Adrenal Function In Children Research Articles

Salivary cortisol level as a marker of adrenal function in children with systemic inflammatory response syndrome in Egypt.

Introduction: Pediatric systemic inflammatory response syndrome (SIRS) criteria is widely used to identify patients who need specialized, advanced therapies. Cortisol plays an important anti-inflammatory in SIRS. Adrenal status and use of corticosteroid in children with SIRS still controversial. Objective: to assess salivary in children with SIRS and its relation to outcome in PICU of Suez Canal University hospital. Methods: prospective case control study was carried out. We analyzed 45 patients with SIRS and45 healthy control children for morning salivary and total serum cortisol level Results: children with SIRS have significantly higher morning salivary and total serum cortisol level than control group (p=.00). Mortality was associated with higher levels of both salivary and total cortisol. Conclusions: Salivary cortisol can be used to estimate cortisol levels in pediatric with SIRS and can foretell outcome. Keywords: systemic inflammatory response syndrome, children, salivary, cortisol.

Central Adrenal Insufficiency Is Not a Common Feature in CHARGE Syndrome: A Cross-Sectional Study in 2 Cohorts

To evaluate whether central adrenal insufficiency (CAI) is present in CHARGE (Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth and/or development, Genital hypoplasia, and Ear abnormalities, including deafness) syndrome, a complex malformation disorder that includes central endocrine dysfunction. Two cross-sectional studies were performed in Dutch (September 2013-February 2015) and Australian (January 2012-January 2014) CHARGE syndrome clinics. Twenty-seven Dutch and 19 Australian patients (aged 16 months-18 years) with genetically confirmed CHARGE syndrome were included. The low-dose adrenocorticotropin (ACTH) test was used to assess CAI in the Dutch cohort. A peak cortisol response less than 18.1μg/dL (500nmol/L) was suspected for CAI, and a glucagon stimulation test was performed for confirmation. Australian patients were screened by single measurements of ACTH and cortisol levels. If adrenal dysfunction was suspected, a standard-dose ACTH test was performed. The low-dose ACTH test was performed in 23 patients (median age 8.4 [1.9-16.9] years). Seven patients showed an insufficient maximum cortisol level (10.3-17.6μg/dL, 285-485nmol/L), but CAI was confirmed by glucagon stimulation test in only 1 patient (maximum cortisol level 15.0μg/dL, 415nmol/L). In the Australian cohort, 15 patients (median age 9.1 [1.3-17.8] years) were screened, and none had CAI. CAI was not common in our cohorts, and routine testing of adrenal function in children with CHARGE syndrome is not indicated.

Efficacy of single serum cortisol reading obtained between 9 AM and 10 AM as an index of adrenal function in children treated with glucocorticoids or synthetic adrenocorticotropic hormone.

.To find a simple method to screen for iatrogenic childhood adrenal insufficiency, we retrospectively examined the results of CRH stimulation tests performed 212 times on 111 subjects (68 males; age at commencement of initial treatment ranged 0.0–19.8 yr; median age, 5.8 yr). Before the commencement of this study, 97 subjects had been treated with glucocorticoids and 14 subjects with West syndrome had been treated with synthetic adrenocorticotropic hormone. Duration of the primary treatment ranged from 15 to 2150 days. CRH stimulation tests were conducted between 09:00 AM and 10:00 AM and peak cortisol values less than 15 µg/dL were considered indicative of adrenal insufficiency. The receiver operating characteristic curve showed that the optimal basal serum cortisol cut-off values when screening for adrenal suppression ranged from 5.35 to 5.80 µg/dL depending on the primary disease. All subjects having a serum cortisol value of less than 2.3 µg/dL had insufficient adrenal function while all subjects having greater than 11 µg/dL had intact adrenal function. We concluded that single serum cortisol values obtained between 09:00 AM and 10:00 AM had the potential to serve as an index of adrenal function in children treated with glucocorticoids or synthetic adrenocorticotropic hormone.

