Adrenal suppression in patients with chronic obstructive pulmonary disease treated with glucocorticoids: Role of specific glucocorticoid receptor polymorphisms

PLoS One. 2022 Feb 4;17(2):e0262898. doi: 10.1371/journal.pone.0262898. eCollection 2022.

Abstract

Background: Single-nucleotide polymorphisms (SNPs) of the glucocorticoid receptor (GR) gene NR3C1 have been associated with an altered sensitivity to glucocorticoids, and thus may alter the therapeutic effects of glucocorticoids. We investigated the prevalence of adrenal suppression after treatment with glucocorticoids and evaluated whether GR SNPs were associated with altered risks of adrenal suppression and metabolic disorders in patients with chronic obstructive pulmonary disease (COPD).

Methods: In an observational prospective cohort study, we recruited 78 patients with severe COPD receiving 5 days glucocorticoid treatment for an exacerbation of COPD. In total, 55% of these patients were also receiving regular inhaled corticosteroids (ICS). Adrenal function was evaluated with a corticotropin test 30 days after the exacerbation. Patients were genotyped for Bcl1, N363S, ER22/23EK, and 9β SNPs.

Results: The prevalence of adrenal suppression (corticotropin-stimulated plasma-cortisol ≤ 420 nmol/L) 30 days after glucocorticoid treatment was 4/78 (5%). There was no difference between carriers and non-carriers of the polymorphisms (Bcl1, 9β, ER22/23K, and N363S) in corticotropin stimulated plasma-cortisol concentrations. In the haplotype analyses, we included the 50 patients who had a high-sensitivity (76%), a low-sensitivity (4%), or a wild-type (20%) GR haplotype. There was no difference in the frequency of adrenal suppression or metabolic disorders between the two stratified groups: (a) high-sensitivity (Bcl1 and/or N363S) haplotypes vs. (b) low-sensitivity (9β and/or ER22/23K) plus wild-type haplotypes (p > 0.05). Carriers of the high-sensitivity GR gene haplotype exhibited a steeper decline in stimulated P-cortisol with increased ICS dose (slope, -1.35 vs. 0.94; p = 0.17), compared to the group with low-sensitivity or wild-type haplotypes, respectively.

Conclusions: In total, 5% of patients exhibited insufficient adrenal function. The Bcl1 and N363S polymorphisms did not seem to increase the risk of glucocorticoid suppression or metabolic disorders in adults treated with glucocorticoids for COPD exacerbations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Glucocorticoids*

Substances

  • Glucocorticoids

Grants and funding

This study was funded by the Danish Regions Medical Fund (5894/16), the Danish Council for Independent Research (6110-00268B) and Herlev-Gentofte University hospital. The research salary of PS was sponsored by Herlev-Gentofte Hospital. The research salary of UFR was sponsored by an unrestricted research grant from the Novo Nordisk Fund. The research salary of SWB was sponsored by Skibsreder Per Henriksen, R. & Hustru’s Foundation; Eva Madura’s Foundation; and The Research Foundation of Copenhagen University Hospital, Rigshospitalet. Alexander G. Mathioudakis and Jørgen Vestbo are supported by the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre (BRC). The funders did not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.