title: Body composition and bone mineral density in women with Cushing's syndrome in remission and the association with common genetic variants influencing glucocorticoid sensitivity.
abstract: OBJECTIVE
  Adverse body compositional features and low bone mineral density (BMD) are the characteristic of patients with active Cushing's syndrome (CS). The aim of this study was to evaluate body composition and BMD in women with CS in long-term remission and the influence of polymorphisms in genes affecting glucocorticoid (GC) sensitivity on these end-points.
  
  
  METHODS
  This was a cross-sectional, case-controlled study, including 50 women previously treated for CS and 50 age and gender-matched controls. Median (interquartile range) remission time was 13 (5-19) years. Body composition and BMD were measured with dual-energy X-ray absorptiometry. Five polymorphisms in four genes associated with GC sensitivity were analysed using TaqMan or Sequenom single-nucleotide polymorphism genotyping.
  
  
  RESULTS
  Patients with CS in remission had increased abdominal fat mass (P<0.01), whereas BMD was not significantly different at any site between patients and controls. In patients, the NR3C1 Bcl1 polymorphism was associated with reduced total (P<0.05) and femur neck BMD (P<0.05). The polymorphism rs1045642 in the ABCB1 gene was associated with increased abdominal fat mass (P<0.05) and decreased appendicular skeletal muscle mass (P<0.05). GC replacement was associated with reduced total BMD (P<0.01), BMD at lumbar spine (P<0.05) and increased abdominal fat (P<0.01).
  
  
  CONCLUSIONS
  Ongoing GC replacement therapy together with polymorphisms in two genes related with GC sensitivity is associated with abdominal obesity and adverse skeletal health in patients with CS in long-term remission.
authors.affiliation: Institute of Medicine at Sahlgrenska AcademyUniversity of Gothenburg, Göteborg, SwedenDepartment of EndocrinologySkaraborg Hospital, Skövde, SwedenDepartment of Internal MedicineNorra Älvsborgs Hospital, Trollhättan, SwedenDepartment of Internal MedicineSödra Älvsborgs Hospital, Borås, SwedenDepartment of SurgerySahlgrenska University Hospital, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden oskar.ragnarsson@medic.gu.se.
authors.forename: Oskar
authors.initials: O
authors.lastname: Ragnarsson
authors.affiliation: Institute of Medicine at Sahlgrenska AcademyUniversity of Gothenburg, Göteborg, SwedenDepartment of EndocrinologySkaraborg Hospital, Skövde, SwedenDepartment of Internal MedicineNorra Älvsborgs Hospital, Trollhättan, SwedenDepartment of Internal MedicineSödra Älvsborgs Hospital, Borås, SwedenDepartment of SurgerySahlgrenska University Hospital, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
authors.forename: Camilla A M
authors.initials: CA
authors.lastname: Glad
authors.affiliation: Institute of Medicine at Sahlgrenska AcademyUniversity of Gothenburg, Göteborg, SwedenDepartment of EndocrinologySkaraborg Hospital, Skövde, SwedenDepartment of Internal MedicineNorra Älvsborgs Hospital, Trollhättan, SwedenDepartment of Internal MedicineSödra Älvsborgs Hospital, Borås, SwedenDepartment of SurgerySahlgrenska University Hospital, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
authors.forename: Ragnhildur
authors.initials: R
authors.lastname: Bergthorsdottir
authors.affiliation: Institute of Medicine at Sahlgrenska AcademyUniversity of Gothenburg, Göteborg, SwedenDepartment of EndocrinologySkaraborg Hospital, Skövde, SwedenDepartment of Internal MedicineNorra Älvsborgs Hospital, Trollhättan, SwedenDepartment of Internal MedicineSödra Älvsborgs Hospital, Borås, SwedenDepartment of SurgerySahlgrenska University Hospital, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
authors.forename: Erik G
authors.initials: EG
authors.lastname: Almqvist
authors.affiliation: Institute of Medicine at Sahlgrenska AcademyUniversity of Gothenburg, Göteborg, SwedenDepartment of EndocrinologySkaraborg Hospital, Skövde, SwedenDepartment of Internal MedicineNorra Älvsborgs Hospital, Trollhättan, SwedenDepartment of Internal MedicineSödra Älvsborgs Hospital, Borås, SwedenDepartment of SurgerySahlgrenska University Hospital, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Ekerstad
authors.affiliation: Institute of Medicine at Sahlgrenska AcademyUniversity of Gothenburg, Göteborg, SwedenDepartment of EndocrinologySkaraborg Hospital, Skövde, SwedenDepartment of Internal MedicineNorra Älvsborgs Hospital, Trollhättan, SwedenDepartment of Internal MedicineSödra Älvsborgs Hospital, Borås, SwedenDepartment of SurgerySahlgrenska University Hospital, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
authors.forename: Håkan
authors.initials: H
authors.lastname: Widell
authors.affiliation: Institute of Medicine at Sahlgrenska AcademyUniversity of Gothenburg, Göteborg, SwedenDepartment of EndocrinologySkaraborg Hospital, Skövde, SwedenDepartment of Internal MedicineNorra Älvsborgs Hospital, Trollhättan, SwedenDepartment of Internal MedicineSödra Älvsborgs Hospital, Borås, SwedenDepartment of SurgerySahlgrenska University Hospital, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Wängberg
authors.affiliation: Institute of Medicine at Sahlgrenska AcademyUniversity of Gothenburg, Göteborg, SwedenDepartment of EndocrinologySkaraborg Hospital, Skövde, SwedenDepartment of Internal MedicineNorra Älvsborgs Hospital, Trollhättan, SwedenDepartment of Internal MedicineSödra Älvsborgs Hospital, Borås, SwedenDepartment of SurgerySahlgrenska University Hospital, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
authors.forename: Gudmundur
authors.initials: G
authors.lastname: Johannsson
mesh_terms: D001823:Body Composition / Q000502:physiology*; D015519:Bone Density / Q000502:physiology*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003480:Cushing Syndrome / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000502:physiology; D056726:Genetic Association Studies / Q000379:methods; D014644:Genetic Variation / Q000502:physiology*; D005938:Glucocorticoids / Q000097:blood*; D006801:Humans; D008875:Middle Aged; D012074:Remission Induction
chemical_list: D005938:Glucocorticoids