Metabolized Cortisol (THF+THE)

Metabolized Cortisol is the sum of a-THF, b-THF and b-THE (the most abundant cortisol metabolites).

While free cortisol is the best assessment for tissue levels of cortisol, it only represents 1-3% of the total produced. The majority of cortisol results in a urine metabolite and the total of these metabolites best represents the total glandular output (=from glands) of cortisol for the day.

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 onto the DUTCH Test.

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 (=fat) 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.

The metabolized cortisol and free cortisol markers are important to use both together and separately in order to tell a more detailed story about the patient. 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.

-------------------------------------------------------------------------------------------

Correlating it with other markers:

-------------------------------------------------------------------------------------------

Metabolized cortisol → elevated

24hr Free cortisol → relatively low

This implies increased cortisol clearance. You see this a lot in people with obesity, people with too much thyroid medication (as it upregulates cortisol metabolism).  

-------------------------------------------------------------------------------------------

Metabolized cortisol → elevated

24hr Free cortisol → elevated

Cortisol throughout the day → elevated

Cortisol at night → elevated 

If cortisol is elevated all day, you have to start thinking about Cushing’s disease or potentially adrenal/pituitary tumors that are pushing out all that cortisol. 

-------------------------------------------------------------------------------------------

Metabolized cortisol → elevated

24hr Free cortisol → elevated

Cortisol throughout the day → elevated

Cortisol at night → normal (going back down)

If cortisol is going back down at the end of the day where it is supposed to be the above (Cushing’s disease, etc)  is not likely the case. In a case like this it seems that the HPA axis is really turned on ‘high’. The total of free cortisol would be very high, especially when they wake up and in the early parts of the day. The metabolites would confirm the story as they would be really high as well. 

-------------------------------------------------------------------------------------------

Metabolic preference:

Cortisol, which is the active hormone, can convert into cortisone, the inactive form. The Dutch report shows you which one you make more of by looking at whether cortisol metabolites (aTHF, bTHF) or cortisone metabolites (bTHE) are made more (compared to what is normal). Balance between the two is usually preferred, but making more cortisol than cortisone is sometimes good to help give you enough cortisol if your levels are low. In some cases this index is important for overall understanding of why symptoms of high or low cortisol may be predominating. In other cases this index is not critically important.

Is cortisol being broken down to its active form (cortisol metabolites) or to its inactive form (cortisone metabolites)?

- If cortisol is low, ideally its leaning towards cortisol metabolites: THF

- If cortisol is high, ideally it's not leaning against cortisol as it could exacerbate a high cortisol situation potentially.

- A preference for cortisone metabolites might be preferable as it is keeping cortisol levels from becoming even higher.