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.
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Correlating it with other markers:
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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).
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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.
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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.
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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.
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High free cortisol (and high free cortisone) and high metabolized cortisol:
In this situation there is an abundance of cortisol.
General signs and symptoms of too much cortisol include:
- weight gain, mostly around the midsection and upper back
- weight gain and rounding of the face
- acne
- thinning skin
- easy bruising
- flushed face
- slowed healing
- muscle weakness
- severe fatigue
- irritability
- difficulty concentrating
- high blood pressure
- headache
Low free cortisol and high metabolized cortisol:
This is a picture of elevated cortisol metabolism and low circulating cortisol.
This can be seen in people with:
- High thyroid
- Obesity (high insulin)
- Long-term stress (high cortisol over long periods of time)
- Long-term glucocorticoid use
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. 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.
Anthony
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As a PRO member and medical practitioner, Healthmatters.io has been an invaluable tool for tracking my clients' data. The layout is intuitive, making it easy to monitor trends and spot patterns over time. The ability to customize reports and charts helps me present information clearly to my clients, improving communication and outcomes. It's streamlined my workflow, saving me time and providing insights at a glance. Highly recommended for any practitioner looking for a comprehensive and user-friendly solution to track patient labs!
High free cortisol and low metabolized cortisol:
==> Slow cortisol clearance
Possible due to hypothyroidism:
Lower Thyroid (free T4) leads to lower metabolized cortisol (THF, THE).
When the thyroid slows down the clearance (or metabolism) of cortisol through the liver slows down. As a result, free cortisol starts to increase and may show up elevated.
Low free cortisol and low metabolized cortisol:
Not a lot of cortisol is being produced.
Some of the possible symptoms might include:
- Extreme fatigue
- Weight loss and decreased appetite
- Darkening of your skin (hyperpigmentation)
- Low blood pressure, even fainting
- Salt craving
- Low blood sugar (hypoglycemia)
- Nausea, diarrhea or vomiting (gastrointestinal symptoms)
- Abdominal pain
- Muscle or joint pains
- Irritability
- Depression or other behavioral symptoms
- Body hair loss or sexual dysfunction in women
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Unlimited Plan Member since 2021
I have been using Healthmatters.io since 2021. I travel all over the world and use different doctors and health facilities. This site has allowed me to consolidate all my various test results over 14 years in one place. And every doctor that I show this to has been impressed. Because with any health professional I talk to, I can pull up historical results in seconds. It is invaluable. Even going back to the same doctor, they usually do not have the historical results from their facility in a graph format. That has been very helpful.
Karin
Advanced Plan Member since 2020
What fantastic service and great, easy-to-follow layouts! I love your website; it makes it so helpful to see patterns in my health data. It's truly a pleasure to use. I only wish the NHS was as organized and quick as Healthmatters.io. You've set a new standard for health tracking!
Paul
Healthmatters Pro Member since 2024
As a PRO member and medical practitioner, Healthmatters.io has been an invaluable tool for tracking my clients' data. The layout is intuitive, making it easy to monitor trends and spot patterns over time. The ability to customize reports and charts helps me present information clearly to my clients, improving communication and outcomes. It's streamlined my workflow, saving me time and providing insights at a glance. Highly recommended for any practitioner looking for a comprehensive and user-friendly solution to track patient labs!
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24hr Free Cortisol, 24hr Free Cortisone, a-Tetrahydrocortisol (a-THF), a-Tetrahydrocortisol (a-THF) (male), b-Tetrahydrocortisol (b-THF), b-Tetrahydrocortisol (b-THF) (male), b-Tetrahydrocortisone (b-THE), b-Tetrahydrocortisone (b-THE) (male), Cortisol A (Waking), Cortisol B (Morning), Cortisol C (Afternoon), Cortisol D (Night), Cortisone A (Waking), Cortisone B (Morning), Cortisone C (Afternoon), Cortisone D (Night), Metabolized Cortisol (THF+THE), Metabolized Cortisol (THF+THE) (male), Saliva Cortisol - Afternoon, Saliva Cortisol - Extra 1, Saliva Cortisol - Insomnia, Saliva Cortisol - Night, Saliva Cortisol - W+30 min., Saliva Cortisol - W+60 min., Saliva Cortisol - Waking, Saliva Cortisol Total, Saliva Cortisone - Afternoon, Saliva Cortisone - Extra 1, Saliva Cortisone - Insomnia, Saliva Cortisone - Night, Saliva Cortisone - W+30 min, Saliva Cortisone - W+60 min., Saliva Cortisone - Waking, Saliva Cortisone Total
