Peak Cortisol Concentrations Research Articles

ForDigitStress: presentation and evaluation of a new laboratory stressor using a digital job interview-scenario.

Since the COVID-19 pandemic, working environments and private lives have changed dramatically. Digital technologies and media have become more and more important and have found their way into nearly all private and work environments. Communication situations have been largely relocated to virtual spaces. One of these scenarios is digital job interviews. Job interviews are usually-also in the non-digital world-perceived as stressful and associated with biological stress responses. We here present and evaluate a newly developed laboratory stressor that is based on a digital job interview-scenario. N = 45 healthy people participated in the study (64.4% female; mean age: 23.2 ± 3.6 years; mean body mass index = 22.8 ± 4.0 kg/m2). Salivary alpha-amylase (sAA) and cortisol were assessed as measures for biological stress responses. Furthermore, perceived stress was rated at the time points of the saliva samplings. The job interviews lasted between 20 and 25 min. All materials, including instructions for the experimenter (i.e., the job interviewer) and the data set used for statistical analysis, as well as a multimodal data set, which includes further measures, are publicly available. Typical subjective and biological stress-response patterns were found, with peak sAA and perceived stress levels observed immediately after the job interviews and peak cortisol concentrations 5 min afterwards. Female participants experienced the scenario as more stressful than male participants. Cortisol peaks were higher for participants who experienced the situation as a threat in comparison to participants who experienced it as a challenge. Associations between the strength of the stress response with further person characteristics and psychological variables such as BMI, age, coping styles, and personality were not found. Overall, our method is well-suited to induce biological and perceived stress, mostly independent of person characteristics and psychological variables. The setting is naturalistic and easily implementable in standardized laboratory settings.

Endocrine Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference.

Endocrine dysfunction is common in critically ill children and is manifested by abnormalities in glucose, thyroid hormone, and cortisol metabolism. To develop consensus criteria for endocrine dysfunction in critically ill children by assessing the association of various biomarkers with clinical and functional outcomes. PubMed and Embase were searched from January 1992 to January 2020. We included studies in which researchers evaluated critically ill children with abnormalities in glucose homeostasis, thyroid function and adrenal function, performance characteristics of assessment and/or scoring tools to screen for endocrine dysfunction, and outcomes related to mortality, organ-specific status, and patient-centered outcomes. Studies of adults, premature infants or animals, reviews and/or commentaries, case series with sample size ≤10, and non-English-language studies were excluded. Data extraction and risk-of-bias assessment for each eligible study were performed by 2 independent reviewers. The systematic review supports the following criteria for abnormal glucose homeostasis (blood glucose [BG] concentrations >150 mg/dL [>8.3 mmol/L] and BG concentrations <50 mg/dL [<2.8 mmol/L]), abnormal thyroid function (serum total thyroxine [T4] <4.2 μg/dL [<54 nmol/L]), and abnormal adrenal function (peak serum cortisol concentration <18 μg/dL [500 nmol/L]) and/or an increment in serum cortisol concentration of <9 μg/dL (250 nmol/L) after adrenocorticotropic hormone stimulation. These included variable sampling for BG measurements, limited reporting of free T4 levels, and inconsistent interpretation of adrenal axis testing. We present consensus criteria for endocrine dysfunction in critically ill children that include specific measures of BG, T4, and adrenal axis testing.

