Daily Free Cortisol and Cortisone + Metabolites (Urine) - DUTCH

Main points to look at in this category:

- What’s the overall free cortisol pattern throughout the day? 

- What’s the total free cortisol for the day?

- What is your Cortisol Awakening Response (CAR)? (here you have to refer to your chart in the DUTCH result PDF)

- What’s the total of the metabolites?

- Do we have a metabolic preference between cortisol and cortisone?

What is the Cortisol Awakening Response (CAR)?

Cortisol is typically the highest within 30 minutes after waking up in the morning. It then declines throughout the day and reaches its lowest point in the evening. The Cortisol Awakening Response (CAR) is the difference between your waking cortisol sample and the sample 30-40 min later. A higher baseline CAR was associated with significantly increased risk for developing major depression disorder (MDD). A low CAR (flat) can be a problem with symptoms related to low cortisol / low HPA axis activity. The hypothalamic pituitary adrenal (HPA) axis is our central stress response system.

Please refer to your DUTCH PDF file and look for this chart to check out whether your CAR is normal or abnormal. 

What if your CAR is low/flat?

Your CAR can be low/flat due to:

- An underactive HPA axis

- Excessive physiological burnout

- Seasonal affective disorder

- Sleep apnea / poor sleep

- PTSD

- Chronic fatigue

- Chronic pain

- Systemic hypertension

- Functional GI distress

- Postpartum depression

- Autoimmune diseases

What if your CAR is high?

Your CAR can be high due to:

- An overactive HPA axis

- Ongoing job-related stress (anticipatory stress for the day)

- Glycemic dysregulation

- Pain (i.e. waking with painful joints or a migraine)

- General depression (not Seasonal affective disorder) 

Different markers in this category:

Free Cortisol:

If high throughout the day: 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. 

Free Cortisone:

If free cortisone is a close match to free cortisol, don’t pay a lot of attention to cortisone.

Metabolites:

- Total (tells you cortisol output by adrenal glands)

- Cortisol vs cortisone preference

- Free cortisol is only about 1% of the total cortisol. The metabolites of the cortisol represent around 70+% of the cortisol. Best marker for overall output.

Different scenarios:

Here are a few different scenarios/examples. Please refer to your actual results for more information. These scenarios listed here are just for general clarifications.

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Free cortisol → Low

Metabolites → Low

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

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Free cortisol → Low

Metabolites → Relatively High

This implies increased cortisol clearance. This can be due to obesity, or hyperthyroidism (people with too much thyroid medication as it upregulates cortisol metabolism)

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Cortisol throughout the day → Elevated

You have to start looking at Cushing’s disease or potentially adrenal/pituitary tumors that are pushing out all that cortisol. 

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Cortisol throughout the day → Elevated

Cortisol evening/night → Normal / going down

Total free cortisol → Elevated

Metabolites → Elevated

If cortisol is going back down at the end of the day where it is supposed to be, the above (Cushing’s disease or potential tumor) 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. It doesn't really help to look at CAR here as the CAR might seem normal, but overall cortisol levels are really high.

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Cortisol evening/night → Relatively high

This needs to be addressed in terms of HPA axis and cortisol support. 

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Free cortisol → Relatively low

Pattern throughout the day → Relatively flat

CAR → Relatively flat 

Total of metabolites → Elevated

Metabolite preferences → cortisone preference

In a case where there is relatively low free cortisol, but relatively high metabolites with a preference for cortisone, cortisol is readily deactivated into the deactive form cortisone. Cortisone does not have any biological activity. It’s being metabolized by the liver for excretion. So there is a lot of cortisol being made, but it’s “running away”. This usually happens in obesity, hyperthyroidism (too much thyroid medication), but it’s not a picture of somebody that is not making cortisol.

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Cortisol throughout the day → Relatively high

Appropriate pattern, but might have elevated CAR in the morning.

Cortisone → Lower than cortisol

Metabolite preferences → cortisol preference (active)

High normal to High free cortisol levels with a high CAR and preference for cortisol metabolites. This can happen in inflammation / low thyroid and/or adrenal condition. The body is making cortisol, but has a hard time deactivating it to cortisone and it has a hard time clearing it as metabolites. 

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Cortisol (active form) vs cortisone (inactive form) metabolite preference? 

- THF (active) vs THE (inactive)

- If cortisol is low, ideally its leaning towards cortisol

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

Note on contamination through cortisol cream:

Another reason to look at Cortisone is when we suspect a contamination, ex. somebody puts cortisol cream on their knees at bedtime. In this situation the evening cortisol levels could be inflated and it would then make more sense to look at the cortisone levels. If cortisone levels go with it (also elevated at night) then we have real physiological production of cortisol. If, on the other hand, the cortisone is much lower at night it is likely that the cortisol cream (hydro-cortisone = cortisol) “contaminated” the cortisol levels on the test. This is a rare case, but when it does happen the cortisone levels become a good representation of the cortisol pattern throughout the day.

