title: Serum free cortisol as an ancillary tool in the interpretation of the low-dose 1-μg ACTH test.
abstract: OBJECTIVE
  Serum free cortisol, rather than serum total cortisol (TC), determines glucocorticoid activity in vivo, but how the considerable inter-subject variation in ambient serum free cortisol affects the outcome of dynamic hypothalamic-pituitary-adrenal (HPA) assessment in noncritically ill subjects is unknown.
  
  
  METHODS
  We performed the low-dose 1-μg ACTH test in 75 subjects referred for HPA evaluation. Serum TC was determined by a chemiluminescence method, and serum free cortisol was measured by the same method following equilibrium dialysis. In a subset of these patients, salivary cortisol was also measured.
  
  
  RESULTS
  Mean fraction of free cortisol was 5·07 ± 4·08% (±SD; range 1·77-10·1%). Although no correlation was seen between TC and the fraction (%) of free serum cortisol, a positive correlation existed between baseline total and free cortisol (R = 0·539 P = 0·01), as well as between peak ACTH-stimulated total and free cortisol (R = 0·619; P = 0·01). There was no correlation between baseline salivary cortisol and serum free cortisol and between peak ACTH-stimulated salivary and serum free cortisol. Using the lowest attained peak serum free cortisol in subjects whose TC response to ACTH was normal (≥ 500 nM), the minimal 'pass' level for normal serum free cortisol response to 1 μg ACTH was set at 25·0 nM. Five of the 19 subjects showing subnormal TC response to 1 μg ACTH had normal serum free cortisol response.
  
  
  CONCLUSIONS
  Discrepancies between the peak free and TC were noted mostly for subjects whose ACTH-stimulated TC peaked between 440 and 580 nm. At this range, the measurement of serum free cortisol allows further refinement of the assessment of borderline responses to 1-μg ACTH.
authors.affiliation: Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Rona
authors.initials: R
authors.lastname: Limor
authors.forename: Karen
authors.initials: K
authors.lastname: Tordjman
authors.forename: Yonit
authors.initials: Y
authors.lastname: Marcus
authors.forename: Yona
authors.initials: Y
authors.lastname: Greenman
authors.forename: Etty
authors.initials: E
authors.lastname: Osher
authors.forename: Yael
authors.initials: Y
authors.lastname: Sofer
authors.forename: Naftali
authors.initials: N
authors.lastname: Stern
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004700:Endocrine System Diseases / Q000175:diagnosis* / Q000503:physiopathology; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D012469:Salivary Glands / Q000378:metabolism*; D012680:Sensitivity and Specificity
chemical_list: D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone