title: An evaluation of measured and calculated serum free cortisol in a group of patients with known adrenal suppression.
abstract: BACKGROUND
  Since more than 90% of cortisol is bound to protein, serum free cortisol (SFC) may be a more appropriate marker of adrenal status than total cortisol. However, measurement of SFC is technically difficult and calculated SFC may offer a more practical alternative.
  
  
  METHODS
  SFC, measured by equilibrium dialysis coupled with immunoassay, and calculated using Coolens' equation from total cortisol and corticosteroid binding globulin (CBG) concentrations, was compared in short Synacthen test (SST) serum from 42 patients, of whom 20 demonstrated a suppressed adrenal response.
  
  
  RESULTS
  Considering the patient group as a whole, calculated SFC was found to be significantly lower than measured SFC, pre- and post-Synacthen (P < 0.05 and <0.001, respectively). Upon classifying the patients as pass or fail based on total cortisol response to Synacthen, the difference in calculated and measured SFC only reached statistical significance for post-Synacthen concentrations in the pass group (P < 0.01), suggesting a greater discrepancy at higher cortisol concentrations. There was no difference in CBG levels between the pass and fail groups and both measured and calculated SFC gave a diminished 30 min response in subjects deemed to have failed the SST.
  
  
  CONCLUSIONS
  Coolens' equation was found to underestimate measured SFC in this cohort of outpatients, as has been previously demonstrated, particularly in patients with a pronounced acute phase response. Although calculated SFC gave a diminished response in individuals deemed to have failed the SST, the concentration-dependent nature of the discrepancy may limit the usefulness of this method for assessing adrenal status.
authors.affiliation: Regional Endocrine Laboratory, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
authors.forename: Nicola L
authors.initials: NL
authors.lastname: Barlow
authors.forename: Jayne
authors.initials: J
authors.lastname: Holme
authors.forename: Robert A
authors.initials: RA
authors.lastname: Stockley
authors.forename: Penelope M
authors.initials: PM
authors.lastname: Clark
mesh_terms: D000309:Adrenal Insufficiency / Q000175:diagnosis*; D000368:Aged; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis*; D007118:Immunoassay; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D014156:Transcortin / Q000032:analysis
chemical_list: D014156:Transcortin; D006854:Hydrocortisone