Inhaled corticosteroid asthma treatment linked to adrenal suppression

Even low-dose treatment courses of inhaled corticosteroids for asthma can lead to adrenal suppression including fatigue, headache, abdominal pain, vomiting and psychiatric symptoms, according to a study published in Nature Medicine.

“The initial motivation was to look at the difference in the metabolome for individuals with asthma relative to controls and to identify some asthma-specific metabolic signatures,” Jessica A. Lasky-Su, DSc, MS, associate statistician with the Channing Division of Network Medicine at Brigham and Women’s Hospital, told Healio.

Jessica A. Lasky-Su

“While metabolomic studies for asthma have been performed before, they have never been done in the size that we utilized here, so we were really curious what we would see,” said Lasky-Su, who also is an associate professor of medicine at Harvard Medical School.

Inhaled corticosteroids (ICS) have been instrumental in reducing asthma exacerbations and improving overall quality of life, the researchers wrote, although the risks that come with their use should be considered as well.

Noting that the Global Initiative for Asthma changed its guidelines in 2021 to recommend “as-needed” low-dose ICS use as a preferred relief option among adolescents and adults, the researchers used metabolomics — or the systematic analysis of small molecules in a biological sample — to study the effect of ICS use on asthma.

The examination of blood plasma from more than 14,000 individuals participating in four independent epidemiological studies yielded 973 steroid metabolites for analysis. According to the researchers, 17 of these metabolites were significantly reduced in individuals with prevalent asthma. These included reductions in DHEA-S and cortisol, which are primary hypothalamic-pituitary-adrenal axis steroid hormones that are biomarkers for adrenal suppression.

Steroid levels were reduced among all asthma cases regardless of medication use, although the largest reductions were associated with ICS use. These effects were dose-dependent, with significant reductions even at low doses, the researchers found.

Additionally, average peak cortisol levels among patients on ICS did not reach the average lowest cortisol levels of other patients across the four reviewed studies throughout the entire 24-hour daily collection period.

Mild asthma cases with ICS use also had significant increases in fatigue (OR = 2.27; 95% CI, 1.61-3.22) and anemia (OR = 2.28; 95% CI, 1.57-3.35) but not in weight loss or hyperpigmentation compared with cases that did not use ICS.

“While we were not surprised to see some dysregulation in corticosteroids among asthma cases in any type of steroid treatment, oral or inhaled, we were surprised by the extent of adrenal suppression that was observed with inhaled steroid treatment among all classes of steroids, such as corticosteroids, pregnenolones, androgens, etc,” Lasky-Su said.

Considering these impacts, the researchers called for research into personalized approaches for asthma treatment specific to ICS use, particularly for individuals with genetic susceptibility to corticosteroid-induced adrenal suppression.

“We are following this up with more careful studies of the effects of inhaled steroids on adrenal function in multiple different frameworks,” Lasky-Su said.

The researchers also recommended regular monitoring of adrenal hormones, particularly morning cortisol levels, among individuals using ICS to identify those at risk and enable treatment modifications, such as use of the lowest dose for symptom control before significant and possibly permanent long-term complications develop.

“The extent of adrenal suppression from inhaled steroid use is more pervasive than originally thought. Regular monitoring of adrenal function is merited among individuals with long-term inhaled steroid treatment to maintain the optimal balance of efficacy between the benefits of inhaled steroids and the potential risks of adrenal suppression,” Lasky-Su said.

Reference:

• Metabolomic study links inhaled cortical steroid treatment for asthma to adrenal suppression. https://www.mrc-epid.cam.ac.uk/blog/2022/03/21/metabolomic-inhaled-cortical-steroid-asthma-adrenal-suppression/. Posted March 21, 2022. Accessed March 23, 2022.

For more information:

Jessica A. Lasky-Su, DSc, MS, can be reached at jessica.a.su@gmail.com.