Patients with Asthma Treated Long-Term with Inhaled Steroids Should Be Monitored for Adrenal Insufficiency

Hormone tests administered to adult patients who used inhaled steroids to treat asthma suggests that such treatments may be associated with adrenal insufficiency.

Investigators performed a rapid adrenocorticotropic hormone stimulation on 121 consecutive asthma patients who have been using inhaled steroids for at least 6 months. They then used median figures for treatment dosage and duration to divide the cohort into both long-term and short-term users and high-dose and low-dose users before comparing adrenal function among the 4 groups. (The mean duration of use turned out to be very different between short-term [3.8 years] and long-term [11.5 years] users.)

The investigators found that the proportion of patients suffering from adrenal insufficiency increased with increased cumulative doses of inhaled steroids. Adrenal insufficiency was diagnosed in 15 of 34 (44.1%) of short-term users with a low-to-medium daily dose (mean cumulative exposure, 502 mg) exhibited adrenal insufficiency, 16 of 26 (61.5%) short-term users with a high daily dose (mean cumulative exposure, 941 mg), 25 of 41 (61.0%) of long-term users with a high daily dose (mean cumulative exposure 1,077 mg) and 13 of 20 (65.0%) long-term users with a high daily dose (cumulative mean exposure 2,805 mg).

The study was not sufficiently powered to find significant associations between cumulative exposure to inhaled steroids and adrenal insufficiency, let alone establish a causal relationship. However, even with a relatively small number of patients, analysis did uncover a significant relationship in short-term users between daily and cumulative inhaled steroid doses and serum cortisol levels 60 minutes after taking adrenocorticotropic hormone (R = -0.300 and -0.287, respectively; p < 0.05).

“A large number of patients with asthma may have adrenal insufficiency, even with low-to medium-dose inhaled steroid treatment when those inhaled steroids are administered over a long period,” the study authors wrote in the Annals of Allergy, Asthma & Immunology. “Thus, it is essential that patients with asthma under inhaled steroid treatment be checked for adrenal insufficiency much more frequently.”

The new study is not the first to find a connection between the usage of inhaled steroids and adrenal function. However, most prior research has focused on the dangers of adrenal insufficiency after patient stopped using corticosteroids.

A 2015 meta-analysis published in the Journal of Clinical Endocrinology & Metabolism analyzed 74 research articles that followed a total of 3,753 patients between 1975 in 2014. The authors found that the risk of adrenal insufficiency was greatest when patients stopped taking oral or injectable corticosteroids and that it was lower when they discontinued inhaled or topical treatments. Indeed, their analysis found that 6.8% of asthma patients developed adrenal insufficiency after they discontinued the use of inhaled steroids but that 43.7% of asthma patients developed adrenal insufficiency after they stopped using other steroid formulations.

The meta-analysis also found that the risk of developing adrenal insufficiency after discontinuation was positively correlated to corticosteroid dosage. About 2.4% of patients who have used the lowest steroid doses developed adrenal insufficiency after discontinuation, compared to about 21.5% of those using the highest doses.

Time was also a consideration. The longer patients used corticosteroids, the greater their risk of developing adrenal insufficiency upon discontinuation.

The authors of both studies recommend more frequent testing of adrenal function in asthma patients who use corticosteroids for any period of time. The authors of the meta-analysis added that patients can also help detect their own problems. Adrenal insufficiency often creates noticeable symptoms such as fatigue, dizziness, weight loss and salt cravings.

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