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Serum free cortisol as an ancillary tool in the interpretation of the low‐dose 1‐μg ACTH test
Author(s) -
Limor Rona,
Tordjman Karen,
Marcus Yonit,
Greenman Yona,
Osher Etty,
Sofer Yael,
Stern Naftali
Publication year - 2011
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2011.04080.x
Subject(s) - medicine , endocrinology , hydrocortisone , free fraction , glucocorticoid , adrenocorticotropic hormone , chemistry , hormone , pharmacokinetics
Summary 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. Design, patients and measurements 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 n m ), the minimal ‘pass’ level for normal serum free cortisol response to 1 μg ACTH was set at 25·0 n m . 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 n m . At this range, the measurement of serum free cortisol allows further refinement of the assessment of borderline responses to 1‐μg ACTH.