What is Metabolized Cortisol (THF+THE)? High and low values | Lab results explained

Metabolized cortisol (for male Metabolized cortisol click here) best reflects total cortisol production.

What is cortisol:

Cortisol is a steroid hormone that is made in the adrenal glands (two triangular organs that sit on top of the kidneys) and then released into the blood, which transports it all round the body. Almost every cell contains receptors for cortisol and so cortisol can have lots of different actions depending on which sort of cells it is acting upon. Some of its functions are:

  • controlling the body’s blood sugar levels
  • acting as an anti-inflammatory
  • influencing memory formation
  • controlling salt and water balance
  • influencing blood pressure

Blood levels of cortisol vary, but generally are high in the morning when we wake up, and then fall throughout the day (this can depend on your specific daily rhythm).

The human body produces cortisol first, and then different glands have the ability to keep it as cortisol or convert it into cortisone.

…back to metabolized cortisol:

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 into the urine.

What is free cortisol:

The majority of cortisol (80-90%) circulates bound to cortisol-binding globulin (CBG) and albumin. Normally, less than 5% of circulating cortisol is free (unbound). Only free cortisol can access the enzyme transporters in liver, kidney, and other tissues that mediate metabolic and excretory clearance.

Free cortisol represents only about 1% of the total cortisol production (including the metabolites).

Why measure free cortisol and metabolized cortisol?

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.

Only a fraction of cortisol is “free” and bioactive. This fraction of cortisol is very important, but levels of metabolized cortisol best represents overall production of cortisol therefore both should be taken into account to correctly assess adrenal function.

Measuring both allows for insight into the rate of cortisol clearance/metabolism.

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 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

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.

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.



The information on is NOT intended to replace a one-on-one relationship with a qualified health care professional and is not intended as medical advice.


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