Peak Cortisol Levels Research Articles

Variations in Morning Serum Cortisol Levels Based on Sex and Pubertal Status

Introduction: Patients with suspected adrenal insufficiency undergo screening with a serum morning cortisol level and confirmatory testing with an adrenocorticotropic hormone (ACTH) stimulation test. However, much of the data collected to determine appropriate values for morning cortisol levels are derived from adult populations and may not accurately represent pediatric physiology. The purpose of this study was to evaluate the mean morning cortisol level in the pediatric population based on pubertal status and sex in order to better understand such influences on laboratory evaluation of adrenal insufficiency. Methods: A retrospective chart review was conducted using electronic medical records of patients seen at Children’s Mercy Kansas City from 11/01/2007 to 11/01/2017. Patients between 2 and 18 years of age who had pubertal staging assessed by a pediatric endocrinologist and confirmed adrenal sufficiency by high-dose ACTH stimulation testing were included. Two-sample Wilcoxon rank sum (Mann-Whitney) tests or t tests were used to compare morning cortisol levels between females and males – both independent of Tanner stage and by Tanner stage. Multivariable regression models were used to evaluate associations among covariates on two outcomes: morning cortisol levels and peak cortisol values with ACTH stimulation. Results: Morning cortisol levels were greater in females than males independent of Tanner staging (p = 0.0054) and also in Tanner stage 1 (p = 0.0042). No differences in mean morning cortisol levels between Tanner stage 2–5 females and males were found (p = 0.4652). Morning cortisol levels were not significantly different between Tanner 1 patients and Tanner 2–5 patients independent of sex (p = 0.0575). Sex was predictive of serum morning cortisol levels (p = 0.015), and morning cortisol levels were predictive of peak cortisol levels during ACTH stimulation testing (p < 0.001). Conclusions: These data suggest that different normative cortisol values may need to be established for pediatric females and males, and by pubertal status. Larger prospective studies are needed to evaluate the role of sex and pubertal status in identifying adrenal insufficiency in the ­pediatric population.

Cortisol Levels in Glucagon Stimulation Test in Children Assessed for Short Stature: Clinical and Laboratorial Correlations.

To assess total cortisol levels in children being evaluating for short stature with normal cortisol reserve and to correlate this response to clinical and laboratory data. Children assessed with glucagon test in our department were recruited in this study retrospectively. Inclusion criteria were: i) age>1 year, ii) absence of chronic illness or medication interfering with ACTH-cortisol axis, iii) GH stimulation levels>3ng/mL at least in one provocation test (glucagon or clonidine), iv) absence of multiple pituitary growth hormone deficiencies, v) normal short Synacthen test in cases of low cortisol response in glucagon test.Two hundred and thirty-seven subjects (160 males, 67.5%) with a mean age of 9.02±3.19 years, were finally included in the analysis. Cortisol peak levels but not cortisol AUC were significantly increased in females compared to males (26.83±7.31 μg/dl vs. 24.04±7.20 μg/dl). When linear correlations were studied, both cortisol peak levels and cortisol AUC were linearly but inversely correlated to age (r=-0.234, p<0.001 and r=-0.315, p<0.001, respectively). Finally, cortisol AUC was inversely correlated to weight Z-scores (r=-0.160, p=0.014). When our analysis was limited only to subjects with intact GH response (GH peak> 7 ng/mL), age was still inversely correlated to cortisol AUC (r=-0.312, p<0.001), and cortisol AUC was linearly correlated to GH AUC assessed with clonidine test (r=0.223, p=0.013). Girls, younger and thinner children exhibit higher cortisol response to glucagon test.

Diagnostic performance of basal cortisol level at 0900-1300h in adrenal insufficiency.

