Cortisone Test · Blood

Your body makes cortisol every day to manage stress, regulate blood sugar, and control inflammation. But cortisol that stays active too long can damage blood vessels, weaken bones, and accelerate aging. Cortisone is the off switch. It is the inactive form your body creates by converting cortisol through a specific enzyme, and measuring it in blood gives you a window into how well that conversion system is working.

Most people have heard of cortisol, but few know about cortisone or the enzyme shuttle between them. This test measures serum cortisone (the inactive metabolite of cortisol) directly in your blood. When paired with a cortisol measurement, the ratio between the two reveals whether your tissues are properly dialing down cortisol's effects, or whether the balance has shifted in a direction that could affect your metabolism, blood pressure, or long-term health.

How Cortisone and Cortisol Work Together

Cortisol is produced in your adrenal glands (small organs sitting on top of your kidneys) in response to signals from the brain. Once cortisol circulates through your body and does its job, an enzyme called 11-beta-hydroxysteroid dehydrogenase type 2 (11-beta-HSD2) converts it into cortisone, which is biologically inactive. This conversion happens most actively in the kidneys, where it prevents cortisol from triggering receptors meant for aldosterone, a separate hormone that controls salt and water balance.

The reverse also happens. A different enzyme, 11-beta-HSD1, converts cortisone back into active cortisol inside specific tissues like the liver, fat cells, and skin. This two-way shuttle allows your body to fine-tune how much active cortisol reaches each tissue without changing the total amount your adrenals produce. Measuring cortisone in blood, especially alongside cortisol, reveals whether this local regulation system is functioning normally.

Cardiovascular Risk

The relationship between cortisol (the active hormone that cortisone reflects) and heart disease is one of the strongest reasons to pay attention to this system. Studies measuring cortisol (not cortisone specifically) have found consistent links between disrupted cortisol patterns and cardiovascular death. In the Whitehall II Study of 4,047 civil servants followed for about 6 years, people with a flatter daily cortisol rhythm were roughly 87% more likely to die from cardiovascular causes (HR 1.87). The InCHIANTI Study found an even more striking result: among 861 adults aged 65 and older, those with the highest urinary cortisol levels had a 5-fold increased risk of cardiovascular death compared to those with the lowest levels.

A meta-analysis pooling data from over 6,680 controls and 696 cardiovascular disease cases found that each standard deviation increase in morning plasma cortisol was associated with an 18% higher risk of cardiovascular disease (OR 1.18). Genetic analyses in the same study supported a potential causal relationship, meaning the cortisol itself may contribute to heart problems rather than simply being elevated alongside them.

The KORA-F3 Study of 1,090 participants followed for about 11 years confirmed that the pattern matters as much as the level. People with elevated late-night cortisol had 49% higher cardiovascular mortality (HR 1.49), while those with a healthy, pronounced daily cortisol rhythm had roughly half the cardiovascular death risk (HR 0.50). These findings all come from cortisol measurements. Because cortisone is the direct metabolic partner of cortisol, your cortisone level and the cortisol-to-cortisone ratio provide complementary information about how this system is behaving in your body.

Type 2 Diabetes and Blood Sugar

Chronic cortisol excess pushes blood sugar higher by stimulating glucose production in the liver and reducing how well your cells respond to insulin. Several large studies have tracked how cortisol levels predict future diabetes, and the signal is consistent. In the Whitehall II cohort of 3,270 people without diabetes, those with raised evening cortisol were 18% more likely to develop type 2 diabetes over roughly a decade (OR 1.18). A flattened daily cortisol slope, meaning cortisol stayed high into the evening rather than dropping normally, predicted both prediabetes and diabetes (OR 1.12).

The Jackson Heart Study, examining 4,206 African American adults, found that people in the highest quarter of morning serum cortisol had about 1.26 times the odds of having type 2 diabetes compared to the lowest quarter. In the Edinburgh Type 2 Diabetes Study of 919 people who already had diabetes, elevated plasma cortisol above roughly 800 nmol/L was associated with ischemic heart disease and its risk factors, suggesting that cortisol excess compounds the cardiovascular danger of diabetes.

These studies all measured cortisol directly. The cortisol-to-cortisone ratio adds a useful dimension: altered conversion between the two (specifically, more cortisol relative to cortisone) has been linked to features of metabolic syndrome and insulin resistance in studies examining 11-beta-HSD enzyme activity.

Cognitive Decline and Dementia

Excess cortisol exposure over years appears to damage the brain, particularly the hippocampus (the region responsible for forming new memories). A meta-analysis covering over 17,000 participants found that people with Alzheimer's disease had moderately elevated morning blood cortisol compared to healthy controls. A long-term study following participants for an average of 10.5 years found that elevated urinary cortisol was associated with a 31% increased risk of developing Alzheimer's disease, detectable roughly 3 years before diagnosis. In a French study of 334 older adults followed for about 8 years, higher total daily cortisol output predicted both dementia (HR 1.09 per unit increase) and Alzheimer's disease specifically (HR 1.12).

These findings suggest that keeping your cortisol regulation system in balance, which cortisone measurement helps assess, may have implications beyond metabolic health.

Cancer Survival

While cortisol does not cause cancer, disrupted cortisol rhythms appear to affect survival in people who have it. In a study of 113 women with ovarian cancer, each standard deviation increase in nighttime cortisol was associated with a 46% greater likelihood of death, and those with high nighttime cortisol survived an estimated 3.3 years compared to 7.3 years for those with low levels. A similar pattern appeared in 62 lung cancer patients: flatter daily cortisol slopes predicted earlier death. An Israeli study of 609 patients with Cushing syndrome (chronic cortisol excess) found they had 78% higher overall cancer risk compared to matched controls.

