Adrenocortex Stress Profile (ASP)
The Adrenocortex Stress Profile measures salivary free cortisol at four timepoints (morning, midday, evening, night) plus DHEA to map the diurnal rhythm of the HPA axis. Ordered in functional and integrative medicine to investigate chronic stress, fatigue, and burnout, it reveals circadian dysregulation and estimates the cortisol:DHEA ratio, guiding lifestyle and nutraceutical interventions.
6
Biomarkers
Saliva
Sample
7–10 business days
Turnaround
Partial
Fasting
What is the ASP test?
The Adrenocortex Stress Profile measures salivary free cortisol at four timepoints across the day plus salivary DHEA to map the diurnal rhythm of the hypothalamic–pituitary–adrenal axis and to estimate adrenal androgen reserve. It is ordered by practitioners working in functional, integrative, and naturopathic medicine to investigate subjective complaints of chronic stress, fatigue, burnout, and sleep disturbance where standard serum cortisol or ACTH testing has been uninformative or where a dynamic picture of HPA function is desired. Unlike a single serum cortisol, which captures only one snapshot and is influenced by cortisol-binding globulin, the four-point salivary profile reveals the shape of the diurnal curve — whether the morning rise is preserved, whether the decline through the day is orderly, and whether the late-night nadir is maintained. Saliva samples the unbound, bioavailable fraction of cortisol, making it particularly sensitive to circadian dysregulation. The addition of DHEA and the derived cortisol:DHEA ratio is intended to integrate the catabolic and anabolic signals of the adrenal cortex. Practitioners order this profile to guide interventions targeting lifestyle, sleep hygiene, adaptogens, and stress reduction rather than to diagnose recognised endocrine disease such as Cushing syndrome or Addison disease, for which standard diagnostic pathways remain the reference.
What does the ASP test measure?
Cortisol secretion follows a circadian rhythm driven by hypothalamic corticotrophin-releasing hormone and pituitary ACTH. Under normal conditions the hypothalamic–pituitary–adrenal axis generates a sharp morning peak 30–45 minutes after waking (the cortisol awakening response), followed by a decline through midday and afternoon to a nadir in the late evening. Salivary cortisol reflects the unbound, biologically active fraction and tracks the dynamics of this diurnal pattern more faithfully than a single serum sample.
The morning post-waking cortisol value captures the cortisol awakening response, which is a sensitive marker of HPA-axis integrity. A blunted morning peak may reflect chronic stress exposure, burnout, or dysregulated HPA feedback, while an exaggerated response can signal heightened psychological stress or anxiety. Interpreted alongside midday, evening, and night samples, the morning value anchors the diurnal profile and identifies loss of normal rhythm.
By midday the morning cortisol peak has declined, reflecting the normal downslope of the circadian rhythm. This timepoint captures the transition from the high arousal of waking to the more modulated HPA tone of the active day.
A midday value that remains elevated or fails to decline from the morning peak may suggest persistent activation or a flattened diurnal curve. Conversely, a premature drop below the expected midday range can signal blunted HPA output or exhaustion of the stress response.
Evening cortisol continues the downward trajectory as the HPA axis prepares for the nocturnal nadir. This phase of the rhythm is governed by the suprachiasmatic nucleus and the need to permit restorative processes during sleep.
An evening cortisol that fails to fall — remaining at midday or even morning levels — indicates loss of circadian rhythm and is seen in Cushing syndrome, chronic stress, and some mood disorders. A very low evening value may reflect adrenal insufficiency or HPA exhaustion.
The late-night nadir is the lowest point of the cortisol curve and occurs during the hours immediately before and during sleep. A preserved nadir is essential for restorative sleep and metabolic recovery.
An elevated late-night salivary cortisol is one of the most sensitive screening tests for Cushing syndrome and also flags loss of circadian rhythm in chronic stress and psychiatric illness. A flat curve with little difference between morning and night values is a hallmark of dysregulated HPA function.
