Elevated Plasma Cortisol Levels Research Articles

Thymic Atrophy and Immune Dysregulation in Infants with Complex Congenital Heart Disease

Congenital heart disease (CHD) is the most common birth defect, and up to 50% of infants with CHD require cardiovascular surgery early in life. Current clinical practice often involves thymus resection during cardiac surgery, detrimentally affecting T-cell immunity. However, epidemiological data indicate that CHD patients face an elevated risk for infections and immune-mediated diseases, independent of thymectomy. Hence, we examined whether the cardiac defect impacts thymus function in individuals with CHD. We investigated thymocyte development in 58 infants categorized by CHD complexity. To assess the relationship between CHD complexity and thymic function, we analyzed T-cell development, thymic output, and biomarkers linked to cardiac defects, stress, or inflammation. Patients with highly complex CHD exhibit thymic atrophy, resulting in low frequencies of recent thymic emigrants in peripheral blood, even prior to thymectomy. Elevated plasma cortisol levels were detected in all CHD patients, while high NT-proBNP and IL-6 levels were associated with thymic atrophy. Our findings reveal an association between complex CHD and thymic atrophy, resulting in reduced thymic output. Consequently, thymus preservation during cardiovascular surgery could significantly enhance immune function and the long-term health of CHD patients.

Behavioral and neurophysiological effects of buspirone in healthy and depression-like state juvenile salmon.

A proportion of farmed salmon in seawater show a behaviorally inhibited, growth stunted profile known as a depression-like state (DLS). These DLS fish are characterized by chronically elevated serotonergic signaling and blood plasma cortisol levels and the inability to react further to acute stress, which is suggestive of chronic stress. In this study, we characterize the neuroendocrine profile of growth stunted freshwater parr and confirm that they show a DLS-like neuroendocrine profile with a blunted cortisol response and no serotonergic increase in response to acute stress. Furthermore, we attempted to reverse this DLS-like profile through pharmacological manipulation of the serotonin (5-HT) system with buspirone, an anxiolytic medication that acts as a serotonin receptor agonist (i.e., decreases serotonergic signaling). We found that while buspirone decreases anxiolytic-type behavior in healthy fish, no quantifiable behavioral change was found in DLS-like fish. However, there was a physiological effect of diminished basal serotonergic signaling. This suggests that at the physiological level, buspirone appears to reverse the neuroendocrine DLS profile. With a deeper understanding of what causes DLS profiles and growth stunting in juvenile fish, steps can be taken in terms of husbandry to prevent repeated stressors and the formation of the DLS profile, potentially reducing losses in aquaculture due to chronic stress.

Combination of Remimazolam, Remifentanil Anesthesia, and Enteral Nutrition Support Restores Vital Signs and Nutritional Status of Patients Undergoing Intravascular Interventional Therapy for Intracranial Aneurysms

Ninety-eight patients from our hospital were included in the study from March 2022 to March 2023. The patients were divided into two groups: 49 patients received propofol + remifentanil in the control group and 49 patients received remimazolam + remifentanil in the observation group. Postoperatively, the control group accepted parenteral nutrition support, while the observation group accepted enteral nutrition support. The observation group experienced a longer duration of consciousness loss but shorter times for consciousness recovery and trachea extubation than the control group. Although both groups experienced elevated mean blood pressure, heart rate, norepinephrine, angiotensin II, and plasma cortisol levels during tracheal intubation and extraction, the observation group showed differences compared to the control group. No statistical significance was discovered in the incidence of postoperative adverse reactions between the two groups (P = 0.29). Furthermore, tumor necrosis factor-α and interleukin-6 levels were lower in the observation group than in the control group, while total protein, albumin, and hemoglobin levels were higher. Overall, remimazolam combined with remifentanil demonstrated superiority over propofol combined with remifentanil in the perioperative period for patients undergoing intravascular interventional therapy for intracranial aneurysms.

