Is this profile recognised by mainstream endocrinology?

No. Mainstream endocrine societies rely on serum cortisol, ACTH, dynamic suppression and stimulation tests, and 24-hour urinary free cortisol for diagnosing Cushing syndrome and adrenal insufficiency. The additional metabolites and ratios in this profile are used in functional and integrative medicine but are not part of standard clinical guidelines.

What is the cortisol-to-cortisone ratio used for?

The urinary free cortisol-to-cortisone ratio estimates 11β-hydroxysteroid dehydrogenase type 2 activity. A high ratio suggests impaired cortisol inactivation, seen in apparent mineralocorticoid excess or liquorice ingestion; a low ratio may indicate upregulated inactivation or reduced cortisol output.

Why are tetrahydrocortisol and tetrahydrocortisone measured?

THF, allo-THF, and THE are the major hepatic metabolites of cortisol and cortisone, representing the bulk of daily glucocorticoid clearance. Their absolute values and ratios characterise hepatic reductase enzyme activity and total cortisol metabolism, adding functional context beyond free cortisol alone.

Does the test require fasting or special preparation?

Fasting is not required, but patients should avoid liquorice-containing foods and supplements for at least 72 hours before collection, as glycyrrhizin inhibits 11β-HSD and distorts the cortisol-to-cortisone ratio. Note all medications, especially corticosteroids, on the requisition.

Can this profile diagnose adrenal fatigue?

The concept of 'adrenal fatigue' is not recognised as a clinical diagnosis by endocrine societies. Low-normal or reduced metabolite excretion may be interpreted in a functional-medicine context as reflecting hypothalamic–pituitary–adrenal dysregulation, but such findings require clinical correlation and do not establish a diagnosis of adrenal insufficiency.

Is a random urine collection as accurate as a 24-hour collection?

No. Random or timed-spot collections introduce variability and do not capture the full diurnal cortisol rhythm. A complete 24-hour collection is preferred for accurate integration of total output; if a random collection is used, interpret with caution and consider creatinine correction.

How long do results take?

Typically 7–10 business days from specimen receipt at Doctor's Data, as the profile uses specialised mass-spectrometry assays that require longer processing than routine chemistry.

Are reference intervals standardised across laboratories?

No. Reference intervals for urinary steroid metabolites are laboratory- and assay-specific. Serial results should be compared within the same performing laboratory, and functional thresholds are not standardised across the field.

BML-ADR-020adrenal stressUSA

Adrenal Corticoids Profile

The Adrenal Corticoids Profile quantifies urinary free cortisol, cortisone, tetrahydrocortisol, allotetrahydrocortisol, and tetrahydrocortisone alongside derived enzyme-activity ratios. It is a functional-medicine tool for investigating hypothalamic–pituitary–adrenal axis output, cortisol metabolism, and 11β-hydroxysteroid dehydrogenase balance over 24 hours, ordered when standard serum or…

Biomarkers

Urine (random)

Sample

7–10 business days

Turnaround

Fasting

What is the Adrenal Corticoids test?

The Adrenal Corticoids Profile is a comprehensive urinary steroid metabolite panel that quantifies free cortisol, cortisone, and their major hepatic metabolites — tetrahydrocortisol, allotetrahydrocortisol, and tetrahydrocortisone — alongside derived ratios. It is offered by specialised laboratories to practitioners seeking a detailed functional assessment of adrenal glucocorticoid production, peripheral metabolism, and enzyme activity over a 24-hour period, beyond the scope of standard serum or salivary cortisol tests. Unlike single-point serum cortisol or overnight dexamethasone suppression, this profile integrates diurnal cortisol secretion and maps the pathways by which cortisol is inactivated and cleared. Practitioners in functional and integrative medicine use it to investigate suspected hypothalamic–pituitary–adrenal axis dysregulation, chronic stress syndromes, and subtle shifts in steroid metabolism that are not captured by conventional endocrine work-up. The panel is interpreted as a whole, with metabolite patterns and ratios providing context that no single analyte can deliver.

What does the Adrenal Corticoids test measure?

