Metabolized cortisol reflects the total cortisol produced and clearing through the liver, while free-cortisol results tell us how much cortisol is free to bind to receptors and allows for assessment of the circadian rhythm.
Cortisol is a steroid hormone, in the glucocorticoid class of hormones. It is increased in response to stress and low blood-glucose concentration. It functions to increase blood glucose levels through gluconeogenesis, to suppress the immune system, and to aid in the metabolism of fat, protein, and carbohydrates. It also decreases bone formation. Cortisol prevents the release of substances in the body that cause inflammation.
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
- Depression or other behavioral symptoms
- Body hair loss or sexual dysfunction in women
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
- thinning skin
- easy bruising
- flushed face
- slowed healing
- muscle weakness
- severe fatigue
- difficulty concentrating
- high blood pressure
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.
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