Inhaled corticosteroid therapy reduces the early morning peak in cortisol and aldosterone.
1. As mineralocorticoid and adrenocorticoid activity are both under the diurnal control of adrenocorticotropic hormone secretion, we aimed to evaluate whether the normal circadian rhythm of cortisol and aldosterone secretion was suppressed by inhaled corticosteroid therapy.2.Ten 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 in a double-blind, randomized crossover design comparing placebo with fluticasone propionate, 1000 microgram administered twice daily at 08:00 h and 20:00 h. After 5 days of repeated dosing at steady state, measurements were made of plasma cortisol and aldosterone at midnight and 08:00 h.3. With placebo there was a significant (P<0.05) difference between cortisol values at 08:00 h (588.6+/-83.8 nmol/l) and midnight (109.6+/-35.0 nmol/l), whereas after treatment with fluticasone propionate there was no significant difference between levels at 08:00 h (143.3+/-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 with 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 with fluticasone propionate, there was no significant difference between 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 abolishes the circadian rhythm of aldosterone and cortisol secretion. This may have possible implications for patients taking inhaled corticosteroids in terms of the beneficial cardiac effects of suppressing early morning aldosterone.
Wilson
A M
AM
Department of Clinical Pharmacology and Respiratory Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, U.K.
Sims
E J
EJ
Struthers
A D
AD
Lipworth
B J
BJ
D000280:Administration, Inhalation; D000287:Administration, Topical; D000328:Adult; D000450:Aldosterone / Q000097:blood*; D000704:Analysis of Variance; D000730:Androstadienes / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001249:Asthma / Q000097:blood* / Q000188:drug therapy; D002940:Circadian Rhythm; D018592:Cross-Over Studies; D003864:Depression, Chemical; D004311:Double-Blind Method; D005260:Female; D000068298:Fluticasone; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D000450:Aldosterone; D000068298:Fluticasone; D006854:Hydrocortisone