An ACTH stimulation test is the standard diagnostic test for adrenal insufficiency (AI). We aimed to investigate the diagnostic performance between serum morning (0800 h) cortisol and serum basal (0900-1300 h) cortisol levels and determine the proper cut-off point to facilitate AI diagnosis to reduce the number of tests. A six-year retrospective study was performed in a tertiary care medical center. We identified 416 patients who had undergone either low (LDT) or high dose (HDT) ACTH stimulation outpatient tests. AI was defined as a peak serum cortisol level of <500 nmol/L at 30 or 60 minutes after LDT or HDT. The associations between AI and serum basal and morning cortisol levels were demonstrated by logistic regression model. Diagnostic performance was evaluated by ROC analysis. Of the 416 patients, 93 (22.4%) were categorized as having AI. The adjusted area under the curve (AUC) for the basal cortisol level for the diagnosis of AI was significantly higher than that for the morning cortisol (0.82 vs 0.69, p <0.001) level. The proposed cut-off values for the basal cortisol were <85 nmol/L (specificity 99.7%) and >350 nmol/L(sensitivity 98.9%). By using these proposed cut-off points, approximately 30% of the ACTH stimulation tests could be eliminated. The serum basal cortisol level with the proposed cut-off points were considered as an alternative option for diagnosis of AI. Utilizing the serum basal cortisol level can facilitate AI diagnosis as it is convenient, is not a time-specific test and has a high diagnostic performance.

Glucocorticoid Replacement Affects Serum Adiponectin Levels and HDL-C in Patients With Secondary Adrenal Insufficiency.

Low serum adiponectin and high-density lipoprotein-cholesterol (HDL-C) levels are risk factors for cardiovascular disease. Patients with primary adrenal insufficiency are at higher risk of cardiovascular complications compared with healthy subjects. However, there is no information on the relationship between adiponectin and glucocorticoid replacement therapy in patients with secondary adrenal insufficiency (SAI). To determine the effects of intrinsic adrenal function and glucocorticoid replacement therapy on serum adiponectin levels and lipid profile in patients with SAI. Part 1: a cross-sectional study. Part 2: a randomized, double-blind, crossover study. Osaka University Hospital, Osaka, Japan. Part 1: 58 patients diagnosed with nonfunctioning pituitary adenoma who underwent insulin tolerance test (ITT) for assessment of adrenal function. Part 2: 12 SAI patients randomly received hydrocortisone replacement therapy at a dose of 10, 20, or 30 mg/d for 4 weeks per term for three terms. Part 1: we analyzed the relationship between serum cortisol levels during ITT and serum adiponectin levels and the lipid profile. Part 2: serum adiponectin levels and lipid profile were measured every 4 weeks. Serum levels of adiponectin and HDL-C correlated significantly with peak cortisol levels after ITT. Serum adiponectin and HDL-C levels were significantly lower in patients with SAI than non-SAI. Serum levels of adiponectin and HDL-C increased in a hydrocortisone dose-dependent manner. Glucocorticoid replacement therapy increased serum levels of adiponectin, an adipose-derived anti-atherogenic factor, and HDL-C in patients with SAI.

Evaluating the Low-Dose ACTH Stimulation Test in Children: Ideal Times for Cortisol Measurement.

Central adrenal insufficiency (AI) can be diagnosed with the low-dose ACTH stimulation test (LDST). Protocols determining timing of cortisol sampling vary, with 30 minutes after stimulation being most common. To determine optimal times to draw cortisol levels and factors predicting timing of peak cortisol levels in children undergoing LDST. Retrospective chart review of LDSTs between February 2014 and September 2017. The Children's Hospital of Eastern Ontario. Patients 3 months to 20 years who underwent LDSTs. LDSTs were performed with cortisol levels at 0, 15, 30, and 60 minutes after 1 μg cosyntropin. Cortisol values <18 μg/dL (500 nmol/L) determined AI. The incremental value of testing cortisol at 15 or 60 minutes, in addition to the standard 30-minute sample, was estimated. A total of 221 patients met inclusion criteria. The mean age was 9.7 years, and 32% were female. Peak cortisol levels were 19%, 67%, and 14% at 15, 30, and 60 minutes, respectively. One false positive LDST result would be prevented for every 24 (95% CI, 13 to 46) or 55 (95% CI, 22 to 141) patients tested at 15 or 60 minutes in addition to the standard 30-minute test. Of the 122 patients who passed the LDST, discontinuing the 15- and 60-minute samples would have misdiagnosed 12 patients (9.8%). Glucocorticoid exposure, age, and body mass index z scores were independent predictors of peak cortisol timing. Although the majority of patients peak 30 minutes after cosyntropin administration, testing cortisol levels at 15 and 60 minutes reduces the risk of false positive LDSTs.