F(Free Cortisol)

Range: Laboratory-specific; typically 20–90 µg/24 h for adults.Optimal: Functional practitioners may interpret mid-range values as optimal, though this approach is not standardised; clinical endocrinology relies on laboratory reference intervals derived from healthy populations.µg/24 h / nmol/24 h

Free cortisol represents the unbound, biologically active glucocorticoid fraction filtered by the glomerulus and excreted unchanged in urine. Its 24-hour excretion integrates total daily cortisol secretion and reflects the diurnal rhythm more comprehensively than a single serum sample. Urinary free cortisol rises in proportion to serum free cortisol when cortisol-binding globulin is saturated, making it a sensitive marker of hypercortisolaemia.

Urinary free cortisol is a first-line screening test for endogenous Cushing syndrome, particularly when day-to-day variability is high. It is also monitored in patients with suspected adrenal insufficiency or those on supraphysiological glucocorticoid therapy, and serves as a functional index of hypothalamic–pituitary–adrenal axis output over 24 hours.

E(Cortisone)

Range: Laboratory-specific; often 10–50 µg/24 h.Optimal: Laboratory-derived reference intervals; functional thresholds are not standardised.µg/24 h / nmol/24 h

Cortisone is the inactive 11-keto metabolite of cortisol, generated by 11β-hydroxysteroid dehydrogenase type 2 in the kidney and other tissues. It is rapidly interconverted with cortisol, and urinary cortisone excretion reflects both direct secretion and peripheral inactivation of cortisol. The cortisol-to-cortisone ratio provides insight into the balance between active glucocorticoid and its inactivation.

Cortisone measurement complements free cortisol in assessing adrenal glucocorticoid output and peripheral metabolism. Altered cortisol-to-cortisone ratios can signal abnormal 11β-HSD enzyme activity, seen in conditions such as apparent mineralocorticoid excess or chronic stress states, though these interpretations remain largely within the functional-medicine domain.

THF(Tetrahydrocortisol)

Range: Laboratory-specific; typically 1000–3000 µg/24 h.Optimal: Determined by laboratory reference populations; functional interpretation is not standardised.µg/24 h / nmol/24 h

Tetrahydrocortisol is a major hepatic metabolite of cortisol, formed by 5α-reductase and 3α-hydroxysteroid dehydrogenase. It is excreted in urine conjugated as a glucuronide and represents a substantial fraction of daily cortisol metabolism, integrating both hepatic enzyme activity and total glucocorticoid turnover.

THF is a component of steroid metabolite profiling used to investigate disorders of cortisol production and metabolism. Elevated THF can be seen in Cushing syndrome, while low values may accompany adrenal insufficiency. The ratio of THF to other metabolites helps characterise the activity of hepatic reductase enzymes.

allo-THF(Allotetrahydrocortisol)

Range: Laboratory-specific; typically 600–2000 µg/24 h.Optimal: Laboratory-derived intervals; no consensus functional range.µg/24 h / nmol/24 h

Allotetrahydrocortisol is the 5β-reduced metabolite of cortisol, formed in the liver and excreted conjugated in urine. It accounts for a smaller proportion of cortisol metabolism than THF but contributes to the overall steroid metabolome. The ratio of THF to allo-THF reflects the balance of 5α- versus 5β-reductase activity.

Allo-THF is measured in comprehensive urinary steroid profiles to characterise cortisol metabolism and hepatic enzyme function. Shifts in the THF-to-allo-THF ratio can indicate changes in reductase activity associated with obesity, metabolic syndrome, or enzyme-inducing medications, though clinical decision algorithms based on these ratios remain limited to specialised endocrine centres.

THE(Tetrahydrocortisone)

Range: Laboratory-specific; often 1500–4000 µg/24 h.Optimal: Laboratory reference intervals; functional thresholds not established.µg/24 h / nmol/24 h

Tetrahydrocortisone is a hepatic metabolite of cortisone, formed by the same 5α/5β-reductase and 3α-HSD pathway as THF. It is the single largest urinary steroid metabolite and reflects both cortisol secretion and its peripheral inactivation to cortisone. THE excretion is a surrogate for total glucocorticoid metabolism.

THE is a major component of 24-hour urinary steroid profiling. Elevated THE is characteristic of Cushing syndrome, while low values accompany adrenal insufficiency. The ratio of THF plus allo-THF to THE is used to estimate 11β-HSD enzyme balance and to screen for rare syndromes of apparent mineralocorticoid excess.