Evaluating cardiac oxygen limitation as a mechanism for female-biased mortality in coho salmon (Oncorhynchus kisutch)

Female-biased mortality has been consistently reported in Pacific salmon during their adult upriver migration. We collected coho salmon ( Oncorhynchus kisutch (Walbaum, 1792)) upon arrival at their spawning grounds to test whether females are more prone to cardiac oxygen limitations following exercise stress. We used a surgical approach to periodically sample arterial and venous blood over 48 h following recovery from a chase protocol to induce maximum metabolic rate. We found no significant differences in arterial or venous partial pressures of O2 between males and females. Female salmon had significantly elevated plasma cortisol levels but there were no effects of sex on either plasma lactate or K+. Our data show that female coho salmon do not suffer oxygen limitations to the spongy myocardium after a single exercise event at moderate temperatures (14 °C)—at least not when arriving to their spawning grounds. This study found no clear support for a cardiac oxygen limitation underlying elevated female mortality in Pacific salmon. Neither, however, does our study design nor specific findings allow us to rule out cardiac limitations in these fish. Future work should address whether potential oxygen limitations to the spongy myocardium at high temperatures or oxygen limitations to the compact myocardium via coronary blood flow contribute to female-biased mortality earlier on the migratory route.

A multi-biomarker approach to assess the sublethal effects of settleable atmospheric particulate matter from an industrial area on Nile tilapia (Oreochromis niloticus)

Iron and steel industries discharge a large amount of atmospheric particulate matter (PM) containing metals and metallic nanoparticles (NPs) that contaminate not only the air, but also settle into the aquatic environments. However, the effects of settleable atmospheric particulate matter (SePM) on aquatic fauna are still poorly understood. This study aimed to evaluate the sublethal effects of a short-term exposure to a realistic concentration of SePM on Nile tilapia (Oreochromis niloticus) using a multi-biomarker approach: relative ventricular mass (RVM) and heart function, blood oxidative stress, stress indicators, hemoglobin concentration, metallic NPs internalization, and metal bioaccumulation. Exposed fish exhibited reduced hemoglobin content and elevated plasma cortisol and glucose levels, reflecting stressed states. Furthermore, SePM caused blood oxidative stress increasing lipid and protein oxidation, decreasing glutathione levels, and inhibiting superoxide and glutathione reductase activities. SePM exposure also increased RVM and improved cardiac performance, increasing myocardial contractile force and rates of contraction and relaxation. In the heart tissue there was a significant accumulation of Fe > Zn > > Cr > Cu > Rb > Ni > V > Mn > Se > Mo > As. On the other hand, in the erythrocytes there was significant accumulation of Sn > Zn > > Cr > Ti > Mn = Ni > Nb > As > Bi. The highest bioaccumulation factors were found for Cr, Zn and Ni in both tissues. NPs (Ti, Sn, Al, Fe, Cu, Si, Zn) were also detected in ventricular myocardium of fish exposed and nanocrystallographic analysis revealed a predominance of anatase phase of TiO2-NP, which is regarded to be more cytotoxic. The association between blood oxidative stress and energy expenditure to sustain increased cardiac pumping capacity under stress condition suggests that SePM has negative impacts on fish physiological performance, threatening their survival, growth rate and/or population establishment.

Combined antagonist treatment of glucocorticoid and mineralocorticoid receptor does not affect weight loss of fasting rainbow trout but inhibits a fasting-induced elevation of cortisol secretion