Mortality and All-Cause Risk

The NAPACA study of 3,656 patients with adrenal masses (tumors found incidentally on imaging) followed them for a median of 7 years. Those whose adrenal glands were autonomously producing extra cortisol, even at levels below the threshold for Cushing syndrome, had 52-77% higher all-cause mortality (HR 1.52 to 1.77). Women with this condition had a particularly elevated mortality risk. A Swedish cohort of 1,048 similar patients confirmed the finding over 6.4 years of follow-up.

Cushing syndrome itself, a condition of outright cortisol excess, increases mortality roughly 3-fold (standardized mortality ratio 3.0) even after treatment, with elevated rates of heart attack (standardized incidence rate 4.4), fractures (4.9), and deep vein thrombosis (13.8).

Reference Ranges

Serum cortisone does not yet have universally standardized clinical interpretation tiers the way cortisol does. The ranges below come from population studies using LC-MS/MS (liquid chromatography-tandem mass spectrometry), the most accurate available measurement method. Your lab may use a different assay, so always compare your results within the same lab over time rather than treating any single threshold as absolute.

Cortisone levels are generally higher in men than in women, though the difference is less pronounced than for some other steroid hormones. Levels are highest in infancy, then decline progressively with age. BMI has a weak negative relationship with cortisone. Oral contraceptive use significantly affects cortisol (by raising its binding protein) but has a less direct effect on cortisone itself.

The cortisol-to-cortisone ratio is often more clinically informative than cortisone alone. In healthy adults, the serum cortisol-to-cortisone ratio typically falls between about 3.3 and 12.3. An elevated ratio (too much cortisol relative to cortisone) can signal that the enzyme responsible for inactivating cortisol is underperforming. This occurs in kidney disease, a rare genetic condition called apparent mineralocorticoid excess, and in some metabolic disorders.

Tracking Your Trend

A single cortisone reading is a snapshot of a system that fluctuates throughout the day, day to day, and across seasons. The within-person biological variation for serum cortisol (cortisone's active counterpart) runs about 18% from week to week, and day-to-day morning cortisol variation can reach roughly 27%. For cortisone specifically, while fewer studies have calculated its individual coefficient of variation, the two molecules track each other closely enough that similar variability applies.

This means one reading might land anywhere within a fairly wide range for the same person on different days. A value that looks borderline high on Monday could look normal on Thursday. The real value of this test comes from seeing your trajectory. Get a baseline, retest in 3 to 6 months if you are making lifestyle changes or starting a new supplement, and then at least annually. If you and your clinician are using the cortisol-to-cortisone ratio to monitor enzyme activity, serial measurements become even more informative because the ratio is more stable than either hormone alone.

Always draw your blood at the same time of day for each test. Cortisone follows a circadian rhythm alongside cortisol, peaking in the early morning and reaching its lowest point around midnight. A morning draw taken at 8 AM will give a very different number than one taken at noon, and comparing the two as if they are equivalent will lead to the wrong conclusion.

When Results Can Be Misleading

Because cortisone is the inactive partner of cortisol, anything that disrupts cortisol levels or the enzyme shuttle between them can make a cortisone reading unreliable. Here are the most common distortions.

• Acute illness or surgery: Illness can raise cortisol production up to 6-fold, proportional to severity. After major surgery, cortisol stays elevated for 2 to 7 days. Both of these will shift the cortisone reading. Wait at least 2 weeks after resolving an acute illness and 4 weeks after surgery before testing.
• Recent intense exercise: A single hard workout can raise cortisol by roughly 7 mcg/dL above baseline, with the effect normalizing within hours. High-intensity interval training and prolonged endurance exercise produce larger spikes than resistance training. Avoid heavy exercise the day before your blood draw.
• Fasting and meals: Fasting for as little as a few days can raise cortisol production nearly 2-fold. On the other end, eating a meal can bump cortisol by about 90 nmol/L through both adrenal secretion and peripheral conversion of cortisone back to cortisol. Follow your lab's fasting instructions and stay consistent between tests.
• Medications that shift the cortisol-cortisone balance: Azole antifungals (ketoconazole, fluconazole) and etomidate inhibit cortisol production enzymes, lowering both cortisol and cortisone. Anticonvulsants (phenytoin, carbamazepine) and rifampin speed up cortisol metabolism. Ritonavir (an HIV medication) slows cortisol breakdown and can amplify the effects of even small steroid doses like inhaled corticosteroids. Chronic opioid use suppresses the brain's signal to make cortisol. If you are taking any of these, let your clinician know before interpreting results.

Binding protein levels also affect interpretation. Oral estrogens (including most birth control pills) and pregnancy raise cortisol-binding globulin, which increases total cortisol without changing the biologically active fraction. This can make the cortisol-to-cortisone ratio harder to interpret from a standard blood draw. Conversely, liver disease, kidney disease (nephrotic syndrome), and severe illness lower binding proteins, potentially making total cortisol look falsely low.

Assay Differences

How your lab measures cortisone matters. LC-MS/MS (the gold standard) is highly specific and distinguishes cortisone from related molecules. Older immunoassay methods can cross-react with other steroids, producing less accurate results. Different immunoassay platforms can produce baseline cortisol cutoffs ranging from 336 to 506 nmol/L for the same clinical threshold, a difference of nearly 50%. If you switch labs, your numbers may shift even if nothing in your body has changed. Stick with the same lab and testing method for serial comparisons.