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


METHODS
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.


METHODS
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.
Bernstein
David I
DI
Department of Internal Medicine, Division of Immunology-Allergy, University of Cincinnati, Cincinnati, Ohio 45267-0563, USA. daveib@fuse.net
Allen
David B
DB
D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000009:adverse effects*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001249:Asthma / Q000188:drug therapy*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000503:physiopathology; D010912:Pituitary-Adrenal Function Tests; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000503:physiopathology
D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D006854:Hydrocortisone