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Potential Transcriptional Biomarkers to Guide Glucocorticoid Replacement in Autoimmune Addison's Disease

Bjorvatn Saevik, Åse (author)
Univ Bergen, Dept Clin Sci, Lab Bldg, 8th Floor, Jonas Lies Vei 91B, N-5021 Bergen, Norway; Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, NO-5021 Bergen, Norway
Wolff, Anette B. (author)
Univ Bergen, Dept Clin Sci, Lab Bldg, 8th Floor, Jonas Lies Vei 91B, N-5021 Bergen, Norway; Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, NO-5021 Bergen, Norway
Björnsdottir, Sigridur (author)
Karolinska Inst, Dept Mol Med & Surg, S-17177 Stockholm, Sweden; Karolinska Univ Hosp, Dept Endocrinol, S-17177 Stockholm, Sweden
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Simunkova, Katerina (author)
Univ Bergen, Dept Clin Sci, Lab Bldg, 8th Floor, Jonas Lies Vei 91B, N-5021 Bergen, Norway
Schei Hynne, Martha (author)
Univ Bergen, Dept Clin Sci, Lab Bldg, 8th Floor, Jonas Lies Vei 91B, N-5021 Bergen, Norway
Dolan, David William Peter (author)
Univ Bergen, Dept Informat, N-5020 Bergen, Norway
Bratland, Eirik (author)
Univ Bergen, Dept Clin Sci, Lab Bldg, 8th Floor, Jonas Lies Vei 91B, N-5021 Bergen, Norway; Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, NO-5021 Bergen, Norway; Haukeland Hosp, Dept Med Genet, NO-5021 Bergen, Norway
Knappskog, Per M. (author)
Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, NO-5021 Bergen, Norway; Haukeland Hosp, Dept Med Genet, NO-5021 Bergen, Norway
Methlie, Paal (author)
Univ Bergen, Dept Clin Sci, Lab Bldg, 8th Floor, Jonas Lies Vei 91B, N-5021 Bergen, Norway; Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, NO-5021 Bergen, Norway; Haukeland Hosp, Dept Med, NO-5021 Bergen, Norway
Carlsen, Siri (author)
Stavanger Univ Hosp, Dept Endocrinol, N-4068 Stavanger, Norway
Isaksson, Magnus (author)
Uppsala universitet,Endokrinologi och mineralmetabolism
Bensing, Sophie (author)
Karolinska Institutet
Kämpe, Olle (author)
Karolinska Institutet
Husebye, Eystein S. (author)
Univ Bergen, Dept Clin Sci, Lab Bldg, 8th Floor, Jonas Lies Vei 91B, N-5021 Bergen, Norway; Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, NO-5021 Bergen, Norway; Haukeland Hosp, Dept Med, NO-5021 Bergen, Norway; Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, S-17177 Stockholm, Sweden
Løvås, Kristian (author)
Univ Bergen, Dept Clin Sci, Lab Bldg, 8th Floor, Jonas Lies Vei 91B, N-5021 Bergen, Norway; Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, NO-5021 Bergen, Norway; Haukeland Hosp, Dept Med, NO-5021 Bergen, Norway
Øksnes, Marianne (author)
Univ Bergen, Dept Clin Sci, Lab Bldg, 8th Floor, Jonas Lies Vei 91B, N-5021 Bergen, Norway; Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, NO-5021 Bergen, Norway; Karolinska Univ Hosp, Dept Endocrinol, S-17177 Stockholm, Sweden; Haukeland Hosp, Dept Med, NO-5021 Bergen, Norway
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 (creator_code:org_t)
2021-01-04
2021
English.
In: Journal of the Endocrine Society. - : Endocrine Society. - 2472-1972. ; 5:3
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • BackgroundNo reliable biomarkers exist to guide glucocorticoid (GC) replacement treatment in autoimmune Addison’s disease (AAD), leading to overtreatment with alarming and persistent side effects or undertreatment, which could be fatal.ObjectiveTo explore changes in gene expression following different GC replacement doses as a means of identifying candidate transcriptional biomarkers to guide GC replacement in AAD.MethodsStep 1: Global microarray expression analysis on RNA from whole blood before and after intravenous infusion of 100 mg hydrocortisone (HC) in 10 patients with AAD. In 3 of the most highly upregulated genes, we performed real-time PCR (rt-PCR) to compare gene expression levels before and 3, 4, and 6 hours after the HC infusion. Step 2: Rt-PCR to compare expression levels of 93 GC-regulated genes in normal versus very low morning cortisol levels in 27 patients with AAD.ResultsStep 1: Two hours after infusion of 100 mg HC, there was a marked increase in FKBP5, MMP9, and DSIPI expression levels. MMP9 and DSIPI expression levels correlated with serum cortisol. Step 2: Expression levels of CEBPB, DDIT4, FKBP5, DSIPI, and VDR were increased and levels of ADARB1, ARIDB5, and POU2F1 decreased in normal versus very low morning cortisol. Normal serum cortisol levels positively correlated with DSIPI, DDIT4, and FKBP5 expression.ConclusionsWe introduce gene expression as a novel approach to guide GC replacement in AAD. We suggest that gene expression of DSIPI, DDIT4, and FKBP5 are particularly promising candidate biomarkers of GC replacement, followed by MMP9, CEBPB, VDR, ADARB1, ARID5B, and POU2F1.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Keyword

Addison's disease
primary adrenal insufficiency
biomarkers
gene expression
glucocorticoid

Publication and Content Type

ref (subject category)
art (subject category)

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