The use of inhaled corticosteroids and the risk of adrenal insufficiency

Adrenal insufficiency is a potential complication of therapy with an inhaled corticosteroid (ICS). Although prior studies found the highest risk of adrenal insufficiency with fluticasone, a more potent ICS, these results might be explained by a channelling bias and concomitant exposure to oral corticosteroids. We re-examined the relationship between the use of ICSs 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 per 10 000 person-years). Although the rate of adrenal insufficiency was not significantly higher among all current users of ICSs, 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. ICS 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.