F/E(Urinary Free Cortisol-to-Cortisone Ratio)

Range: Laboratory-specific; typically 0.5–2.0.Optimal: Mid-range values are considered balanced; extremes warrant further investigation.ratio

The urinary free cortisol-to-cortisone ratio reflects the balance between active glucocorticoid and its inactivation by 11β-hydroxysteroid dehydrogenase type 2 in the kidney. A high ratio suggests impaired cortisol inactivation, allowing excessive mineralocorticoid receptor activation; a low ratio may indicate upregulated inactivation or reduced cortisol output.

The F/E ratio is used to investigate disorders of cortisol metabolism, including apparent mineralocorticoid excess (high ratio) and chronic stress or hypothalamic–pituitary–adrenal dysregulation (variable ratios). It is a niche marker in functional endocrinology and is not part of routine clinical algorithms.

(THF+allo-THF)/THE(THF + allo-THF to THE Ratio)

Range: Laboratory-specific; typically 0.7–1.5.Optimal: Mid-range values; clinical significance of deviations outside the functional-medicine literature is limited.ratio

This ratio estimates the relative activity of 11β-hydroxysteroid dehydrogenase enzymes by comparing the sum of cortisol metabolites (THF and allo-THF) to the cortisone metabolite (THE). A high ratio suggests deficient cortisol-to-cortisone conversion, while a low ratio indicates enhanced inactivation.

The ratio is used in specialised endocrine investigation of apparent mineralocorticoid excess, polycystic ovary syndrome, and metabolic syndrome. It is a research and functional-medicine tool rather than a mainstream diagnostic marker.

Why is the Adrenal Corticoids test ordered?

Functional investigation of suspected chronic stress, adrenal fatigue, or hypothalamic–pituitary–adrenal axis dysregulation when standard serum cortisol and ACTH are unrevealing
Screening for endogenous Cushing syndrome when urinary free cortisol alone is borderline or when integrated 24-hour output is preferred over single-point serum samples
Assessment of cortisol metabolism in patients with obesity, metabolic syndrome, or polycystic ovary syndrome, where shifts in reductase and 11β-HSD enzyme activity may contribute to phenotype
Investigation of apparent mineralocorticoid excess or unexplained hypertension with hypokalaemia, using the cortisol-to-cortisone ratio and THF-plus-allo-THF-to-THE ratio
Monitoring of patients on long-term glucocorticoid therapy or those recovering from exogenous steroid suppression, when detailed metabolite patterns inform tapering
Evaluation of suspected adrenal insufficiency when salivary or serum cortisol is equivocal, and integrated 24-hour output adds diagnostic clarity
Exploration of steroid metabolism in patients with refractory fatigue, mood disturbance, or cognitive symptoms attributed to adrenal dysfunction in a functional-medicine context
Pre- and post-intervention monitoring in integrative protocols targeting stress resilience, where practitioners seek objective biomarkers of hypothalamic–pituitary–adrenal response

Sample collection and turnaround

Sample type

Urine (random)

Fasting required

Collection method

At-home collection kit

Turnaround

7–10 business days

Collection notes

Patient collects a random urine specimen at home using the kit provided by Doctor's Data. The laboratory may specify a first morning void or a timed collection depending on the protocol; follow the kit instructions precisely. Avoid liquorice-containing foods and supplements for at least 72 hours before collection. Note all medications, especially corticosteroids, on the requisition form.

Specimen requirements

Minimum volume as specified in the kit (typically 10–50 mL). Collect in the preservative-containing vial if provided; refrigerate immediately and ship on ice per kit instructions. Collection completeness and timing affect interpretation; document the collection interval and any deviations.

What can affect Adrenal Corticoids results?

variableIncomplete or poorly timed urine collection

A 24-hour collection that is incomplete or includes extra hours will under- or overestimate total excretion; creatinine measurement can verify adequacy, but random-urine collections introduce timing variability that limits interpretation.

elevatesGlucocorticoid or mineralocorticoid medication

Exogenous corticosteroids suppress endogenous ACTH and alter urinary free cortisol and metabolite excretion; even inhaled or topical steroids can interfere if systemically absorbed. Patients must discontinue where clinically safe, or results must be interpreted with caution.