Early Basal Cortisol Level as a Predictor of Hypothalamic-Pituitary-Adrenal (HPA) Axis Function After Pituitary Tumor Surgery.

The purpose of this study was to evaluate the clinical relevance of the early postoperative basal cortisol level in assessing the postoperative hypothalamic-pituitary-adrenal (HPA) axis function after pituitary tumor surgery. We performed a prospective observational study that enrolled 83 patients operated for pituitary adenoma or other sellar lesions at the University Hospital Center Zagreb between December 2013 and April 2017 (44 nonfunctioning pituitary adenomas, 28 somatotropinomas, 5 craniopharyngiomas, 2 prolactinomas resistant to medical therapy and 4 other lesions - Rathke's cleft cyst, arachnoid cyst, chondroma and gangliocytoma). Exclusion criteria were Cushing's disease, chronic therapy with glucocorticoids prior to surgery and preoperative adrenal insufficiency. Early postoperative basal cortisol levels (measured on the second postoperative day) and the Synacthen stimulation test (performed 3 months after the surgery with the peak cortisol level of>500 nmol/L considered as a normal response) were analyzed to assess HPA axis function during follow-up. ROC analysis showed a cut-off of the basal cortisol level of ≥300 nmol/L measured on the second postoperative day to predict normal postoperative HPA axis function with the sensitivity of 92.31%, specificity of 87.14% and positive predictive value of 57.14%. The basal cortisol level on the second postoperative day is a valuable tool to predict integrity of the HPA axis after pituitary tumor surgery. Our data suggest that the cortisol level of ≥300 nmol/L accurately predicts adrenal sufficiency and that in these patients glucocorticoid therapy can be withdrawn.

Habitual and acute exercise effects on salivary biomarkers in response to psychosocial stress

ObjectivePrevious research suggests beneficial effects of physical exercise on stress reactivity due to cross-stressor adaptions of physiological stress response systems. However, results remain inconclusive and it is unclear whether only regular engagement in exercise modulates these physiological adaptations or if acute bouts of exercise can elicit similar adaptations. Thus, the aim of the current study was to investigate and compare the effects of habitual and acute exercise on physiological stress responses. Methods84 male participants between 18 and 30 years (half of them were screened to be habitually high active or low active) were randomized into one of two groups: either an acute exercise intervention group (n = 42 with 50% being habitually high active) which engaged in 30 min of moderate-to-high intensity ergometer bicycling, or a control (placebo exercise) group which engaged in 30 min of light stretching (n = 42 with 50% being habitually high active). Following the intervention period, participants took part in a well validated psychosocial stress paradigm. Saliva samples were taken repeatedly to derive alpha-amylase and cortisol as stress-specific parameters. A multilevel growth curve approach was applied to analyse changes in the stress parameters over time. ResultsBoth, acute and habitual exercise have shown to be positively related to stress reactivity. In particular, a reduction in stress activation was found for both types of exercise, but only habitual engagement in exercise exhibited a beneficial effect on peak cortisol levels. ConclusionsTaken together, people can profit from regular exercise (i.e. reduced activity of stress–response systems). However, even acute bouts of exercise preceding stress exposure showed beneficial effects on stress reactivity. This finding is particularly important as it may provide a (self-)regulatory mechanism for people facing conceivable acute stress situations.

Triploidy in white sturgeon (Acipenser transmontanus): Effects of acute stress and warm acclimation on physiological performance

Previous studies have demonstrated reduced performance in triploid fish when reared under suboptimal conditions, which may be the result of a higher susceptibility to stressors when compared to diploids. The goal of this project was to investigate differences in the capacity of diploid (8 N) and triploid (12 N) white sturgeon, Acipenser transmontanus, to respond to both warm acclimation (6-weeks of acclimation to either 18 or 22 °C) and a subsequent acute stress (10-min low water stress). Following the 6-week acclimation, fish were sampled either before or following an acute low water stress. Bioindices of the primary and secondary stress response, hematology and cellular metabolic status were measured. We also sought to determine if time to peak cortisol levels were similar between diploid and triploid sturgeon after exposure to a severe acute stressor (netting stress). While both ploidies had similar primary and secondary responses to acute stress, both with and without warm acclimation, warm acclimation impacted the ability of diploid and triploid white sturgeon to mount a typical stress response to an acute stressor. In response to warm acclimation, triploids exhibited little change in branchial lactate dehydrogenase activity, while diploids increased activity. After exposure to an acute water reduction stress, diploids increased citrate synthase activity, yet triploids showed a decrease in activity. Differences in metabolic enzyme activity in response to warm acclimation and acute stress suggest triploid white sturgeon may have a reduced cellular metabolic capacity under chronic and acute stress, which may impact performance of triploid sturgeon in suboptimal conditions.

