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Cortisol is a steroid produced and secreted by the adrenal glands.

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.

The biomarker 24hr Free Cortisol is the sum of your free cortisol measurements throughout one day. In the DUTCH test those individual measurements are labeled as:

- Cortisol (Waking)

- Cortisol B (Morning)

- Cortisol C (Afternoon)

- Cortisol D (Night)

If you add those four readings together you get your 24hr Free Cortisol reading.

Free cortisol results tell us how much cortisol is free to bind to receptors and allows for assessment of the circadian rhythm. 

In the DUTCH test it is important to compare the 24hr Free Cortisol with the Metabolized Cortisol (a different marker in the DUTCH test), as the metabolized cortisol number is a good indication of how much cortisol was produced in total. 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 (=metabolized cortisol is a good indication for that) 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/metabolismThe metabolized cortisol and free cortisol markers are important to use both together and separately in order to tell a more detailed story. 

Example: Increased cortisol clearance

For example, higher levels of metabolized cortisol (compared to free cortisol) are often seen in obesity where adipose tissue (=fat) 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.

Example: High Free Cortisol, but decreased Metabolized cortisol (=total levels)

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 on the DUTCH Test. The literature is more definitive for lower metabolized vs. higher “free”.

What does it mean if your 24hr Free Cortisol result is too low?

In the DUTCH test it is important to compare the 24hr Free Cortisol with the Metabolized Cortisol (a different marker in the DUTCH test), as the metabolized cortisol number is a good indication of how much cortisol was produced in total.

The amount of cortisol produced (=metabolized cortisol is a good indication for that) 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/metabolismThe metabolized cortisol and free cortisol markers are important to use both together and separately in order to tell a more detailed story. 

Here are a two different scenarios:

Free cortisol → Low

Metabolized Cortisol → Low

This is a good indication for overall low production of cortisol.

A low level of cortisol may indicate Addison’s disease, a disorder in which the adrenal glands do not produce sufficient steroid hormones.

Symptoms include: weight loss, fatigue, low blood pressure, abdominal pain, dark patches of skin.

You may also have hypopituitarism, which occurs when cortisol production by the adrenal glands is low because the pituitary gland is not sending proper signals.

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Free cortisol → Low

Metabolized Cortisol → Relatively High

This implies increased cortisol clearance. This can be due to obesity, or hyperthyroidism.

Higher levels of metabolized cortisol (compared to free cortisol) are often seen in obesity where adipose tissue (=fat) 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.

What does it mean if your 24hr Free Cortisol result is too high?

In the DUTCH test it is important to compare the 24hr Free Cortisol with the Metabolized Cortisol (a different marker in the DUTCH test), as the metabolized cortisol number is a good indication of how much cortisol was produced in total.

The amount of cortisol produced (=metabolized cortisol is a good indication for that) 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/metabolismThe metabolized cortisol and free cortisol markers are important to use both together and separately in order to tell a more detailed story. 

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”.

Here are a few different scenarios:

  • 24hr Free Cortisol → Elevated
  • Metabolized CortisolElevated

Possible reasons for high cortisol throughout the day:

- Cushing’s disease (where the pituitary gland releases too much ACTH, stimulating the adrenals to release too much cortisol) [L]

- High levels of stress (including mental stress)

- Insulin resistance [L, L]

- Hyperthyroidism [L]

- HPA axis dysfunction

- A tumor in the adrenal gland or somewhere in the body involved in cortisol production can also cause higher-than-normal cortisol levels.

- Pregnancy or birth control pills are also known to cause a high blood cortisol level.

Suggestions for lowering cortisol levels:

- Evaluate lab results correctly to help pinpoint and address the root cause

- Reduce stress levels [L]

- Improve sleep quality (and quantity if needed) [L]

- Meditation [L, L]

- Massage [L]

- Support the HPA axis [L, L]

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  • 24hr Free Cortisol → Elevated
  • Metabolized CortisolElevated
  • Cortisol throughout the day (pattern) → Elevated
  • Cortisol evening/night [Cortisol D (Night)] → Normal / going down

If cortisol is going back down at the end of the day [Cortisol D (Night)where it is supposed to be, scenarios like Cushing’s disease or potential tumors are not likely the case. In a case like this it seems that the HPA axis (stress response system) is really turned on ‘high’. The total of 24hr Free Cortisol would be very high, especially when you wake up [Cortisol (Waking)] and in the early parts of the day [Cortisol B (Morning)]. Metabolized Cortisol would confirm the story as they would be really high as well.

It doesn't really help to look at CAR here as the CAR might seem normal, but overall cortisol levels are really high.

Possible treatment:

Treatment of elevated cortisol should be directed at the root cause of the stressor. Lifestyle modification with relaxation methods, dietary changes, pain management, and overall HPA axis support with nutrition and/or adaptogens can be helpful. Glandulars may be added if additional support is necessary.

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  • 24hr Free Cortisol → Relatively higher
  • Metabolized CortisolRelatively lower

In people with low thyroid, this 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 [Metabolized CortisolRelatively lower]. As a result, free cortisol starts to increase [24hr Free Cortisol → Relatively higher] and may show up elevated on the DUTCH Test. The literature is more definitive for lower metabolized vs. higher “free”.

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

  • 24hr Free Cortisol → Relatively higher
  • 24hr Free Cortisone → Relatively lower

Possible reasons for a relatively higher cortisol compared to cortisone: hypothyroid, licorice, grapefruit, inflammation, visceral obesity, high insulin, excess sodium

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