Plasma free cortisol fraction reflects levels of functioning corticosteroid-binding globulin.
BACKGROUND
In normal plasma free cortisol accounts for less than 6% of the total with 80-90% bound to corticosteroid-binding globulin (CBG) and the remainder associated albumin. However little is known about the distribution of free cortisol in plasma where CBG is inactivated or in congenital CBG deficiency.


RESULTS
Here we describe ligand binding experiments revealing that while free cortisol in unstressed individuals is less than 6% of total cortisol this rises markedly to 25% when CBG is totally inactivated by heat. Similar elevations of the free cortisol fraction were noted in a patient with a rare genetically determined complete lack of CBG (mean 32% on frequent circadian sampling). Following heat inactivation of CBG or in the congenital absence of CBG, there is a shift in cortisol binding from CBG to albumin. That this shift occurs is further supported by experiments adding [3H]-cortisol to physiological human serum albumin solutions, where 25% of cortisol remained in the free fraction.


CONCLUSIONS
Taken together the data provide strong evidence that when CBG is inactivated or congenitally absent then more than 25% of the total cortisol appears in the free fraction with the remainder associated with albumin. The proportion of free cortisol measured in plasma thus reflects a simple measure of functional corticosteroid-binding globulin.
Lewis
John G
JG
Steroid and Immunobiochemistry Laboratory, Canterbury Health Laboratories, PO Box 151 Christchurch, New Zealand. john.lewis@cdhb.govt.nz
Bagley
Christopher J
CJ
Elder
Peter A
PA
Bachmann
Anthony W
AW
Torpy
David J
DJ
D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008024:Ligands; D012709:Serum Albumin / Q000378:metabolism; D014156:Transcortin / Q000172:deficiency / Q000378:metabolism*
D008024:Ligands; D012709:Serum Albumin; D014156:Transcortin; D006854:Hydrocortisone