An unusual cause of adrenal insufficiency and bilateral adrenal masses.

SummaryPrimary adrenal insufficiency secondary to syphilis is extremely rare, with only five cases being reported in the literature. We report a case of adrenal insufficiency as a manifestation of Treponema pallidum infection (tertiary syphilis). A 69-year-old, previously fit and well Caucasian male was found to have adrenal insufficiency after being admitted with weight loss, anorexia and postural dizziness resulting in a fall. Biochemical testing showed hyponatraemia, hyperkalaemia, and an inadequate response to Synacthen testing, with a peak cortisol level of 302 nmol/L after administration of 250 µg Synacthen. Abdominal imaging revealed bilateral adrenal hyperplasia with inguinal and retroperitoneal lymphadenopathy. He was started on hydrocortisone replacement; however, it was not until he re-attended ophthalmology with a red eye and visual loss 1 month later, that further work-up revealed the diagnosis of tertiary syphilis. Following a course of penicillin, repeat imaging 5 months later showed resolution of the abnormal radiological appearances. However, adrenal function has not recovered and 3 years following initial presentation, the patient remains on both glucocorticoid and mineralocorticoid replacement. In conclusion, this case highlights the importance of considering syphilis as a potential differential diagnosis in patients presenting with adrenal insufficiency and bilateral adrenal masses, given the recent re-emergence of this condition. The relative ease of treating infectious causes of adrenal lesions makes accurate and timely diagnosis crucial.Learning points:Infectious causes, including syphilis, should be excluded before considering adrenalectomy or biopsy for any patient presenting with an adrenal mass.It is important to perform a full infection screen including tests for human immunodeficiency virus, other blood-borne viruses and concurrent sexually transmitted diseases in patients presenting with bilateral adrenal hyperplasia with primary adrenal insufficiency.Awareness of syphilis as a potential differential diagnosis is important, as it not only has a wide range of clinical presentations, but its prevalence has been increasing in recent times.

Adrenal Suppression Secondary to Interaction of Combined Inhaled Corticosteroid and Antifungal Agent

Objective: Inhaled corticosteroids (ICS) are exogenous glucocorticoids that typically have minimal systemic effects at standard doses. They are metabolized by the cytochrome P450 (CYP450) enzyme pathway in the liver; thus, they can cause unwanted side effects when used in conjunction with medications affecting this system. Here, we present a case of adrenal suppression (AS) secondary to combined usage of ICS and posaconazole, a known CYP450 inhibitor. Methods: Clinical and laboratory data were isolated and are presented. Results: A 9-year-old Caucasian female with history of hyper IgE syndrome. On chronic fluticasone and posaconazole for Aspergillus infection, she presented with fatigue and “facial puffiness” (cushingoid features). Low morning cortisol (0.3 μg/dL) prompted further evaluation. Low-dose (1 μg) adrenocorticotropic hormone (ACTH)-stimulation test with peak cortisol level <1 μg/dL. Other causes of hypocortisolism were ruled out. Started on physiologic hydrocortisone (10 mg/m2/day) and fluticas...

Clinical characteristics and prevalence of adrenal insufficiency in hemodynamically stable patients with cirrhosis

