Low Dose Short Synacthen Test Research Articles

Value of low-dose short synacthen test (1μg) vs high-dose synacthen test (250 μg) for assessment of the adrenal axis

Value of low-dose short synacthen test (1μg) vs high-dose synacthen test (250 μg) for assessment of the adrenal axis

Glucocorticoid induced adrenal insufficiency in children: Morning cortisol values to avoid LDSST.

Glucocorticoid-induced adrenal insufficiency (GI-AI) is a common side effect of glucocorticoid therapy. However, its diagnosis currently relies on the realization of a Low Dose Short Synacthen Test (LD-SST) that requires an outpatient hospital and several blood samples. Our goal was to evaluate whether morning cortisol values could predict the response to LD-SST, in children, to avoid useless dynamic tests and facilitate diagnosis of glucocorticoid induced adrenal insufficiency. We recorded data of 91 pediatric patients who underwent a LD-SST in our center between 2016 and 2020 in a retrospective observational study. We selected LD-SST realized following administration of supra-physiologic doses of glucocorticoids during more than 3 weeks and performed at least four weeks after treatment was stopped. Adrenal deficiency was defined as a plasma cortisol concentration inferior to 500 nmol/l at LD-SST. Glucocorticoid-induced adrenal insufficiency was diagnosed in 60% of our cohort. Morning cortisol values were predictive of the response to the LD-SST (AUC ROC 0.78). A plasma cortisol concentration of less than 144 nmol/l predicted glucocorticoid induced adrenal insufficiency with a specificity of 94% and a value over 317 nmol/l predicted recovery of the HPA axis with a sensitivity of 95%. We did not find any other predictive factor for glucocorticoid-induced adrenal insufficiency. Morning cortisol values can safely assess recovery of the HPA axis in children treated chronically with glucocorticoids. Using these thresholds, more than 50% of LD-SST could be avoided in children.

Relative adrenal insufficiency in the non-critically ill patient with cirrhosis: A systematic review and meta-analysis.

Characterization of relative adrenal insufficiency (RAI) in cirrhosis is heterogeneous with regard to studied patient populations and diagnostic methodology. We aimed to describe the prevalence and prognostic importance of RAI in non-critically ill patients with cirrhosis. A systematic review and meta-analysis was performed using MeSH terms and Boolean operators to search five large databases (Ovid-MEDLINE, ScienceDirect, Web of Science, Cochrane Library and ClinicalTrials.gov). The population of interest was patients with cirrhosis and without critical illness. The primary outcome was the pooled prevalence of RAI as defined by a peak total cortisol level <18 μg/dl, delta total cortisol <9μg/dl or composite of the two thresholds in response either a standard-dose or low-dose short synacthen test. Odds ratios and standardized mean differences from random-effects models estimated important clinical outcomes and patient characteristics by adrenal functional status. Twenty-two studies were included in final analysis, comprising 1991 patients with cirrhosis. The pooled prevalence of RAI was 37% (95% CI 33-42%). The prevalence of RAI varied by Child-Pugh classification, type of stimulation test used, specific diagnostic threshold and by severity of illness. Ninety-day mortality was significantly higher in patients with RAI (OR 2.88, 95% CI 1.69-4.92, I2=15%, p < 0.001). Relative adrenal insufficiency is highly prevalent in non-critically ill patients with cirrhosis and associated with increased mortality. Despite the proposed multifactorial pathogenesis, no studies to date have investigated therapeutic interventions in this specific population.

Baseline and Peak Cortisol Response to the Low-Dose Short Synacthen Test Relates to Indication for Testing, Age, and Sex.

