24 hour and fractionated profiles of adrenocortical activity in asthmatic patients receiving inhaled and intranasal corticosteroids
- Department of Clinical Pharmacology and Therapeutics and Department of Respiratory Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK
- Professor B J Lipworth.
- Received 5 June 1998
- Revision requested 17 August 1998
- Revised 1 September 1998
- Accepted 16 September 1998
BACKGROUND As both rhinitis and asthma are allergic conditions, they frequently occur together. The objective of this study was to assess the diurnal adrenocortical activity in asthmatics receiving inhaled (inh) and intranasal (n) formulations of two different corticosteroids, fluticasone propionate (FP) and triamcinolone acetonide (TAA), both given at clinically recommended doses.
METHODS Twelve stable moderately severe asthmatic subjects of mean age 23.9 years and mean forced expiratory volume in one second (FEV1) 84% predicted were recruited into a randomised placebo (PL) controlled two-way crossover study comparing nPL + inhPL, nPL + inhFP (880 μg bid), and nFP (200 μg once daily) + inhFP (880 μg bid) with nPL + inhPL, nPL + inhTAA (800 μg bid) and nTAA (220 μg once daily) + inhTAA (800 μg bid), each given for five days with a 10 day washout period. Twenty four hour integrated and fractionated (overnight, 08.00 hours, daytime) serum cortisol levels and urinary cortisol/creatinine excretion were measured.
RESULTS For 24 hour and fractionated serum cortisol levels and corrected urinary cortisol/creatinine excretion there were significant (p<0.05) differences between all active treatments and placebo. For 24 hour integrated serum cortisol levels the ratio between inhaled TAA and FP was 2.3 fold (95% CI 1.2 to 4.3), and for 24 hour urinary cortisol/creatinine excretion the ratio was two-fold (95% CI 1.2 to 3.4). For 24 hour urinary cortisol excretion, with all active treatments, individual abnormal low values of <40 nmol (<14.4 μg) occurred in 17/24 with FP compared with 4/24 with TAA (p<0.0005). The 24 hour serum cortisol profile was flattened by FP but not with TAA. The addition of nasal corticosteroid did not produce further significant suppression of mean cortisol values, although with intranasal FP there were three more abnormal values for 24 hour urinary cortisol excretion than with inhaled FP alone.
CONCLUSIONS Both inhaled FP and TAA caused significant suppression of adrenocortical activity which was twice as great with FP, the latter being associated with significantly more individual abnormal values and loss of the normal diurnal circadian rhythm. Fractionated serum cortisol levels and urinary cortisol/creatinine excretion were as sensitive as the respective integrated 24 hour measurements. Although the addition of intranasal formulations did not produce further significant suppression of mean values, there were more individual abnormal cortisol values associated with the addition of intranasal FP.