The gastrointestinal system of fish reacts rapidly to food deprivation. The relative masses of digestive organs and activities of digestive enzymes decrease within days of fasting. This is believed to be an energy-conserving strategy as the metabolic cost of maintaining digestive capacity is high. Cortisol is known for its role in energy mobilization following stress exposure, and prolonged elevated cortisol levels have been shown to reduce growth rates in fish. Fish experiencing chronic cortisol elevations show structural changes to their digestive tissues and overall reductions in relative digestive tissue masses. In fish fasting for prolonged periods, circulating cortisol levels have been reported to be downregulated, upregulated, or unchanged compared to feeding fish. This study aimed to investigate if RU486 and spironolactone, antagonists of the glucocorticoid receptor (GR), and mineralocorticoid receptor (MR), respectively, alone or in combination affect circulating cortisol levels during prolonged starvation. In addition, we tested the effects of blocking GR and MR, on the down-regulation of relative digestive tissue mass during starvation, and its effects on weight loss. Three treatment groups of rainbow trout were intraperitoneally implanted with either GR, MR, or GR and MR blockers. A fourth group was implanted with cortisol, while a fifth group served as a control. All treatment groups were sampled over a course of four weeks of food deprivation and compared against each other and fed control fish at day 0 of the trial. Starvation for 2 weeks and longer significantly increased circulating cortisol levels in all groups except for the group implanted with GR and MR antagonists. Loss of body mass occurred most rapidly during the first week of starvation. Spironolactone treatment resulted in significantly reduced loss of mass during the first week, however, over the following weeks, no differences in mass loss were observed in the groups implanted with blockers, while cortisol-treated fish showed the highest decrease in body mass over time. Relative digestive tissue mass decreased in all groups but apparently, the fasting-induced elevation in plasma cortisol levels did not affect the relative weight loss of digestive tissues as no differences were observed between control fish and GR + MR antagonist treated fish. Very high cortisol levels caused by cortisol treatment however caused a faster decrease in the relative mass of some digestive organs, particularly the stomach.

Hormone contraceptive use in young women: Altered mood states, neuroendocrine and inflammatory biomarkers

Oral contraceptives are used by millions of women worldwide, yet there are questions regarding the psychological and biological consequences of these medications. Considering that sex steroid hormones can regulate neuroendocrine and behavioral responses to stress, the current study examined mood and stress symptomatologies, as well as circulating levels of cortisol and inflammatory biomarkers among young women (N = 388), of whom, 47.0 % (n = 182) were using a form of hormonal contraception. Women using hormone contraceptives displayed significantly higher depressive and stress scores compared to non-users, whereas no differences were found for anxiety symptoms. Moreover, contraceptive users had markedly elevated plasma cortisol and C-reactive protein levels in comparison to non-users. Upon assessing women at different phases of their menstrual cycle, hormone contraceptive users displayed higher levels of cortisol compared to women in the follicular and luteal phases, in addition to higher levels of CRP levels compared to women in the luteal phase. Together, these findings suggest that hormone contraceptive use is linked to exaggerated basal neuroendocrine and inflammatory profiles, which could potentially increase sensitivity to the impacts of stressors and mood disturbances.

Regulation of cortisol production during chronic social stress in rainbow trout

Chronic stress resulting from social interactions impacts the endocrine stress response in many vertebrates, including teleost fishes. Juvenile rainbow trout held in pairs form a dominance hierarchy with the subordinate individual exhibiting chronic elevation of plasma cortisol and an attenuated cortisol response to an additional acute stressor. The current study investigated the mechanisms underlying this apparent dichotomy in cortisol production at the level of the head kidney (adrenal homolog). Following four days of chronic social stress, subordinate rainbow trout exhibited elevated plasma cortisol levels that correlated with basal cortisol production by the head kidney in vitro. Subordinate trout had higher transcript abundances of steroidogenic acute regulatory protein and cytochrome p450 side chain cleavage enzyme, which facilitate key steps in steroidogenesis, as well as two paralogs of steroidogenic factor 1. Despite elevation of basal steroidogenesis, acute cortisol production in response to ACTH (in vivo and in vitro) was lower in subordinate trout. Transcript abundances of the ACTH receptor accessory proteins were elevated in subordinate fish, but head kidney cortisol production in response to a cAMP analogue was lower than in dominant fish. Together, the data suggest that the attenuated acute cortisol response of subordinate trout reflects limitations on cortisol production downstream of cAMP signalling in steroidogenic cells of the head kidney, despite the increased basal abundance of key components of the steroidogenic pathway.