24hr Free Cortisol

Optimal range: 65 - 200 ug

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.

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24hr Free Cortisone

Optimal range: 220 - 450 ug

Cortisone is the inactive form of cortisol. Cortisone shows minimal biological activity per se, reflecting negligible affinity for the glucocorticoid and aldosterone receptors. The kidney, colon and saliva gland have lots of activity for changing cortisol to cortisone (active to inactive) to keep cortisol off the aldosterone receptor. Cortisone is converted back in the liver, fat, etc. (inactive to active).

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a-Tetrahydrocortisol (a-THF)

Optimal range: 75 - 370 ng/mg

This is one of the three cortisol metabolites. The total some of the three cortisol metabolites gives us a good indication of the overall cortisol production in your body. 

Two of the 3 metabolites are the active form of cortisol (THF). The other metabolite is in the inactive form cortisone.

This particular marker (a-THF) hence is an active cortisol metabolite.

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a-Tetrahydrocortisol (a-THF) (male)

Optimal range: 175 - 700 ng/mg

Metabolized cortisol is the sum of a-tetrahydrocortisol (a-THF), b-tetrahydrocortisol (b-THF), and b-tetrahydrocortisone (b-THE). They are a good indication of the total cortisol output from the adrenal gland or clearance out the body.

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b-Tetrahydrocortisol (b-THF)

Optimal range: 1050 - 2500 ng/mg

B-Tetrahydrocortisol [aka 5-beta-Tetrahydrocortisol (5b-THF)] is a metabolite of cortisol.

Tetrahydrocortisone, Tetrahydrocortisol and Allo-Tetrahydrocortisol are cortisol metabolites that reflect approximately 50% of daily cortisone synthesis. These will often reflect a chronic adrenal picture if levels are out of normal limits.

Urine contains free cortisol, but it also contains many cortisol metabolites, like cortisone or 5-alpha- tetrahydrocortisol, 5-beta-tetrahydrocortisol, tetrahydrocortisone, etc.

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b-Tetrahydrocortisol (b-THF) (male)

Optimal range: 1750 - 4000 ng/mg

B-Tetrahydrocortisol [aka 5-beta-Tetrahydrocortisol (5b-THF)] is a metabolite of cortisol.

Tetrahydrocortisone, Tetrahydrocortisol and Allo-Tetrahydrocortisol are cortisol metabolites that reflect approximately 50% of daily cortisone synthesis. These will often reflect a chronic adrenal picture if levels are out of normal limits.

Urine contains free cortisol, but it also contains many cortisol metabolites, like cortisone or 5-alpha- tetrahydrocortisol, 5-beta-tetrahydrocortisol, tetrahydrocortisone, etc.

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b-Tetrahydrocortisone (b-THE)

Optimal range: 1550 - 3800 ng/mg

This is one of the three cortisol metabolites. The total some of the three cortisol metabolites gives us a good indication of the overall cortisol production in your body. 

Two of the 3 metabolites are the active form of cortisol (THF). The other metabolite is in the inactive form cortisone.

This particular marker (b-THE) hence is an inactive cortisol metabolite.

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b-Tetrahydrocortisone (b-THE) (male)

Optimal range: 2350 - 5800 ng/mg

This is one of the three cortisol metabolites. The total some of the three cortisol metabolites gives us a good indication of the overall cortisol production in your body. 

Two of the 3 metabolites are the active form of cortisol (THF). The other metabolite is in the inactive form cortisone.

This particular marker (b-THE) hence is an inactive cortisol metabolite.

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Cortisol A (Waking)

Optimal range: 10 - 50 ng/mg

Cortisol is a hormone produced by the adrenal glands, which are located on top of the kidneys. It is normally released in response to events and circumstances such as waking up in the morning, exercising, and acute stress.

In the Dutch test there are 4 individual free cortisol readings that were measured at different times throughout one day:

- Cortisol A (Waking)

- Cortisol B (Morning)

- Cortisol C (Afternoon)

- Cortisol D (Night)

When you are looking at Cortisol A (Waking) it is essential to also look at Cortisol B (Morning). The difference between those 2 cortisol samples is called the cortisol awakening response (or CAR). 

An elevated CAR would mean that the difference between those 2 markers is really big.

Different possible reasons for an elevated CAR:

- an overactive HPA axis (=plays an important role in the stress response), ongoing job-related stress (anticipatory stress for the day)

- blood sugar dysregulation

- pain (i.e. waking with painful joints or a migraine), 

- and general depression (not Seasonal affective disorder/”winter depression”)

Neither the waking nor post-waking cortisol results correlated to Major Depressive Disorder, but the CAR calculation (the change between the first two samples) does. So this means that if your morning free cortisol reading spikes up high first thing in the morning, there is something to look at. Is there an overactivity to stress? Are you anticipating a stressful day at work? If your morning free cortisol levels are high, this can be due to stress or anticipating stress. 

