Cortisone (U1 Waking) Test

Your body produces a sharp surge of the stress hormone cortisol in the morning. That surge is what pulls you out of sleep, sets your energy for the day, and primes your blood pressure and metabolism. What happens next matters just as much: your tissues switch some of that cortisol off, converting it to a less active form called cortisone. The waking urine sample captures the inactive form right when your daily rhythm peaks.

This is an exploratory marker, not a routine clinical test. It is most often ordered as part of a dried urine hormone panel (commonly known as the DUTCH test) for people who want a fuller picture of how their stress-response system is behaving than a single blood cortisol can offer. The reading reflects both how much cortisol your adrenal glands are making and how aggressively your body is inactivating it.

What This Test Actually Measures

Cortisone is what cortisol becomes after an enzyme in your tissues, especially your kidneys, switches it off. Your adrenal glands make the active hormone, cortisol. A protective enzyme in mineralocorticoid-sensitive tissues converts it to inactive cortisone. A different enzyme in your liver, fat, and muscle does the reverse, regenerating cortisol back from cortisone. The constant back-and-forth between these two forms is what sets your tissue-level exposure to active cortisol.

This particular test takes a dried urine sample from your first waking pee and reports cortisone normalized to creatinine (a marker of urine concentration). It is part of a family of waking glucocorticoid measurements that includes salivary cortisone, salivary cortisol, and serum cortisol. These measurements correlate but are not identical, and most published research uses saliva or blood, not dried urine. Where the evidence behind a claim comes from a different specimen than this test, you will see that called out.

Why Adrenal Insufficiency Screening Matters Here

The strongest human evidence for waking cortisone (in saliva, a related but different specimen) is in screening for adrenal insufficiency, a condition where your adrenal glands cannot produce enough cortisol. In a prospective study of 220 high-risk adults, a single home waking salivary cortisone sample distinguished people with adrenal insufficiency from those without it extremely well. The area under the curve, a standard accuracy measure where 1.0 is perfect and 0.5 is a coin flip, was 0.95 (95% CI 0.92 to 0.97).

In that same trial, a high waking salivary cortisone reading correctly cleared adrenal insufficiency in about 96 out of 100 people, and a very low reading correctly confirmed it in about 95 out of 100. About 83% of participants preferred the home saliva test to a hospital-based stimulation test. The dried urine waking cortisone in this panel is a different specimen from saliva, so these specific accuracy numbers do not transfer directly, but the underlying biology is the same: a low first-morning reading suggests blunted adrenal output.

The Cortisol Awakening Response Connection

When you wake up, your cortisol jumps by 50 to 100% within 30 to 45 minutes. This is called the cortisol awakening response, and it reflects how reactive your HPA axis (the hypothalamic-pituitary-adrenal system, your central stress-response network) is in the moments after sleep. In a small study of 12 men with frequent sampling, salivary cortisone showed its own clear awakening response that tracked closely with serum cortisol dynamics. Several measures of the cortisone awakening response correlated significantly with serum cortisol indices, suggesting cortisone may mirror blood cortisol behavior more faithfully than salivary cortisol alone.

For you, this means a waking cortisone reading is essentially a snapshot of where your morning cortisol surge stands. A flat or low waking value can signal a blunted awakening response, a pattern that has been associated with chronic stress, burnout, depression, and inflammation in cohort studies of salivary cortisol.

Hypercortisolism and Cushing Syndrome

Cortisone measurements are also used to investigate the opposite problem: too much cortisol. Late-night salivary cortisone (not waking) has shown strong accuracy for diagnosing Cushing syndrome, a condition of cortisol excess that drives weight gain, high blood pressure, muscle loss, and skin changes. In a diagnostic study at a tertiary endocrine centre, late-night salivary cortisone alone reached an area under the curve of 0.79, and combining late-night salivary cortisone with late-night salivary cortisol increased the area under the curve to 0.91.

In people with adrenal incidentalomas (incidentally discovered adrenal nodules) and mild autonomous cortisol secretion, late-night salivary cortisone above 15 nmol/L was abnormal in 9 of 10 cases, whereas late-night salivary cortisol was abnormal in only 4 of 10. Cortisone may be more sensitive than cortisol in that setting. These findings come from late-night sampling, not from waking, but they reinforce that cortisone tracks meaningful adrenal pathology when it goes in either direction.