Meta-analyses report that the low dose short Synacthen test (LDSST) is more sensitive but less specific than the standard dose test for the diagnosis of adrenal insufficiency, and there are concerns regarding the accuracy of dosing in the LDSST. Perform a retrospective, observational study to review the outcomes of LDSSTs performed in a tertiary endocrine service from 2008 to 2014 (N = 335) and 2016 to 2020 (N = 160), and examine for relationships between cortisol measurements and indication for testing, age and sex. LDSST were performed by endocrine nurses. Synacthen 500 ng/1.73m2 administered as IV bolus, sampling at 0, 15, 25, and 35 minutes. Mean (± 1SD) baseline cortisol was 221 ± 120 nmol/L, peak 510 ± 166 nmol/L and increment 210 ± 116 nmol/L. 336 (70%) patients had a normal response (baseline cortisol >100 nmol/L, peak >450 nmol/L), 78 (16%) a suboptimal response (peak cortisol 350-450 nmol/L) and were prescribed hydrocortisone to during periods of stress only, 67 (14%) an abnormal response (baseline <100nmol/L or peak <350nmol/L) and were prescribed daily hydrocortisone. Basal, peak, and incremental increases in cortisol were higher in females (P = .03, P < .001, P = .03, respectively). Abnormal results occurred most frequently in patients treated previously with pharmacological doses of glucocorticoids or structural brain abnormalities (P < .001). The low prevalence and strong association of abnormal results with indication for testing, suggests that over diagnosis occurred infrequently in this clinical setting.

Low-dose short synacthen test with salivary cortisol in patients with suspected central adrenal insufficiency.

ContextThe low-dose short synacthen test (LDSST) is recommended for patients with suspected central adrenal insufficiency (AI) if their basal serum cortisol (F) levels are not indicative of an intact hypothalamic–pituitary–adrenal (HPA) axis.ObjectiveTo evaluate diagnostic threshold for salivary F before and 30 min after administering 1 μg of synacthen, performed before 09:30 h.DesignA cross-sectional study from 2014 to 2020.SettingA tertiary referral university hospital.PatientsIn this study, 174 patients with suspected AI, 37 with central AI and 137 adrenal sufficient (AS), were included.Main outcome measureThe diagnostic accuracy (sensitivity (SE), specificity (SP)) of serum and salivary F levels measured, respectively, by chemiluminescence immunoassay and liquid chromatography-tandem mass spectrometry.ResultsLow basal serum or salivary F levels could predict AI. For the LDSST, the best ROC-calculated threshold for serum F to differentiate AI from AS was 427 nmol/L (SE 79%, SP 89%), serum F > 500 nmol/L reached SP 100%. A salivary F peak > 12.1 nmol/L after administering synacthen reached SE 95% and SP 84% for diagnosing central AI, indicating a conclusive reduction in the likelihood of AI. This ROC-calculated threshold for salivary F was similar to the 2.5th percentile of patients with a normal HPA axis, so it was considered sufficient to exclude AI. Considering AS those patients with salivary F > 12.1 nmol/L after LDSST, we could avoid unnecessary glucocorticoid treatment: 99/150 subjects (66%) had an inadequate serum F peak after synacthen, but salivary F was >12.1 nmol/L in 79 cases, who could, therefore, be considered AS.ConclusionsSalivary F levels > 12.1 nmol/L after synacthen administration can indicate an intact HPA axis in patients with an incomplete serum F response, avoiding the need to start glucocorticoid replacement treatment.

Cut-off values for sufficient cortisol response to low dose Short Synacthen Test after surgery for non-functioning pituitary adenoma.

The aim was to study the prevalence of secondary adrenal insufficiency before and after surgery for non-functioning pituitary adenomas, as well as determine risk factors for developing secondary adrenal insufficiency. A secondary aim was to determine adequate p-cortisol response to a 1-μg Short Synacthen Test after surgery. Longitudinal cohort study. One hundred seventeen patients (52/65 females/males, age 59years) undergoing primary surgery for clinically non-functioning pituitary adenomas were included. P-cortisol was measured in morning blood samples. Three months after surgery, a Short Synacthen Test was performed. All tumours were macroadenomas (mean size 26.9mm, range 13-61mm). The surgical indications were visual impairment (93), tumour growth (16), pituitary apoplexy (6) and headache (2). Before surgery, 17% of the patients had secondary adrenal insufficiency (SAI), decreasing to 15% 3months postoperatively. Risk of SAI was increased in patients operated for pituitary apoplexy (p < 0.001), while age, sex, tumour size and complication rate were not different from the remaining cohort. Three months after surgery, all patients with baseline p-cortisol ≥ 172nmol/l (6.2μg/dl) and peak p-cortisol during Short Synacthen Test ≥ 320nmol/l (11.6μg/dl) tapered cortisone unproblematically. In patients with intact hypothalamic-pituitary-adrenal axis, p-cortisol peaked < 500nmol/l (18.1μg/dl) during Short Synacthen Test in 48% of patient. Pituitary surgery is safe and transsphenoidal surgery rarely causes new SAI. Relying solely on morning p-cortisol for diagnosing secondary adrenal insufficiency gives false positives and the Short Synacthen Test remains useful. A peak p-cortisol ≥ 320 during (11.6μg/dl) Short Synacthen Test indicates a sufficient response, while < 309nmol/l (11.2μg/dl) indicates secondary adrenal insufficiency.

