Monitoring growth in asthmatic children treated with high dose inhaled glucocorticoids does not predict adrenal suppression

Aims: To determine whether routine outpatient monitoring of growth predicts adrenal suppression in prepubertal children treated with high dose inhaled glucocorticoid. Methods: Observational study of 35 prepubertal children (aged 4–10 years) treated with at least 1000 µg/day of inhaled budesonide or equivalent potency glucocorticoid for at least six months. Main outcome measures were: changes in HtSDS over 6 and 12 month periods preceding adrenal function testing, and increment and peak cortisol after stimulation by low dose tetracosactrin test. Adrenal suppression was defined as a peak cortisol ⩽500 nmol/l. Results: The areas under the receiver operator characteristic curves for a decrease in HtSDS as a predictor of adrenal insufficiency 6 and 12 months prior to adrenal testing were 0.50 (SE 0.10) and 0.59 (SE 0.10). Prediction values of an HtSDS change of –0.5 for adrenal insufficiency at 12 months prior to testing were: sensitivity 13%, specificity 95%, and positive likelihood ratio of 2.4. Peak cortisol reached correlated poorly with change in HtSDS (ρ = 0.23, p = 0.19 at 6 months; ρ = 0.33, p = 0.06 at 12 months). Conclusions: Monitoring growth does not enable prediction of which children treated with high dose inhaled glucocorticoids are at risk of potentially serious adrenal suppression. Both growth and adrenal function should be monitored in patients on high dose inhaled glucocorticoids. Further research is required to determine the optimal frequency of monitoring adrenal function.     

Adrenal axis function after high-dose steroid therapy for childhood acute lymphoblastic leukemia

Background A 4‐week course of high‐dose glucocorticoids may cause prolonged adrenal suppression even after a 9‐day tapering phase. In this study, adrenal function and signs and symptoms of adrenal insufficiency were prospectively assessed in children with acute lymphoblastic leukemia (ALL) after induction treatment including high‐dose prednisone (PDN) or dexamethasone (DXM). Procedures Sixty‐four children with ALL, treated according to the AIEOP ALL 2000 Study protocol, underwent low dose ACTH (LD‐ACTH) stimulation 24 hr after the last tapered steroid dose. In those with impaired cortisol response, additional LD ACTH tests were performed every 1–2 weeks until cortisol levels normalized. Signs and symptoms of adrenal insufficiency were recorded during the observation period. Results All patients had normal basal cortisol values at diagnosis. Twenty‐four hours after last glucocorticoid dose, morning cortisol was reduced in 40/64 (62.5%) patients. LD‐ACTH testing showed adrenal suppression in 52/64 (81.5%) patients. At the following ACTH test 7–14 days later, morning cortisol values were reduced in 8/52 (15.4%) patients and response to the test was impaired in 12/52 (23%). Adrenal function completely recovered in all patients within 10 weeks. No difference was found between patients treated with PDN or DXM. Almost 35% of children with impaired cortisol values at the first test developed signs or symptoms of adrenal insufficiency. One child developed a severe adrenal crisis during adrenal suppression. Conclusions High‐dose glucocorticoid therapy in ALL children may cause prolonged adrenal suppression and related clinical symptoms. Laboratory monitoring of cortisol levels and steroid coverage during stress episodes may be indicated. Pediatr Blood Cancer 2008;50:537–541. © 2007 Wiley‐Liss, Inc.     

Growth and adrenal suppression in asthmatic children on moderate to high doses of fluticasone propionate

OBJECTIVE: Growth and adrenal suppression have been reported in asthmatic children using high-dose inhaled fluticasone propionate (FP). Inhaled FP, given at moderate doses (250-750 microg/day), has not been documented to be associated with growth or adrenal suppression in asthmatic children until recently. We report three cases illustrating these side effects. METHODS: Growth and adrenal suppression, after the introduction of inhaled FP, were observed in three prepubertal young asthmatic children referred to our asthma clinic and growth clinic. Growth centile and velocity were assessed by longitudinal stadiometry height measurements. Early morning plasma cortisol levels, and glucagon stimulation tests were used to assess the pituitary adrenal axis. RESULTS: Severe growth and adrenal suppression were noted in three children while they were on moderate doses of inhaled FP. Improvements in growth and adrenal function were observed following cessation or dose reduction of inhaled FP. CONCLUSIONS: Unexpected growth and adrenal suppression may occur in young asthmatic children using moderate doses of inhaled FP.     