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Cortisol B (Morning)

Optimal range: 30 - 130 ng/mg

This is the 2nd cortisol sample of the day. Usually measured 30 to 60 minutes after waking. 

Cortisol is a hormone produced by the adrenal glands, which are located on top of the kidneys. It is normally released in response to events and circumstances such as waking up in the morning, exercising, and acute stress.

In the Dutch test there are 4 individual free cortisol readings that were measured at different times throughout one day:

- Cortisol A (Waking)

- Cortisol B (Morning)

- Cortisol C (Afternoon)

- Cortisol D (Night)

When you are looking at Cortisol B (Morning) it is essential to also look at Cortisol A (Waking). The difference between those 2 cortisol samples is called the cortisol awakening response (or CAR)

An elevated CAR would mean that the difference between those 2 markers is really big.

Different possible reasons for an elevated CAR:

- an overactive HPA axis (=plays an important role in the stress response), ongoing job-related stress (anticipatory stress for the day)

- blood sugar dysregulation

- pain (i.e. waking with painful joints or a migraine), 

- and general depression (not Seasonal affective disorder/”winter depression”)

Neither the waking nor post-waking cortisol results correlated to Major Depressive Disorder, but the CAR calculation (the change between the first two samples) does. So this means that if your morning free cortisol reading spikes up high first thing in the morning, there is something to look at. Is there an overactivity to stress? Are you anticipating a stressful day at work? If your morning free cortisol levels are high, this can be due to stress or anticipating stress. 

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Cortisol C (Afternoon)

Optimal range: 7 - 30 ng/mg

This is the 3rd cortisol sample of the day. Usually measured in the afternoon. 

Cortisol is a hormone produced by the adrenal glands, which are located on top of the kidneys. It is normally released in response to events and circumstances such as waking up in the morning, exercising, and acute stress.

In the Dutch test there are 4 individual free cortisol readings that were measured at different times throughout one day:

- Cortisol A (Waking)

- Cortisol B (Morning)

- Cortisol C (Afternoon)

- Cortisol D (Night)

LEARN MORE

Cortisol D (Night)

Optimal range: 0 - 14 ng/mg

This is the 4th cortisol sample of the day (=evening/night).

Cortisol is a hormone produced by the adrenal glands, which are located on top of the kidneys. It is normally released in response to events and circumstances such as waking up in the morning, exercising, and acute stress.

In the Dutch test there are 4 individual free cortisol readings that were measured at different times throughout one day:

- Cortisol A (Waking)

- Cortisol B (Morning)

- Cortisol C (Afternoon)

- Cortisol D (Night)

LEARN MORE

Cortisone A (Waking)

Optimal range: 40 - 120 ng/mg

Cortisone is the inactive form of cortisol. Cortisone shows minimal biological activity per se, reflecting negligible affinity for the glucocorticoid and aldosterone receptors. The kidney, colon and saliva gland have lots of activity for changing cortisol to cortisone (active to inactive) to keep cortisol off the aldosterone receptor. Cortisone is converted back in the liver, fat, etc. (inactive to active).

Cortisone A (Waking) can help to confirm the marker Cortisol A (Waking).

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Cortisone B (Morning)

Optimal range: 90 - 230 ng/mg

Cortisone is the inactive form of cortisol. Cortisone shows minimal biological activity per se, reflecting negligible affinity for the glucocorticoid and aldosterone receptors. The kidney, colon and saliva gland have lots of activity for changing cortisol to cortisone (active to inactive) to keep cortisol off the aldosterone receptor. Cortisone is converted back in the liver, fat, etc. (inactive to active).

Cortisone B (Morning) can help to confirm the marker Cortisol B (Morning).

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Cortisone C (Afternoon)

Optimal range: 32 - 95 ng/mg

Cortisone is the inactive form of cortisol. Cortisone shows minimal biological activity per se, reflecting negligible affinity for the glucocorticoid and aldosterone receptors. The kidney, colon and saliva gland have lots of activity for changing cortisol to cortisone (active to inactive) to keep cortisol off the aldosterone receptor. Cortisone is converted back in the liver, fat, etc. (inactive to active).

Cortisone C (Afternoon) can help to confirm the marker Cortisol C (Afternoon).

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Cortisone D (Night)

Optimal range: 0 - 55 ng/mg

Cortisone is the inactive form of cortisol. Cortisone shows minimal biological activity per se, reflecting negligible affinity for the glucocorticoid and aldosterone receptors. The kidney, colon and saliva gland have lots of activity for changing cortisol to cortisone (active to inactive) to keep cortisol off the aldosterone receptor. Cortisone is converted back in the liver, fat, etc. (inactive to active).

Cortisone D (Night) can help to confirm the marker Cortisol D (Night).

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Metabolized Cortisol (THF+THE)

Optimal range: 2750 - 6500 ng/mg

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.

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Metabolized Cortisol (THF+THE) (male)

Optimal range: 4550 - 10000 ng/mg

Metabolized cortisol best reflects total cortisol production.

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