DHEA is an androgen precursor secreted by the zona reticularis of the adrenal cortex under ACTH stimulation. Its levels decline with age and are modulated by chronic stress, sleep, and metabolic state. In saliva DHEA represents the unbound, bioavailable fraction.
Salivary DHEA is used to estimate adrenal androgen reserve and to compute the cortisol:DHEA ratio, which integrates catabolic (cortisol) and anabolic (DHEA) signals. A low DHEA or a high cortisol:DHEA ratio is interpreted in functional medicine as a marker of adrenal exhaustion or chronic stress, though these frameworks are not universally accepted in endocrinology.
This derived marker integrates the catabolic arm of the HPA axis (cortisol) with the anabolic androgenic arm (DHEA). The ratio is proposed to reflect the balance between stress-induced catabolism and anabolic reserve.
A high cortisol:DHEA ratio is interpreted in functional and integrative medicine as a sign of chronic stress, HPA dysregulation, or adrenal fatigue. Mainstream endocrinology does not recognise adrenal fatigue as a distinct entity, so this marker remains exploratory and is used to guide lifestyle and nutraceutical interventions rather than to diagnose disease.
Why is the ASP test ordered?
- Investigation of chronic fatigue, low energy, and subjective burnout in patients with normal routine biochemistry and thyroid function
- Assessment of suspected HPA-axis dysregulation in individuals with chronic stress, anxiety, or post-traumatic stress disorder
- Evaluation of insomnia, non-restorative sleep, or difficulty waking, where a flattened or inverted cortisol curve may contribute
- Patients with fibromyalgia, chronic pain syndromes, or chronic fatigue syndrome in whom neuroendocrine dysregulation is suspected
- Monitoring response to stress-reduction interventions, adaptogenic herbs, or adrenal-support protocols in functional and integrative practice
- Screening for loss of circadian cortisol rhythm in shift workers, carers, or individuals under sustained psychosocial stress
- Adjunct to evaluation of metabolic syndrome, central adiposity, or insulin resistance, where chronic cortisol elevation may play a pathogenic role
- Exploration of mood disorders, irritability, or cognitive fog in which HPA-axis tone may be contributory
Sample collection and turnaround
Sample type
Saliva
Fasting required
Partial
Collection method
At-home collection kit
Turnaround
7–10 business days
Collection notes
Patients collect four timed saliva samples at home using Salivette devices or passive drool: morning (30 minutes post-waking), midday (around 12:00), evening (around 18:00–20:00), and late night (before bed, around 23:00–24:00). Record exact collection times rather than intended times, since reference intervals are collection-time-specific and a sample taken outside its window cannot be correctly interpreted. Record waking time, sleep quality, and any intercurrent illness or unusual stress. Collect on a representative day, avoiding acute illness, vigorous exercise, and days of atypical stress. Abstain from food, drink, caffeine, alcohol, and tooth brushing for at least 30 minutes before each collection per protocol. Avoid collection where gingival bleeding or recent dental work may contaminate the sample with blood. Document all corticosteroid use including topical, inhaled, and intranasal preparations, oral contraceptives and oestrogen therapy, pregnancy, shift work, and sleep schedule.
Specimen requirements
Four timed saliva samples (minimum volume per Genova protocol, typically 1–2 mL per collection). Store samples refrigerated or frozen after collection and ship with cold pack. Avoid contamination with blood, food particles, or tobacco. Samples taken outside the designated time windows or without exact time documentation cannot be interpreted.
What can affect ASP results?
Cortisol reference intervals are collection-time-specific; a sample taken outside its designated window cannot be correctly interpreted. Recording exact collection times rather than intended times is essential. Poor adherence to the fasting and abstinence instructions or contamination with food, blood, or tobacco invalidates results.
Exogenous corticosteroids — oral, topical, inhaled, intranasal, or injected — raise salivary cortisol and suppress endogenous ACTH and DHEA. Document all steroid exposure, including dermatological and respiratory preparations, before interpretation.