Effect of glucocorticoid therapy on adrenal function in children with acute lymphoblastic leukemia

BackgroundGlucocorticoids play an important role in thetreatment ofacute lymphoblastic leukemia (ALL), but can causeside effects such as suppression of the hypothalamic-pituitaryadrenal (HPA) axis. Suppression of the HPA axis causes adrenal insufficiency, disturbs the cortisol response to stress, and may be a cause of morbidity and mortality in children with ALL.ObjectiveTo evaluate adrenal function in children with ALL afterinduction chemotherapy with high dose glucocorticoids.MethodsThe adrenal function of 20 children with ALL wasevaluated using a standard dose (250 μ g) adrenocorticotropinhormone (ACTH) test performed before and after a 6 week oftreatment with glucocorticoids induction phase chemotherapy,which was followed by a week period tapering off. Adrenalinsuffien cy was defined as blood cortisol level of < 18 μg/dLResultsAdrenal insufficiency was found in 14/20 subjects afterthe induction phase followed by a week period of tapering off.Median cortisol levels pre- and post-stimulation before inductionphase were 14.72 (range 2.0 1- 46. 1) μg/dL and 29.29 (range 21.65 - 55 .15) μg/dL, respectively. Median cortisol levels pre- and poststimulation after induction phase were 5.87 (range 0.2 - 20.53)μg/dL and 10.49 (range 0.33 - 28.69) μg/dL, respectively. Clinicalsigns and symptoms did not differ between those with and withoutadrenal insufficiency.ConclusionOf 20 children with ALL, 14 develop adrenalinsufficiency after a 6-week induction therapy with glucocorticoidsand followed by a week period of tapering off. No specific clinicalsigns and symptoms are identified to be related to the adrenalinsufficiency.

Effect of glucocorticoid therapy on adrenal function in children with acute lymphoblastic leukemia

Effect of glucocorticoid therapy on adrenal function in children with acute lymphoblastic leukemia

Effect of glucocorticoid therapy on adrenal function in children with acute lymphoblastic leukemia

Glucocorticoids play an important role in thetreatment ofacute lymphoblastic leukemia (ALL), but can causeside effects such as suppression of the hypothalamic-pituitaryadrenal (HPA) axis. Suppression of the HPA axis causes adrenal insufficiency, disturbs the cortisol response to stress, and may be a cause of morbidity and mortality in children with ALL.

Cortisol hyporesponsiveness to the low dose ACTH test is a frequent finding in a pediatric population with type 1 diabetes mellitus

In adults with type 1 diabetes mellitus (DM1), a 25% of risk of hypocortisolism has been found through a low dose ACTH test with negative antibodies suggesting other causes of hypothalamic-pituitary-adrenal axis dysfunction. To evaluate adrenal function in pediatric patients with DM1 and correlate the results with the frequency of hypoglycemia and metabolic control. Sixty-nine patients were enrolled, age 12.3 (5.7-18.1); 50 boys and 19 girls. A 20% had additional autoimmune diseases. Mean hemoglobin A1c (HbA1c) was 8.1% and insulin dose was 1.14 U/kg/d. After an overnight fast, a low dose ACTH test (1 µg) was performed. Basal and stimulated cortisol concentrations, DHEAS, and plasma renin activity (PRA) were measured. A cortisol response post-ACTH below 18 µg/dL was considered abnormal. 58% of the tested patients had an abnormal response to ACTH test. These patients also had lower DHEAS concentrations, but were not different in diabetes duration, HbA1C, severe hypoglycemia, ACTH, or PRA concentrations compared to those who had a normal cortisol post-ACTH. One patient out of 59, had a positive anti-21-hydroxylase antibody (21OHA) and presented a poor response to ACTH. We found a significant proportion of our patients having a subnormal cortisol response independent of the presence of anti-adrenal cell antibodies. We did not find a correlation with metabolic control, probably due to the good metabolic control of this group. The absence of 21OHA does not rule out subclinical hypocortisolism in this population. Our results suggest testing adrenal function in children with DM1.

The effects of three specific conditions related to critical care on adrenal function in children

To evaluate the effects of three specific conditions related to critical care on adrenal function with special regard to the levels of serum cortisol, corticotropin (ACTH), dehydroepiandrosterone sulfate, and cytokines. The study enrolled a total of 74 children who were divided into three groups. Group 1 comprised 23 patients who had acute critical illness (ACI) associated with severe sepsis/septic shock. Group 2 comprised 27 patients who had ACI without sepsis. Group 3 comprised 24 patients who underwent major surgery. Blood samples were obtained for baseline measurements and a low-dose ACTH stimulation test (LD-ST) was performed. Serial ACTH and cortisol levels were measured with an interval of 3 days and LD-ST was repeated on day 14 for all groups. Baseline cortisol, ACTH, and dehydroepiandrosterone sulfate levels were significantly higher in patients with adrenal insufficiency (AI) than those of without AI. AI was detected in four patients in group 1, seven in group 2, and ten in group 3. Consecutive cortisol and ACTH levels did not differ significantly among the groups. On day 14, the recovery rate in patients with AI was 82 % in the whole group. Patient's age and interleukin-10 level were found to be independent predictors of AI. A considerable proportion of patients in these three groups had AI with a high spontaneous recovery rate in 2 weeks. The presence of sepsis was not associated with an increased risk of AI. Our serial cortisol and ACTH values in these different groups could be used as reference values for further studies.

