Percent Free Cortisol, Serum refers to the proportion of cortisol in your blood that is not attached to proteins such as corticosteroid-binding globulin (CBG) or albumin. While about 90–95% of circulating cortisol is bound to these proteins and biologically inactive, the remaining 5–10% is “free” and able to enter cells, where it triggers important physiological effects-including the stress response, metabolism regulation, and immune system modulation.
Most standard cortisol tests measure total cortisol, which includes both bound (inactive) and free (active) forms. However, only free cortisol is immediately available for your body to use. Measuring the percentage of free cortisol (rather than just the total or absolute free cortisol level) provides insight into how much of your cortisol is active versus stored. This is particularly important in situations where the levels of binding proteins change, such as during pregnancy, liver disease, or with certain medications, which can make total cortisol results misleading.
Calculating percent free cortisol-or using related indices like the Free Cortisol Index (total cortisol divided by CBG)-can reveal subtle imbalances in adrenal function that may not show up in standard tests.
Note: Direct measurement of free cortisol in blood is technically challenging and not always available. Sometimes, percent free cortisol is calculated based on total cortisol and binding protein levels. Salivary cortisol is also used as a noninvasive surrogate for free cortisol in some settings.
An elevated percent free cortisol can indicate:
Reduced cortisol-binding proteins: Seen in liver disease or high estrogen states (e.g., pregnancy).
Increased cortisol production: Such as from chronic stress or Cushing’s syndrome.
Overuse of corticosteroid medications: Which can disrupt normal cortisol regulation.
A low value may suggest:
Increased levels of cortisol-binding globulin: This reduces the free fraction, and is seen with estrogen therapy or oral contraceptive use.
Adrenal insufficiency or reduced cortisol production: The adrenal glands are not making enough cortisol.
Certain inflammatory or autoimmune conditions: These can affect cortisol availability or binding.
Percent free cortisol testing is especially helpful when total cortisol results do not match a patient’s symptoms. It may be ordered during investigations of:
Adrenal disorders (like Addison’s disease or Cushing’s syndrome)
Unexplained fatigue or weakness
Abnormal stress responses
Situations where binding protein levels are altered (e.g., pregnancy, liver disease, critical illness)
| Aspect | Bound Cortisol (CBG + Albumin) | Free Cortisol (Percent Free) |
|---|---|---|
| Fraction of total | 90–95% | 5–10% |
| Biological activity | Inactive | Active (enters cells, exerts effects) |
| Affected by protein changes | Yes | No |
| Clinical relevance | May mislead in illness, pregnancy | Reflects true adrenal function |
In summary: Measuring percent free cortisol helps provide a more accurate picture of your adrenal health, especially when total cortisol levels are difficult to interpret due to changes in binding proteins or unusual clinical situations.
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An elevated level of free or percent free cortisol indicates that more biologically active cortisol is circulating in the body. This can have various clinical implications depending on the context:
Chronic Stress: Persistent psychological or physical stress activates the hypothalamic-pituitary-adrenal (HPA) axis, increasing cortisol production to help the body cope with ongoing demands.
Cushing’s Syndrome or Disease: Excessively high free cortisol is a hallmark of Cushing’s syndrome, often due to a pituitary tumor (Cushing’s disease), adrenal tumor, or ectopic ACTH production.
Adrenal or Pituitary Tumors: Tumors in these glands may drive excessive cortisol secretion, contributing to elevated free cortisol levels.
Medication Effects: Corticosteroid use can elevate free cortisol directly. Estrogen-containing medications (like oral contraceptives or hormone therapy) may increase free cortisol indirectly by altering cortisol-binding protein levels.
Physiological States: Pregnancy, severe infection, and critical illness can raise free cortisol due to shifts in hormone production and changes in binding protein concentrations.
Obesity and Hyperthyroidism: In obesity, increased cortisol clearance may lead to compensatory overproduction. Hyperthyroidism can accelerate cortisol metabolism, influencing free cortisol levels.
Chronic elevation of free cortisol can lead to a range of symptoms and complications, including:
Central weight gain (especially around the face and abdomen)
Acne and skin thinning
Muscle weakness and persistent fatigue
Elevated blood pressure
Mood disturbances, such as irritability or poor concentration
Increased cardiovascular risk (e.g., heart attack, stroke)
In critical illness or sepsis, high free cortisol often reflects a heightened stress response and may correlate with disease severity or poor prognosis.
Elevated levels may also occur due to decreased cortisol-binding proteins, such as in liver disease, without an actual increase in cortisol production.
Elevated free or percent free cortisol typically reflects an overactive stress response, a hormonal disorder like Cushing’s, medication influence, or altered cortisol metabolism. Persistent elevation warrants further evaluation to identify the underlying cause and manage potential health risks.
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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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17-Hydroxypregnenolone, MS (female), 17-Hydroxyprogesterone (female), 17-OH Progesterone, 5 Alhpa-Dihydrotestosterone (male), ACTH, Plasma, ADH, Aldos/Renin Ratio, Aldosterone, Aldosterone/Plasma Renin Activity Ratio, Anti-Mullerian Hormone (AMH), b-hCG (BHCG), C-Telopeptide, Serum, Calcitonin, Serum, Cortisol - ACTH (Cortrosyn) Stimulation Test, Cortisol - AM (Serum), Cortisol – saliva, Cortisol, Serum, Cortisol-Binding Globulin (CBG), Dexamethasone, DHEA - Saliva, DHEA, Unconjugated, DHEA-S : Cortisol Ratio, DHEAS (Serum), DHT, Free, DHT, Percent Free Dialysis, Estradiol, Estradiol (male), Estradiol - Saliva, Estradiol, Free (Male), Estradiol, Ultrasensitive, LC/MS, Estradiol, ultrasensitive, LC/MS (Male), Estriol, Serum, Estrogens, Total (female), Estrogens, Total (male), Estrone Sulfate, Estrone, Serum (Female), Estrone, Serum (Male), Free Cortisol, Serum, Free Estradiol, Percent, Free Estradiol, Serum, Free Testosterone - Saliva, Glucagon, Gonadotropin Releasing Hormone (GnRH), Growth Hormone, Human Chorionic Gonadotropin (hCG), Total, IA-2 Autoantibodies, IGF Binding Protein 1 (IGFBP 1), IGF Binding Protein 3 (IGFBP 3), IGF-BP3, Leptin, Luteinizing Hormone, Human (hLH), Percent Free Cortisol, Serum, Pregnenolone (male), Progesterone (male), Progesterone (Serum), Prolactin, Renin Activity, Plasma, Total Testosterone (Female/ng/mL)