Prolonged cortisol elevation alters whole body and tissue metabolism in rainbow trout (Oncorhynchus mykiss)

Chronic elevation of circulating cortisol is known to have deleterious effects on fish, but information about the consequences of prolonged cortisol elevation on the metabolism of fish is scarce. To test the effects of chronic cortisol elevation on the aerobic performance of rainbow trout, we examined how two severities of chronically elevated plasma cortisol levels affected the oxygen uptake during rest and after exhaustive exercise using a high (HC) and a medium cortisol (MC) treatment. High cortisol doses significantly affected standard (SMR) and maximum metabolic rates (MMR) compared to control fish. In comparison, the medium cortisol treatment elevated maximum metabolic rates (MMR) but did not significantly influence SMR compared to a sham group (S) and control group (C). The medium cortisol treatment resulted in a significantly increased metabolic scope due to an elevation of MMR, an effect that was abolished in the HC group due to co-occuring elevations in SMR. The elevated SMR of the HC-treated fish could be explained by increased in vitro oxygen uptake rates (MO2) of specific tissues, indicating that the raised basal metabolism was caused, in part, by an increase in oxygen demand of specific tissues. Haematological results indicated an increased reliance on anaerobic metabolic pathways in cortisol-treated fish under resting conditions.

Assessing the role of cortisol in cancer: a wide-ranged Mendelian randomisation study.

Cortisol's immunosuppressive, obesogenic, and hyperglycaemic effects suggest that it may play a role in cancer development. However, whether cortisol increases cancer risk is not known. We investigated the potential causal association between plasma cortisol and risk of overall and common site-specific cancers using Mendelian randomisation. Three genetic variants associated with morning plasma cortisol levels at the genome-wide significance level (P < 5 × 10-8) in the Cortisol Network consortium were used as genetic instruments. Summary-level genome-wide association study data for the cancer outcomes were obtained from large-scale cancer consortia, the UK Biobank, and the FinnGen consortium. Two-sample Mendelian randomisation analyses were performed using the fixed-effects inverse-variance weighted method. Estimates across data sources were combined using meta-analysis. A standard deviation increase in genetically predicted plasma cortisol was associated with increased risk of endometrial cancer (odds ratio 1.50, 95% confidence interval 1.13-1.99; P = 0.005). There was no significant association between genetically predicted plasma cortisol and risk of other common site-specific cancers, including breast, ovarian, prostate, colorectal, lung, or malignant skin cancer, or overall cancer. These results indicate that elevated plasma cortisol levels may increase the risk of endometrial cancer but not other cancers. The mechanism by which this occurs remains to be investigated.

Detection of SARS-CoV-2 virus using an alternative molecular method and evaluation of biochemical, hematological, inflammatory, and oxidative stress in healthcare professionals

In early December 2019, an outbreak of coronavirus disease 2019 caused by a new strain of coronavirus (SARS-CoV-2), occurred in the city of Wuhan, Hubei Province, China. On January 30, 2020, the World Health Organization (WHO) declared the outbreak a public health emergency of international concern. Since then, frontline healthcare professionals have been experiencing extremely stressful situations and damage to their physical and mental health. These adverse conditions cause stress and biochemical, hematological, and inflammatory changes, as well as oxidative damage, and could be potentially detrimental to the health of the individual. The study population consisted of frontline health professionals working in BHU in a city in southern Brazil. Among the 45 participants, two were infected with the SARS-CoV-2 virus and were diagnosed using immunochromatographic tests such as salivary RT-LAMP and qRT-PCR. We also evaluated biochemical, hematological, inflammatory, and oxidative stress markers in the participants. The infected professionals (CoV-2-Prof) showed a significant increase in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol, lactic dehydrogenase, lymphocytes, and monocytes. In this group, the levels of uric acid, triglycerides, leukocytes, neutrophils, hemoglobin, hematocrit, and platelets decreased. In the group of uninfected professionals (NoCoV-2-Prof), significant increase in HDL levels and the percentages of eosinophils and monocytes, was observed. Further, in this group, uric acid, LDH, triglyceride, and cholesterol levels, and the hematocrit count and mean corpuscular volume were significantly reduced. Both groups showed significant inflammatory activity with changes in the levels of C-reactive protein and mucoprotein. The NoCoV-2-Prof group showed significantly elevated plasma cortisol levels. To our kowledge, this study is the first to report the use of the RT-LAMP method with the saliva samples of health professionals, to evalute of SARS-CoV-2.