Testing the hypothalamo-pituitary-adrenal axis

Aims There remains considerable debate about the best way to assess adrenal function. In our unit, adrenal function in children with suspected pituitary disease is initially tested using dynamic testing of the HPA axis (insulin tolerance test (ITT) or glucagon stimulation test (GST)), with failures (peak cortisol Methods This study took place in a single paediatric endocrinology unit. Endocrine records from November 1999– March 2010 identified patients having anterior pituitary function testing with ITT or GST, and also subsequent SST. Demographic, clinical and endocrine data were subsequently extracted from clinical and laboratory records. Results Over the 11 year collection period 509 ITTs and 164 GSTs were performed. Subsequent SSTs for failed tests were performed in 11 (2.2%) ITTs and 18 (11.0%) GSTs. Overall 42 children with paired tests were identified; 19 underwent ITT (median age 15.2 years, 12 males) and 23 GST (median age 8.8 years, 12 males), followed by SST within one year. The correlation coefficient between baseline (9 am) cortisols on the 2 consecutive tests was 0.36 (p=0.02); using a cutoff of ≥200 nmol/L there was concordance in 29/42 (69%). For ITTs there was a correlation coefficient of 0.34 (p=0.15) between the peak ITT cortisol compared to the 30 minute SST value. Using cutoffs of a peak ITT/GST cortisol level of ≥500 nmol/l and ≥550 nmol/l for the 30 minute SST cortisol level there was concordance in 14/19 (73.7%) ITTs. For GST the correlation coefficient was 0.56 (p=0.0057), and concordance in 11/23 (47.8%). Conclusion There is considerable variation in baseline cortisol levels, making its use and also that of incremental cortisol levels unhelpful in the diagnosis of adrenal insufficiency. Whilst there is a better correlation between the SST cortisol levels at 30 minutes and peak cortisol levels during the GST compared to the ITT concordance between tests is better in the latter. It would appear that the ITT is a good diagnostic test for the HPA axis; the GST less so. For patients having a subnormal cortisol response during the GST we would recommend SST testing.

Intranasal Corticosteroids and Adrenal Suppression

Allergic rhinitis is a common condition that frequently coexists with asthma and atopic dermatitis. It is commonly treated with intranasal corticosteroids which may increase the potential inception of side effects of the same type of drugs used for the treatment of other allergic diseases. A method to assess the systemic effect of corticosteroids is the evaluation of their effect on the hypothalamic-pituitary-adrenal (HPA) axis. However, it is not clear which test is best for detection of clinically relevant HPA axis suppression in children Morning plasma cortisol levels are twice that of late afternoon and evening values and a delay in the time of onset in peak cortisol levels has been observed in children treated with inhaled corticosteroids. Single morning cortisol level has a low sensitivity for detecting adrenal insufficiency in children. 24-Hour plasma cortisol is a good test because it is a non-invasive measure of the biologically active free cortisol levels for the entire day. For research purposes, the 24-hour integrated concentration plasma cortisol test is preferred. Studies that have looked at HPA axis suppression with intranasal corticosteroids indicate that overall, intranasal corticosteroids have a minimal effect on the HPA axis. A review of the literature reveals one study in which there was a decreased output of urinary cortisol during treatment with either budesonide or fluticasone propionate in adults. Other studies with fluticasone propionate or budesonide have shown no effect on the HPA axis in children. Beclomethasone dipropionate was shown to affect urinary cortisol output in one study on healthy volunteers. However, in a long-term study in children, no effect on the HPA axis was found. Mometasone furoate has been extensively studied in more than 20 trials of adults and children. No effects on the HPA axis were detected in either children or adults. Fluticasone furoate nasal spray was not associated with HPA axis suppression. It is unlikely that children are more sensitive to corticosteroids than adults. There is no reason to perform routine monitoring of adrenal function in children who are treated with intranasal corticosteroid unless those drugs are used concomitantly with inhaled corticosteroids and/or steroid ointments for the possible concomitant presence of asthma and/or atopic dermatitis.

