Faculty Collaboration Database

A comparison of methods for assessing hypothalamic-pituitary-adrenal (HPA) axis activity in asthma patients treated with inhaled corticosteroids. J Clin Pharmacol 2002 Mar;42(3):319-26

Date

02/28/2002

Pubmed ID

11865969

DOI

10.1177/00912700222011355

Scopus ID

2-s2.0-0036181435 (requires institutional sign-in at Scopus site)   23 Citations

Abstract

Suppression of the hypothalamic-pituitary-adrenal (HPA) axis is an accepted indicator of potential side effects from inhaled corticosteroids. Although cortisol monitoring is frequently used to detect changes in HPA axis activity, the optimal method for identifying the subset of asthma patients on inhaled steroids who experience severe cortisol suppression of potential clinical significance has not been established. The objective of this study was to compare several methods for assessing HPA axis activity in asthma patients taking inhaled corticosteroids. After screening, 153 patients with mild to moderate asthma were randomly assigned to receive inhaled fluticasone propionate (110, 220, 330, or 440 microg bid), flunisolide (500 microg or 1000 microg bid), or one of two control regimens (prednisone or placebo) for 21 days. Salivary (8 a.m.) and urinary (24-h) cortisol determinations were compared against 22-hour area under the serum cortisol concentration-time curve (AUC0-22 h) measured at baseline and on day 21. Comparisons were also made against 8 a.m. serum cortisol. A significant positive correlation was found between AUC0-22 h of serum cortisol and 8 a.m. serum cortisol level (r = 0.5140; p = 0.0001). The AUC0-22 h of serum cortisol was weakly correlated with 24-hour urinary cortisol levels, both corrected (r = 0.4388; p = 0.0001) and uncorrected (r = 0.3511; p = 0.0001) for creatinine excretion. The 8 a.m. salivary cortisol level correlated positively with the 8 a.m. serum cortisol level (r = 0.5460; p = 0.0001). Salivary cortisol was both sensitive and specific for the detection of a 50% decline in AUC0-22 h of serum cortisol. Cortisol reductions of this magnitude have been observed following repeated use of inhaled steroids. Because it is noninvasive, salivary cortisol measurement offers distinct advantages as a screening method for detecting pronounced HPA axis suppression in asthma patients receiving corticosteroid therapy.

Author List

Nelson HS, Stricker W, Casale TB, Raff H, Fourré JA, Aron DC, Newman KB

Author

Hershel Raff PhD Professor in the Academic Affairs department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Administration, Inhalation
Adrenocorticotropic Hormone
Adult
Analysis of Variance
Androstadienes
Anti-Inflammatory Agents
Area Under Curve
Asthma
Female
Fluocinolone Acetonide
Fluticasone
Humans
Hydrocortisone
Hypothalamo-Hypophyseal System
Male
Nebulizers and Vaporizers
Patients
Pituitary-Adrenal System