the management of primary aldosteronism

Objective: To investigate the feasibility and efficacy of localized, subtotal, cortical-sparing microwave thermal ablation (MTA) as a potential curative management for primary aldosteronism. The study investigated with equal importance the selected ablation of small volumes of adrenal cortex while sparing adjacent cortex.Method: An in-vivo study was carried out in swine (n = 8) where MTA was applied under direct visualization, to the adrenal glands at 45 W or 70 W for 60 s, using a lateral, side-firing probe and a non-penetrative approach. Animals were survived for 48 h post-procedurally. Animals were investigated for markers of histological, immunohistochemical and biochemical evidence of adrenal function and adrenal damage by assessing samples drawn intra-operatively and at the time of euthanasia.Results: Selected MTA (70 W for 60 s) successfully ablated small adrenocortical volumes (∼0.8 cm3) characterized by coagulative necrosis and abnormal expression of functional markers (CYP11B1 and CYP17). Non-ablated, adjacent cortex was not affected and preserved normal expression of functional markers, without increased expression of markers of heat damage (HSP-70 and HMGB-1). Limited adrenal medullary damage was demonstrated histologically, clinically and biochemically.Conclusion: MTA offers potential as an efficient methodology for delivering targeted subtotal cortical-sparing adrenal ablation. Image-guided targeted MTA may also represent a safe future modality for curative management of PA, in the setting of both unilateral and bilateral disease.

ВПЛИВ ПРЕПАРАТУ L-АРГІНІНУ НА ЗМІНИ ПРОЦЕСІВ ПЕРОКСИДНОГО ОКИСНЕННЯ ЛІПІДІВ ТА АНТИОКСИДАНТНОЇ СИСТЕМИ В КРОВІ ЗА УМОВ КОМОРБІДНОЇ ПАТОЛОГІЇ – ІММОБІЛІЗАЦІЙНОГО СТРЕСУ ТА АДРЕНАЛІНОВОГО УШКОДЖЕННЯ МІОКАРДА

Вступ. Активація адренергічної і гіпоталамо-гіпофізарно-адреналової систем призводить до виникнення стресорної тріади Сельє, першим компонентом якої є гіпертрофія надниркових залоз із збільшенням синтезу ними глюкокортикоїдів та катехоламінів. Аргінін слугує необхідним компонентом для синтезу білків і багатьох біологічно важливих молекул, таких, як орнітин, пролін, поліаміни, креатин і агматин. Однак головна його роль в організмі людини – бути субстратом для синтезу оксиду азоту. 
 Мета дослідження –вивчити вплив препарату L-аргініну на зміни процесів пероксидного окиснення ліпідів та антиоксидантної системи, що виникають у крові білих щурів під впливом гострого іммобілізаційного стресу й адреналіну.
 Методи дослідження.Дослід проводили на білих щурах-самцях лінії Вістар масою 180–200 г, яких було поділено на три групи по 10 тварин у кожній (дві дослідні та одну контрольну).
 Результати й обговорення. Встановлено, що за умов поєднаної патології (іммобілізаційного стресу й адреналінового ушкодження міокарда) до лікування L-аргініном активність у крові показників антиоксидантної системи – каталази і супероксиддисмутази зменшувалася на 5-ту добу експерименту. Було відзначено збільшення рівня продуктів пероксидного окиснення ліпідів – дієнових кон’югатів та малонового діальдегіду проти контролю. Використання L-аргініну протягом 5-ти днів призвело до підвищення активності каталази (на 107,2 %) і супероксиддисмутази (на 74,5 %) відносно групи тварин з поєднаною патологією в експерименті (іммобілізаційним стресом і адреналіновим ушкодженням міокарда) до лікування, що свідчить про антиоксидантний вплив даного препарату. Застосування L-аргініну протягом 5-ти днів знизило рівень дієнових кон’югатів (на 80,16 %, р<0,05) та малонового діальдегіду (на 42,26 %, р<0,05), що вказує на зменшення процесів пероксидного окиснення ліпідів. 
 Висновок.L-аргінін доцільно в подальшому і перспективно вивчати в експерименті та клініці з метою корекції метаболічних порушень за умов експериментального іммобілізаційного стресу й адреналінового ушкодження міокарда і розробки методичних рекомендацій.

Effect of Intravenous Fluid Volumes on the Adrenal Glucocorticoid Response After Burn Injury in Swine.

