Adrenal suppression in patients with chronic obstructive pulmonary disease treated with glucocorticoids: Role of specific glucocorticoid receptor polymorphisms
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 glucoco...
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| Veröffentlicht in: | PloS one 2022-02, Vol.17 (2), p.e0262898 |
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| creator | Sivapalan, Pradeesh Borresen, Stina Willemoes Eklöf, Josefin Klose, Marianne Holm, Freja S Feldt-Rasmussen, Ulla Rossing, Maria Jørgensen, Niklas R Marvig, Rasmus L Saeed, Mohamad Isam Wilcke, Torgny Seersholm, Niels Mathioudakis, Alexander G Vestbo, Jørgen Jensen, Jens-Ulrik Stæhr |
| description | 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).
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.
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.
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. |
| doi_str_mv | 10.1371/journal.pone.0262898 |
| format | Article |
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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.
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.
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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0262898</identifier><identifier>PMID: 35120172</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Addison's disease ; Adrenal Glands - drug effects ; Adrenal Glands - metabolism ; Aged ; Biology and Life Sciences ; Chronic obstructive pulmonary disease ; Clinical medicine ; Complications and side effects ; Corticoids ; Corticosteroids ; Diabetes ; Drug dosages ; Drug therapy ; Endocrinology ; Female ; Glucocorticoid receptors ; Glucocorticoids ; Glucocorticoids - administration & dosage ; Glucocorticoids - adverse effects ; Glucocorticoids - therapeutic use ; Haplotypes ; Health risks ; Health sciences ; Hormones ; Hospitals ; Humans ; Hydrocortisone - blood ; Lung diseases ; Male ; Medical treatment ; Medicine ; Medicine and Health Sciences ; Metabolic disorders ; Middle Aged ; Nucleotides ; Obstructive lung disease ; Patients ; Polymorphism ; Polymorphism, Single Nucleotide ; Prospective Studies ; Pulmonary Disease, Chronic Obstructive - drug therapy ; Pulmonary Disease, Chronic Obstructive - genetics ; Receptors ; Receptors, Glucocorticoid - genetics ; Rheumatoid arthritis ; Risk factors ; Single-nucleotide polymorphism ; Steroids</subject><ispartof>PloS one, 2022-02, Vol.17 (2), p.e0262898</ispartof><rights>COPYRIGHT 2022 Public Library of Science</rights><rights>2022 Sivapalan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 Sivapalan et al 2022 Sivapalan et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c653t-41b5679202c91f21f525121dab719ada9a3c5eea69904d38cb5d8325b02c25003</citedby><cites>FETCH-LOGICAL-c653t-41b5679202c91f21f525121dab719ada9a3c5eea69904d38cb5d8325b02c25003</cites><orcidid>0000-0002-4675-9616 ; 0000-0002-8620-3655 ; 0000-0002-5267-3173 ; 0000-0002-5903-3355</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8815987/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8815987/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35120172$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sivapalan, Pradeesh</creatorcontrib><creatorcontrib>Borresen, Stina Willemoes</creatorcontrib><creatorcontrib>Eklöf, Josefin</creatorcontrib><creatorcontrib>Klose, Marianne</creatorcontrib><creatorcontrib>Holm, Freja S</creatorcontrib><creatorcontrib>Feldt-Rasmussen, Ulla</creatorcontrib><creatorcontrib>Rossing, Maria</creatorcontrib><creatorcontrib>Jørgensen, Niklas R</creatorcontrib><creatorcontrib>Marvig, Rasmus L</creatorcontrib><creatorcontrib>Saeed, Mohamad Isam</creatorcontrib><creatorcontrib>Wilcke, Torgny</creatorcontrib><creatorcontrib>Seersholm, Niels</creatorcontrib><creatorcontrib>Mathioudakis, Alexander G</creatorcontrib><creatorcontrib>Vestbo, Jørgen</creatorcontrib><creatorcontrib>Jensen, Jens-Ulrik Stæhr</creatorcontrib><title>Adrenal suppression in patients with chronic obstructive pulmonary disease treated with glucocorticoids: Role of specific glucocorticoid receptor polymorphisms</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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).
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.
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.