Careful Evaluation of Cosyntropin Dose in the Diagnosis of Adrenal Insufficiency

Introduction: The use of the 250μg cosyntropin dose or otherwise called high-dose ACTH test is the gold standard test for diagnosis of primary adrenal insufficiency. The 1μg dose test or the low-dose test is mostly reserved for diagnosis of secondary adrenal insufficiency. Careful consideration of the results produced during the diagnostic process is imperative to avoid mislabeling of patients with a disease that requires lifelong treatment. Case Report: This is the case of a 45-year-old female with a history of asthma and psoriasis who presented with emesis. Home medications included monthly TNF-alpha inhibitor injections for psoriasis, triamcinolone acetonide topical spray and budesonide-formoterol inhaler. On admission, she also had nausea, chills and diaphoresis, as well as palpitations, lightheadedness, and shortness of breath. When she arrived at the ER, vitals were remarkable for low blood pressure. Labs were unremarkable except for CMP concerning for anion gap metabolic acidosis, hyponatremia, and hypokalemia. A random serum cortisol was 6.4 mcg/dL, which was relatively low. ACTH was within normal range. Due to concern for adrenal insufficiency, a 1μg cosyntropin test was performed which showed a peak cortisol concentration of less than 18 mcg/dL. As the response was assessed as suboptimal, endocrinology was consulted to offer a treatment plan for steroids. However, the test was repeated using the gold standard 250μg cosyntropin dose and the patient then showed an adequate response and she was not started on steroids. Conclusions: This is a case that demonstrates how the 250 μg ACTH or high-dose stimulation test should be used for diagnosis of primary adrenal insufficiency (AI), as it is the gold standard. The 1 μg ACTH or low-dose stimulation test can be used for diagnosis of primary AI but only when the high dose test is not available. On the other hand, the 1 μg ACTH stimulation test has been shown to be more sensitive than the 250 μg test in diagnosing secondary adrenal insufficiency. When using the most appropriate test correctly, the clinician can only then offer the patient the best treatment strategies. Our patient did not require chronic replacement therapy. The steroids in this case could have harmed the patient as chronic administration could cause adrenal gland suppression.

Effect of age of suckler beef calves on stress indicators and growth performance in response to Burdizzo castration

ABSTRACT The study objective was to examine effect of age at castration on stress indicators and performance of 40 crossbred suckler beef calves. Calves were assigned to two age groups and two castration treatments; calves 2.5- or 5.0-mo-old (mean body weight (SD) = 120.8 (29.3), 218.1 (30.8) kg, respectively) were sham (control) or Burdizzo castrated (n = 10 per treatment) in a 2 × 2 factorial design. Following castration, peak plasma cortisol concentrations were greater in 2.5-mo-old and 5.0-mo-old calves compared with corresponding controls, while peak cortisol concentrations in control animals were greater in 5-mo-old compared with 2.5-mo-old calves. The integrated cortisol responses for the first 4 h after castration were not different between 2.5- and 5.0-mo-old calves. However, the integrated cortisol response was greater in 5.0-mo-old calves from 4 to 9 h post treatment. The increase in scrotal circumference after castration was greater in 5.0-mo-old calves, and abnormal postures were observed more often in 5-mo-old castrates. There was no effect of castration on haematology profiles, haptoglobin, metabolites, body temperature and growth performance. In conclusion, the physiological stress, inflammation and pain-related behaviours caused by Burdizzo castration were reduced when castrating calves at 2.5- than at 5.5-mo-old.

Chronobiologic parameter changes in patients with major depressive disorder and sleep disturbance treated with adjunctive brexpiprazole: An open-label, flexible-dose, exploratory substudy

BackgroundCircadian rhythm disturbances have been reported in patients with major depressive disorder (MDD). Among these is an increased phase angle between peak cortisol concentration and dim-light melatonin onset (DLMO). The aim of this study was to evaluate changes in chronobiologic parameters of sleep in patients with MDD receiving adjunctive brexpiprazole. MethodsThis was an interventional, multicenter, open-label, flexible-dose, exploratory study in patients with MDD and inadequate response to antidepressant treatment who were experiencing sleep disturbances. Patients received adjunctive brexpiprazole 2–3 mg/day for 8 weeks. Outcome measures included cortisol and melatonin levels, used to calculate phase angle, and the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN). ResultsThe mean (standard error) phase angle between peak cortisol and DLMO increased by 108 (61) minutes from baseline to Week 8 (n = 9). BRIAN Total score changed (improved) by –14.6 (4.6) points from baseline to Week 8 (n = 9). Change in phase angle and BRIAN Total score showed a moderate-to-high correlation (Pearson coefficient: 0.68; 95% confidence limits: 0.04, 0.93; p = 0.040). LimitationsThis study is limited by its small sample size, and its single-arm, open-label design. ConclusionsThe findings provide a preliminary indication that the phase angle between peak cortisol and DLMO is of interest as a potential biomarker for depression and therapeutic response. Adjunctive brexpiprazole may represent a strategy for correcting circadian dysfunction in patients with MDD and inadequate response to antidepressant treatment. ClinicalTrials.gov identifier: NCT01942733.

