The effect of an inhaled steroid on the hypothalamic‐pituitary‐adrenal axis‐which tests should be used?

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Abstract
Summary: Inhaled corticosteroids may produce systemic effects which include decreased hypothalamic pituitary‐adrenal (HPA) axis activity. Four tests of HPA axis function were assessed in 12 healthy volunteers, during inhalation of two actuations of beclomethasone dipropionate (250 μg) aerosol four times daily for 15 days, to determine the most appropriate test for this effect of inhaled corticosteroids. Measurement of basal adrenal activity showed that both 24‐hr urinary free cortisol and 0900 hr plasma cortisol were decreased by the fourth day of steroid treatment. All 12 subjects had decreases in basal adrenal activity. Overall the 24‐hr urinary free cortisol showed the greater change, with mean pre‐steroid baseline values of 497 and 515 nmol/24 hr reduced to 167 nmol/24 hr on the ninth day of treatment (P < 0.001). The single‐dose metyrapone test showed marked changes in each of the six subjects tested. The mean 11‐deoxycortisol response was 96 nmol/l on the eleventh day of treatment, compared to baseline and eighth‐day post‐treatment values of 439 and 407 nmol/1 respectively (P < 0.001). In contrast, no consistent treatment‐related changes were observed with the short tetracosactrin test. Only two out of six subjects had an abnormal short tetracosactrin test, although all showed a decrease in basal adrenal activity. From these results, the 24‐hr urinary free cortisol and single‐dose metyrapone test at 0600 hr are recommended to assess the effect of inhaled glucocorticoids on the HPA axis. The short tetracosactrin test failed to detect an effect from the same dose of inhaled beclomethasone dipropionate and cannot therefore be recommended to exclude the systemic effect of an inhaled steroid.