Decreased cortisol response to insulin induced hypoglycaemia in asthmatics treated with inhaled fluticasone propionate.

AIMS: To assess adrenal function in asthmatic children treated with inhaled fluticasone propionate for up to 16 weeks. METHODS: Children with asthma and bronchial hyperresponsiveness to inhaled methacholine were treated with inhaled fluticasone 250-750 microg/day via Volumatic spacer. The insulin tolerance test (ITT) was performed to assess adrenal function. RESULTS: Eighteen asthmatic patients (10 boys, 8 girls), aged 7-17 years received inhaled fluticasone therapy at a median dose of 477 microg/m2 per day for 5-16 weeks. Adrenal suppression, defined as 60 minute serum cortisol less than 500 nmol/l, was found in 9 of 18 children. Following the ITT, the median basal and 60 minute serum cortisol concentrations of the suppressed group were 135.0 and 350.0 nmol/l, respectively; the corresponding values for the unsuppressed group were 242.2 and 564.7 nmol/l. Repeat ITT in the suppressed group 2-3 months after discontinuation of fluticasone revealed that all patients had a 60 minute serum cortisol greater than 500 nmol/l. CONCLUSION: After therapy for asthma with inhaled fluticasone at approximately 500 microg daily for up to 16 weeks, half the children had evidence of adrenal suppression.     

Decreased cortisol response to insulin induced hypoglycaemia in asthmatics treated with inhaled fluticasone propionate

Aims: To assess adrenal function in asthmatic children treated with inhaled fluticasone propionate for up to 16 weeks. Methods: Children with asthma and bronchial hyperresponsiveness to inhaled methacholine were treated with inhaled fluticasone 250–750 µg/day via Volumatic spacer. The insulin tolerance test (ITT) was performed to assess adrenal function. Results: Eighteen asthmatic patients (10 boys, 8 girls), aged 7–17 years received inhaled fluticasone therapy at a median dose of 477 µg/m² per day for 5–16 weeks. Adrenal suppression, defined as 60 minute serum cortisol less than 500 nmol/l, was found in 9 of 18 children. Following the ITT, the median basal and 60 minute serum cortisol concentrations of the suppressed group were 135.0 and 350.0 nmol/l, respectively; the corresponding values for the unsuppressed group were 242.2 and 564.7 nmol/l. Repeat ITT in the suppressed group 2–3 months after discontinuation of fluticasone revealed that all patients had a 60 minute serum cortisol greater than 500 nmol/l. Conclusion: After therapy for asthma with inhaled fluticasone at approximately 500 µg daily for up to 16 weeks, half the children had evidence of adrenal suppression.     

Adrenal suppression in children with the human immunodeficiency virus treated with megestrol acetate

Symptoms and laboratory evidence of adrenal suppression developed in 2 children with the human immunodeficiency virus after megestrol acetate (MA) therapy was discontinued; both required transient glucocorticoid replacement therapy. High-dose corticotropin stimulation testing performed on children with the human immunodeficiency virus treated or not treated with MA showed that baseline and post-corticotropin cortisol levels were extremely low in 7 of 10 treated patients and normal in 10 of 10 members of a control group (P <.01). MA may suppress adrenal function, and replacement glucocorticoids may prevent or relieve associated symptoms at times of severe stress or on discontinuation of MA therapy.     

Inhaled glucocorticoids and adrenal function: an update

For the vast majority of asthmatic children, treatment with inhaled glucocorticoids is safe and effective. Mild impairment of adrenal function of doubtful clinical significance is known to occur in some children inhaling > or = 400 micro g/day budesonide and beclomethasone or > or = 200 micro g fluticasone. Recent reports of life-threatening adrenal failure in asthmatic children inhaling glucocorticoids, some of whom were prescribed licensed doses, have prompted the recommendation that the use of high-dose inhaled glucocorticoids, particularly fluticasone, should be avoided. However, the importance of correctly diagnosing asthma, of using the minimum dose of inhaled glucocorticoid required for symptom control and of regular growth-velocity assessment cannot be over-emphasised. Appropriate asthma management including the early introduction of steroid-sparing agents such as a long-acting beta-agonist or leukotriene antagonist may reduce the morbidity associated with inhaled glucocorticoid use but some children, for reasons as yet unknown, may exhibit increased sensitivity to the systemic effects of inhaled glucocorticoid treatment. Possible explanations for this, with reference to the pharmacology and molecular mechanisms of glucocorticoid action, are accompanied in this review by a summary of the recent case reports and discussion of assessment of adrenal function.     