Minding the gap between cortisol levels measured with second-generation assays and current diagnostic thresholds for the diagnosis of adrenal insufficiency: a single-center experience

PurposeThe current cut-offs for the diagnosis of adrenal insufficiency (AI) have been established using outdated immunoassays. We compared the cortisol concentrations measured with Roche Cortisol I (R1), the newly available Roche Cortisol II (R2), and liquid chromatography tandem mass spectrometry (LC-MS/MS), the gold standard procedure to measure steroids in patients undergoing the corticotropin (ACTH) test.MethodsWe enrolled 30 patients (age 47 ± 21 years) referred to undergo the ACTH test (1 or 250 μg). Cortisol was measured at 0, 30, and 60 min after stimulation with R1, R2, and LC-MS/MS. AI was diagnosed for R1-stimulated peak cortisol concentrations < 500 nmol/L.ResultsMean cortisol concentrations measured with R2 and LC-MS/MS were comparable, while mean cortisol concentrations measured by R1 were higher than those of both R2 and LC-MS/MS (respectively, basal 411 ± 177, 287 ± 119, and 295 ± 119 nmol/L; at 30 min, 704 ± 204, 480 ± 132, and 500 ± 132 nmol/L; at 60 min, 737 ± 301, 502 ± 196, and 519 ± 201 nmol/L, p ≤ 0.01 for R1 vs. both R2 and LC-MS/MS at each point). Considering the 500 nmol/L cortisol peak cut-off, AI was diagnosed in 5/30 patients using R1 and in 12/30 using R2 (+ 140%). Based on the correlation between R1 and R2, the threshold of 500 nmol/L became 351 nmol/L (12.7 μg/dL) when cortisol was measured with R2, and 368 nmol/L (13.3 μg/dL) with LC-MS/MS.ConclusionsThe use of more specific cortisol assays results in lower cortisol concentrations. This could lead to misdiagnosis and overtreatment when assessing AI with the ACTH test if a different cut-off for cortisol peak is not adopted.

Hair cortisol concentration in pre- and postpartum dairy cows, and its association with body condition, hock health, and reproductive status.

The objective of this study was to investigate the profiles of hair cortisol concentrations as an index of chronic stress in dairy cows in association with their health, nutrition, and reproductive parameters. For 25 Holstein dairy cows, hair was collected from the tail switch -19.2±11.4, 44.8±11.9, 103.0±9.9, and 168.0±9.7days postpartum (L0, L1, L2, and L3, respectively). Body condition scores were negatively correlated with hair cortisol concentrations (r=-0.255), and hock health scores were positively correlated with hair cortisol concentrations (r=0.236, p<0.05). Hair cortisol concentrations during the postpartum period showed different patterns according to the time of first artificial insemination (AI) and fertility. Cows that were submitted to first AI by 86days postpartum showed a peak hair cortisol concentration at L1, whereas cows with delayed first AI had a peak at L2. The hair cortisol concentrations of subfertile (≥168days) cows were significantly higher at L1 and L2 compared with L0, whereas hair cortisol concentrations of fertile cows (<168days) were not different among the sampling times. These results indicate that cows with health problems appear to experience greater chronic stress, which may impair their reproductive function.

Cortisol and Aldosterone Responses to Insulin-Induced Hypoglycemia and Sodium Depletion in Women with Non-Classic 21-Hydroxylase Deficiency

Background: Non-classic 21-hydroxylase deficiency is usually diagnosed in post-pubertal women because of androgen excess. Indication of systematic steroid replacement therapy is controversial because the risk of acute adrenal insufficiency is unknown. In order to specify this risk we evaluated the cortisol and aldosterone secretions in response to appropriate pharmacological challenges. Methods: In this prospective case-control non-inferiority study we investigated 20 women with non-classic 21-hydroxylase deficiency carrying biallelic CYP21A2 mutations and with serum 17-hydroxyprogesterone (17OHP) >10ng/mL after stimulation with Synacthen® (tetracosactrin) and 20 ageand BMI-matched healthy women with 17OHP after Synacthen® <2ng/mL. Each participant underwent sequentially an insulin tolerance test to evaluate cortisol secretion and a sodium depletion test, obtained by oral administration of 40 mg furosemide under low sodium diet (< 20 mmol during 24 hours), to evaluate renin and aldosterone secretion. Findings: The peak serum cortisol concentration after insulin hypoglycemia was lower in patients than in controls (mean difference -47 ng/mL, 90%CI: -66, p=0.0026). A peak serum cortisol above a cutoff value of 170 ng/mL was obtained in all controls but only in 55% of patients (p=0.0039). 24- hours after sodium depletion, blood pressure, plasma sodium, potassium and serum aldosterone concentrations were comparable between the two groups, but patients had higher stimulated renin concentrations than controls (p=0.0044). Interpretation: Patients with non-classic 21-hydroxylase deficiency frequently display partial cortisol insufficiency and compensated defect in aldosterone secretion. Their clinical management should systematically include assessment of adrenal functions. Trial Registration Number: The trial was registered in ClinicalTrials.gov number NCT01862380. Funding Statement: Institutional grant from APHP AOR11111. Declaration of Interests: The authors state that they have nothing to disclose. Ethics Approval Statement: The study was approved by the local Ethics Committee (Comite de Protection des Personnes Ile de France VII) and the competent authority (ANSM). All subjects gave written informed consent to participate to the study.