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.</description><subject>Addison's disease</subject><subject>Adrenal Glands - drug effects</subject><subject>Adrenal Glands - metabolism</subject><subject>Aged</subject><subject>Biology and Life Sciences</subject><subject>Chronic obstructive pulmonary disease</subject><subject>Clinical medicine</subject><subject>Complications and side effects</subject><subject>Corticoids</subject><subject>Corticosteroids</subject><subject>Diabetes</subject><subject>Drug dosages</subject><subject>Drug therapy</subject><subject>Endocrinology</subject><subject>Female</subject><subject>Glucocorticoid receptors</subject><subject>Glucocorticoids</subject><subject>Glucocorticoids - administration & dosage</subject><subject>Glucocorticoids - adverse effects</subject><subject>Glucocorticoids - therapeutic use</subject><subject>Haplotypes</subject><subject>Health risks</subject><subject>Health sciences</subject><subject>Hormones</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Hydrocortisone - blood</subject><subject>Lung diseases</subject><subject>Male</subject><subject>Medical treatment</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Metabolic disorders</subject><subject>Middle Aged</subject><subject>Nucleotides</subject><subject>Obstructive lung disease</subject><subject>Patients</subject><subject>Polymorphism</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Prospective Studies</subject><subject>Pulmonary Disease, Chronic Obstructive - drug therapy</subject><subject>Pulmonary Disease, Chronic Obstructive - genetics</subject><subject>Receptors</subject><subject>Receptors, Glucocorticoid - genetics</subject><subject>Rheumatoid arthritis</subject><subject>Risk factors</subject><subject>Single-nucleotide 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suppression in patients with chronic obstructive pulmonary disease treated with glucocorticoids: Role of specific glucocorticoid receptor polymorphisms</title><author>Sivapalan, Pradeesh ; Borresen, Stina Willemoes ; Eklöf, Josefin ; Klose, Marianne ; Holm, Freja S ; Feldt-Rasmussen, Ulla ; Rossing, Maria ; Jørgensen, Niklas R ; Marvig, Rasmus L ; Saeed, Mohamad Isam ; Wilcke, Torgny ; Seersholm, Niels ; Mathioudakis, Alexander G ; Vestbo, Jørgen ; Jensen, Jens-Ulrik Stæhr</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c653t-41b5679202c91f21f525121dab719ada9a3c5eea69904d38cb5d8325b02c25003</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Addison's disease</topic><topic>Adrenal Glands - drug effects</topic><topic>Adrenal Glands - metabolism</topic><topic>Aged</topic><topic>Biology and Life Sciences</topic><topic>Chronic obstructive pulmonary disease</topic><topic>Clinical 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Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sivapalan, Pradeesh</au><au>Borresen, Stina Willemoes</au><au>Eklöf, Josefin</au><au>Klose, Marianne</au><au>Holm, Freja S</au><au>Feldt-Rasmussen, Ulla</au><au>Rossing, Maria</au><au>Jørgensen, Niklas R</au><au>Marvig, Rasmus L</au><au>Saeed, Mohamad Isam</au><au>Wilcke, Torgny</au><au>Seersholm, Niels</au><au>Mathioudakis, Alexander G</au><au>Vestbo, Jørgen</au><au>Jensen, Jens-Ulrik Stæhr</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adrenal suppression in patients with chronic obstructive pulmonary disease treated with glucocorticoids: Role of specific glucocorticoid receptor polymorphisms</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2022-02-04</date><risdate>2022</risdate><volume>17</volume><issue>2</issue><spage>e0262898</spage><pages>e0262898-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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).
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.
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.
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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>35120172</pmid><doi>10.1371/journal.pone.0262898</doi><tpages>e0262898</tpages><orcidid>https://orcid.org/0000-0002-4675-9616</orcidid><orcidid>https://orcid.org/0000-0002-8620-3655</orcidid><orcidid>https://orcid.org/0000-0002-5267-3173</orcidid><orcidid>https://orcid.org/0000-0002-5903-3355</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2022-02, Vol.17 (2), p.e0262898 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2625529473 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Addison's disease Adrenal Glands - drug effects Adrenal Glands - metabolism Aged Biology and Life Sciences Chronic obstructive pulmonary disease Clinical medicine Complications and side effects Corticoids Corticosteroids Diabetes Drug dosages Drug therapy Endocrinology Female Glucocorticoid receptors Glucocorticoids Glucocorticoids - administration & dosage Glucocorticoids - adverse effects Glucocorticoids - therapeutic use Haplotypes Health risks Health sciences Hormones Hospitals Humans Hydrocortisone - blood Lung diseases Male Medical treatment Medicine Medicine and Health Sciences Metabolic disorders Middle Aged Nucleotides Obstructive lung disease Patients Polymorphism Polymorphism, Single Nucleotide Prospective Studies Pulmonary Disease, Chronic Obstructive - drug therapy Pulmonary Disease, Chronic Obstructive - genetics Receptors Receptors, Glucocorticoid - genetics Rheumatoid arthritis Risk factors Single-nucleotide polymorphism Steroids |
| title | Adrenal suppression in patients with chronic obstructive pulmonary disease treated with glucocorticoids: Role of specific glucocorticoid receptor polymorphisms |
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