Adrenal function in children with severe asthma treated with high-dose inhaled glucocorticoids: recommended screening tests in outpatient conditions

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.     

A randomised controlled trial of short term growth and collagen turnover in asthmatics treated with inhaled formoterol and budesonide.

AIMS: To determine effects on short term growth and collagen turnover of adding formoterol (Eformoterol) to half the glucocorticoid dose in children with asthma, treated with inhaled budesonide (Pulmicort Turbuhaler). DESIGN: A randomised double blind, placebo controlled crossover study with two six-week periods. SETTING: Outpatient clinic in secondary referral centre. SUBJECTS: A total of 27 prepubertal children aged 6-13 years. INTERVENTIONS: Formoterol 12 microg and dry powder budesonide 100 microg twice daily in one period; placebo and dry powder budesonide 200 microg twice daily in the other. OUTCOME MEASURES: Primary outcome measures were lower leg growth rate, and serum and urine markers of type I and type III collagen turnover. Secondary outcome measures were inflammation markers in serum, and parameters of asthma control. RESULTS: During budesonide 200 microg twice daily treatment, mean lower leg growth rate was 0.14 mm/week (p = 0.02) lower than during the formoterol and budesonide period. Similar statistically significant effects on markers of collagen turnover were found, whereas inflammation markers and asthma control did not vary statistically significantly between the two periods. CONCLUSIONS: In children treated with inhaled glucocorticoids, halving the dose and adding formoterol is associated with faster short term growth and an increase in markers of collagen turnover, with no loss of asthma control.     

Adrenocortical suppression increases the risk of relapse in nephrotic syndrome.

OBJECTIVE: Children with nephrotic syndrome (NS) are usually treated with long-term low dose alternate day prednisolone with or without glucocorticoid sparing therapy, such as levamisole or ciclosporin, to maintain remission. The degree of hypothalamic-pituitary-adrenal axis (HPA) suppression with such therapeutic strategies has not been studied systematically. HPA suppression could cause a relapse or adrenal crisis. STUDY DESIGN: To study the risks of HPA suppression, a modified low dose synacthen test (0.5 mug) was administered to 32 patients (22 male,10 female) with a mean age of 9.7 years (range 3.8-17.6 years) with NS receiving long-term alternate day prednisolone for over 12 months. Twelve patients received alternate day prednisolone, 11 alternate prednisolone+levamisole and nine alternate prednisolone+ciclosporin. All patients were followed up for 3 years and the relapse rate noted. RESULTS: 20/32 (62.5%) patients had a peak serum cortisol concentration of <500 nmol/l, which suggested suboptimal cortisol secretion and possible HPA suppression. 10/12 children in the prednisolone group and 8/11 in the levamisole group had a suboptimal cortisol response compared with 2/9 in the ciclosporin group. During follow-up, the 20 children who had a suboptimal cortisol response had significantly more relapses (95 relapses) compared to the 12 children with a normal cortisol response who had 24 relapses (p = 0.01). CONCLUSIONS: Children with NS receiving long-term alternate day prednisolone therapy are at risk of developing HPA suppression and should be evaluated using the modified synacthen test. Children with evidence of HPA suppression are at a greater risk of relapse.     