Effect of long term inhaled corticosteroid therapy on adrenal suppression, growth and bone health in children with asthma

BackgroundInhaled corticosteroids (ICS) are the most effective treatment for children with persistent asthma. However adverse effects of ICS on Hypothalamo Pituitary Adrenal (HPA) axis, growth and bone metabolism are a concern. Hence the primary objective of this study was to describe the effects of long term inhaled corticosteroid therapy (ICS) on adrenal function, growth and bone health in children with asthma in comparison to an age and sex matched group of children with asthma who were not on long term ICS. Describing the association between the dose of ICS and duration of therapy on the above parameters were secondary objectives.MethodSeventy children with asthma on ICS and 70 controls were studied. Diagnosis of asthma in selected patients was reviewed according to the criteria laid down by GINA 2018 guidelines. The estimated adult heights were interpreted relative to their Mid Parental Height (MPH) range. Serum calcium, alkaline phosphatase and vitamin D levels were analyzed in both groups and cortisol value at 30 min following a low dose short synacthen test was obtained from the study group. The average daily dose of ICS (Beclamethasone) was categorized as low, medium and high (100–200, 200–400, > 400 μg /day) respectively according to published literature.ResultsHeights of all children were within the MPH range. There was no statistically significant difference in the bone profiles and vitamin D levels between the two groups (Ca: p = 0.554, vitamin D: p = 0.187) but vitamin D levels were insufficient (< 50 nmol/l) in 34% of cases and 41% of controls. Suppressed cortisol levels were seen in 24%. Doses of ICS were low, medium and high in 56, 32 and 12% of children respectively. The association between adrenal suppression with longer duration of therapy (p < 0.01) and with increasing dose of ICS (p < 0.001) were statistically significant.ConclusionICS had no impact on the growth and bone profiles but its dose and duration were significantly associated with adrenal suppression.

Susceptibility to corticosteroid-induced adrenal suppression: a genome-wide association study

SummaryBackgroundA serious adverse effect of corticosteroid therapy is adrenal suppression. Our aim was to identify genetic variants affecting susceptibility to corticosteroid-induced adrenal suppression.MethodsWe enrolled children with asthma who used inhaled corticosteroids as part of their treatment from 25 sites across the UK (discovery cohort), as part of the Pharmacogenetics of Adrenal Suppression with Inhaled Steroids (PASS) study. We included two validation cohorts, one comprising children with asthma (PASS study) and the other consisting of adults with chronic obstructive pulmonary disorder (COPD) who were recruited from two UK centres for the Pharmacogenomics of Adrenal Suppression in COPD (PASIC) study. Participants underwent a low-dose short synacthen test. Adrenal suppression was defined as peak cortisol less than 350 nmol/L (in children) and less than 500 nmol/L (in adults). A case-control genome-wide association study was done with the control subset augmented by Wellcome Trust Case Control Consortium 2 (WTCCC2) participants. Single nucleotide polymorphisms (SNPs) that fulfilled criteria to be advanced to replication were tested by a random-effects inverse variance meta-analysis. This report presents the primary analysis. The PASS study is registered in the European Genome-phenome Archive (EGA). The PASS study is complete whereas the PASIC study is ongoing.FindingsBetween November, 2008, and September, 2011, 499 children were enrolled to the discovery cohort. Between October, 2011, and December, 2012, 81 children were enrolled to the paediatric validation cohort, and from February, 2010, to June, 2015, 78 adults were enrolled to the adult validation cohort. Adrenal suppression was present in 35 (7%) children in the discovery cohort and six (7%) children and 17 (22%) adults in the validation cohorts. In the discovery cohort, 40 SNPs were found to be associated with adrenal suppression (genome-wide significance p<1 × 10−6), including an intronic SNP within the PDGFD gene locus (rs591118; odds ratio [OR] 7·32, 95% CI 3·15–16·99; p=5·8 × 10−8). This finding for rs591118 was validated successfully in both the paediatric asthma (OR 3·86, 95% CI 1·19–12·50; p=0·02) and adult COPD (2·41, 1·10–5·28; p=0·03) cohorts. The proportions of patients with adrenal suppression by rs591118 genotype were six (3%) of 214 patients with the GG genotype, 15 (6%) of 244 with the AG genotype, and 22 (25%) of 87 with the AA genotype. Meta-analysis of the paediatric cohorts (discovery and validation) and all three cohorts showed genome-wide significance of rs591118 (respectively, OR 5·89, 95% CI 2·97–11·68; p=4·3 × 10−9; and 4·05, 2·00–8·21; p=3·5 × 10−10).InterpretationOur findings suggest that genetic variation in the PDGFD gene locus increases the risk of adrenal suppression in children and adults who use corticosteroids to treat asthma and COPD, respectively.FundingDepartment of Health Chair in Pharmacogenetics.

