Metabolized cortisol best reflects total cortisol production.
What is cortisol:
Cortisol is a steroid hormone that is made in the adrenal glands (two triangular organs that sit on top of the kidneys) and then released into the blood, which transports it all round the body. Almost every cell contains receptors for cortisol and so cortisol can have lots of different actions depending on which sort of cells it is acting upon. Some of its functions are:
- controlling the body’s blood sugar levels
- acting as an anti-inflammatory
- influencing memory formation
- controlling salt and water balance
- influencing blood pressure
Blood levels of cortisol vary, but generally are high in the morning when we wake up, and then fall throughout the day (this can depend on your specific daily rhythm).
The human body produces cortisol first, and then different glands have the ability to keep it as cortisol or convert it into cortisone.
…back to metabolized cortisol:
Cortisol is metabolized into 5-alpha-Tetrahydrocortisol (5a-THF) and 5-beta-Tetrahydrocortisol (5b-THF) and cortisone is metabolized into 5-beta-Tetrahydrocortisone (5b-THE). Since all production and output originally started as cortisol, the cortisone metabolites are added to the cortisol metabolites when evaluating the “total metabolized cortisol”.
It essentially reflects how much cortisol was made in the body and has been processed out through the liver, into the kidney, and into the urine.
What is free cortisol:
The majority of cortisol (80-90%) circulates bound to cortisol-binding globulin (CBG) and albumin. Normally, less than 5% of circulating cortisol is free(unbound). Only free cortisol can access the enzyme transporters in liver, kidney, and other tissues that mediate metabolic and excretory clearance.
Free cortisol represents only about 1% of the total cortisol production (including the metabolites).
Why measure free cortisol and metabolized cortisol?
Metabolized cortisol answers the question of how much cortisol is being made in total and clearing through the liver. Whereas free-cortisol results tell us how much cortisol is free to bind to receptors and allows for assessment of the circadian rhythm.
Only a fraction of cortisol is “free” and bioactive. This fraction of cortisol is very important, but levels of metabolized cortisol best represents overall production of cortisol therefore both should be taken into account to correctly assess adrenal function.
Measuring both allows for insight into the rate of cortisol clearance/metabolism.
References:
- https://www.ncbi.nlm.nih.gov/pubmed/23505190
- https://www.ncbi.nlm.nih.gov/pubmed/11834433
- https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2265.2005.02412.x
- https://www.ncbi.nlm.nih.gov/pubmed/8257864
- https://www.ncbi.nlm.nih.gov/pubmed/18340018
- https://www.ncbi.nlm.nih.gov/pubmed/16402926
Metabolized Cortisol (THF+THE) (male)
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