The ACTH challenge and its repeatability in fattening bulls—influences of physiological state, challenge time standardization, and horn status

Adrenocorticotropic hormone (ACTH) challenges are frequently performed in repetition when evaluating stress or welfare in animals. To our knowledge, the repeatability of ACTH challenges in cattle, although fundamental to further studies of this type, has not yet been the subject of research. Therefore, the objective of this study was to evaluate the repeatability of ACTH challenges in fattening bulls of different horn status. Eight-one bulls were subjected to 3 consecutive ACTH challenges. The first challenge (C1) was performed in calves aged 1.5 mo. Subsequently, animals were characterized as high or low cortisol responders and either disbudded or left with horns. They were then assigned to 1 of 3 rearing groups: a horned group (H+), a disbudded group (H−), and a mixed group (M; 50% horned and 50% disbudded), with each group containing an equal number of high and low responders. The second ACTH challenge (C2) was performed at the age of 11 mo. Time of day (TOD) of challenge was either fixed (ST = same TOD) or alternated (AT = alternate TOD) between C1 and C2. The third ACTH challenge (C3) was performed 7 d after and at the same TOD as C2. Saliva samples were taken 60 and 30 min before and 30, 60, 90, 120, and 150 min after each intravenous ACTH injection. The area under the curve (AUC) was calculated with respect to both ground (AUCG) and to increase (AUCI). The AUCI increased markedly between C1 and C2 (P < 0.05) in ST bulls, and no effects were observed for AUCG between C1 and C2 in ST or AT bulls, nor for any AUC between C2 and C3 (P > 0.1). The overall repeatability of AUCG and AUCI between C1 and C2, reflecting the repeatability between 2 different physiological states, was poor and moderate, respectively, for ST bulls (AUCG: r = 0.24, P > 0.1, intraclass correlation coefficient (ICC) = 0.21; AUCI: r = 0.48, P < 0.01, ICC = 0.41) and lacked in AT bulls (AUCG: r = 0.07, P > 0.1; ICC = 0.03; AUCI: r = 0.08, P > 0.1, ICC = 0.06). The repeatability of AUCG and AUCI between C2 and C3, reflecting the repeatability within the same physiological state, was moderate (AUCG: r = 0.59, P < 0.001; ICC = 0.53; AUCI: r = 0.58, P < 0.001, ICC = 0.52). Assignment to high and low responder groups based on peak cortisol concentration in C1 did not persist over time. H+ bulls showed higher AUCI in C2 and C3 (P < 0.1 and P < 0.05, respectively) than H− bulls. The M group differed from the H− group only in C3 (P < 0.05). Thus, the effect of horn status on ACTH challenges needs further investigation. In conclusion, our results report poor repeatability of the cortisol response to ACTH challenges for challenges performed in different physiological states and moderate repeatability for challenges performed within the same physiological state. Moreover, they point out the importance of standardization of TOD when performing repeated ACTH challenge.

Pharmacokinetics of Glucocorticoid Replacement Before and After Bariatric Surgery in Patients With Adrenal Insufficiency.

Adequate glucocorticoid replacement in patients with primary or secondary adrenal insufficiency is essential to maintain general well-being. Little is known about the effects of bariatric surgery on glucocorticoid absorption. This study evaluates glucocorticoid absorption before and after bariatric surgery, with assessment of plasma cortisol profiles in five patients receiving glucocorticoid replacement therapy for primary (n = 1) or secondary (n = 4) adrenal insufficiency. One patient underwent sleeve gastrectomy (SG), one a one-anastomosis gastric bypass (mini-GB), and three a Roux-en-Y gastric bypass (RYGB). Pharmacokinetic calculations were based on plasma cortisol measurements performed during the first 6 hours after ingestion of the morning dose. Plasma cortisol profiles were very similar before and after surgery; only minor differences were observed. After SG, plasma peak cortisol concentration and cortisol area under the curve (AUC) were higher by 23% and 24%, respectively, and time to peak cortisol was 10 minutes shorter. The mini-GB had no marked effect on pharmacokinetic parameters. In the three patients who underwent RYGB, AUC changes ranged from −12% to 20%. In conclusion, in this small number of patients with adrenal insufficiency, plasma cortisol profiles were similar before and after bariatric surgery. However, in view of individual differences in response to different types of surgery, we recommend postoperative cortisol profiling to guide appropriate glucocorticoid dose adjustment.