The clinical course after glucocorticoid treatment in patients with inflammatory bowel disease is linked to suppression of the hypothalamic-pituitary-adrenal axis: a retrospective observational study.

Background:Adrenal insufficiency (AI) secondary to treatment with glucocorticoids (GCs) is common in patients with inflammatory bowel disease (IBD), but little is known about the relationship between AI and the clinical course in IBD. The aim of the study was to compare the clinical course in IBD patients with normal adrenal function versus patients with subnormal adrenal function.Methods:A retrospective observational study on 63 patients with IBD who had performed a low-dose short Synacthen test (LDSST) (1 μg) immediately (1–7 days) after a standard course of GCs. A subnormal LDSST was defined as serum cortisol <550 nmol/L. Outcomes were time to next flare and fecal calprotectin levels.Results:Sixty-three percent (n = 40) of the IBD patients had a subnormal LDSST. Patients who were steroid-free (n = 41) after the LDSST were observed for 3 years. Patients with a peak serum cortisol <400 nmol/L immediately after GC treatment had significantly longer time until the next flare-up of their IBD and tended to use a lower cumulative prednisolone dose during the study period in comparison to the other subgroups. Fecal calprotectin levels were significantly lower in patients with a peak s-cortisol <550 nmol/L versus patients with peak s-cortisol ⩾550 nmol/L (median 336 µg/g (IQR 521) versus 955 µg/g (IQR 1867); p = 0.012).Conclusions:GC-induced AI is common in patients with IBD and is associated with lower disease activity. This suggests a link between responsiveness to GC treatment and suppression of the hypothalamic–pituitary–adrenal axis in IBD.

Salivary Cortisol and Cortisone After Low-Dose Corticotropin Stimulation in the Diagnosis of Adrenal Insufficiency.

Context:Basal and poststimulation salivary cortisol and cortisone levels can be useful in the diagnosis of adrenal insufficiency. However, little is known about the optimal cutoffs and performance characteristics of these tests.Objective:To derive the cutoff values and study the performance characteristics of salivary cortisol and salivary cortisone in the diagnosis of adrenal insufficiency.Design and Setting:Prospective study in a regional hospital in Hong Kong from January 2014 to September 2015.Participants:Fifty-six Chinese healthy volunteers and 171 patients suspected of having adrenal insufficiency.Main Outcome Measures:All participants underwent low-dose short Synacthen test (LDSST) with intravenous injection of 1 μg of tetracosactide (Synacthen 1–24). Serum cortisol, salivary cortisol and cortisone levels were measured at baseline and 30 and 60 minutes afterward.Results:Using the reference cutoff (mean − 2 standard deviations of post-LDSST peak serum cortisol) derived from healthy volunteers as the gold standard, receiver operating characteristic analysis of patients’ data revealed that both post-LDSST peak salivary cortisol and cortisone performed better than basal tests. The most optimal cutoff values for serum cortisol as measured by immunoassay and for salivary cortisol and salivary cortisone as measured by liquid chromatography–tandem mass spectrometry (LC-MS/MS) were 376, 8.6, and 33.5 nmol/L, respectively, for post-LDSST peak values, and 170, 1.7, and 12.5 nmol/L, respectively, for basal values.Conclusions:We established method-specific reference cutoffs for serum cortisol, salivary cortisol, and salivary cortisone during LDSST. Both post-LDSST peak salivary cortisol and cortisone performed well as diagnostic tests for adrenal insufficiency. Their measurements by LC-MS/MS can alleviate problems associated with serum cortisol immunoassays.

