INHALED CORTICOSTEROID-THERAPY REDUCES THE EARLY-MORNING PEAK IN CORTISOL AND ALDOSTERONE

1. As mineralocorticoid and adrenocorticoid activity are both under th e diurnal control of adrenocorticotropic hormone secretion, we aimed t o evaluate whether the normal circadian rhythm of cortisol and aldoste rone secretion was suppressed by inhaled corticosteroid therapy. 2. Te n normotensive patients with mild-moderate asthma, mean age 24.0 (S.D. 9.8) years and mean arterial pressure 90.7 (9.8) mmHg, were studied i n a double-blind, randomized crossover design comparing placebo with f luticasone propionate, 1000 mu g administered twice daily at 08:00 h a nd 20:00 h. After 5 days of repeated dosing at steady state, measureme nts were made of plasma cortisol and aldosterone at midnight and 08:00 h. 3. With placebo there was a significant (P < 0.05) difference betw een cortisol values at 08:00 h (588.6 +/- 83.8 nmol/l) and midnight (1 09.6 +/- 35.0 nmol/l), whereas after treatment with fluticasone propio nate there was no significant difference between levels at 08:00 h (14 3.3 +/- 57.4 nmol/l) and midnight (64.3 +/- 22.3 nmol/l). For cortisol at 08:00 h there was also a significant (P < 0.05) difference between placebo and fluticasone propionate. The same pattern was observed for aldosterone. Plasma aldosterone levels at 08:00 h after treatment wit h placebo (129.6 +/- 30.9 nmol/l) were significantly different (P < 0. 05) to those seen at midnight (40.4 +/- 6.2 nmol/l). After treatment w ith fluticasone propionate, there was no significant difference betwee n levels at midnight (55.4 +/- 11.7 nmol/l) and 08:00 h (64.8 +/- 12.7 nmol/l). 4. These results show that inhaled corticosteroid therapy ab olishes the circadian rhythm of aldosterone and cortisol secretion. Th is may have possible implications for patients taking inhaled corticos teroids in terms of the beneficial cardiac effects of suppressing earl y morning aldosterone.