It is well known that adrenal insufficiency is common in septic shock or hemodynamically unstable patients. But, there is as yet no sufficient clinically significant data about the exact prevalence or differences in the cause of cirrhosis with adrenal insufficiency. To investigate adrenal insufficiency prevalence in hemodynamically stable patients with cirrhosis and determine differences based on cirrhosis severity or etiology.From July 2011 to December 2012, 69 hemodynamically stable patients with cirrhosis without infection admitted at Hallym University Medical Center were enrolled. Adrenal insufficiency was defined as a peak cortisol level < 18 μg/dL, 30 or 60 minutes after 250 μg Synacthen injection.The study included 55 male patients (79.7%), and the mean age was 57.9 ± 12.9 years. Cirrhosis etiology was alcohol consumption, HBV, HCV, both viral and alcohol related, and cryptogenic in 49, 15, 7, 11, 9 patients, respectively. Adrenal insufficiency occurred in 24 patients (34.8%). No differences were found in age, sex, mean arterial pressure, heart rate, HDL, cirrhosis etiology, degree of alcohol consumption, encephalopathy, variceal bleeding history, or hepatocellular carcinoma between patients with or without adrenal insufficiency. Serum albumin level was lower (P < .05), and INR was higher (P < .05) in patients with than in those without adrenal insufficiency. However, multivariate analysis revealed no independent adrenal insufficiency predictor. Significant negative correlations were found between Child–Pugh score and peak cortisol levels (γ=−0.365, P = .008).Adrenal insufficiency was frequent even in hemodynamically stable patients with cirrhosis and tended to be associated with only liver disease severity, being unrelated to cirrhosis etiology.

Comparison of glucose, peak growth hormone &amp; peak cortisol levels during insulin tolerance testing with two different doses (0.15 vs 0.10 U/kg)

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Relative Adrenal Insufficiency Is Associated With Prolonged Postoperative Hemodynamic Instability

We assessed the hypothesis that a significant proportion of patients undergoing cardiac surgery have postoperative relative adrenal insufficiency (RAI), and that this puts them at higher risk of persistent hemodynamic instability. A prospective study included 135 patients who underwent cardiac surgery using cardiopulmonary bypass between July 2006 and December 2007. Adrenal function was assessed 36 hours after surgery using a 1-μg cosyntropin (adrenocorticotropic hormone [ACTH]) stimulation test. Relative adrenal insufficiency was defined as a peak cortisol level inferior to 500 nmol/L or an increase in cortisol of less than 250 nmol/L, or both, compared with baseline. The primary endpoint was hemodynamic instability at 48 hours after surgery, defined as persistent requirement for any vasoactive drug. The secondary endpoint was long-term survival. Postoperative RAI was diagnosed in 75 patients (56%). Compared with patients who showed a normal response to the ACTH stimulation test, patients with RAI had significantly higher rates of hemodynamic instability at 48 hours (40% versus 22%, p= 0.03). On multivariable analysis, adrenal response to the ACTH test was a significant independent predictor of hemodynamic instability at 48 hours after surgery (odds ratio1.06 [95% confidence interval: 1.02 to 1.11] per 10nmol/L cortisol decrease; p= 0.002). At a mean follow-up of 8.3 ± 2.8 years, patients without perioperative RAI had survival equivalent to that of the general population, whereas patients with RAI had lower than expected survival. Postoperative RAI is common among patients undergoing cardiac surgery and is associated with an increased risk of persistent hemodynamic instability.

Delayed peak response of cortisol to insulin tolerance test in patients with Prader-Willi syndrome.

Deaths among children with Prader-Willi syndrome (PWS) are often related to only mild or moderate upper respiratory tract infections, and many causes of death remain unexplained. Several reports have hypothesized that patients with PWS may experience latent central adrenal insufficiency. However, whether PWS subjects suffer from alteration of the hypothalamus-pituitary-adrenal (HPA) axis remains unclear. This study aimed to explore the HPA axis on PWS. We evaluated the HPA axis in 36 PWS patients (24 males, 12 females; age range, 7 months to 12 years; median age 2.0 years; interquartile range [IQR], 1.5-3.4 years) using an insulin tolerance test (ITT) in the morning between 08:00 and 11:00. For comparison, ITT results in 37 age-matched healthy children evaluated for short stature were used as controls. In PWS patients, basal levels of adrenocorticotropic hormone (ACTH) were 13.5 pg/ml (IQR, 8.3-27.5 pg/ml) and basal levels of cortisol were 18.0 μg/dl (IQR, 14.2-23.7 μg/dl). For all patients, cortisol levels at 60 min after stimulation were within the reference range (>18.1 μg/dl), with a median peak of 41.5 μg/dl (IQR, 32.3-48.6 μg/dl). Among control children, basal level of ACTH and basal and peak levels of cortisol were 10.9 (IQR, 8.5-22.0 pg/ml), 15.6 (IQR, 11.9-21.6 μg/dl), and 27.8 μg/dl (IQR, 23.7-30.5 μg/dl), respectively. Basal and peak levels of cortisol were all within normal ranges, but peak response of cortisol to ITT was delayed in the majority of PWS patients (64%). Although the mechanismremains unclear, this delay may signify the existence of central obstacle in adjustment of the HPA axis.