Medical Treatment for Acromegaly does not Increase the Risk of Central Adrenal Insufficiency: A Long-Term Follow-Up Study.

Central adrenal insufficiency (CAI) in acromegaly may be related to pituitary adenoma or induced by various medical treatments, transsphenoidal neurosurgery (TNS) or radiotherapy (RT), alone or combined. We assessed the role of all available treatments for acromegaly in inducing CAI. We retrospectively studied 97 patients. CAI was diagnosed if morning serum cortisol was <138 nmol/l, or if its response was inadequate in the low-dose short synacthen test. Seventy-four subjects underwent TNS (and 17 of whom also underwent RT), and 23 were on primary medical therapy: overall we diagnosed 21 cases of CAI. Duration of acromegaly, invasion of cavernous sinus, disease control, and type of medical treatment were much the same for patients with and without CAI, which was identified in 18% of patients (10/57) after one TNS, and in 53% (9/17) after RT (p=0.01); repeat surgery increased the risk of CAI (p=0.02). The risk of CAI onset during the follow-up was lower among patients treated with TNS or medical therapy than after RT (p=0.035). Medical treatment did not raise the risk of CAI, whereas a 5- and 4-fold higher risk of CAI was associated with repeat TNS and RT, respectively. Basal or stimulated cortisol levels were similar among acromegalic patients without CAI and matched controls with nonsecreting pituitary lesions. A significant proportion of patients with acromegaly developed CAI over time. While primary or secondary medical treatment did not contribute to the risk of CAI, repeat TNS and RT correlated with pituitary-adrenal axis impairment.

Assessment of the effect of continuous sedation with mechanical ventilation on adrenal insufficiency in patients with traumatic brain injury

The aim of this study was to assess the effect of continuous propofol sedation plus prolonged mechanical ventilation on adrenal insufficiency (AI) in patients with traumatic brain injury (TBI). Eighty-five...

ASSESSMENT OF ADRENOCORTICAL DYSFUNCTION IN PATIENTS WITH STABLE LIVER CIRRHOSIS.

Relative adrenal insufficiency (RAI) is common in the setting of critical illness as well as in hemodynamically instable cirrhotic patients with sepsis. Several studies have also shown that RAI is frequent in patients with stable cirrhosis without sepsis. The aim of this study was to prospectively assess the incidence of RAI in patients with stable cirrhosis. Forty-seven patients with hemodynamically stable liver cirrhosis without sepsis were prospectively included. RAI, assessed by using low dose-short Synacthen test (LD-SST), was defined as either a basal total cortisol concentration below 3.6 µg/dL or a peak total serum cortisol ≤ 16 µg/dL at 30 min after stimulation. RAI was present in 10 (21.3%) of 47 cirrhotic patients. Peak cortisol level was negatively correlated with the severity of cirrhosis evaluated by Child-Turcotte-Pugh (CTP) (r=-0.46; P=0.001) and Model for End-Stage Liver Disease (MELD) (r=-0.51; P=0.001) scores. The frequency of RAI increased from CTP-A (10%) to CTP-B (30%) to CTP-C (60%). RAI diagnosed by LD-SST is frequent in patients with stable cirrhosis and is related to the severity of liver disease. Further studies are needed to define clinical importance of RAI in stable cirrhotic patients.

