Adrenal Insufficiency Associated with Long-Term Use of Inhaled Steroid in Asthma

Background: We previously reported that as much as 1/3 of hospitalized asthmatics treated with inhaled steroids (ICS) for average 4.5 years showed adrenal insufficiency in a dose-dependent manner. Because the result might be overestimated due to subject selection bias, this study examined adrenal function in out-patient asthmatics of a tertiary hospital.

Methods: Twelve normal control and 135 consecutive adult asthmatics under ICS treatment for 6 months or more underwent a rapid ACTH stimulation test. Adrenal insufficiency was defined as a serum morning cortisol level < 3 μg/dL or failure in rising of the level to >18 μg/dL after an administration of 250 μg ACTH.

Results: The mean duration of ICS use in the patients were 8.30±0.43 years. Adrenal insufficiency was found in a manner dependent on the ICS daily doses [control 2/12 (16.7%), low 17/29 (58.6%), medium 34/54 (63.0%), and high 32/52 (61.5%); X²=4.23, P=0.04]. The total doses of nasal steroid (NCS) and ICS were significantly related with each other (r=0.529, P=0.000). The number of NCS canisters (32.5±2.7 vs. 24.8±2.6, P=0.04), but not the duration/total dose of ICS, was significantly higher in the patients with adrenal insufficiency than the others. Only the NCS dose seemed to relate with adrenal insufficiency [odds ratio: 1.016 (95% CI: 1.000-1.033); P=0.056].

Conclusion: Even low dose ICS seems to induce adrenal insufficiency in more than a half of asthmatics when it was administered for a very long time, especially in the patients used NCS together.