elevatesLiquorice ingestion and glycyrrhizin

Glycyrrhizin inhibits 11β-hydroxysteroid dehydrogenase type 2, raising the cortisol-to-cortisone ratio and mimicking apparent mineralocorticoid excess. Patients should avoid liquorice-containing foods and supplements before collection.

variableSevere hepatic or renal impairment

Hepatic disease alters steroid metabolism and conjugation, while renal disease affects glomerular filtration and tubular handling of steroids; both can distort urinary metabolite patterns independent of adrenal function.

variableEnzyme-inducing or -inhibiting medications

Drugs that induce or inhibit cytochrome P450 and steroid-metabolising enzymes (e.g. rifampicin, St John's wort, certain antiepileptics) can shift the ratios of cortisol metabolites, confounding functional interpretation.

elevatesAcute stress, illness, or surgery

Acute physiological stress activates the hypothalamic–pituitary–adrenal axis and raises cortisol secretion, so collection during intercurrent illness will not reflect baseline adrenal function.

What do Adrenal Corticoids results mean?

Elevated

Elevated free cortisol and metabolite excretion: endogenous Cushing syndrome (pituitary, adrenal, or ectopic ACTH), exogenous glucocorticoid exposure, or acute stress. Very high free cortisol (>3–4× the upper limit) strongly suggests Cushing syndrome and warrants confirmatory dynamic testing. Isolated elevation of cortisol-to-cortisone ratio: apparent mineralocorticoid excess, liquorice ingestion, or 11β-HSD type 2 deficiency. High THF-plus-allo-THF-to-THE ratio: reduced cortisol inactivation, seen in some patients with metabolic syndrome.

Normal

Mid-range free cortisol and metabolite excretion with balanced ratios suggests intact adrenal glucocorticoid production and normal peripheral metabolism. A normal result does not exclude mild or early-stage adrenal dysfunction, nor does it rule out intermittent or context-dependent hypothalamic–pituitary–adrenal dysregulation, so clinical correlation and serial testing may be necessary.

Reduced

Low free cortisol and metabolite excretion: primary adrenal insufficiency, secondary (hypothalamic or pituitary) adrenal insufficiency, or recovery from exogenous steroid suppression. Low values may also be seen in states of chronic hypothalamic–pituitary–adrenal suppression attributed to prolonged stress, though this interpretation is contested and not widely accepted in mainstream endocrinology. Functional practitioners may interpret low-normal or reduced metabolite patterns as 'adrenal fatigue,' a concept not recognised as a clinical diagnosis by endocrine societies.

Note: This profile is a functional tool rather than a first-line diagnostic test for adrenal disease. Mainstream endocrinology relies on serum cortisol, ACTH, dynamic suppression and stimulation tests, and urinary free cortisol for Cushing syndrome; the additional metabolites and ratios in this panel are not part of standard guidelines and their clinical thresholds are laboratory- and method-specific. Interpretation requires familiarity with steroid biochemistry and should be integrated with history, symptoms, and confirmatory testing. Results from dried-urine or random-urine collections are not interchangeable with 24-hour timed collections, and reference intervals are assay-dependent.

Frequently asked questions

Serum cortisol is a single-point snapshot of circulating glucocorticoid at the time of draw, while the Adrenal Corticoids Profile integrates total 24-hour cortisol secretion and maps the hepatic and renal metabolite pathways. The profile is a functional tool for detailed investigation, not a replacement for acute diagnostic serum cortisol.

How to access the Adrenal Corticoids test

The Adrenal Corticoids reference page is free and open to all practitioners. Create a free practitioner account to see pricing, save tests to your list, and generate requisition forms. Verification takes 1–2 business days.

Create Free Account

About this page

Published: October 7, 2026

Last reviewed: October 7, 2026

References:

Nieman LK, et al. The diagnosis of Cushing's syndrome: an Endocrine Society clinical practice guideline. (2008)
Bornstein SR, et al. Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society clinical practice guideline. (2016)
Tomlinson JW, et al. 11β-Hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response. Endocr Rev. (2004)
Arlt W, et al. Steroid metabolome analysis reveals prevalent glucocorticoid excess in primary aldosteronism. JCI Insight. (2017)
Honour JW. Urinary steroid profiling in adults. Ann Clin Biochem. (2020)

This content is for licensed healthcare practitioners only and does not constitute medical advice. Clinical decisions should be based on the full clinical picture and not on any single test result.

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