title: Differential glucocorticoid metabolism in patients with persistent versus resolving inflammatory arthritis.
abstract: BACKGROUND
  Impairment in the ability of the inflamed synovium to generate cortisol has been proposed to be a factor in the persistence and severity of inflammatory arthritis. In the inflamed synovium, cortisol is generated from cortisone by the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme. The objective of this study was to determine the role of endogenous glucocorticoid metabolism in the development of persistent inflammatory arthritis.
  
  
  METHODS
  Urine samples were collected from patients with early arthritis (symptoms ≤12 weeks duration) whose final diagnostic outcomes were established after clinical follow-up and from patients with established rheumatoid arthritis (RA). All patients were free of disease-modifying anti-rheumatic drugs at the time of sample collection. Systemic measures of glucocorticoid metabolism were assessed in the urine samples by gas chromatography/mass spectrometry. Clinical data including CRP and ESR were also collected at baseline.
  
  
  RESULTS
  Systemic measures of 11β-HSD1 activity were significantly higher in patients with early arthritis whose disease went on to persist, and also in the subgroup of patients with persistent disease who developed RA, when compared with patients whose synovitis resolved over time. We observed a significant positive correlation between systemic 11β-HSD1 activity and ESR/CRP in patients with established RA but not in any of the early arthritis patients group.
  
  
  CONCLUSIONS
  The present study demonstrates that patients with a new onset of synovitis whose disease subsequently resolved had significantly lower levels of systemic 11β-HSD1 activity when compared with patients whose synovitis developed into RA or other forms of persistent arthritis. Low absolute levels of 11β-HSD1 activity do not therefore appear to be a major contributor to the development of RA and it is possible that a high total body 11β-HSD1 activity during early arthritis may reduce the probability of disease resolution.
authors.affiliation: Rheumatology Research Group, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. dxn861@bham.ac.uk.|Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. dxn861@bham.ac.uk.
authors.forename: Dominika E
authors.initials: DE
authors.lastname: Nanus
authors.affiliation: Rheumatology Research Group, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. A.FILER@bham.ac.uk.|Rheumatology, University Hospitals Birmingham NHS Foundation Trust, Edgbaston, Birmingham, B15 2TH, UK. A.FILER@bham.ac.uk.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Filer
authors.affiliation: Rheumatology Research Group, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. lorraine.yeo@kcl.ac.uk.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Yeo
authors.affiliation: Rheumatology Research Group, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. D.Scheel@bham.ac.uk.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Scheel-Toellner
authors.affiliation: Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. R.Hardy@bham.ac.uk.
authors.forename: Rowan
authors.initials: R
authors.lastname: Hardy
authors.affiliation: Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. G.G.Lavery@bham.ac.uk.
authors.forename: Gareth G
authors.initials: GG
authors.lastname: Lavery
authors.affiliation: Faculty of Medicine and Health, University of Leeds, Worsley Building, Leeds, LS2 9JT, UK. p.m.stewart@leeds.ac.uk.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Stewart
authors.affiliation: Rheumatology Research Group, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. C.D.BUCKLEY@bham.ac.uk.|Rheumatology, Sandwell and West Birmingham Hospitals NHS Trust, Dudley Road, Birmingham, B18 7QH, UK. C.D.BUCKLEY@bham.ac.uk.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Buckley
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LE, UK. jeremy.tomlinson@ocdem.ox.ac.uk.
authors.forename: Jeremy W
authors.initials: JW
authors.lastname: Tomlinson
authors.affiliation: ANZAC Research Institute, Concord Repatriation General Hospital, University of Sydney, Hospital Road, Sydney, NSW 2139, Australia. mark.cooper@sydney.edu.au.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Cooper
authors.affiliation: Rheumatology Research Group, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. K.Raza@bham.ac.uk.|Rheumatology, Sandwell and West Birmingham Hospitals NHS Trust, Dudley Road, Birmingham, B18 7QH, UK. K.Raza@bham.ac.uk.
authors.forename: Karim
authors.initials: K
authors.lastname: Raza
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism*; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology*; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000032:analysis*; D015331:Cohort Studies; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D010507:Periodicity; D011379:Prognosis; D011446:Prospective Studies; D012008:Recurrence; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D013585:Synovitis / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology
chemical_list: D018501:Antirheumatic Agents; D002097:C-Reactive Protein; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1