Differential effects of inhaled budesonide on serum osteocalcin in children and adolescents with asthma

In recent years, measurement of serum osteocalcin has been introduced for assessment of bone turnover in patients treated with exogeneous glucocorticoids. Studies in children with asthma on inhaled glucocorticoids, however, have shown inconsistent results. The aim of the present study is to assess bone turnover in prepubertal children and in adolescents with asthma treated with inhaled budesonide using three different osteocalcin assays: the Pharmacia Osteocalcin CAP FEIA, the CIS OSTK-PR and CIS IRMA ELSA-OSTEO assays. Two studies were conducted: 1) a randomised double blind two-period crossover study of 22 prepubertal children aged 5-12 years. In one period 800 μg budesonide was given once in the morning, in the other 400 μg was given twice daily; 2) a randomised double blind placebo controlled two period crossover study of inhaled budesonide 400 μg twice daily in fourteen 13-16 year old adolescents with pubertal stages II-V. In both studies, treatment periods were of four weeks duration, and blood samples were collected at the last day of each period. In the prepubertal children none of the osteocalcin assays detected any statistically significant differences between any of the periods. In the adolescent group reduced levels of osteocalcin were seen during budesonide treatment. The suppression reached statistical significance with the CAP FEIA (P = 0.03) and the OSTK-PR (P =0.01) assays, but not with the ELSA-OSTEO assay (P = 0.06). Correlation analyses showed statistically significant correlation coefficients varying between 0.58 and 0.91 (P=0.03 and P < 0.0001, respectively). The effect of inhaled glucocorticoids on serum osteocalcin may depend on the assay applied, and inhaled glucocorticoids have differential effects in children and adolescents.     

Growth of asthmatic children is slower during than before treatment with inhaled glucocorticoids

Reports on the influence of inhaled glucocorticoids on growth have been controversial. We studied the growth of prepubertal asthmatic children prior to and during glucocorticoid therapy. We collected retrospectively the notes of 201 asthmatic children aged 1–11 years receiving inhaled beclomethasone dipropionate or budesonide. We calculated their height and height velocity standard deviation scores (HSDS and HVSDS, respectively) before the treatment and up to 5 years during the treatment and compared those with the growth of healthy peers. The dose of the medication was calculated and the severity of asthma was assessed. The asthmatic children grew similarly to their healthy peers before treatment with inhaled glucocorticoids: the mean HSDS was +0.02 and the mean HVSDS +0.01 for boys and -0.16 and +0.13 for girls, respectively. Growth retardation took place soon after the start of the treatment, the most profound decrease in the growth velocity (the change in the mean HVSDS from +0.05 to -0.88) occurring during the first year of treatment. The growth-retarding effect of inhaled glucocorticoids was not dose dependent. In the covariance analysis the increasing severity of asthma had a significant interaction with repeated measurements, showing more growth retardation along with more severe asthma, especially during long-term treatment. Asthma per se does not impair growth, but inhaled glucocorticoids may do so. Careful monitoring of the growth of all asthmatic children receiving inhaled glucocorticoids is necessary because the growth-retarding effect of the medication is not dose dependent. Individual sensitivity might explain the differences seen in the growth patterns of children receiving inhaled glucocorticoids.     

Adrenal insufficiency in the critically ill neonate and child

PURPOSE OF REVIEW: Adrenal insufficiency, common in critically ill patients of all ages, has recently gained prominence as a significant pathologic entity in pediatrics. This review describes the current diagnostic approach to detecting adrenal insufficiency and the clinical consequences in critically ill children and infants. It also discusses the current therapeutic approach to adrenal insufficiency in critically ill patients. RECENT FINDINGS: Relative adrenal insufficiency and its clinical implications have recently come into focus with observational studies demonstrating a high prevalence in pediatric septic shock patients and a significant associated morbidity. Neonatal studies have clarified diagnostic testing and defined clinical outcomes associated with adrenal insufficiency in preterm infants. Comparisons of bioavailable and total cortisol levels demonstrate the utility of total cortisol testing in pediatric septic shock patients. SUMMARY: Adrenal insufficiency contributes to morbidity in critically ill neonates and children. Diagnostic testing by adrenocorticotropin stimulation tests should be done in patients unresponsive to standard treatment of shock. Prospective, randomized clinical trials in critically ill neonates and children with adrenal insufficiency are required to determine if these populations will benefit from glucocorticoid replacement therapy.     