Oestrogen raises cortisol-binding globulin, which increases total serum cortisol but has a smaller effect on salivary free cortisol. Pregnancy, oral contraceptives, and hormone replacement can modestly elevate salivary cortisol and must be documented.
Acute stress — physical or psychological — activates the HPA axis and raises cortisol. Collect on a representative day, avoiding acute illness, injury, or atypical stressors, to obtain a baseline profile.
The cortisol rhythm is entrained to the light–dark cycle and habitual sleep pattern. Shift work, transmeridian travel, and irregular sleep fragment the diurnal curve and make interpretation difficult. Document the patient's sleep schedule and waking time.
Blood contains cortisol at concentrations higher than saliva; gingival bleeding, recent dental work, or oral ulceration can contaminate the sample and spuriously raise results. Avoid collection immediately after tooth brushing or if oral bleeding is present.
What do ASP results mean?
Elevated
Morning cortisol elevated with preserved rhythm: acute stress, anxiety, or early-phase chronic stress. Elevated at multiple timepoints with loss of the evening nadir: chronic stress, loss of circadian rhythm, or screening-positive for Cushing syndrome (requires endocrine follow-up with midnight serum cortisol, 24-hour urine free cortisol, or dexamethasone suppression test). Elevated cortisol:DHEA ratio: interpreted in functional medicine as catabolic predominance or adrenal exhaustion, though not a recognised diagnostic category in endocrinology.
Normal
A preserved diurnal rhythm with a robust morning peak, orderly decline through the day, a clear evening fall, and a late-night nadir, combined with age-appropriate DHEA, suggests intact HPA-axis function. A normal profile does not exclude significant psychological stress or other causes of fatigue, which may be non-endocrine.
Reduced
Blunted morning cortisol awakening response with flat diurnal curve: chronic stress, burnout, or functional HPA exhaustion (a contested concept). Low cortisol at all timepoints: raises suspicion of adrenal insufficiency and mandates formal endocrine evaluation with serum cortisol, ACTH, and ACTH stimulation test. Low DHEA: age-related decline, chronic illness, or functional adrenal under-reserve.
Note: The four-point salivary cortisol profile is a functional and integrative tool, not a first-line endocrine diagnostic test. Concepts such as adrenal fatigue and adrenal exhaustion are not recognised by the Endocrine Society or other mainstream bodies, and the cortisol:DHEA ratio is an exploratory marker without consensus validation. Use this profile to guide lifestyle and nutraceutical interventions and to decide when formal endocrine evaluation is warranted. Markedly abnormal results — particularly a persistently elevated late-night cortisol or profoundly low values at all timepoints — require follow-up with standard diagnostic testing. Document all interfering factors, exact collection times, and the patient's sleep and stress context.
Frequently asked questions
Salivary cortisol measures the unbound, biologically active fraction and tracks the diurnal rhythm more faithfully than a single serum sample, which reflects total cortisol (bound plus free) and is influenced by cortisol-binding globulin. Salivary cortisol is preferred for mapping circadian rhythm; serum cortisol is the standard for diagnosing Cushing syndrome and adrenal insufficiency.
How to access the ASP test
The ASP 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.
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Published: October 7, 2026
Last reviewed: October 7, 2026
- Endocrine Society clinical practice guideline on the diagnosis of Cushing's syndrome. (2008)
- Hellhammer DH, et al. Salivary cortisol as a biomarker in stress research. Psychoneuroendocrinology. (2009)
- Cadegiani FA, Kater CE. Adrenal fatigue does not exist: a systematic review. BMC Endocr Disord. (2016)
- Bornstein SR, et al. Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society clinical practice guideline. (2016)
- Kudielka BM, Kirschbaum C. Awakening cortisol responses are influenced by health status and awakening time but not by menstrual cycle phase. Psychoneuroendocrinology. (2003)
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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