Development of Portable Electrochemical Enzyme Immunoassay for Hormone-Level Determination Utilizing Pencil-Lead Electrodes

Electrochemical detection or analysis of bio-molecules is an effective technique in laboratories due to its simplicity over conventional optical approaches. The technique is usually performed using three-electrode voltammetry composed of a working, counter and reference electrode that are made of noble metals. Graphite electrodes are major alternatives for resource-limiting experimental conditions such as point-of-care diagnostics and rapid screening, which would require disposable electrodes. To further reduce the cost of graphite-based electrodes for personal hormone-level monitoring in which several sampling activities are needed each day in months, pencil leads are proposed as an electrode material in this paper. Competitive-based enzyme immunoassay (EIA) is a method for the quantification of hormones, which is performed in a 96-well plate where the plate surface is coated with a capturing antibody in charge of hormone binding. Target hormones in the sample and artificial hormones conjugated with a peroxidase compete for limited binding sites on the plate surface. Peroxidase is an enzyme catalyzing the oxidation by hydrogen peroxide of 3, 3', 5, 5'-Tetramethylbenzidine (TMB), an electro-active redox dye indicator. The low-level hormone in the sample would lead to a high signal of oxidized TMB due to the large presence of the conjugated peroxidase, and vice versa. In this paper, the use of pencil leads allows a direct dip-in process to measure electrochemical signals from tested solution in a 96-well plate. Our work presents a portable enzyme immunoassay system that contains an electrochemical voltammetry composed of a three-electrode sensor module, potentiostat and data acquisition. The devices are intended for generic employment in the quantification of cortisol, a steroid hormone and indicator of human stress level. The three-electrode sensors were developed based on mechanical pencil-leads. We also report the preparation of Ag/AgCl reference electrodes, for the first time, fabricated by directly casting and chemically modifying silver epoxy on pencil-lead electrodes to form Ag/AgCl layers. The electrochemical properties of the redox indicator, TMB, were studied by cyclic voltammetry. The enzymatic activity of peroxidase was evaluated to indicate its linear characteristics in terms of time. The amperometric responses of varying concentration of cortisol samples (3200, 800, 400, 200, and 0 pg/ml) were obtained by our system. The results are consistent to the mechanism of competitive-based EIA in which a low amount of oxidized TMB should be measured due to a low amount of conjugated peroxidase molecules captured by the antibody is in presence if the cortisol level of a test sample is high. The non-linear relationship between the peak current values and cortisol concentration of samples at low and high concentration range was demonstrated indicating diffusion-limited reactions. The electrochemical enzyme immunoassay was for the first time performed using the pencil-lead based sensors as presented in this paper. The results promise that the proposed electrochemical assay is able to quantify hormone levels and serve as an ultra-low-cost biosensing system for point-of-care diagnostics and personal health monitoring. Figure 1

Recovery of hypothalamo-pituitary-adrenal axis suppression during treatment with inhaled corticosteroids for childhood asthma.