Spot and Morning Cortisol in Comparison to Low Dose Short Synacthen® Test

Objective. While the low dose short Synacthen® test (LDSST) is considered to be the gold standard to evaluate adrenal function, it is labor-intensive, invasive and inconvenient. The aim of the study is to identify cut-offs for spot serum cortisol for in-patients and morning serum cortisol for out-patients. The study also aims to describe the disease spectrum leading to suspicion of adrenal insufficiency in a Chinese out-patient cohort. Methodology. Adult patients were recruited from a tertiary hospital in Hong Kong. 423 in-patients were included consecutively from July 2013 to December 2013, and 422 out-patients from June 2014 to October 2014. Serum cortisol responses at 0, 20 and 30 minutes were evaluated. Results. For in-patients admitted for acute illness, a spot serum cortisol of ≤92 nmol/L indicated adrenal insufficiency, and a value of ≥494 nmol/L signaled adequate adrenal reserve. The respective morning cortisol values for out-patients who were ambulatory and not under stress were ≤124 nmol/L and ≥428 nmol/L. The percentage of unnecessary LDSST was higher in the in-patient cohort than the out-patient cohort (43% and 37%, respectively). The most common referral for out-patient LDSST was for suspected iatrogenic Cushing’s syndrome (ie: iatrogenic adrenal suppression) from Rheumatology. Conclusions. The LDSST is of little added value in in-patients with spot serum cortisol of ≤92 nmol/L or ≥494 nmol/L and out-patients with morning serum cortisol of ≤124 nmol/L or ≥428 nmol/L. Spot and morning cortisol levels, for in and out-patients respectively, should be incorporated into endocrine protocols preceding the LDSST in the workup of adrenal insufficiency

Neuroendocrine dysfunction and insomniain mild traumatic brain injury patients

Mild traumatic brain injury (mTBI) has been a growing public health concern in the worldwide. To investigate the subjective and objective characteristics of insomnia following mTBI and the association between insomnia and hypothalamic–pituitary–adrenal (HPA) function of mTBI patients, 59 patients with mTBI (mTBI group) were compared with 50 healthy participants (control group) in the present study. The subjective and objective measures of insomnia were respectively obtained from Pittsburgh Sleep Quality (PSQI) and polysomnography (PSG). HPA function was measured with low-dose short synacthen test (LDSST). According to the comparative and correlation analysis of the two groups, for PSQI, the scores of sleep syndrome, sleep latency, sleep efficiency, overall sleep quality and daytime dysfunction of mTBI patients were all higher, however only sleep efficiency and daytime dysfunction of mTBI patients were related with peak cortisol on lDSST; while for PSG, sleep efficiency (SE) was lower and wake after sleep onset (WASO) was longer in mTBI patients, moreover SE and WASO of mTBI patients were correlated with peak cortisol on LDSTT; for HPA function indexes, only peak cortisol on LDSST was lower in mTBI patients. These findings suggested that mTBI patients experienced more serious subjective insomnia symptoms than objective measurement, which were associated with HPA dysfunction. This study may contribute to identifying better treatment for mTBI patients with insomnia.

Hypothalamus-pituitary dysfunction is common in patients with stable cirrhosis and abnormal low dose synacthen test

BackgroundAdrenal insufficiency is often present in cirrhosis. We hypothesize that a prolonged adrenocorticotropic hormone (ACTH) stimulus can restore cellular capacity of adrenal glands to secrete cortisol. Aim of our study was to assess adrenal responsiveness to prolonged ACTH stimulation in cirrhotics. MethodsProspective observational study in 121 consecutively admitted cirrhotic patients undergoing a low dose short synacthen test and plasma ACTH measurement using a chemiluminescence immunoassay. Long synacthen test was performed if the low dose was abnormal. Results46 patients had abnormal low dose short test (38%), and 29 underwent the long test: 41% showed normal response (Group 1), 55% showed delayed response (Group 2) and 1 had abnormal response (4%). Baseline ACTH levels did not significantly differ between the two groups. Median basal cortisol was higher in Group 1 (296 vs. 198nmol/L; p=0.02). Using ROC curve basal cortisol <254nmol/L was associated with a delayed long synacthen test response (AUC 0.78, p=0.001) with good accuracy (sensitivity 67%, specificity 81%). ConclusionA delayed cortisol response after a prolonged ACTH stimulation is found in over fifty percent of cirrhotics with abnormal low dose short synacthen test, confirming that the mechanism of hypoadrenalism in these patients could be related both to adrenal cellular dysfunction and hypothalamus-pituitary adrenal axis impairment.