Adrenal Function in Children with Asthma and Allergic Rhinitis Treated with Combination of Inhaled and Nasal Corticosteroids

Introduction: Children with asthma and allergic rhinitis are often treated with a combination of inhaled and nasal corticosteroids. Safety data on this combination treatment in children are not available. This study evaluates adrenal function in children receiving combination therapy with nasal and inhaled corticosteroid using a low-dose adrenocorticotropin (ACTH) test. Methods: Twelve children aged 6–12 years with severe asthma and allergic rhinitis were given combination therapy with high-dose inhaled HFA-beclomethasone dipropionate (HFA-BDP) (320 μg/day for first 2 months and 160 μg/day thereafter) and flunisolide nasal spray (116 μg/day). A low-dose ACTH test was performed before treatment and 6 months later. Results: There was no significant change (mean ± SD) in both baseline (7.78 ± 5.34 before treatment and 7.53 ± 4.02 after treatment, p = 0.42) and stimulated (22.58 ± 6.97 before treatment and 19.2 ± 3.53, p = 0.09 after treatment) cortisol levels. Conclusion: Combination therapy with high-dose HFA-BDP and flunisolide nasal spray did not cause suppression of adrenal function in pediatric patients with severe asthma and allergic rhinitis.

One single dose of etomidate negatively influences adrenocortical performance for at least 24 h in children with meningococcal sepsis

ObjectiveTo investigate the effect of one single bolus of etomidate used for intubation on adrenal function in children with meningococcal sepsis.DesignRetrospective study conducted between 1997 and 2004.SettingUniversity-affiliated paediatric intensive care unit (PICU).Patients and participantsSixty children admitted to the PICU with meningococcal sepsis, not treated with steroids.InterventionsAdrenal hormone concentrations were determined as soon as possible after PICU admission, and after 12 h and 24 h. To assess disease severity, PRISM score and selected laboratory parameters were determined.Measurements and main resultsOn admission, before blood was drawn, 23 children had been intubated with etomidate, 8 without etomidate and 29 were not intubated. Children who were intubated had significantly higher disease severity parameters than those not intubated, whereas none of these parameters significantly differed between children intubated with or without etomidate. Children who received etomidate had significantly lower cortisol, higher ACTH and higher 11-deoxycortisol levels than those who did not receive etomidate. Arterial glucose levels were significantly lower in children who were intubated with etomidate than in non-intubated children. When children were intubated with etomidate, cortisol levels were 3.2 times lower for comparable 11-deoxycortisol levels. Eight children died, seven of whom had received etomidate. Within 24 h cortisol/ACTH and cortisol/11-deoxycortisol ratios increased significantly in children who received etomidate, but not in children who did not, resulting in comparable cortisol/ACTH ratios with still significantly lowered cortisol/11-deoxycortisol ratios 24 h after admission.ConclusionsOur data imply that even one single bolus of etomidate negatively influences adrenal function for at least 24 h. It might therefore increase risk of death.

A Low Dose Adrenocorticotropin Test (1 μg ACTH) for the Evaluation of Adrenal Function in Children with ß-Thalassemia Receiving Hypertransfusion with Suboptimal Iron-chelating Therapy

A cross-sectional study of adrenal function was carried out in 48 patients with beta-thalassemia who were receiving hypertransfusion with suboptimal desferoxamine. A low dose adrenocorticotropic hormone (1 microg ACTH) stimulation test was performed using the cut-off criteria of peak cortisol for adrenal sufficiency >18 microg/dl. Adrenal impairment was diagnosed in 22 patients, giving a prevalence of 45.8%. The peak cortisol concentrations in normal and impaired adrenal function groups were 26.22 +/- 2.84 and 14.03 +/- 3.12 microg/dl, respectively, and the mean basal morning cortisol was 8.93 +/- 2.97 and 6.52 +/- 2.45 microg/dl, respectively. There was no significant difference in any clinical characteristic between the patients with impaired adrenal function and those with normal adrenal function.

