title: Thrombospondin-1 is a glucocorticoid responsive protein in humans.
abstract: OBJECTIVE
  Thrombospondin-1 (TSP1) is a matricellular protein whose gene expression has previously been shown to increase acutely after exposure to dexamethasone in vitro. The aim of this study was to determine if TSP1 is altered by acute and chronic states of glucocorticoid excess in human subjects.
  
  
  METHODS
  Three studies have been undertaken to assess the difference or change in TSP1 in response to altered glucocorticoid activity: i) an acute interventional study assessed the effects of a single 4 mg dose of dexamethasone in 20 healthy volunteers; ii) a cross-sectional study compared plasma TSP1 in 20 healthy volunteers and eight patients with Cushing's syndrome; iii) an interventional study assessed the effect on plasma TSP1 of an increase in hydrocortisone dose from ≤20 mg/day to 30 mg/day for 7 days in 16 patients with secondary adrenal insufficiency.
  
  
  RESULTS
  In healthy volunteers, 4 mg dexamethasone significantly increased peripheral blood mononuclear cell (PBMC) TSP1 mRNA levels (P<0.0001) and plasma TSP1 concentrations (P<0.0001), peaking at 12 h. Median (interquartile range) plasma TSP1 was higher in Cushing's, 638 (535-756) ng/ml, than in healthy volunteers, 272 (237-336) ng/ml (P<0.0001). Plasma TSP1 >400 ng/ml diagnosed Cushing's syndrome with sensitivity of 100% and specificity of 85%. The higher hydrocortisone dose increased plasma TSP1 from 139 (86-199) to 256 (133-516) ng/ml, (P<0.01) in patients with secondary adrenal insufficiency.
  
