The use of inhaled corticosteroids and the risk of adrenal insufficiency

Francesco Lapi, Abbas Kezouh, Samy Suissa, Pierre Ernst


Adrenal insufficiency is a potential complication of therapy with inhaled corticosteroids (ICS). Although prior studies found the highest risk of adrenal insufficiency with fluticasone, a more potent ICS, these results might be explained by a channeling bias and concomitant exposure to oral corticosteroids.

We re-examined the relationship between the use of ICS and adrenal insufficiency by using a cohort of patients treated for respiratory conditions during 1990–2005, identified in the healthcare databases from the province of Quebec, Canada, with follow-up until 2007. A nested case-control analysis was performed within this cohort. Cases of adrenal insufficiency were matched with up to 10 controls.

392 cases were identified (incidence rate=1.1/10,000 person-years). Although the rate of adrenal insufficiency was not significantly higher among all current users of ICS, patients receiving the highest dosages showed a greater risk (OR=1.84; 95% CI: 1.16–2.90). Consistently, an increased risk was estimated for the highest tertile of ICS dose (OR=1.90; 95% CI: 1.07–3.37) cumulated in the year before the event.

Inhaled corticosteroids at high doses appear to be a significant independent risk factor for adrenal insufficiency. Physicians prescribing ICS at such dosages should be sensitive to the signs and symptoms of adrenal insufficiency in their patients.