ObjectiveTo describe recovery of adrenal insufficiency in asthmatic children treated with inhaled corticosteroids (ICS) and cortisol replacement therapy.DesignRetrospective, observational study.PatientsA total of 113 patients, 74 male; age 10.4 (3.3–16.5) years; beclomethasone-equivalent ICS dose, 800 μg, (100–1,000), tested by low dose short Synacthen (tetracosactide) test (LDSST), were studied. Test results were classified by basal and peak cortisol concentration: “normal” (basal >100 nmol/L, peak >500 nmol/L), “suboptimal” (basal >100 nmol/L, peak 350–499 nmol/L), “abnormal” (basal <100 nmol/L and/or peak <350 nmol/L). Patients with suboptimal results received hydrocortisone during periods of stress only, and those with abnormal responses received daily hydrocortisone, increased during periods of stress. A total of 73 patients (68%) had ≥2 LDSSTs over 2.2 years (0.2–7.7).MeasurementsChange in cortisol response to repeat LDSST (movement between diagnostic groups, difference in basal and peak cortisol >15% [2× the inter-assay coefficient of variation]), change in BMI and height standard deviation score (SDS).ResultsBaseline test results were abnormal in 17 patients (15%) and all of them had repeat tests. In 13 patients (76%), test results improved (normal in six, suboptimal in seven) and four (24%) remained abnormal. Baseline tests results were suboptimal in 54 patients (48%), of whom 50 (93%) were retested. Repeat tests were normal in 36 patients (72%), remained suboptimal in 11 (22%), and were abnormal in three (6%). Baseline tests results were normal in 42 patients, of whom six patients (14%) were retested. Results remained normal in three (50%), were suboptimal in two (33%), and abnormal in one (17%). Basal and peak cortisol levels increased by >15% in 33/73 (45%) and 42/73 (57%) patients, respectively, and decreased by >15% in 14/73 (19%) and 7/73 (10%), respectively. There was no significant change in height or BMI SDS.ConclusionRecovery of adrenal function is common and occurs during continued ICS and cortisol replacement therapy.

Assessing the utility of urinary and fecal cortisol as an indicator of stress ingolden snub-nosed monkeys (Rhinopithecus roxellana).

Cortisol concentration (CC) is often used as a stress indicator in animals, as high CC is associated with elevated stress levels. During field research, non-invasive methods of measuring CC, such as collection of urine and feces, are superior to using blood samples when monitoring free-ranging animals’ stress levels. However, due to different metabolic pathways, whether CC can be detected in urine and feces to reliably assess stress varies across species. Therefore, it is important to ascertain whether urine and fecal samples are a reliable source for determining CCs and to determine a suitable sampling regime. In this study, we subjected three captive adult golden snub-nosed monkeys (Rhinopithecus roxellana) to a high-stress situation (capture and injection). Urine and feces were collected for four days before and for four days after the manipulations for laboratory analysis. Immunoreactive CC was detected with a commercial enzyme immunoassay (EIA) kit and showed distinct rises. Peak CC values in urine were detected within 5 h, while peak fecal CC ranged between 5 and 24 hours post-interference. These results provide evidence that CC in urine and feces can be used to assess stress levels in the golden snub-nosed monkey. The optimal time frame to collect urinary and fecal samples for CC analysis is within one day of a potential stressful event.

The role of stressful life events on the cortisol reactivity patterns of breast cancer survivors

Objective: Atypical patterns of cortisol secretion following an acute stressor have been commonly reported in breast cancer survivors. Stressful life events have been associated with blunted acute cortisol levels in other populations. The purpose of this study was to explore the role of stressful life events on cortisol secretion patterns of breast cancer survivors following an acute stressor.Design: The Trier Social Stress (TSST) was used to elicit a moderate stress response in breast cancer survivors (n = 19) and a control group (n = 17). Saliva samples were collected before, during and after the TSST to provide cortisol concentrations. During recovery, we recorded the frequency and subjective impact of stressful life events in the past year using the Life Experience Survey.Results: Simple regressions analyses were performed; results suggest no group differences between the total number of stressful life events and their subjective impact. However, the total number of stressful life events as well as their subjective impact correlated negatively with the peak cortisol concentration in breast cancer survivors.Conclusions: The cumulative effect of stressful life events, positive and negative, may impact the endocrine stress system of breast cancer survivors more so than that of women with no history of cancer.

Secondary Adrenal Insufficiency Is Associated with Poor Survival Outcomes in Multiple Myeloma

