TY - JOUR
T1 - Adrenal suppression in patients with chronic obstructive pulmonary disease treated with glucocorticoids
T2 - Role of specific glucocorticoid receptor polymorphisms
AU - Sivapalan, Pradeesh
AU - Borresen, Stina Willemoes
AU - Ekloef, Josefin
AU - Klose, Marianne
AU - Holm, Freja S.
AU - Feldt-Rasmussen, Ulla
AU - Rossing, Maria
AU - Jorgensen, Niklas R.
AU - Marvig, Rasmus L.
AU - Saeed, Mohamad Isam
AU - Wilcke, Torgny
AU - Seersholm, Niels
AU - Mathioudakis, Alexander G.
AU - Vestbo, Jorgen
AU - Jensen, Jens-Ulrik Staehr
PY - 2022/2/4
Y1 - 2022/2/4
N2 - BackgroundSingle-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).MethodsIn 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 9 beta SNPs.ResultsThe prevalence of adrenal suppression (corticotropin-stimulated plasma-cortisol 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.ConclusionsIn 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.
AB - BackgroundSingle-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).MethodsIn 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 9 beta SNPs.ResultsThe prevalence of adrenal suppression (corticotropin-stimulated plasma-cortisol 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.ConclusionsIn 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.
KW - INHALED CORTICOSTEROIDS
KW - GENETIC ASSOCIATIONS
KW - BCLI POLYMORPHISM
KW - IN-VIVO
KW - SENSITIVITY
KW - ASTHMA
KW - EXPRESSION
KW - BETA
U2 - 10.1371/journal.pone.0262898
DO - 10.1371/journal.pone.0262898
M3 - Journal article
C2 - 35120172
SN - 1932-6203
VL - 17
JO - PLoS ONE
JF - PLoS ONE
IS - 2
M1 - 0262898
ER -