Cortisol affects feed utilization, digestion and performance in juvenile rainbow trout (Oncorhynchus mykiss)

To quantify bioenergetic consequences of chronically or acutely elevated plasma cortisol levels, growth rates, feed conversion ratios and digestive performance was investigated in juvenile rainbow trout (Oncorhynchus mykiss) reared at 15 °C. Plasma cortisol levels were elevated using coconut oil based implants. A sham group received coconut oil without cortisol, (S), while a low (LC) and high (HC) cortisol group received implants containing 30 or 60 μg cortisol g−1 fish. An additional group of fish was reared under moderate thermal stress (22 °C, TS), while acute increases in plasma cortisol were achieved by subjecting fish to a daily stressor by chasing (DS). An undisturbed treatment group, reared at 15 °C served as control (C). Although feed intake was not affected by treatments, cortisol treated fish showed reduced growth rate and feed conversion efficiency compared to all other treatments. This was caused, in part, by impaired digestibility of protein, lipids and nitrogen free extract in the HC treatment, leading to a decrease in available metabolizable energy. The observed decrease in lipid digestibility did not appear to be caused by a reduced digestive lipase activity in the pyloric caeca and anterior intestine as this was not significantly different between treatments 90 min after feeding. Chronically elevated cortisol levels led to atrophy of the digestive system revealed by a loss in tissue mass of the intestine and pyloric caeca in the high cortisol treatment, as well as an overall decrease in viscerosomatic index. In addition, the energetic cost of growth was higher in both cortisol treated groups compared to all other treatments. The chronic temperature elevation resulted in improved lipid digestion compared to the control treatment, while growth performance was impaired, however apparently not correlated with elevated plasma cortisol levels. A moderate random daily stress event did not result in any changes of the studied parameters. The results obtained suggest both an atrophic effect of chronically elevated plasma cortisol levels on digestive tissues resulting in impaired nutrient assimilation, less available metabolizable energy, and an increased routine energy expenditure, leading to a higher cost of growth.

The Effect of Continuous Stress on Spatial Learning and Memory, Anxiety-Like Behavior, and Depression in Male NMRI Mice

The present study examined the effect of continuous immobilization stress on anxiety-like behavior, spatial learning and memory, and a forced swim test in NMRI male mice. The plasma cortisol changes and the brain-derived neurotrophic factor (BDNF) were also evaluated. The male NMRI mice were divided into control and stress groups (n = 10/group). The stress group was placed in restrained PVC tube for 360 min. Twenty-four hours later, the mice were tested for spatial learning and memory, anxiety-like behavior, and depression using the Barnes maze, an elevated plus maze, and a forced swim test, respectively. Also, the plasma cortisol level and the brain BDNF content were assessed by the ELISA method. Results indicated that the mice in the stress group had an elevated plasma cortisol level. There were no differences between the stress and control groups in the time taken and the distance traveled to reach the target hole. The animals in the stress group spent more time in the open arms of the maze and in entering the open arms, compared to the control group. Continuous immobilization stress caused a significant decrease in swim time for the animals in the stress group, compared to the control group. The brain BDNF concentration also found to be significantly in the stress group than the control group. In conclusion, acute sustained stress increases the brain BDNF level. It can facilitate anxiety-like behavior and depression, which may be due to a plasma glucocorticoid increment. However, the stress does not affect spatial learning and memory.

Sex-specific differences in physiological recovery and short-term behaviour following fisheries capture in adult sockeye salmon (Oncorhynchus nerka)

Numerous laboratory and field studies have found that female Pacific salmon have higher mortality than males during their once-in-a-lifetime upriver spawning migration. However, the proximate cause(s) of this increased mortality are poorly understood. This study exposed sockeye salmon (Oncorhynchus nerka) to a mild capture and tagging stressor and evaluated physiological recovery and movement behaviour at 1 and 4 h postrelease. Female sockeye salmon did not expend more anaerobic energy in response to the stressor but did have higher plasma lactate levels 4 h after the stressor, indicating that females took longer to physiologically recover compared with males. In addition, female salmon had lower plasma glucose but higher plasma cortisol, plasma K+, and cardiac lactate levels compared with males. Male and female salmon had markedly different postrelease behaviours within the first hour of release; males were more likely to hold position within the staging area. Two potential mechanisms leading to increased mortality in female salmon were identified in this study: (a) prolonged recovery duration (possibly mediated by elevated plasma cortisol levels) and (b) insufficient oxygen delivery to the heart.

