Original Article
Evaluation of adrenocortical function in 3-7 aged asthmatic children treated with moderate doses of fluticasone propionate: reliability of dehydroepiandrosterone sulphate (dhea-s) as a screening test

https://doi.org/10.1016/j.aller.2010.06.005Get rights and content

Abstract

Background

Inhaled corticosteroids (ICS) are the first-line therapy in the treatment of persistent asthma. At medium to high doses and prolonged usage, ICS can supresss the hypothalamic-pituitary-adrenal axis. Dehydroepiandrosterone sulphate (DHEA-S) is a corticotropin-dependent adrenal androgen precursor that is supressible in patients treated with ICS.

Objectives

To evaluate the adrenal axis in asthmatic children treated with moderate doses of fluticasone propionate and to evaluate the DHEA-S as a possible marker for adrenal axis ın preadrenarchal children.

Methods

Twenty-eight children with persistent asthma with a mean age of 4.4 years (median 4.2; range 2.5-7.1) on long term treatment (mean 6.16; median 6; range 4.5-9 months) with moderate doses (mean 250; median 253; range 158-347 (g/m2/day) of inhaled fluticasone propionate were evaluated with low-dose ACTH stimulation test to assess adrenal function, and DHEA-S levels were compared with the results.

Results

One out of 28 patients (3.57%) demonstrated an abnormal cortisol response to low-dose ACTH test. There was no correlation between DHEA-S and peak cortisol, morning cortisol and fasting blood glucose levels. However, mean inhaled corticosteroid dosages were inversely correlated with the DHEA-S.

Conclusıons

In most of the children with persistent asthma, mild to moderate fluticazone propionate doses supress the hypothalamic-pituitary-adrenal axis rarely. Chronic moderate doses of ICS may suppress adrenal androgen levels without supression of cortisol production. DHEA-S levels may be used as a practical method to follow adrenal functions and may be an earlier indicator of adrenal dysfunction in children.

Introduction

Inhaled corticosteroids (ICS) are the first-line treatment in the management of persistent asthma.1 Recently there have been reports of symptomatic adrenal insufficiency in children on chronic ICS treatment.2, 3, 4 Most of these children were treated with high doses of inhaled fluticasone. For most patients aged <12 years, the recommended dose of fluticasone propionate (FP) is classified as low (88-176 μg/day); medium (176-440 μg/day); or high (> 440 μg/day).1 Fluticasone has the highest receptor binding affinity of any of the commercially available ICS.5 Use of FP has been reported to produce dose-related adrenal suppresion greater than that of other commercially available ICS.6, 7, 8 Studies using low or medium doses of FP in adults with mild to moderate asthma have conflicting results.9, 10, 11, 12 Children may be even more susceptible to adrenal supression than adults. The number of studies concerning the effects of FP on adrenal axis at low to medium doses in children is limited and results are also conflicting.13, 14, 15, 16

For the evaluation of the hypothalamic-pituitary-adrenal (HPA) axis, insulin induced hypoglycaemia and metyrapone are considered the most sensitive tests but they are associated with unpleasant symptoms and significant potential complications.17 Recently, low dose cosyntropin has been found to be a sensitive test for determining adrenal supression.18, 19, 20 However, it is an invasive and time-consuming test and not reliable for screening purposes.

Dehydroepiandrosterone sulphate (DHEA-S) is an adrenal androgen precursor secreted by the zona reticularis, under the dominant regulation of corticotropin. Serum levels of DHEA-S are affected by several factors, the most important of which are age, gender, chronic illness and the prior use of glucocorticoids. DHEA-S has a long half-life (10-12 hours) and concentrations do not fluctuate throughout the day.21 There are some reports indicating that the adrenal androgen secretion is sensitive and suppressible with the exogenous glucocorticoids.22, 23, 24 However, data on the use of DHEA-S in the assessment of adrenal function, especially in preadrenarchal children, are limited.

In the present study, we evaluated the effect of moderate doses of FP on HPA axis in preadrenarchal children and compared the results with DHEA-S levels. Our aim was to document the effects of FP at moderate doses in HPA and determine whether there was a correlation between DHEA-S levels and HPA functions in preadrenarchal children.

Section snippets

Patients and methods

Twenty-eight children with persistent asthma and using moderate doses of fluticasone propionate between doses of 158-347 μg/m2/day and for at least 4 months were enrolled in the study. Patients were all at preadrenarchal ages and this was confirmed by a detailed physical examination. None of the children were exposed to systemic corticosteroids more than two courses (each of which at most 5 days and 1 mg/kg/day) within the last 6 months. Any patient with exposure of systemic or topical

Results

The average age of the patients was 4.4 (median 4.2, range 2.5-7.1) and the male-female ratio was 17/11. Demographic data and the other characteristics of patients are shown in Table 1.

One out of 28 asthmatic children (3.57%) demonstrated biochemical adrenal suppression, that is he had a peak serum cortisol response to low-dose ACTH test <19.8 μg/dl. No patient presented symptoms suggestive of adrenal insufficiency. When Pearson's correlation coefficient test was performed no significant

Discussion

Inhaled corticosteroids (ICS) are the first-line treatment in the management of persistent asthma.1 There have been reports of symptomatic adrenal insufficiency in children who were treated with high doses of inhaled fluticasone.2, 3, 4 In adolescent and adult asthmatics most of the therapeutic benefit of FP is achieved at doses of 100-250 μg/day and the use of FP in doses up to 500 μg/day rarely causes adrenal supression.26

In children, comparable dose response relation for FP has not been

Conflict of interest

The authors have no conflict of interest to declare.

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