Adrenal Function in Children with Severe Asthma Treated with High-Dose Inhaled Glucocorticoids: Recommended Screening Tests in Outpatient Conditions

A number of previous studies have suggested that adrenal suppression occurs in asthmatic children treated with high-doses of inhaled glucocorticoids (IGC). This study was designed to determine the frequency of adrenal suppression in children with severe asthma treated with recommended doses of IGC: namely 500-1,000 microg/day of fluticasone propionate or the equivalent of budesonide (1,000-2,000 microg/day) for a period of at least 12 months. Early morning cortisol (F) and ACTH serum levels were measured in 27 severe asthmatics aged 6-16 years old. The children underwent a low dose ACTH test (1 microg/1.73 m2) with a parallel glucose measurement. Twenty-four hour urine collection was performed before examination for free F (UfF) and creatinine levels. There were no clinical manifestations of adrenal hypofunction in the analyzed children. Of the 27 patients, 22 had normal basal and post-stimulatory levels of F and normal UfF, and the other five (18.5%) had basal serum F levels of <400 nmol/l. Four of the five also had normal post-stimulatory levels of F and normal UfF. One child had a subnormal peak F value of 484 nmol/l during the ACTH test. None of the patients had a suppressed serum ACTH level, but an elevated ACTH level was found in four children. This study provided biochemical evidence of suboptimal adrenal function in one child in the examined group (3.7%) and a good response to stimulation in all the others, even in those with slightly reduced basal cortisol levels. This study showed that the use of fluticasone in doses of up to 1,000 microg/day (or the equivalent of budesonide) as long-term treatment of children with severe asthma did not substantially affect their adrenal function.

Adrenal function in 23 children with paracoccidioidomycosis

Adrenal involvement by Paracoccidioides brasiliensis was described at necropsies and in many clinical studies, but only in adults. Therefore, the aim of this study was to evaluate adrenal function in children with paracoccidioidomycosis. Twenty-three children with the systemic form of paracoccidioidomycosis were evaluated and divided in two Groups: Group A (n = 8) included children before treatment and Group B (n = 15) children after the end of treatment. Plasma cortisol (basal and after ACTH test), ACTH, renin activity, aldosterone, sodium and potassium were measured. They were within normal range in all cases, except for renin activity and aldosterone, which were elevated in some cases. Group A patients showed basal and post-ACTH cortisol levels significantly greater than Group B patients. The results showed that adrenal function was not compromised in these children with paracoccidioidomycosis.

Short‐term growth and adrenal function in children with asthma treated with inhaled beclomethasone dipropionate hydroflouroalkane‐134a

Inhaled beclomethasone dipropionate (BDP) with the propellant hydrofluoroalkane-134a (HFA) has been designed to be equivalent in terms of safety to chlorofluorocarbon (CFC)-formulated metered dose inhalers (MDI). The aim was to assess whether BDP HFA MDI 100 microg twice daily was equivalent to BDP CFC MDI 100 microg twice daily in terms of effects on short-term lower leg growth rate (LLGR) and measures of hypothalamic-pituitary-adrenal (HPA) function. The study consisted of a randomized double-blind cross-over trial with three active, a run-in and two wash-out periods each consisting of 2 wk. The place of study was a secondary referral outpatient clinic. The subjects involved were 14 boys and 10 girls with asthma, aged 7-12 yr. They were all administered BDP HFA 100 microg, BDP CFC 100 microg and 200 microg twice daily. The outcome measures included LLGR and 24-h urine-free cortisol (UFC) and total cortisol metabolites (TCM). Mean (SD) LLGR during run-in and BDP HFA 100 microg, BDP CFC 100 microg and 200 microg twice daily periods were 0.43 (0.23), 0.09 (0.29), 0.10 (0.45) and 0.08 (0.27) mm/wk. The one-sided 97.5% confidence interval for the difference in LLGR between BDP HFA 100 microg and BDP CFC 100 microg was 0.24, thus, below the predefined criterion of 0.20 mm/week. Inter-period comparisons of active treatments showed no differences between means of LLGR, UFC or TCM. Though non-inferiority between BDP HFA and CFC 100 microg twice daily in terms of effects on LLGR was not found, equivalence was suggested by comparisons of LLGR during run-in and active treatments and by HPA function measures.