Chronic Social Defeat Stress Up-Regulates Spexin in the Brain of Nile Tilapia (Oreochromis niloticus)

Spexin (SPX), a neuropeptide evolutionarily conserved from fish to mammals, is widely distributed in the brain and peripheral tissues and associated with various physiological functions. Recently SPX has been suggested to be involved in neurological mechanism of stress. The current study investigates the involvement of SPX in chronic social defeat stress, using male teleost, the Nile tilapia (Oreochromis niloticus) as an animal model due to its distinct social hierarchy of dominant and subordinate relationship. The tilapia genome has SPX1a and SPX1b but has no SPX2. In the Nile tilapia, we localized SPX1a and SPX1b in the brain using in-situ hybridization. Next, using qPCR we examined gene expression of SPX1a and SPX1b in chronically stress (socially defeated) fish. SPX1a expressing cells were localized in the semicircular torus of the midbrain region and SPX1b expressing cells in the telencephalon. Chronically stress fish showed elevated plasma cortisol levels; with an upregulation of SPX1a and SPX1b gene expression in the brain compared to non-stress (control) fish. Since social defeat is a source of stress, the upregulated SPX mRNA levels during social defeat suggests SPX as a potentially inhibitory neuropeptide capable of causing detrimental changes in behaviour and physiology.

Purine levels and purinergic signaling in plasma and spleen of Brycon amazonicus exposed to acute heat thermal stress: An attempt to regulate the immune response.

Amazon fish are vulnerable to climate change. Several lines of evidence suggest that the temperature of Amazonian rivers will increase in the coming years. Elevated temperature disturbs homeostasis and subjects fish to physiological stress; however, the effects of temperature on immunity remain poorly understood, particularly those effects involving purinergic signaling. This system fine-tunes the inflammatory and immune responses triggered by stress. Therefore, the aims of this study were to determine whether acute heat stress induces the release of nucleotides into extracellular compartment and to determine whether purinergic enzymes modulate the proinflammatory effects of adenosine triphosphate (ATP) in plasma and spleen of matrinxã (Brycon amazonicus) exposed to acute heat stress. We exposed juvenile matrinxã to four temperature regimes (28°C as control, 30, 32 and 34°C) for 72h and observed the effects on purinergic signaling. Plasma cortisol levels were significantly higher in fish exposed to 34°C than in the control group, while spleen ATP, adenosine diphosphate (ADP) and adenosine monophosphate (AMP) levels were significantly higher in this group than in controls. Activities of spleen nucleoside triphosphate diphosphohydrolase (NTPDase) and 5'-nucleotidase were significantly higher in fish exposed to 34°C than those of the control group, while spleen interleukin-1 (IL-1) and interleukin-6 (IL-6) levels were higher in this same group than in the control group. No significant differences were observed between the groups regarding plasma parameters. Based on these data, we concluded that acute heat stress at 34°C caused physiological stress in matrinxã, manifesting as elevated plasma cortisol levels. The most important finding is that purinergic enzymes were modulated, though not efficiently, in response to the excessive release of nucleotides into the extracellular space. In summary, the purinergic signaling pathway may be involved in the impairment of immune and inflammatory responses in matrinxã exposed acutely to 34°C.

Performance and welfare of Atlantic salmon, Salmo salar L. post‐smolts in recirculating aquaculture systems: Importance of salinity and water velocity

AbstractProducing a larger post‐smolt in recirculating aquaculture systems (RAS) could shorten the production time in sea cages and potentially reduce mortality. Knowledge of the biological requirements of post‐smolts in closed‐containment systems is however lacking. In the present study, the effects of salinity and water velocity on growth, survival, health, and welfare of Atlantic salmon reared in RAS were examined. Salmon smolts were stocked in three separate RAS with salinities of 12, 22, and 32‰ and subjected to high (1.0 body lengths per s−1) or low (0.3 body lengths second−1) water velocity. Growth performance, survival, welfare, and physiological stress responses were monitored until the fish reached a bodyweight of around 450 g. Growth rate was higher at lower salinity and higher water velocity generally had a positive effect on growth in all salinities. Feed conversion ratio was lower at 12‰ compared to the 22 and 32‰ when the fish were between 250 and 450 g. Higher mortality, elevated plasma cortisol levels, higher incidence of cataract, and a higher expression of stress‐induced genes in the skin (iNOS, Muc5ac‐like) indicated a negative effect of higher salinity on fish welfare. Male maturation was low (&lt;1%), and not affected by salinity or water velocity.