Glucocorticoid receptor gene methylation moderates the association of childhood trauma and cortisol stress reactivity

Exposure to childhood trauma (CT) has been linked to sustained dysregulations of major stress response systems, including findings of both exaggerated and attenuated hypothalamus–pituitary–adrenal (HPA) axis activity. Likewise, CT constitutes a common risk factor for a broad range of psychiatric conditions that involve distinct neuroendocrine profiles. In this study, we investigated the role of epigenetic variability in a stress-related gene as a potential mediator or moderator of such differential trajectories in CT survivors. For this, we screened adult volunteers for CT and recruited a healthy sample of 98 exposed (67 with mild-moderate, 31 with moderate-severe exposure) and 102 control individuals, with an equal number of males and females in each group. DNA methylation (DNAM) levels of the glucocorticoid receptor exon 1F promoter (NR3C1-1F) at functionally relevant sites were analyzed via bisulfite pyrosequencing from whole blood samples. Participants were exposed to a laboratory stressor (Trier Social Stress Test) to assess salivary cortisol stress responses. The major finding of this study indicates that DNAM in a biologically relevant region of NR3C1-1F moderates the specific direction of HPA-axis dysregulation (hypo- vs. hyperreactivity) in adults exposed to moderate-severe CT. Those trauma survivors with increased NR3C1-1F DNAM displayed, on average, 10.4 nmol/l (62.3%) higher peak cortisol levels in response to the TSST compared to those with low DNAM. In contrast, unexposed and mildly-moderately exposed individuals displayed moderately sized cortisol stress responses irrespective of NR3C1-1F DNAM. Contrary to some prior work, however, our data provides no evidence for a direct association of CT and NR3C1-1F DNAM status. According to this study, epigenetic changes of NR3C1-1F may provide a more in-depth understanding of the highly variable neuroendocrine and pathological sequelae of CT.

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.

Corticotrophin-releasing hormone stimulation tests for the infants with relative adrenal insufficiency.

Very low birthweight (VLBW) infants are considered to be vulnerable to relative adrenal insufficiency (RAI); however, diagnosis is difficult in some clinical settings. Considering this background, it is necessary to establish a diagnosis of RAI in preterm infants. In this study, we attempted to clarify the difference in response to CRH stimulation tests for preterm infants with or without RAI. Between June 2009 and December 2015, we performed CRH stimulation tests for preterm infants born at a gestational age of <30weeks at around 2weeks of age. Retrospectively, subjects were classified into two groups: infants with RAI (n=9) or without RAI (n=17) based on the clinical symptoms and responsiveness to hydrocortisone. We found no difference in base or peak serum cortisol levels related to CRH stimulation tests between the two groups; however, delta cortisol levels and responsive ratio (peak-to-base ratio) were significantly reduced in infants with RAI. 140nmol/L for delta cortisol or 1.5 times for peak-to-base ratio may be cut-off levels in preterm infants. This study provides evidence that base cortisol levels of preterm infants with RAI were not different from those without RAI; however, CRH stimulation tests may be a useful tool for the diagnosis of RAI in preterm infants.