Apolipoprotein AI and HDL are reduced in stable cirrhotic patients with adrenal insufficiency: a possible role in glucocorticoid deficiency

Backgrounds and aims: Adrenal insufficiency (AI) has been reported in patients with stable cirrhosis. A lack of substrates has been suggested as a possible contributing pathogenic mechanism leading to glucocorticoid deficiency in these subjects. To better explore this hypothesis, we studied lipoproteins in cirrhotics with and without AI. Methods. A total of 81 cirrhotic patients and 30 normal volunteers were enrolled. The severity of liver disease was graded by Child-Pugh score. Total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG), and apolipoprotein AI (Apo-AI) levels were evaluated. HDL subfractions were measured by gradient gel electrophoresis. Adrenal function was assessed by the Low-Dose Short Synacthen Test. Results. Cirrhotic patients showed a significant reduction of TC, HDL, LDL, TG, and Apo-AI levels compared with controls. HDL3 was significantly lower, while HDL2 was higher, in cirrhotics compared with the controls. AI was observed in 26 patients. TC, TG, HDL, and Apo-AI were significantly reduced in cirrhotics with AI compared with those with normal adrenal function. HDL2 and HDL3 did not differ between these two groups. Delta cortisol was related to TC (r = 0.30, p < 0.01), TG (r = 0.22, p = 0.05), and Apo-AI (r = 0.37, p < 0.001). Multivariate analysis revealed that Apo-AI and HDL were independently associated with AI. Conclusion. Our study shows that TC, TG, HDL, and Apo-AI are reduced in cirrhotics with AI. In particular, because both HDL and Apo-AI play a primary role in providing substrates for steroidogenesis to adrenal cells, this deficiency may contribute to the pathogenesis of AI in these patients.

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.

Different cut‐off values of the insulin tolerance test, the high‐dose short Synacthen test (250 μg) and the low‐dose short Synacthen test (1 μg) in assessing central adrenal insufficiency

The short Synacthen test (SST) is widely used as alternative test to the insulin tolerance test (ITT) to investigate central adrenal insufficiency (CAI), but the methodology and cut-off values of the SST are controversial. Our aim was to evaluate the cut-off value of the ITT in normal subjects and to assess the different cut-off values of the high-dose SST (250 μg, HDT) and the low-dose SST (1 μg, LDT) in subjects with suspected CAI. We conducted ITTs in 208 normal subjects to establish the cut-off value for the ITT, and 28 of those subjects underwent the HDT and LDT. From 1999 to 2007, 182 patients with suspected CAI were recruited and underwent ITTs, LDTs and HDTs to establish cut-off values and compare the diagnostic accuracy between the LDT and HDT. The 95th percentile of the peak cortisol level during the ITT in the normal control subjects was 14·8 μg/dl. Receiver operator characteristics (ROC) analysis revealed that the optimal cut-off values of peak cortisol in the LDT and HDT in patients with suspected CAI were 15·8 and 17·4 μg/dl, respectively. However, the cut-off values from normative data (mean - 2 SD) were 18·3 μg/dl for the LDT and 20·5 μg/dl for the HDT in normal control. The optimal cut-off values of SSTs needed to be individualized according to the type of SST and tested patient population.

Early morning salivary cortisol and cortisone, and adrenal responses to a simplified low‐dose short Synacthen test in children with asthma

To examine serum cortisol responses to a simplified low-dose short Synacthen test (LDSST) in children treated with inhaled corticosteroids (ICS) for asthma and to compare these to early morning salivary cortisol (EMSC) and cortisone (EMSCn) levels. Early morning salivary cortisol and EMSCn samples were collected for three consecutive days. On day three, Synacthen 500 ng/1·73 m(2) was administered intravenously. Samples were collected at 0, 15, 25, 35 min. A total of 269 subjects (160 M: 109 F), median (range) age 10·0 (5·1-15·2) years were studied. Peak cortisol in the LDSST was <500 nmol/l in 101 subjects (37·5%) and <350 nmol/l in 12 subjects (4·5%). Basal cortisol correlated with peak cortisol: r = 0·55, (95% CI: 0·46, 0·63, P < 0·0001). Time at which peak cortisol concentration was achieved was significantly related to the value of peak cortisol (P < 0·0001), with higher cortisol peaks occurring later in the test and lower cortisol peaks occurring earlier. EMSC and EMSCn had no predictive value for the identification of patients with a peak cortisol <500 nmol/l. EMSCn was superior to EMSC in identifying patients with a peak cortisol <350 nmol/l: a minimum EMSCn cut-off value of 12·5 nmol/l gave a negative predictive value of 99·2% and positive predictive value of 30·1%. Our data illustrate that basal measures of cortisol are likely to be of value in screening populations for patients at greatest risk of adrenal crisis. EMSCn shows promise as a screening tool for the identification of patients with severe adrenal insufficiency.