SUN-LB031 An Atypical Case of Diabetic Keto-Alkalosis with Severe Hypernatremic Hyperosmolarity in a Patient with Amphetamine Abuse

Introduction- Acid base disturbances have a complex interplay in Diabetic Ketoacidosis (DKA). Substance abuse in DKA is associated with more severe metabolic acidosis with higher acidosis-ketosis gap. Severe hypernatremia and alkalosis are rare in DKA but were exhibited in our case. Case- A 31-year-old female with Type 1 diabetes and schizophrenia was hospitalized after she was found to be minimally responsive at home. She had abdominal pain and polyuria since few days and wasn’t compliant with her medications. There was no history of vomiting, diarrhea, alkali ingestion, laxative or diuretic use. On admission, she was severely dehydrated, obtunded and only responsive to painful stimuli. Initial biochemical findings: serum glucose 1323 mg/dl (n 70-140 mg/dl), sodium 135 mEq/L (n 136-148 mEq/L, corrected sodium 154, bicarbonate 32 mEq/L (n 22-28 mEq/L), serum osmolality 379 (n 275-295 mOsm/Kg), beta hydroxybutyrate 62.56 mg/dl (n <=4.17 mg/dl), anion gap 30 (n 12-16) and delta gap of 24. Venous blood gas showed: pH-7.40 (n 7.31-7.41), pCO2-62 (n 41-51), HCO3-38.4 (23-27). She was adequately managed and was fully awake and alert with closed anion-gap within 24 hours of admission. Serum sodium initially peaked to 163 but normalized over the next 36-42 hours. She was also admitted with HHS (Hyperglycemic Hyperosmolar State) 3 months before and 1 month after this admission. Urine drug screen was positive for amphetamines in all 3 admissions. Discussion- Our patient exhibited mixed metabolic acidosis (elevated anion gap, ketonemia), metabolic alkalosis (elevated bicarbonate, elevated delta gap) and compensatory respiratory acidosis. Osmotic diuresis due to glycosuria and amphetamine abuse led to severe volume depletion and bicarbonate reabsorption leading to severe contraction alkalosis. Studies have shown that methamphetamine use leads to elevated plasma cortisol and corticosterone levels via hyper-activation of the hypothalamic-pituitary-adrenal axis. Ecstasy use has been shown to cause an acute increase in cortisol levels of around 150% in sedentary humans and 800% in dance clubbers. Excess glucocorticoids promote Hᶧ secretion from kidneys via mineralocorticoid receptors contributing to alkalosis. DKA/HHS patients usually present with eunatremia/hyponatremia. Adult schizophrenics who receive psychostimulants have been shown to develop polydipsia and hyponatremia. Ecstasy intoxication can precipitate both DKA and hyponatremia in Type1 diabetics. Combined DKA/HHS and hypernatremic hyperosmolarity has been reported due to huge intake of sugar-rich carbonated beverages to quench thirst especially in pediatric population. There is frequent association between decompensated diabetes and illicit drug use. Substance abuse should be suspected in young Type 1 diabetics presenting with recurrent hyperglycemic emergencies especially with atypical biochemical features. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

SAT-370 Clinical Characteristics and Metabolic Features of Patients with Subclinical Cushing's Syndrome and Its Correlation with Cortisol Level