What Cortisone-to-Cortisol Balance Reflects in Metabolic Health

Cortisone exists in constant exchange with cortisol, controlled by two enzymes called 11-beta-hydroxysteroid dehydrogenase types 1 and 2. Shifts in this balance show up in meaningful conditions. In obesity, enhanced regeneration of cortisol from cortisone inside fat tissue and liver has been linked to weight gain, elevated blood pressure, and type 2 diabetes risk. Studies measuring tissue-specific cortisone-to-cortisol cycling in obese adults found increased local cortisol regeneration in body fat and altered hepatic activity.

On the other side, reduced conversion of cortisol to cortisone (low 11-beta-HSD2 activity in the kidneys) lets cortisol act on mineralocorticoid receptors, causing sodium retention, low potassium, and hypertension. This is the mechanism behind licorice-induced high blood pressure. A waking cortisone reading interpreted alongside waking cortisol gives you a rough view of where your own balance sits. These observations come from studies of urinary steroid metabolite ratios and tissue-specific cortisol-cortisone cycling, not from dried urine waking cortisone specifically.

Reference Ranges and How to Read Them

There is no universal clinical cutpoint for dried urine waking cortisone. This is a Tier 3 research marker, and reference ranges are derived from each lab's own population of test-takers rather than from large outcome trials. The ranges below illustrate the categories you may see on a DUTCH-style report. They are orientation, not targets.

Compare your results within the same lab and the same assay method over time. Different labs use different cutpoints, units (ng/mg of creatinine versus nmol/L), and reporting conventions, so a number that looks high in one report may sit comfortably in another lab's range.

When Results Can Be Misleading

A single waking cortisone value is sensitive to a number of short-term factors. The most important ones to know about:

• Collection timing: the sample must be from your first morning urine, ideally within minutes of waking. A sample taken hours later will not capture the peak.
• Acute stress or poor sleep the night before: a single bad night can spike or flatten your waking response without reflecting your typical pattern.
• Glucocorticoid medications: hydrocortisone, prednisone, dexamethasone, and topical or inhaled steroids can shift cortisone readings via direct contribution or feedback suppression, without indicating a primary adrenal problem.
• Kidney function and urine concentration: the result is reported per gram of creatinine. Severely reduced kidney function or very dilute urine can distort the ratio independent of your adrenal output.

If you are taking glucocorticoid medications and a clinician needs to assess your underlying adrenal function, the test will not give a clean read. The drug-induced shift is a confounder of the measurement, not evidence of disease.

Why One Reading Is Not Enough

Cortisone, like cortisol, has meaningful within-person variability from day to day. Sleep, stress, illness, menstrual cycle phase, and even the time you woke up can shift a single sample. A study of day-to-day variation in salivary cortisol and cortisone (a related but different specimen) found measurable biological noise, supporting the value of repeated measurements rather than relying on one snapshot. Treat any single reading as a data point, not a verdict.

A reasonable cadence: get a baseline, then retest in 3 to 6 months if you are making meaningful changes to sleep, stress management, exercise, or medication. After that, annual monitoring lets you see whether your morning hormone pattern is drifting. Serial samples, ideally collected on similar days of the week and at the same time after waking, give you a trend line that is far more interpretable than any single number.

What to Do If Your Result Is Abnormal

An unexpectedly low waking cortisone result, particularly if paired with low waking cortisol in the same panel, deserves a confirmation step. The clinically validated next test is an ACTH stimulation test, a same-day office procedure that measures whether your adrenal glands can mount a normal cortisol response when chemically prompted. If you have been taking opioids, glucocorticoid medications, or have a history of pituitary issues, an endocrinologist should interpret the workup.

A high waking cortisone, especially if it accompanies a high waking cortisol or a flat diurnal pattern, is worth pairing with at least one of: a late-night salivary cortisol, a 24-hour urinary free cortisol, or a 1-mg dexamethasone suppression test. These are the standard screens for cortisol excess, and your primary care doctor or an endocrinologist can order them. The dried urine waking cortisone is not a stand-alone diagnostic for Cushing syndrome, but it can be the signal that prompts the right next test.