Effect of inhaled corticosteroids on the hypothalamic-pituitary-adrenal axis and growth in children.

Measurement of early morning, overnight, and 24-hour urinary free cortisol levels and/or cortisol metabolites and/or ratio to creatinine has also produced divergent results. No apparent effects,7,11 equivocal effects,8 or suppressive effects13,14,18-20 on the HPA axis have been reported. It is of interest to note that some investigators have found that the most significant effects on serum or urinary cortisol occur in the late night/early morning period.18 This suggests that the HPA axis is more sensitive to the suppressive effects of exogenous steroids at that time. Corticotropin stimulation tests with 125 to 250 μg of corticotropin given intramuscularly or intravenously have resulted in normal cortisol responses in the majority of children,7,9-11,13,15,17,18 although occasional low cortisol responses have been documented.13,17,19,21 In the very limited experience with lowdose corticotropin stimulation testing in asthmatic children receiving inhaled steroids, an inadequate cortisol response to 0.5 μg/1.73 m2 corticotropin has been reported in some but not all patients.19,21,22 Inadequate or decreased response to insulin-induced hypoglyInhaled corticosteroids are increasingly used as first-line therapy in childhood asthma.1 Indications for their use have expanded from moderate and severe asthma to mild asthma as well.2,3 Intranasal steroids for treatment of allergic rhinitis have also grown in popularity.1,4 As the use of these “non systemic” and “locally applied” glucocorticoids has increased dramatically, it has become increasingly important to be aware of and to investigate the potential risks. The systemic effects of inhaled corticosteroids depend on the potency of the drug, the dose used, the proportion of the steroid deposited in the oropharynx and swallowed, the amount that reaches the airways, the affinity with which the steroid binds to the glucocorticoid receptor, the amount absorbed into the lungs and reaching the systemic circulation, and the metabolic clearance rate of the steroid. There Effect of inhaled corticosteroids on the hypothalamic-pituitary-adrenal axis and growth in children