肾移植术后人肾存活患儿生长发育的队列研究

目的探讨儿童肾移植后生长发育的临床特征及影响移植后追赶性生长的因素。方法收集2017年7月至2019年11月由广州市妇女儿童医疗中心和中山大学附属第一医院合作进行肾移植手术的受者术后随访的病历资料，生长发育指标：身高生长速率（ΔHtSDS）、末次身高标准差（HtSDS），生存指标：血肌酐、血清白蛋白、Hb、血钙、血磷、尿蛋白/肌酐、尿RBC计数、血压，并发症，用药情况（糖皮质激素、免疫抑制剂、降压药和骨化三醇等）。结果接受移植术受者18例，中位随访时间17.5（11，24.5）月，肾移植后第1年ΔHtSDS为0.8（0.1，1.2），追赶率为61%，第2年ΔHtSDS为-0.1（-03，0.4），末次随访HtSDS为-1.94±0.99，达标率50%。HtSDS移植前与末次随访呈正相关（r=0.64，P=0.005），与随访12个月时的ΔHtSDS呈负相关（r=-0.61，P=0.008）。随访期人肾存活率均100%，8例出现并发症，其中3例重症感染、4例抗体介导性排异反应、1例原发肾病复发。糖皮质激素（GC）累积量（143.6±86.6）mg·kg-1，每天剂量为（0.30±0.15）mg·kg-1，使用降压药10例，骨化三醇9例。多因素分析显示，移植前HtSDS、移植年龄和血压是肾移植后身高追赶性生长的危险因素，降压药的使用是身高追赶性生长的独立保护因素。结论肾移植受者术后随访终点身高低于同年龄同性别正常儿童身高2个标准差，移植前较低的HtSDS、较小的移植年龄及正常低限的平均动脉压是儿童肾移植后提高ΔHtSDS的有利因素，降压药的使用是肾移植后身高追赶性生长的保护因素。     

Effects of inhaled or nasal glucocorticosteroids on adrenal function and growth

Inhaled and nasal glucocorticosteroids (GCS) have being shown to be very effective in the treatment of persistent asthma and allergic rhinitis. However, there has been great concern about the possible effects of these inhaled or nasally administered drugs upon the growth of patients of pediatric age. One of the possible glucocorticoid actions of GCS is reflected by the suppression of adrenal function, suggesting a peripheral direct effect of circulating GCS on the cartilage. The present review addresses the safety of inhaled and nasal GCS by assessing the literature on their effects on adrenal gland function and on growth in children and adolescents. It can be concluded that, at recommended doses, adrenal function is rarely suppressed. High doses of inhaled GCS seem to decrease short-term prepubertal growth, but available studies of final height show that it is not affected at licensed doses. Despite these observations, physicians should monitor the growth of their patients, particularly when a new drug is introduced.     

Safety of medications and hormones used in pediatric endocrinology: adrenal

Glucocorticoids have been prescribed for several decades in treating adrenal insufficiency of various etiologies. These drugs are also heavily used in treating non-endocrine disease. This article will focus on adverse side effects encountered in the chronic use of different types of glucocorticoids in children and young adults with endocrine causes of adrenal insufficiency. Dosing guidelines are discussed with a view toward minimizing the common co-morbidities of growth suppression, excess weight gain, and osteopenia, among others. This article also discusses the use of several inhibitors of adrenal steroid biosynthesis and one glucocorticoid receptor antagonist for the medical treatment of Cushing syndrome.     

Adrenal response in children receiving high doses of ketoconazole for systemic coccidioidomycosis

The effect of ketoconazole on adrenal cortical function was studied in 10 prepubertal children receiving long-term (3 to 52 months) high-dose (10 to 23 mg/kg/d) orally administered ketoconazole treatment because of systemic coccidioidomycosis. Four hours after the once daily morning dose of ketoconazole, the patients had significantly elevated baseline desoxycorticosterone (DOC) and precursor/product ratios, and blunted cortisol and aldosterone responses to ACTH stimulation. Twenty-four hours after ketoconazole ingestion, both DOC and DOC/corticosterone ratio were approaching normal; the cortisol response to ACTH was normal in all but two of the 10 study patients, and these two had significantly improved response compared with their own 4-hour values. There appeared to be no differential adrenal response related to either duration of treatment (greater than 12 vs less than 12 months) or dose of medication per kilogram (greater than 18 or less than 18 mg/kg/d). Our data suggest that ketoconazole impairs production of cortisol and aldosterone by imposing a partial and temporary block at the 11-beta-hydroxylase step of steroid hormone synthesis. None of the patients required adrenal steroid replacement therapy in times of acute illness or surgery, and none had clinical evidence of adrenal insufficiency.     

