Pediatric Pulmonology 12:84-89 (1992)
Integrated Plasma Cortisol Concentration in Children With Asthma Receiving Long-Term Inhaled Corticosteroids Moshe Phillip, MD‘, Micha Aviram, MD, Esther Leiberman, MD, Zvi Zadik, MD, Yehudit Giat, Josef Levy, PhD, and Asher Tal, MD‘ Summary. We assessed the effect of long-termtherapy with inhaled beclomethasone dipropionate (BDP) on the pituitary-adrenal axis, by measuring the integrated concentration (IC) of plasma cortisol in eight children with asthma (age, 6-16 years) who regularly used inhaled BDP in doses ranging from 8 to 26.5 pg/kg (200-450 pg/day) for 6 months to 4 years. The control group included six children (age, 6-1 6 years) who had the IC of plasma cortisol measured as part of an endocrinological evaluationand were found to be healthy. Cortisol concentration was measured in blood samples collected continuously over a 24-hr period. Mean IC of plasma cortisol in the study group was significantly lower than in the healthy controls (mean SD, 4.9 2 3.3 vs 9.1 5 1.9 pg/mL; P < 0.02). Cortisol response to 0.25 rng ACTH (iv) was abnormal in one of the eight BDP-treated patients. No correlationwas found between IC of plasma cortisol and the BDP dose, severity of asthma, height percentile, or the Tanner stage. We conclude that long-term therapy, even with relatively conventional doses of inhaled BDP may cause reduction in the normal physiologicalsecretion of cortisol. The clinical relevance of low IC of plasma cortisol is not clear, but it may reflect partial suppression of the pituitary-adrenal axis. Pediatr Pulmonoll992; 12:84-89.
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Key words: In hospital testing; radioimmunoassayfor cortisol; ACTH-stimulation; roentgenologic bone age; growth rate by height; correlations with BPD; severity of asthma; height percentile; Tanner stage.
INTRODUCTION
available on the effect of inhaled steroid therapy on diurnal variations in plasma The 24-hr inteSince the introduction of beclomethasone dipropionate grated concentration (IC) of plasma cortisol has recently (BDP)in the early 197Os, inhaled corticosteroids have been suggested to be a sensitive test of HPA axis funcproved to be effective and safe long-term treatment for t i ~ n . ’ ~ .We * ~ have decided to measure the IC of plasma chronic asthma in children. I Based on their safety record cortisol in children with chronic asthma, treated with and their potent antiinflammatory effect, inhaled steroids long-term inhaled steroids, in order to assess the effect of are widely considered a better choice than theophylline.’ such treatment on the HPA axis. The current trend is to prescribe steroids earlier in the treatment of chronic asthma.3 This widespread use of inhaled steroids is based, in part, on the belief that there MATERIALS AND METHODS are only few adverse effects, in particular that they do not Patients significantly affect the hypothalamic-pituitary-adrenal The study group included 8 children aged 6 to 16 years (HPA) axis when doses of
Integrated Plasma Cortisol Concentration in Children With Asthma Receiving Long-Term Inhaled Corticosteroids Moshe Phillip, MD‘, Micha Aviram, MD, Esther Leiberman, MD, Zvi Zadik, MD, Yehudit Giat, Josef Levy, PhD, and Asher Tal, MD‘ Summary. We assessed the effect of long-termtherapy with inhaled beclomethasone dipropionate (BDP) on the pituitary-adrenal axis, by measuring the integrated concentration (IC) of plasma cortisol in eight children with asthma (age, 6-16 years) who regularly used inhaled BDP in doses ranging from 8 to 26.5 pg/kg (200-450 pg/day) for 6 months to 4 years. The control group included six children (age, 6-1 6 years) who had the IC of plasma cortisol measured as part of an endocrinological evaluationand were found to be healthy. Cortisol concentration was measured in blood samples collected continuously over a 24-hr period. Mean IC of plasma cortisol in the study group was significantly lower than in the healthy controls (mean SD, 4.9 2 3.3 vs 9.1 5 1.9 pg/mL; P < 0.02). Cortisol response to 0.25 rng ACTH (iv) was abnormal in one of the eight BDP-treated patients. No correlationwas found between IC of plasma cortisol and the BDP dose, severity of asthma, height percentile, or the Tanner stage. We conclude that long-term therapy, even with relatively conventional doses of inhaled BDP may cause reduction in the normal physiologicalsecretion of cortisol. The clinical relevance of low IC of plasma cortisol is not clear, but it may reflect partial suppression of the pituitary-adrenal axis. Pediatr Pulmonoll992; 12:84-89.
*
Key words: In hospital testing; radioimmunoassayfor cortisol; ACTH-stimulation; roentgenologic bone age; growth rate by height; correlations with BPD; severity of asthma; height percentile; Tanner stage.
INTRODUCTION
available on the effect of inhaled steroid therapy on diurnal variations in plasma The 24-hr inteSince the introduction of beclomethasone dipropionate grated concentration (IC) of plasma cortisol has recently (BDP)in the early 197Os, inhaled corticosteroids have been suggested to be a sensitive test of HPA axis funcproved to be effective and safe long-term treatment for t i ~ n . ’ ~ .We * ~ have decided to measure the IC of plasma chronic asthma in children. I Based on their safety record cortisol in children with chronic asthma, treated with and their potent antiinflammatory effect, inhaled steroids long-term inhaled steroids, in order to assess the effect of are widely considered a better choice than theophylline.’ such treatment on the HPA axis. The current trend is to prescribe steroids earlier in the treatment of chronic asthma.3 This widespread use of inhaled steroids is based, in part, on the belief that there MATERIALS AND METHODS are only few adverse effects, in particular that they do not Patients significantly affect the hypothalamic-pituitary-adrenal The study group included 8 children aged 6 to 16 years (HPA) axis when doses of