Algorithm for Screening of Adrenal Function in Stable Patients with Cirrhosis

Introduction and aimsAdrenal insufficiency (AI) is common in patients with cirrhosis. We aimed to assess the presence of AI in stable patients with cirrhosis using the gold-standard insulin tolerance test (ITT) and to propose an algorithm for screening AI in these patients. Material and methodsWe studied 40 stable patients with cirrhosis. We determined the basal total (BTC) and peak cortisol (PTC) levels. Using the ITT, we defined AI as a serum PTC < 18 ng/dL at 30 min after insulin-induced hypoglycemia. We assessed the diagnostic accuracy of BTC in different stages of liver disease to discriminate between those with NAF and AI. ResultsOf the 40 patients, 24 (60%) presented with AI. Child-Pugh and MELD scores differed between the NAF and AI groups (Child-Pugh: NAF 7.2 ± 1.7 vs. AI 8.8 ± 2.4, p = 0.024 and MELD: NAF 9.9 ± 2.5 vs. AI 14.9 ± 6.3, p = 0.001). The BTC level was lower in patients with AI than in those with NAF (7.2 ± 2.4 vs. 12.5 ± 5.2, p < 0.001). A BTC value <10.0 |ig/dL had a 96% sensitivity (negative predictive value: 90%) for identifying AI. This cutoff value (BTC <10.0 |ig/dL) provided 100% specificity (positive predictive value: 100%) in patients with advanced liver disease (Child-Pugh >9 or MELD >12). ConclusionAn algorithm including the use of BTC and the severity of liver disease may be a useful and simple method for assessing adrenal function in stable patients with cirrhosis.

Redefining the stress cortisol response to surgery.

Cortisol levels rise with the physiological stress of surgery. Previous studies have used older, less-specific assays, have not differentiated by severity or only studied procedures of a defined type. The aim of this study was to examine this phenomenon in surgeries of varying severity using a widely used cortisol immunoassay. Euadrenal patients undergoing elective surgery were enrolled prospectively. Serum samples were taken at 8 am on surgical day, induction and 1hour, 2hour, 4hour and 8hour after. Subsequent samples were taken daily at 8 am until postoperative day 5 or hospital discharge. Total cortisol was measured using an Abbott Architect immunoassay, and cortisol-binding globulin (CBG) using a radioimmunoassay. Surgical severity was classified by POSSUM operative severity score. Ninety-three patients underwent surgery: Major/Major+ (n=37), Moderate (n=33) and Minor (n=23). Peak cortisol positively correlated to severity: Major/Major+ median 680 [range 375-1452], Moderate 581 [270-1009] and Minor 574 [272-1066] nmol/L (Kruskal-Wallis test, P=.0031). CBG fell by 23%; the magnitude of the drop positively correlated to severity. The range in baseline and peak cortisol response to surgery is wide, and peak cortisol levels are lower than previously appreciated. Improvements in surgery, anaesthetic techniques and cortisol assays might explain our observed lower peak cortisols. The criteria for the dynamic testing of cortisol response may need to be reduced to take account of these factors. Our data also support a lower-dose, stratified approach to dosing of steroid replacement in hypoadrenal patients, to minimize the deleterious effects of over-replacement.

ANALYSIS OF INDUCTION PHASE GLUCOCORTICOID USE ON ADRENAL SUPPRESSION IN PEDIATRIC PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA

Glucocorticoids play an important role in the treatment of acute lymphoblastic leukemia (ALL). However, supraphysiological doses may cause suppression of the adrenal. Adrenal suppression resulting in reduced cortisol response may cause an inadequate host defence against infections, which remains a cause of morbidity and mortality in children with ALL. The occurrence of adrenal suppression before and after glucocorticoid therapy for childhood ALL is unclear. The aim of this study is to analysis the effect of glucocorticoid on cortisol levels during induction phase chemotherapy in children with acute lymphoblastic leukemia. A cross-sectional, observational prospective study was conducted to determine the effect of glucocorticoid on cortisol levels in children with acute lymphoblastic leukemia. Patients who met inclusion criteria were given dexamethasone or prednisone therapy for 49 days according to the 2013 Indonesian Chemotherapy ALL Protocol. Cortisol levels were measured on days 0, 14, 28, 42 and 56 of induction phase chemotherapy. There were 24 children, among 31 children recruited, who suffered from acute lymphoblastic leukemia. Before treatment, the means of cortisol levels were 228.95 ng/ml in standard risk group (prednisone) and 199.67 ng/ml in high risk group (dexamethasone). In standard risk group, the adrenal suppression occurs at about day 56. There was a significant decrement of cortisol levels in high risk group in days 14, 28, 42 against days 0 of induction phase (p=0.001). Both groups displayed different peak cortisol levels after 6 week of induction phase (p=0.028). Dexamethasone resulted in lower cortisol levels than prednisone during induction phase chemotherapy in children with acute lymphoblastic leukemia.