24 Hour Free Cortisone Test

Cortisol is the hormone your body releases under stress. Cortisone is what cortisol becomes once an enzyme in your kidneys flips it from active to inactive. Measuring free cortisone in your urine across 24 hours captures the size of that conversion, which is a quieter but important part of how your body keeps stress hormone signaling in check.

This number tells you two things at once. It reflects how much cortisol your body produced through the day, and how efficiently your kidneys converted that cortisol to its inactive partner. When the conversion machinery slows, cortisol lingers longer at tissue receptors, which has been linked in human studies to higher heart muscle mass in some groups and to features of cardiometabolic strain.

What Free Cortisone Actually Reveals

Most stress-hormone testing focuses on cortisol alone. Cortisone is the form cortisol becomes after an enzyme called 11β-HSD2 (an off-switch enzyme found mostly in your kidneys) converts it. Because that conversion happens largely in kidney tissue, the free cortisone showing up in urine gives a window into whether the off-switch is keeping up with cortisol output. A 24-hour collection averages out the natural rise-and-fall pattern of cortisol release across waking, working, eating, and sleeping hours.

Subcutaneous tissue sampling in 214 healthy adults showed that free cortisone follows a clear daily rhythm that parallels cortisol, with low levels after sleep onset and peaks around wake time. That rhythm is the baseline pattern this test is designed to capture across a full 24-hour window rather than at a single moment.

Heart Muscle and Blood Pressure

The most-studied way to interpret 24-hour free cortisone is alongside 24-hour free cortisol, as a ratio. The cortisol-to-cortisone ratio reflects how aggressively your kidney enzyme is converting one to the other. A higher ratio means more cortisol is escaping inactivation, which can keep cortisol's effects pressing on kidney and vascular tissue longer than intended.

In a study of 43 men with type 2 diabetes and stage 1 hypertension, those with a 24-hour cortisol-to-cortisone ratio above 1.0 had higher left ventricular mass (the size of the main pumping chamber of the heart) than those with a lower ratio. The association held independent of other risk factors. A thicker pumping chamber is a known marker of future cardiovascular complications, so the ratio appears to flag heart strain that standard blood pressure or cholesterol tests would miss in this group.

What this means for you: if your free cortisone is low relative to your free cortisol, that pattern suggests your kidney off-switch may not be keeping pace. This is more informative if you already have diabetes or borderline blood pressure, where every additional pressure on the heart matters.

Where the Ratio Does Not Apply

The cortisol-to-cortisone ratio is not a universal explanation for high blood pressure. In a study of 93 people with treatment-resistant hypertension, the ratio averaged around 0.22 in patients and 0.19 in controls, with no meaningful difference. Reduced cortisol-to-cortisone conversion does not appear to be the mechanism behind hard-to-treat blood pressure in most cases.

What this means for you: a normal ratio does not rule out other hypertension drivers, and an abnormal ratio is most informative when paired with diabetes, early heart muscle changes, or unexplained metabolic findings.

Adrenal Disease Context

Free cortisone is also reported alongside 24-hour urinary free cortisol in workups for Cushing's syndrome (a condition of long-term cortisol excess) and adrenal incidentaloma (a benign-appearing adrenal lump found on imaging). In these settings, urinary free cortisol does most of the diagnostic work. Using a cutoff above 170 nmol per 24 hours measured by mass spectrometry, urinary free cortisol caught Cushing's cases with 100% sensitivity and 98.7% specificity in a 209-person study. The cortisol-to-cortisone ratio added little for first-line diagnosis.

Treatment of cortisol excess illustrates how free cortisone moves in response to real biology. In a randomized trial of 62 patients with mild autonomous cortisol secretion, adrenalectomy (surgical removal of one adrenal gland) improved blood pressure and blood sugar control over six months. In 51 patients with adrenal insufficiency, switching from standard three-times-daily hydrocortisone to a once-daily dual-release version normalized the urinary cortisone-to-cortisol ratio, indicating restored kidney enzyme activity.

Reference Ranges

This is an exploratory marker. There is no consensus clinical cutpoint for 24-hour free cortisone in any single population. The most cited published ranges come from a 209-person Italian cohort measured by mass spectrometry in standard wet 24-hour urine collections (not dried urine strips). Treat the table below as orientation only. Your lab may report different numbers and may use different units depending on its collection method.

Source: Ceccato et al. 2014 (wet 24-hour urine reference and Cushing's cutoff); Tang et al. 2015 (ratio and left ventricular mass). Compare your results within the same lab over time for the most meaningful trend, since collection method, assay platform, and creatinine normalization all shift the numbers.

Tracking Your Trend

A single 24-hour cortisone reading is a snapshot. Daily cortisol output naturally varies with sleep, stress, illness, and the menstrual cycle, and free cortisone moves with it. In a 3,127-person study of 24-hour urinary free cortisol, short and long-term stability was only moderate, and urine volume and kidney filtration rate affected results more than sex did. The same logic applies to cortisone.

Get a baseline. If you are making targeted changes (treating a thyroid issue, addressing chronic stress, adjusting a glucocorticoid medication), retest in 3 to 6 months. Otherwise retest at least annually. What you want to see is a trend across two or three collections, not a single number weighed in isolation.

When Results Can Be Misleading

• Kidney filtration changes: in chronic kidney disease, the enzyme that converts cortisol to cortisone is reduced, and urinary steroid excretion shifts. A low cortisone reading in someone with reduced kidney function may reflect kidney biology rather than adrenal output.
• Incomplete collection: missing even one urination during the 24-hour window underestimates total output. For dried urine kits that sample four spot collections, missing or mistimed samples distort the daily pattern more than a wet 24-hour collection would.
• Acute stress or illness in the past few days: cortisol output rises in response to infection, injury, surgery, or sleep loss, and free cortisone tracks alongside. Wait at least a few days after recovery from an acute illness before testing.
• Medications that change conversion: licorice root extract containing glycyrrhizin blocks the 11β-HSD2 enzyme, which lowers cortisone and raises measured cortisol. The number shifts, but the change is reversible once you stop the licorice.

What an Abnormal Result Should Trigger

If your free cortisone is unusually low or high, the next step is to look at the full picture rather than acting on one value. Pair it with 24-hour free cortisol from the same collection and calculate the ratio. If the ratio is above 1.0 and you have diabetes, hypertension, or unexplained heart strain, an endocrinologist or cardiologist can help decide whether to image the heart and adrenal glands. If urinary free cortisol is markedly elevated, that pattern points toward Cushing's syndrome workup, which typically adds a dexamethasone suppression test and late-night salivary cortisol. If both cortisol and cortisone are very low and you have fatigue, low blood pressure, or salt cravings, adrenal insufficiency screening is the right next step.

A single off-range reading is not a diagnosis. Retest after at least a few weeks before making clinical decisions, and bring the full panel to a clinician who looks at hormone networks rather than single numbers.