Evaluation of corticotropin releasing factor stimulation and basal markers of hypothalamic-pituitary-adrenal axis suppression in asthmatic patients.
OBJECTIVE
The aim of our study was to compare basal unstimulated levels of plasma cortisol and adrenocorticotropic hormone (ACTH) with stimulated levels produced by the corticotropin releasing factor (CRF) test in asthmatics taking high-dose inhaled steroid therapy. In theory, the CRF test would appear to be a suitable replacement for tetracosactrin (cosyntropin) (synthetic ACTH) as a test of hypothalamic-pituitary-adrenal (HPA) axis suppression.


METHODS
Ten patients with stable asthma and a mean age of 28.8 years, FEV1 of 88.9% predicted, and forced expiratory flow between 25% and 75% of FVC of 57.0% predicted, were studied in a double-blind placebo-controlled crossover design comparing 4 days with budesonide, 1,000 microg bid, and placebo. Each dose was given at 8 AM and 10 PM for 4 days by metered-dose inhaler. Measurements were made at steady-state of basal 8 AM plasma cortisol and ACTH 10 h after the eighth dose, and CRF test (100-microg i.v. bolus) was then performed.


RESULTS
The results for 8 AM plasma cortisol (nmol/L, means and 95% confidence interval [CI] for difference) showed that budesonide produced significant suppression compared with placebo: budesonide (284.1) vs placebo (360.9) (95% CI, 9.3 to 144.3). Suppression also occurred for peak plasma cortisol in response to CRF: budesonide (375.9) vs placebo (470.2) (95% CI, 27.0 to 161.6). ACTH (ng/L, means and 95% CI for difference) demonstrated a similar nonsignificant trend to cortisol, with suppression in both basal and stimulated forms: 8 AM ACTH, budesonide (36.6) vs placebo (42.2) (95% CI, -2.6 to 13.8); CRF peak response, budesonide (49.9) vs placebo (62.8) (95% CI, -3.6 to 29.5).


CONCLUSIONS
In asthmatic patients receiving inhaled budesonide, 1,000 microg bid, the suppression of basal unstimulated 8 AM plasma cortisol was mirrored by the suppression of the CRF stimulation response. These results highlight the point that when basal 8 AM plasma cortisol levels are suppressed, a comparable degree of dynamic impairment of HPA axis response is also likely to be found with physiologic testing.
Clark
D J
DJ
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, University of Dundee, Scotland.
Lipworth
B J
BJ
D000280:Administration, Inhalation; D000287:Administration, Topical; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001249:Asthma / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D019819:Budesonide / Q000008:administration & dosage / Q000627:therapeutic use; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005540:Forced Expiratory Flow Rates; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D011237:Predictive Value of Tests; D011863:Radioimmunoassay
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D019819:Budesonide; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone