Evaluation of tests of hypothalamic-pituitary-adrenal axis function used to measure effects of inhaled corticosteroids

Abstract

Objectives: To review the evidence supporting the evaluation of hypothalamic-pituitary-adrenal (HPA) axis function as a measure of systemic exposure and clinical adverse events, discuss factors that affect systemic exposure to inhaled corticosteroids (ICSs), and review the effects of various ICSs that are currently available or under development on HPA axis function from a therapeutic perspective.

Data sources: Randomized published clinical trials and review articles on the topic of HPA axis suppression were retrieved in MEDLINE. Searches dating back to 1988 were restricted to human studies published in English.

Study selection: Studies that evaluated HPA axis function and the methods used to measure its activities and the effects of ICSs (fluticasone propionate, budesonide, beclomethasone dipropionate, mometasone furoate, and ciclesonide) were selected.

Results: Factors that influence adverse events caused by ICSs include pharmacokinetic and pharmacodynamic properties, delivery devices, and therapeutic dose and duration. Basal measurements of blood and urinary cortisol levels, reflecting basal HPA axis function, are the most sensitive markers for assessing systemic ICS bioavailability but, compared with dynamic stimulation tests, are poor clinical predictors of adrenal dysfunction.

Conclusions: Basal serologic and urinary cortisol tests provide the best measures of assessing and comparing systemic ICS exposure. Long-term clinical studies are needed to determine whether such tests are predictive of ICS toxicity.