Background: Glucocorticoids has been a backbone of various treatment regimens for multiple myeloma (MM). The repeated and chronic use of high doses of glucocorticoids is associated with development of secondary adrenal insufficiency (AI), and AI could be a major problem in critically-ill patients. However, there has been no specialized data about incidence and clinical significance of secondary AI in hospitalized patients with MM.Purpose: The objective of this retrospective study is to evaluate incidence, predictive factors, and clinical significance of secondary AI in hospitalized patients with MM.Methods: We retrospectively evaluated medical records of MM patients who were hospitalized in Chonnam National University Hwasun Hospital, South Korea from December 2014 to December 2015. The definite AI was diagnosed when the peak cortisol concentration was less than < 500 nmol/L (18 mcg/dL) after ACTH administration.Results: Between December 2014 and December 2015, 77 patients were hospitalized, and 58 underwent rapid ACTH stimulation test. The most frequent cause of hospitalization was infection (70.7%), followed by weakness (24.1%), and the others (5.3%). The definite AI was confirmed in 19 patients (32.7%). To evaluate the predictive factors of AI, all variables including clinical characteristics, laboratory results, cumulative steroid dose, and treatment duration at hospitalization were analyzed, but there were no significant predictors for AI. In addition, the patients with AI had a significantly poor survival outcomes compared to those without AI (the median overall survival of 42.3 months vs. 82.7 months; P = 0.037) (Figure 1).Conclusions: This study showed that the secondary AI is not a rare condition among hospitalized patients with MM, and there was no specific predictable symptoms or signs. In addition, development of AI in the treatment period is associated with a poor prognosis. This study suggests that evaluation of AI is routinely needed in hospitalized patients with MM. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The effect of potential fall distance on hormonal response in rock climbing

ABSTRACTThe aim of this study was to examine the effect of alterations in potential lead fall distance on the hormonal responses of rock climbers. Nine advanced female climbers completed two routes while clipping all (PRO-all) or half (PRO-½) of the fixed points of protection. Venous blood samples were analysed for total catecholamines, noradrenaline (norepinephrine), adrenaline (epinephrine), dopamine, lactate, cortisol and serotonin. Differences between the two conditions pre, immediately post and 15 min post climbing were assessed using a 2 × 3 repeated measures ANOVA. All hormones and blood lactate concentrations increased significantly (P < 0.05) immediately post climb, except for cortisol. Peak cortisol concentrations did not occur until 15 min post ascent. Further, significant interactions between climbing and clipping conditions were found for total catecholamines (890% of basal concentration in PRO-½ vs. 568% in PRO-all), noradrenaline (794% vs. 532%) and dopamine (500% vs. 210%). There were no significant interactions for adrenaline (1920% vs. 1045%), serotonin (150% vs. 127%) or lactate (329% vs. 279%). The study showed a greater catecholamine response with an increase in potential lead fall distance. The most pronounced increases seen in catecholamine concentration were reported for dopamine and noradrenaline.

Cortisol Response in Healthy and Diseased Dogs after Stimulation with a Depot Formulation of Synthetic ACTH.

BackgroundThe ACTH stimulation test is used to evaluate the adrenocortical reserve. Recently, the availability of the synthetic ACTH formulation was limited, causing major problems in clinical practice.ObjectivesThe objective of this study was to evaluate poststimulation peak cortisol concentrations and the duration of the stimulatory effect of a depot ACTH preparation in dogs.AnimalsTwenty‐two healthy dogs, 10 dogs with suspected hypoadrenocorticism (HA) and 15 dogs with suspected hyperadrenocorticism (HC).MethodsProspective study. An ACTH stimulation test using a synthetic depot tetracosactide, administered intramuscularly (5 μg/kg or at least 0.1 mL) was performed. Blood samples for determination of cortisol were taken immediately before and 1, 2, 3, 4, 6, and 24 hours after stimulation.ResultsPeak cortisol concentrations were reached after 2–4 hours in all dogs. Cortisol concentrations 1 hour after stimulation were >9 μg/dL in all healthy dogs and >5 μg/dL in all dogs in which HA was excluded. None of the dogs with HA showed a cortisol‐increase above the detection‐limit of the assay. After 6 hours, cortisol concentrations had decreased in the healthy and HC group and were back to baseline after 24 hours.Conclusions and Clinical ImportanceThe depot formulation can be used in place of the short‐acting ACTH to evaluate the adrenocortical reserve. Blood for peak cortisol concentrations should be drawn 3 hours after stimulation in cases in which HC is suspected; in HA‐suspected cases, blood sampling can take place after 1 hour. As the stimulatory effect is gone after 24 hours, interference with other hormonal tests is unlikely after that time.