Severe thermal injury induces metabolic and physiological stress, prompting a disruption in the hypothalamic-pituitary-adrenal axis. The objective of this study was to evaluate potential confounding effects of Lactated Ringer's (LR) resuscitation on adrenal damage and cortisol production following burn. Anesthetized swine were instrumented with jugular catheters and sustained 40% TBSA burns from brass probes heated to 100°C. Animals recovered to consciousness and received IV fluid resuscitation with LR at two different volumes: 15 ml/kg/d (limited volume [LV], n = 6) or 2 ml/kg/%TBSA/d (modified Brooke [MB], n = 6). Nonburned animals (Sham) were both oral and IV fluid restricted (S-FR, n = 4) to induce stress. Computed tomography (CT) angiographies were performed at baseline (BL) and 48 hours postburn, while blood and urine samples were collected at BL, 6, 24, and 48 hours postburn, with euthanasia at 48 hours for adrenal harvesting. Urinary cortisol was elevated following burn/surgery in all animals and returned back to BL in S-FR (404 ± 48 pg/mg creatinine) but not MB (1332 ± 176 pg/mg creatinine; P = .005) or LV (1223 ± 335 pg/mg creatinine; P = .07) by 48 hours. Gene expression of cleavage enzymes (3β-HSD, CYP17, CYP11, and CYP21) along the cortisol synthesis pathway showed minimal changes. Adrenal apoptosis (Terminal deoxynucleotidyl transferase dUTP nick-end labeling [TUNEL] staining) was greatest in the MB group (P ≤ .01) when compared to S-FR, partly due to elevations in c-Jun N-terminal kinase. Adrenal hemorrhaging was also greatest in MB animals, with no differences in tissue volume or wet-to-dry ratio. However, tissue levels of cytokines IL-1β, IL-10, and IL-12 were greatest in LV. Burn injury elevates urinary cortisol and compromises adrenal gland integrity, which is affected by IV fluid volume.

Intravenous Fluids Used for Resuscitation Alters the Adrenal Response to Traumatic Burn injury Depending on the Volume Given

Severe thermal injury induces hypermetabolic stress which initiates a disruption in the hypothalamic‐pituitary‐adrenal (HPA) axis. While glucocorticoids contribute to maintaining blood pressure in healthy individuals, severely burned patients (i.e., >30% total body surface area; TBSA) have increased circulating cortisol levels that correspond to the extent of injury. However, little is known about adrenal damage following burn injury and the potential effects of common treatments such as intravenous (IV) fluid resuscitation. The objective of this study was to evaluate the effect of IV lactated Ringer's (LR) resuscitation on circulating cortisol, steroidogenic enzymes, and adrenal pathology following burn. Anesthetized Yorkshire swine sustained 40% TBSA burns from brass probes heated to 100 °C and placed on the skin for 30 s. Animals were recovered in metabolic cages to regain consciousness. Burned swine received IV fluid resuscitation with LR at two different volumes: 15 mL/kg body weight (BW)/day (Limited Volume; LV, n=6) or 2 mL/kg/%TBSA/day (Modified Brooke; MB, n=6). Non‐burned animals (Sham) were also Fluid Restricted (S‐FR, n=4) to induce some level of stress. Computerized tomography (CT) scans were performed before and 48 h post‐burn. Blood and urine was collected at baseline (BL), 6, 24, and 48 h following burn, with euthanasia at 48 h for adrenal gland collection. Adrenal histopathology was examined, as well as tissue cytokine levels. Heart and respiratory rate was similar in all animals, while temperature was elevated with burn. Urinary cortisol was elevated following surgery in all animals, however by 24 h S‐FR returned back to BL. Urinary cortisol levels at 48 h levels remained elevated in both MB (13,320±1,760 pg/mg creatinine; p=0.005) and LV (12,230±3,350 pg/mg creatinine; p=0.07) animals when compared with S‐FR (4,040±480 pg/mg creatinine). Similarly, while elevated at baseline, circulating cortisol was higher in the MB group (35449 ± 6878 pg/mL) but not the LR group (16511 ± 6077 pg/mL) compared to S‐FR (20549 ± 3078) at 48 hours. Gene expression of cleavage enzymes (3β‐HSD, CYP17, CYP11, and CYP21) along the cortisol synthesis pathway was not different between burned and S‐FR animals. No changes in CT‐angiography determined volume or Hounsfield units were found. Histologically, adrenal hemorrhaging was found in the cortex of burned animals. Intensity of TUNEL stain on adrenal sections was greatest in LV and MB groups within the cortex (p≤0.05) when compared to S‐FR. Protein levels of IL‐2, IL1ra, IL‐10, and IL‐12 were significantly elevated in LV, but not in MB when compared to S‐FR animals. This study demonstrates that at 48 h after a 40% burn in swine, cortisol remains elevated and adrenal gland integrity is compromised. Data from these studies can help shape resuscitative efforts of burn casualties for potentiating homeostasis of the HPA axis.Support or Funding InformationThis study was supported by Military Burn Research Program Award# W81XWH‐16‐2‐0041.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Investigation of aquaporin-1 expression and diffusion weighted imaging with multiple b values in adrenal gland in a rat model of diabetes mellitus

