Persistent Long-Term Hypothalamic-Pituitary-Adrenal-Axis Suppression After Maintenance Oral Corticosteroid Withdrawal in Severe Asthma: Biochemical Assessment Is Essential.

Abstract

There is no consensus on the approach to maintenance oral corticosteroid (mOCS) withdrawal in severe asthma (SA) in the presence of hypothalamic-pituitary-adrenal-axis (HPA-axis) suppression. The objective of this study is identify the prevalence of persistent HPA-axis suppression after long-term follow-up and factors that predictively correlate to persistent HPA-axis suppression. The secondary objective is to validate the morning cortisol cut points using short Synacthen test results and evaluate the use of dynamic testing. Retrospective analysis was carried out on data from Northern Ireland patients registered to the United Kingdom Severe Asthma Registry. At baseline, 83% (149 of 180, 95% confidence interval [CI]: 76%-88%) of the cohort demonstrated adrenal insufficiency. After a median test time of 58.5 (33.5-78.5) months, 48 of 180 (27%) had persistent adrenal insufficiency, and of these, 32 (66.7%) had complete adrenal insufficiency. Of those with adrenal insufficiency at baseline, 68% (101 of 149, 95% CI: 60%-75%) achieved HPA-axis recovery. The median time from baseline to the most recent test in those who recovered was 21 (6-40) months. Those with persistent adrenal insufficiency had a significantly lower baseline cortisol than those who achieved HPA-axis recovery (43 nmol/L [1.56 μg/dL] [interquartile range (IQR): 21.5-105 nmol/L] vs 165 nmol/L [5.98 μg/dL] [IQR: 77-222 nmol/L], P < .0001). A proportion of patients with SA withdrawing from mOCS will have persistent adrenal insufficiency. These patients are asymptomatic and, if not identified through serial biochemical assessment, will be at risk of harm. These data also have implications for other diseases treated with long-term OCS.