Hypothalamic–Pituitary–Adrenal Axis Response to Sustained Stress after Major Burn Injury in Children

The hypothalamic-pituitary-adrenal (HPA) axis is responsible for stress response after injury, yet its function after severe burn injury in children is unclear. The purpose of this study was to define the effects of burn injury on the HPA axis and to evaluate the utility of total serum cortisol in measuring adrenal function in children with major burns in the 2 months after injury. Children ages 0 to 17 years who were admitted within 72 hours to our pediatric burn center with 20% TBSA or greater full-thickness burns were eligible for the study. Serum total cortisol, adrenocorticotropic hormone (ACTH), dehydroepiandrosterone, vasopressin, Pediatric Risk of Mortality (PRISM) score, serum albumin level, and electrolytes were obtained on admission and weekly for 8 weeks. An ACTH stimulation test (250 microg for children >2 years, 125 microg for children < or =2 years) was administered weekly at 8:00 am. Total serum cortisol was measured before and 60 minutes after the administration of ACTH. Twenty-five children with mean age 7.6 +/- 1.1 years and TBSA burn 41.8 +/- 3.8% were enrolled in the study. Baseline total serum cortisol was 12.4 +/- 0.7 microg/dl in the 8 weeks after injury and increased to 24.4 +/- 0.8 microg/dl after the administration of ACTH. Cortisol level did not correlate with PRISM score, albumin, vasopressin, ACTH, or mortality. Although the adrenal response to acute and chronic stress is intact after severe burn injury, the ACTH/adrenal feedback loop is disrupted. Random total serum cortisol measurements overestimate adrenal dysfunction; thus, ACTH stimulation testing should be used to assess adrenal function before the administration of exogenous steroids.

Suppression of Adrenal Function in Children With Acute Lymphoblastic Leukemia Following Induction Therapy With Corticosteroid and Other Cytotoxic Agents

Suppression of Adrenal Function in Children With Acute Lymphoblastic Leukemia Following Induction Therapy With Corticosteroid and Other Cytotoxic Agents

Comparison of Adrenal Function Tests in Children - The Glucagon Stimulation Test Allows the Simultaneous Assessment of Adrenal Function and Growth Hormone Response in Children

The accurate assessment of adrenal function is necessary in many children with suspicion of pituitary insufficiency. The objective of this study was to evaluate the adrenal response during the glucagon stimulation test (GST) and its diagnostic utility in children. A total of 290 children, aged 10.1 +/- 5.0 years, were evaluated for adrenal function using the corticotrophin releasing hormone (CRH) test, the GST, and/or the insulin tolerance test (ITT). Glucagon stimulation provoked a substantial rise in cortisol and adrenocorticotropin (ACTH) that was independent of gender, age, or underlying growth hormone deficiency. There were no differences in peak cortisol levels in the GST compared to the CRH test in pair-wise intra-individual analyses in children with both tests performed within one year (615.4 +/- 30.5 vs 602.8 +/- 22.4 nmol/l, n=52). Similarly, there were no differences in the cortisol response between the ITT and CRH test. Peak cortisol levels in the CRH test correlated with the GST and the ITT. The magnitude of ACTH response, in contrast, was highest in the ITT with a 9.8-fold increase over baseline, while the increase in the GST (3.1-fold) and CRH test (1.6-fold) were more subtle. Since there is controversy concerning reliable cut-off values for adrenal function tests in children, we analyzed cut off levels in 186 children, including 26 children with adrenal insufficiency, using the CRH test. A peak cortisol level of 450 nmol/l provided the best balance of sensitivity (88.5%) and specificity (86.8%), while higher cut-off levels did not increase sensitivity but lost in specificity. In summary, the GST constitutes an1 equally sensitive test for the assessment of adrenal function in children that is not confounded by anthropometric parameters and is generally not accompanied by major side effects. It allows the simultaneous assessment of corticotroph and somatotroph function and may thus constitute a valuable alternative to the ITT.

Disturbed Adrenal Function in Adolescents with Chronic Fatigue Syndrome

To investigate adrenal function in children and adolescents with chronic fatigue syndrome (CFS) compared with age-matched controls. Case-control study of low dose (500 ng/m2) synacthen tests (LDST) in 23 adolescents with CFS and 17 age-matched controls. Serum cortisol concentrations were measured at 5-min intervals from 10 to 45 minutes. Peak serum cortisol concentration, time to peak, rise in cortisol and area under the curve (AUC) were derived. Patients with CFS had significantly lower mean cortisol levels during the LDST (p <0.001), lower peak cortisol (p <0.025), reduced cortisol AUC (p <0.005) and longer time to peak cortisol (p <0.05). Abnormalities were seen in both sexes but were more pronounced in females. Unstimulated adrenal androgen and 17-hydroxyprogesterone concentrations were normal. Adolescents with CFS have subtle alterations in adrenal function suggesting a reduction in central stimulation of the adrenal glands. The more pronounced effects in females may reflect differential central effects of stress on hypothalamic-pituitary-adrenal axis regulation between the sexes.