Objective To investigate the character of aquaporin-1 (AQP-1) expression in adrenal gland in diabetes mellitus and evaluate adrenal gland damage and function alterations by DWI with multiple b values. Methods Twenty male Sprague-Dawley rats were randomly selected by computer and randomized into 2 groups: untreated controls(n=10)and diabetes(DM)(n=10). Rats in diabetes group were fed with high-sucrose and high-fat diet, controls were fed with common diet. After fed with high-sucrose and high-fat diet for 4 weeks, rats in diabetes group were injected with streptozotocin(STZ). Forty days after diabetes induction with streptozotocin(STZ), MR imaging was performed in a 7.0 T scanner. Venous blood from the tails was collected before MRI scan to measure blood glucose, blood glucose more than 16.7 mmol/L was regarded as diabetic status. All the rats underwent DWI with 18 b values(0 to 4 500 s/mm2). Maps of pure diffusion coefficients(D), pseudo-diffusion coefficients(D*)and ultra-high ADC(ADCuh)were acquired. Rats were sacrificed after MRI scan for adrenal gland histopathology, AQP-1 immunohistochemistry analysis and AQP-1 optical density(OD)measurements. Student t test was used to compare the difference of D*, D, ADCuh and OD of AQP-1 between two groups. Results Eight diabetic animals developed hyperglycemia(two rats died during the modeling process). MRI scan was performed in all of the 18 rats. Signal intensity of D* map, D map and ADCuh map decreased gradually. ADCuh increased significantly in DM animals(0.24±0.06)×10-3mm2/s compared with control animals(0.18±0.07)×10-3 mm2/s(P 0.05). There was a noticeable increase in the AQP-1 labeling in the adrenal cell membrane and cytoplasm in DM animals compared with control animals. DM rats showed an increased OD value of AQP-1 in adrenal gland compared with the control animals(P<0.05). Conclusions We found significantly higher AQP-1 expression in adrenal gland in DM animals compared with controls. Ultra-high b-Values DWI may work as a useful way for noninvasive evaluation the change of adrenal function in DM. Key words: Diabetes mellitus; Magnetic resonance imaging; Adrenal gland

PD3-04 LESS POSTERIOR RETROPERITONEOSCOPIC ADRENALECTOMY: STEP-BY-STEP TECHNIQUE DESCRIPTION AND COMPARISON WITH 3-PORTS LATERAL RETROPERITONEAL APPROACH

INTRODUCTION AND OBJECTIVES: When a biochemically active adrenal mass is found surgery is usually recommended. While partial adrenalectomy is gaining popularity for small adrenal masses, it is not clear which patients will benefit from adrenal sparing to preserve adrenal function in case of contralateral adrenal pathology. We reviewed the available literature to evaluate the frequency of bilaterality of adrenal involvement with most common primary adrenal tumors and frequency of other pathologies potentially threatening the health of the adrenal gland. METHODS: We reviewed the PUBMED literature to evaluate the reported bilaterality of primary adrenal tumors including hereditary and nonhereditary pheochromocytomas (PHEOs), aldosterone producing adenomas (APAs), and cortisol producing adenomas and identified 25 articles describing the frequency of bilaterality of adrenalmasses.Wealso reviewed the literature to assess the etiologies of adrenal damage due to other pathological processes that may affect the adrenal gland in the lifespan of a patient and calculated the combined probability for adrenal damage. RESULTS: Table 1 reports the bilaterality of adrenal tumors in hereditary and non-hereditary diseases and demonstrates that adrenal tumors range in bilaterality between 4.25 e 80%. Hereditary PHEOs were bilateral in up to 80% of cases, while nonhereditary PHEOs were bilateral in up to 25%. APAs were bilateral in about 4% of cases, while only case reports reported bilaterality in cortisol producing tumors. Additionally, review of other processes such as infections, infiltrative etiologies, metastasis to adrenal, and others accounted for about 1% chance for the adrenal damage from all possible causes. CONCLUSIONS: Partial adrenalectomy is a valid option for patients with hereditary syndromes as there is an increased likelihood of disease in the contralateral gland. PHEOs followed by APAs appear to have the highest rate of bilateral involvement. Coupled with a possibility that an additional 1% of the population may have adrenals affected by various pathologic processes, partial adrenalectomy in patients with PHEO and APAs should be strongly considered. Percentage of bilaterality of adrenal tumors in hereditary syndromes and non-hereditary disease