Objective The aim of this study was to examine the clinical characteristics and metabolic features of subclinical Cushing’s syndrome (SCS), and to investigate the association of the cortisol level with the metabolic features in patients with SCS. Methods 52 patients with non-functioning adenoma (NFA), 45 patients diagnosed with SCS and 61 patients with overt adrenal Cushing’s syndrome (CS) participated in this study. Clinical data and endocrine function of the patients as well as histological findings were all reviewed. Results 1) The average age of patients with SCS was 52.56±13.25 years, 68.9% patients were female. No difference was detected in age, gender and BMI between patients with SCS and NFA (P > 0.05). Compared to patients with SCS, CS was more common in younger and female patients (43.90±13.83, 83.6%). The prevalence of diabetes mellitus, hypertension, and osteopenia/osteoporosis were significantly higher in patients with SCS compared to those with nonfunctioning tumors (57.8% vs 32.7%, 73.3% vs 53.8%, 41.2% vs 19.2%; P < 0.05). No difference was detected between SCS and CS patients in the prevalence of metabolic disease. 2) Compared to patients with NFA, plasma ACTH level is lower in patients with SCS (P < 0.05). Whereas, the midnight cortisol level and cortisol level after 1mg overnight dexamethasone suppression is higher in SCS than NFA (P < 0.05). No difference was detected between SCS and NFA in 24h urinary free cortisol and early-morning cortisol level (P > 0.05). Compared to SCS, the derangement of ACTH-cortisol axis is more prominent in CS patients demonstrated as suppressed plasma ACTH level and elevated plasma and 24h urine cortisol level. 3) In SCS cohort, SBP, FBG and HbA1c correlated positively with 24h urinary free cortisol (r =0.394, P =0.021; r =0.426, P =0.011, r =0.398, P =0.015; respectively). When controlling for age and gender, the correlation was also significant (P < 0.05). No correlations were found between BMI, TG, HDL and 24h urinary free cortisol. Conclusion Patients with SCS showed slight derangement of the circadian rhythm of cortisol and cortisol excess, and increased prevalence of metabolic disease. Furthermore, the cortisol level was related closely to blood glucose and blood pressure. Our findings might suggestive in therapeutic decision making (conservative vs surgery approach) in patients with SCS.

Exacerbation of Cushing's syndrome during pregnancy: stimulation of a cortisol-secreting adrenocortical adenoma by ACTH originating from the foeto-placental unit.

SummaryA 29-year-old G4A3 woman presented at 25 weeks of pregnancy with progressive signs of Cushing’s syndrome (CS), gestational diabetes requiring insulin and hypertension. A 3.4 × 3.3 cm right adrenal adenoma was identified during abdominal ultrasound imaging for nephrolithiasis. Investigation revealed elevated levels of plasma cortisol, 24 h urinary free cortisol (UFC) and late-night salivary cortisol (LNSC). Serum ACTH levels were not fully suppressed (4 and 5 pmol/L (N: 2–11)). One month post-partum, CS regressed, 24-h UFC had normalised while ACTH levels were now less than 2 pmol/L; however, dexamethasone failed to suppress cortisol levels. Tests performed in vivo 6 weeks post-partum to identify aberrant hormone receptors showed no cortisol stimulation by various tests (including 300 IU hLH i.v.) except after administration of 250 µg i.v. Cosyntropin 1–24. Right adrenalectomy demonstrated an adrenocortical adenoma and atrophy of adjacent cortex. Quantitative RT-PCR analysis of the adenoma revealed the presence of ACTH (MC2) receptor mRNA, while LHCG receptor mRNA was almost undetectable. This case reveals that CS exacerbation in the context of pregnancy can result from the placental-derived ACTH stimulation of MC2 receptors on the adrenocortical adenoma. Possible contribution of other placental-derived factors such as oestrogens, CRH or CRH-like peptides cannot be ruled out.Learning points:Diagnosis of Cushing’s syndrome during pregnancy is complicated by several physiological alterations in hypothalamic–pituitary–adrenal axis regulation occurring in normal pregnancy.Cushing’s syndrome (CS) exacerbation during pregnancy can be associated with aberrant expression of LHCG receptor on primary adrenocortical tumour or hyperplasia in some cases, but not in this patient.Placental-derived ACTH, which is not subject to glucocorticoid negative feedback, stimulated cortisol secretion from this adrenal adenoma causing transient CS exacerbation during pregnancy.Following delivery and tumour removal, suppression of HPA axis can require several months to recover and requires glucocorticoid replacement therapy.