Prospective analysis of adrenal function in patients with acute exacerbations of COPD: The REDUCE* trial (*Reduction in the Use of Corticosteroids in Exacerbated COPD).

OBJECTIVE: To analyze prospectively the hypothalamic-pituitary-adrenal (HPA) axis and clinical outcome in patients treated with prednisone for exacerbated chronic obstructive pulmonary disease (COPD). DESIGN: Prospective observational study. METHODS: Patients presenting to the emergency department were randomized to receive 40 mg prednisone daily for 5 or 14 days in a placebo-controlled manner. The HPA axis was longitudinally assessed with the 1 μg corticotropin test and a clinical hypocortisolism score at baseline, on day 6 prior to blinded treatment, at hospital discharge, and for up to 180 days of follow-up. Prednisone was stopped abruptly, irrespective of test results. Patients discharged with pathological test results received instructions about emergency hydrocortisone treatment. RESULTS: A total of 311 patients were included in the analysis. Mean basal and stimulated serum total cortisol levels were highest on admission (496 ± 398 and 816 ± 413 nmol/l, respectively) and lowest on day 6 (235 ± 174 and 453 ± 178 nmol/l, respectively). Pathological stimulation tests were found in 63%, 38%, 9%, 3% and 2% of patients on day 6, at discharge, and on days 30, 90 and 180, respectively; without significant difference between treatment groups. Clinical indicators of hypocortisolism did not correlate with stimulation test results, but cortisol levels were inversely associated with reexacerbation risk. There were no hospitalizations or deaths due to adrenal crisis. CONCLUSIONS: Dynamic changes in the HPA axis occur during and after treatment of acute exacerbations of COPD. In hypocortisolemic patients, provided with instructions about stress prophylaxis, abrupt termination of prednisone appeared safe.