P.1.e.017 A decrease in phosphorylation of CREB may explain delayed place learning and attenuated long-term potentiation in adult-onset hyperthyroidism

The hippocampal mineralocorticoid receptor (MR) is critical for the regulation of the basal activity of the hypothalamus–pituitary–adrenocortical (HPA) system. It has been hypothesized that reduced capacity of the hippocampal MR is involved in the HPA-system dysregulation found in depression and aging. We applied the combined dexamethasone suppression/corticotropin releasing hormone stimulation (DEX/CRH) test to six healthy young females both before and after 12 days of treatment with the MR antagonist spironolactone to assess HPA regulation. Treatment with spironolactone caused a significant increase in post-dexamethasone cortisol concentrations (75.1±56.7 vs. 36.6±24.6 nmol/l, p<0.05). Furthermore, we observed a significant rise in peak cortisol concentration after additional human CRH (hCRH) application (223.6±139.1 vs. 126.7±73.3 nmol/l, p<0.02). There was no change in ACTH plasma concentrations. We thus conclude that (1) the MR antagonist spironolactone affects HPA system regulation as reflected in the DEX/CRH test and (2) these findings are in accordance with the assumption that MR dysfunction may underlie HPA-system dysfunction in depression and/or aging.

Adrenal responses to a low-dose short synacthen test in children with asthma.

Corticosteroids are known to cause adrenal suppression. The aim of this study was to assess clinical factors affecting responses to a low dose short synacthen test (LDSST) in asthmatic children using corticosteroids. Patients were recruited from secondary care paediatric asthma populations within the UK. Asthmatic children (5-18 years), receiving corticosteroids, underwent a LDSST (n = 525). Demographics and corticosteroid doses were tested for association with baseline and peak (stimulated) cortisol concentrations. Baseline cortisol was significantly associated with age (log baseline increased 0·04 nm per year of age, P < 0·0001), but not with gender or corticosteroid dose. Peak cortisol was significantly associated with total corticosteroid cumulative dose (decreased 0·73 nm per 200 mcg/day, P < 0·001) but not with age, gender inhaled/intranasal corticosteroid cumulative dose or number of courses of rescue corticosteroids. Biochemically impaired response (peak cortisol ≤500 nm) occurred in 37·0% (161/435) overall, including children using GINA low (200-500 mcg/day beclomethasone-CFC equivalent 32%, n = 60), medium (501-1000 mcg/day (33%, n = 57) and high (>1000 mcg/day 40%, n = 13) doses of inhaled corticosteroid (ICS) similarly, and 36·6% of those using fluticasone ICS ≥500 mcg/day (71/194). Impaired response was more frequent in patients on regular oral corticosteroids (66%, n = 27, P < 0·001). Children with asthma can develop biochemical adrenal suppression at similar frequencies for all ICS preparations and doses. The clinical consequence of biochemical suppression needs further study.

Plasma, salivary and urinary cortisol levels following physiological and stress doses of hydrocortisone in normal volunteers.

BackgroundGlucocorticoid replacement is essential in patients with primary and secondary adrenal insufficiency, but many patients remain on higher than recommended dose regimens. There is no uniformly accepted method to monitor the dose in individual patients. We have compared cortisol concentrations in plasma, saliva and urine achieved following “physiological” and “stress” doses of hydrocortisone as potential methods for monitoring glucocorticoid replacement.MethodsCortisol profiles were measured in plasma, saliva and urine following “physiological” (20 mg oral) or “stress” (50 mg intravenous) doses of hydrocortisone in dexamethasone-suppressed healthy subjects (8 in each group), compared to endogenous cortisol levels (12 subjects). Total plasma cortisol was measured half-hourly, and salivary cortisol and urinary cortisol:creatinine ratio were measured hourly from time 0 (between 0830 and 0900) to 5 h. Endogenous plasma corticosteroid-binding globulin (CBG) levels were measured at time 0 and 5 h, and hourly from time 0 to 5 h following administration of oral or intravenous hydrocortisone. Plasma free cortisol was calculated using Coolens’ equation.ResultsPlasma, salivary and urine cortisol at 2 h after oral hydrocortisone gave a good indication of peak cortisol concentrations, which were uniformly supraphysiological. Intravenous hydrocortisone administration achieved very high 30 minute cortisol concentrations. Total plasma cortisol correlated significantly with both saliva and urine cortisol after oral and intravenous hydrocortisone (P <0.0001, correlation coefficient between 0.61 and 0.94). There was no difference in CBG levels across the sampling period.ConclusionsAn oral dose of hydrocortisone 20 mg is supraphysiological for routine maintenance, while stress doses above 50 mg 6-hourly would rarely be necessary in managing acute illness. Salivary cortisol and urinary cortisol:creatinine ratio may provide useful alternatives to plasma cortisol measurements to monitor replacement doses in hypoadrenal patients.