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

Eur J Endocrinol. 2015 Jul;173(1):19-27. doi: 10.1530/EJE-15-0182. Epub 2015 Apr 8.

Abstract

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.

Subjects and 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 before blinded treatment, at hospital discharge, and for up to 180 days of follow-up. Prednisone was stopped abruptly, irrespective of the 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 re-exacerbation risk. There were no hospitalizations or deaths as a result of adrenal crisis.

Conclusion: Dynamic changes in the HPA axis occur during and after the treatment of acute exacerbations of COPD. In hypocortisolemic patients who were provided with instructions about stress prophylaxis, the abrupt termination of prednisone appeared safe.

Publication types

  • Multicenter Study
  • Observational Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Function Tests
  • Adrenal Cortex Hormones / adverse effects*
  • Adrenal Cortex Hormones / therapeutic use*
  • Adrenal Glands / physiopathology*
  • Adrenal Insufficiency / physiopathology
  • Adrenocorticotropic Hormone
  • Aged
  • Female
  • Follow-Up Studies
  • Humans
  • Hydrocortisone / deficiency
  • Hypothalamo-Hypophyseal System / drug effects
  • Male
  • Middle Aged
  • Pituitary-Adrenal System / drug effects
  • Prednisone / adverse effects
  • Prednisone / therapeutic use
  • Prospective Studies
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology*
  • Treatment Outcome

Substances

  • Adrenal Cortex Hormones
  • Adrenocorticotropic Hormone
  • Prednisone
  • Hydrocortisone