Glucocorticoids inhaled, hypothalamic-pituitary-adrenal

In healthy volunteers, high doses of both budesonide and fluticasone were readily absorbed after inhalation from a mete red-dose aerosol (2). Fluticasone is extensively metabolized by the liver, so measurable concentrations of parent drug in the systemic circulation reflect efficient absorption across the lung. Lower doses of these inhaled glucocorticoids also result in some systemic absorption, reflected in effects on the hypothalamic-pituitary-adrenal axis (3). 

Hypothalamic-pituitary-adrenal axis function provides one of the most sensitive markers of the systemic activity of inhaled glucocorticoids (35), and suppression can be used as a surrogate marker for adverse effects of inhaled glucocorticoids in other tissues. 

The different methods of assessing hypothalamic-pituitary-adrenal axis activity in patients using inhaled glucocorticoids have been compared (35). The AUC of serum cortisol concentrations was the most reliable method. There were significant positive correlations between AUC and the 8 a.m. serum and salivary cortisol concentrations. The authors favored the non-invasive method of salivary concentration measurement. However, 24-hour urine collection is not recommended, as it correlated only moderately well. This finding is consistent with the results of other studies. Urinary free-cortisol estimation based on immunoassay after inhaled glucocorticoids may be an unreliable surrogate marker of... 

In a double-blind, randomized pilot study of the efficacy and adverse effects of inhaled fluticasone in 25 newborn preterm infants who required mechanical ventilation for treatment of respiratory distress syndrome, the infants were randomized to receive inhaled fluticasone 1000 micrograms/day or placebo (47). The hypothalamic-pituitary-adrenal axis was assessed by the response to corticotropin-releasing factor. AU basal and post-stimulation plasma corticotropin and serum cortisol concentrations were significantly less with inhaled fluticasone than placebo. Cumulative high-dose inhaled glucocorticoids caused moderately severe suppression of both the pituitary and the adrenal glands. This systemic activity is probably associated with pulmonary vascular absorption that avoids hepatic first-pass metabolism. 

Different inhaled glucocorticoids have been compared for their suppressing effects on the hypothalamic-pituitary-adrenal axis (18). In a large meta-analysis, budesonide or beclomethasone dipropionate in doses of over 1500 micrograms/day was associated with adrenal... 

Endocrine The effects of inhaled glucocorticoids on the hypothalamic-pituitary-adrenal axis in adults and children were reviewed in SEDA-31 (p. 305). In summary, at low doses inhaled glucocorticoids have little effect, but at high doses (2000 micrograms beclometasone equivalents) adrenal suppression can occur. In a French survey of 11 783 hospital specialists combined with a pharmacovigilance database, there were 46 cases of adrenal insufficiency attributable to inhaled corticosteroids at doses of over 500 micrograms beclometasone equivalents in children and over 1000 micrograms beclometasone equivalents in adults 12 cases were associated with concomitant use of enzyme inhibitors [10 ]. 

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