Metabolized Cortisol (THF+THE)

DUTCH

A healthy result should fall into the range 2750 - 6500 ng/mg.

Cortisol is made from cholesterol in the Zona fasciculata layer of the adrenal cortex. 80-90% of cortisol is bound to cortisol-binding globulin (CBG); much like thyroid is bound to thyroid-binding globulin (TBG) and testosterone is bound to sex hormone-binding globulin (SHBG). A very small percentage of cortisol is free and unbound, while the remaining is in transition. The human body produces cortisol first, and then different glands have the ability to keep it as cortisol or convert it into cortisone, which is biologically inactive, through the enzyme 11-beta-hydroxysteroiddehydrogenase (11bHSD).

Cortisol is then 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.

The amount of cortisol produced and the amount of free cortisol available can be very different in some scenarios. Measuring both allows for insight into the rate of cortisol clearance/metabolism. For example, higher levels of metabolized cortisol (compared to free cortisol) are often seen in obesity where adipose tissue is likely pulling cortisol from its binding protein and allowing for metabolism and clearance. The adrenal gland has to keep up with this cortisol sequestering and excretion, so cortisol production is often quite high (as seen in the levels of metabolized cortisol) even though free cortisol does not correlate positively with adipose tissue or BMI. This insight is quite helpful for those looking to lose belly fat and suspect cortisol/stress is a major factor. These patients are often misdiagnosed as having low cortisol production when only free cortisol is measured. Increased cortisol clearance may also be seen in hyperthyroidism and is suspected to be part of the chronic fatigue story as well.

In patients with low thyroid, the opposite pattern is often seen. When the thyroid slows down or if there is peripheral hypothyroidism where free T3 cannot get into the cells, the clearance (or metabolism) of cortisol through the liver slows down. The literature is more definitive for lower metabolized vs. higher “free”. 

The metabolized cortisol and free cortisol markers are important to use both together and separately in order to tell a more detailed story. 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. The metabolites of cortisol also give insight into the relative activity of 11b-HSD types I and II, which controls the activation and inactivation (to cortisone) of cortisol. Having the most comprehensive testing available with the DUTCH Test™ allows for a more complete look at the overall HPA-axis picture. This in turn leads to better treatment and clinical outcomes.

Metabolized Cortisol (THF+THE) result calculator

insert the value from you Metabolized Cortisol (THF+THE) test result.

What does it mean if your Metabolized Cortisol (THF+THE) result is too high?

Higher levels of metabolized cortisol (vs free):

For example, higher levels of metabolized cortisol (compared to free cortisol) are often seen in obesity where adipose tissue is likely pulling cortisol from its binding protein and allowing for metabolism and clearance. The adrenal gland has to keep up with this cortisol sequestering and excretion, so cortisol production is often quite high (as seen in the levels of metabolized cortisol) even though free cortisol does not correlate positively with adipose tissue or BMI. This insight is quite helpful for those looking to lose belly fat and suspect cortisol/stress is a major factor. These people are often misdiagnosed as having low cortisol production when only free cortisol is measured. Increased cortisol clearance may also be seen in hyperthyroidism and is suspected to be part of the chronic fatigue story as well.

In people with low thyroid, the opposite pattern is often seen. When the thyroid slows down or if there is peripheral hypothyroidism where free T3 cannot get into the cells, the clearance (or metabolism) of cortisol through the liver slows down. As a result, free cortisol starts to increase and may show up elevated in urine.

The metabolized cortisol and free cortisol markers are important to use both together and separately in order to tell a more detailed story. 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. The metabolites of cortisol also give insight into the relative activity of 11b-HSD types I and II, which controls the activation and inactivation (to cortisone) of cortisol.



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