  
  CONCLUSIONS
  TSP1 is a glucocorticoid responsive protein in humans. Further research is required to determine if plasma TSP1 has a role as a glucocorticoid biomarker.
authors.affiliation: Mater Research InstituteUniversity of Queensland, Brisbane, AustraliaSchool of MedicineFlinders University, Adelaide, AustraliaSouthern Adelaide Diabetes and Endocrine ServicesRepatriation General Hospital, Adelaide, AustraliaSchool of MedicineUniversity of Queensland, Brisbane, AustraliaDepartment of Diabetes and EndocrinologyPrincess Alexandra Hospital, Woolloongabba, Brisbane, Queensland 4102, AustraliaDiscipline of MedicineUniversity of Adelaide, Adelaide, Australia.
authors.forename: Johanna L
authors.initials: JL
authors.lastname: Barclay
authors.affiliation: Mater Research InstituteUniversity of Queensland, Brisbane, AustraliaSchool of MedicineFlinders University, Adelaide, AustraliaSouthern Adelaide Diabetes and Endocrine ServicesRepatriation General Hospital, Adelaide, AustraliaSchool of MedicineUniversity of Queensland, Brisbane, AustraliaDepartment of Diabetes and EndocrinologyPrincess Alexandra Hospital, Woolloongabba, Brisbane, Queensland 4102, AustraliaDiscipline of MedicineUniversity of Adelaide, Adelaide, Australia Mater Research InstituteUniversity of Queensland, Brisbane, AustraliaSchool of MedicineFlinders University, Adelaide, AustraliaSouthern Adelaide Diabetes and Endocrine ServicesRepatriation General Hospital, Adelaide, AustraliaSchool of MedicineUniversity of Queensland, Brisbane, AustraliaDepartment of Diabetes and EndocrinologyPrincess Alexandra Hospital, Woolloongabba, Brisbane, Queensland 4102, AustraliaDiscipline of MedicineUniversity of Adelaide, Adelaide, Australia.
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Petersons
authors.affiliation: Mater Research InstituteUniversity of Queensland, Brisbane, AustraliaSchool of MedicineFlinders University, Adelaide, AustraliaSouthern Adelaide Diabetes and Endocrine ServicesRepatriation General Hospital, Adelaide, AustraliaSchool of MedicineUniversity of Queensland, Brisbane, AustraliaDepartment of Diabetes and EndocrinologyPrincess Alexandra Hospital, Woolloongabba, Brisbane, Queensland 4102, AustraliaDiscipline of MedicineUniversity of Adelaide, Adelaide, Australia.
authors.forename: Sahar
authors.initials: S
authors.lastname: Keshvari
authors.affiliation: Mater Research InstituteUniversity of Queensland, Brisbane, AustraliaSchool of MedicineFlinders University, Adelaide, AustraliaSouthern Adelaide Diabetes and Endocrine ServicesRepatriation General Hospital, Adelaide, AustraliaSchool of MedicineUniversity of Queensland, Brisbane, AustraliaDepartment of Diabetes and EndocrinologyPrincess Alexandra Hospital, Woolloongabba, Brisbane, Queensland 4102, AustraliaDiscipline of MedicineUniversity of Adelaide, Adelaide, Australia.
authors.forename: Jane
authors.initials: J
authors.lastname: Sorbello
authors.affiliation: Mater Research InstituteUniversity of Queensland, Brisbane, AustraliaSchool of MedicineFlinders University, Adelaide, AustraliaSouthern Adelaide Diabetes and Endocrine ServicesRepatriation General Hospital, Adelaide, AustraliaSchool of MedicineUniversity of Queensland, Brisbane, AustraliaDepartment of Diabetes and EndocrinologyPrincess Alexandra Hospital, Woolloongabba, Brisbane, Queensland 4102, AustraliaDiscipline of MedicineUniversity of Adelaide, Adelaide, Australia.
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Mangelsdorf
authors.affiliation: Mater Research InstituteUniversity of Queensland, Brisbane, AustraliaSchool of MedicineFlinders University, Adelaide, AustraliaSouthern Adelaide Diabetes and Endocrine ServicesRepatriation General Hospital, Adelaide, AustraliaSchool of MedicineUniversity of Queensland, Brisbane, AustraliaDepartment of Diabetes and EndocrinologyPrincess Alexandra Hospital, Woolloongabba, Brisbane, Queensland 4102, AustraliaDiscipline of MedicineUniversity of Adelaide, Adelaide, Australia Mater Research InstituteUniversity of Queensland, Brisbane, AustraliaSchool of MedicineFlinders University, Adelaide, AustraliaSouthern Adelaide Diabetes and Endocrine ServicesRepatriation General Hospital, Adelaide, AustraliaSchool of MedicineUniversity of Queensland, Brisbane, AustraliaDepartment of Diabetes and EndocrinologyPrincess Alexandra Hospital, Woolloongabba, Brisbane, Queensland 4102, AustraliaDiscipline of MedicineUniversity of Adelaide, Adelaide, Australia.
authors.forename: Campbell H
authors.initials: CH
authors.lastname: Thompson
authors.affiliation: Mater Research InstituteUniversity of Queensland, Brisbane, AustraliaSchool of MedicineFlinders University, Adelaide, AustraliaSouthern Adelaide Diabetes and Endocrine ServicesRepatriation General Hospital, Adelaide, AustraliaSchool of MedicineUniversity of Queensland, Brisbane, AustraliaDepartment of Diabetes and EndocrinologyPrincess Alexandra Hospital, Woolloongabba, Brisbane, Queensland 4102, AustraliaDiscipline of MedicineUniversity of Adelaide, Adelaide, Australia Mater Research InstituteUniversity of Queensland, Brisbane, AustraliaSchool of MedicineFlinders University, Adelaide, AustraliaSouthern Adelaide Diabetes and Endocrine ServicesRepatriation General Hospital, Adelaide, AustraliaSchool of MedicineUniversity of Queensland, Brisbane, AustraliaDepartment of Diabetes and EndocrinologyPrincess Alexandra Hospital, Woolloongabba, Brisbane, Queensland 4102, AustraliaDiscipline of MedicineUniversity of Adelaide, Adelaide, Australia.
authors.forename: Johannes B
authors.initials: JB
authors.lastname: Prins
authors.affiliation: Mater Research InstituteUniversity of Queensland, Brisbane, AustraliaSchool of MedicineFlinders University, Adelaide, AustraliaSouthern Adelaide Diabetes and Endocrine ServicesRepatriation General Hospital, Adelaide, AustraliaSchool of MedicineUniversity of Queensland, Brisbane, AustraliaDepartment of Diabetes and EndocrinologyPrincess Alexandra Hospital, Woolloongabba, Brisbane, Queensland 4102, AustraliaDiscipline of MedicineUniversity of Adelaide, Adelaide, Australia Mater Research InstituteUniversity of Queensland, Brisbane, AustraliaSchool of MedicineFlinders University, Adelaide, AustraliaSouthern Adelaide Diabetes and Endocrine ServicesRepatriation General Hospital, Adelaide, AustraliaSchool of MedicineUniversity of Queensland, Brisbane, AustraliaDepartment of Diabetes and EndocrinologyPrincess Alexandra Hospital, Woolloongabba, Brisbane, Queensland 4102, AustraliaDiscipline of MedicineUniversity of Adelaide, Adelaide, Australia.
authors.forename: Morton G
authors.initials: MG
authors.lastname: Burt
authors.affiliation: Mater Research InstituteUniversity of Queensland, Brisbane, AustraliaSchool of MedicineFlinders University, Adelaide, AustraliaSouthern Adelaide Diabetes and Endocrine ServicesRepatriation General Hospital, Adelaide, AustraliaSchool of MedicineUniversity of Queensland, Brisbane, AustraliaDepartment of Diabetes and EndocrinologyPrincess Alexandra Hospital, Woolloongabba, Brisbane, Queensland 4102, AustraliaDiscipline of MedicineUniversity of Adelaide, Adelaide, Australia.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Whitehead
authors.affiliation: Mater Research InstituteUniversity of Queensland, Brisbane, AustraliaSchool of MedicineFlinders University, Adelaide, AustraliaSouthern Adelaide Diabetes and Endocrine ServicesRepatriation General Hospital, Adelaide, AustraliaSchool of MedicineUniversity of Queensland, Brisbane, AustraliaDepartment of Diabetes and EndocrinologyPrincess Alexandra Hospital, Woolloongabba, Brisbane, Queensland 4102, AustraliaDiscipline of MedicineUniversity of Adelaide, Adelaide, Australia Mater Research InstituteUniversity of Queensland, Brisbane, AustraliaSchool of MedicineFlinders University, Adelaide, AustraliaSouthern Adelaide Diabetes and Endocrine ServicesRepatriation General Hospital, Adelaide, AustraliaSchool of MedicineUniversity of Queensland, Brisbane, AustraliaDepartment of Diabetes and EndocrinologyPrincess Alexandra Hospital, Woolloongabba, Brisbane, Queensland 4102, AustraliaDiscipline of MedicineUniversity of Adelaide, Adelaide, Australia warrick.inder@health.qld.gov.au.
authors.forename: Warrick J
authors.initials: WJ
authors.lastname: Inder
mesh_terms: D000309:Adrenal Insufficiency / Q000097:blood* / Q000188:drug therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D003480:Cushing Syndrome / Q000097:blood*; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity; D019700:Thrombospondin 1 / Q000097:blood* / Q000187:drug effects*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D005938:Glucocorticoids; D019700:Thrombospondin 1; D003907:Dexamethasone; D006854:Hydrocortisone