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Evaluation of Corticotropin Releasing Factor Stimulation and Basal Markers of Hypothalamic-Pituitary-Adrenal Axis Suppression in Asthmatic Patients FREE TO VIEW

D. J. Clark; Brian J. Lipworth
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From the Department of Clinical Pharmacology, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland

1997 by the American College of Chest Physicians

Chest. 1997;112(5):1248-1252. doi:10.1378/chest.112.5.1248
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Purpose: 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.

Patients and 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 µg 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-µg IV 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).

Conclusion: In asthmatic patients receiving inhaled budesonide, 1,000 µg 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.




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