Low-dose adrenocorticotropic hormone stimulation testing in term infants

BACKGROUND: Low-dose adrenocorticotropic hormone (ACTH) stimulation testing is a commonly accepted way to evaluate adrenal function in children. However, there are no published data on the use of this test in term infants less than 12 months of age outside the newborn period. METHODS: We identified 14 infants at our center who were full term and had one or more ACTH tests at less than 12 months of age to evaluate for secondary adrenal insufficiency (AI). We retrospectively assessed peak cortisol response in these infants to determine whether a cut-off of 20 microg/dl is appropriate to distinguish normal from abnormal adrenal function in this age group. RESULTS: Five infants had peak cortisol > or =20 microg/dl on their first ACTH test and had a clinical picture consistent with normal adrenal function. Nine infants had peak cortisol <20 microg/dl on their first ACTH test. When retested later in infancy, four of these patients achieved peak cortisol > or =20 microg/dl. CONCLUSIONS: In term infants, the low-dose ACTH stimulation test is useful for demonstrating normal adrenal function but is of limited value in diagnosing secondary AI. For infants with peak cortisol <20 microg/dl, clinical observation and repeat ACTH testing later in infancy clarified diagnosis.     

Systematic review of the dose-response relation of inhaled fluticasone propionate.

AIMS: To examine the dose-response relation of inhaled fluticasone for both efficacy and adrenal function in children with asthma. METHODS: Systematic review of double blind randomised dose-response studies of fluticasone in children of at least 4 weeks duration. MAIN OUTCOME MEASURES: FEV1, morning peak expiratory flow, night awakenings, beta agonist use, major exacerbations, 12 or 24 hour urinary cortisol, peak plasma cortisol post-stimulation. RESULTS: Seven studies of 1733 children with asthma met the inclusion criteria for efficacy. The dose-response curve for each efficacy outcome measure suggested that the response began to plateau between 100 and 200 microg per day with additional efficacy at the 400 microg per day dose shown in one study of severe asthmatics. Five studies of 1096 children with asthma met the inclusion criteria for assessment of adrenal function. The largest placebo controlled study of 437 children reported no difference in 24 hour urinary cortisol between placebo and fluticasone at doses of 100 and 200 microg per day. The non-placebo controlled study of 528 children reported significant suppression of overnight urinary cortisol levels with fluticasone at 400 compared with 200 microg per day. CONCLUSIONS: There is insufficient data to determine the dose-response of fluticasone in children at doses >400 microg per day. The dose-response curve for fluticasone appears to plateau between 100 and 200 microg per day for efficacy. There was additional efficacy at the 400 microg per day dose in children with severe asthma; however there was evidence of adrenal suppression at this dose.     

Adrenal function and high dose inhaled corticosteroids for asthma

OBJECTIVE: To investigate effects on adrenal function of fluticasone, a recently released inhaled steroid preparation with lower systemic bioavailability than beclomethasone dipropionate. METHODS: 34 children on high doses (400-909 micrograms/m2/d) of inhaled beclomethasone dipropionate or budesonide were recruited into a double blind, crossover study investigating the effects on adrenal function of beclomethasone and fluticasone propionate, given using a standard spacer (Volumatic). The 24 hour excretion rates of total cortisol and cortisol metabolites were determined at baseline (after a two week run in), after six weeks treatment with an equal dose of beclomethasone, and after six weeks of treatment with half the dose of fluticasone, both given through a spacer device. RESULTS: The comparison of effects between fluticasone and beclomethasone during treatment periods, although favouring fluticasone in all measured variables, reached significance only after correction for urinary creatinine excretion (tetrahydrocortisol and 5 alpha-tetrahydrocortisol geometric means: 424 v 341 micrograms/m2/d). The baseline data showed adrenal suppression in the children taking beclomethasone (total cortisol geometric means: 975 v 1542 micrograms/d) and a dose related suppression in the children taking budesonide. Suppressed adrenal function in the children who were taking beclomethasone at baseline subsequently improved with fluticasone and beclomethasone during treatment periods. CONCLUSIONS: Fluticasone is less likely to suppress adrenal function than beclomethasone at therapeutically equivalent doses. The baseline data also support the claim that spacer devices should be used for the administration of high doses of inhaled topical steroids.