The HPA axis and cortisol's role in your body
Cortisol is the primary glucocorticoid hormone produced by the adrenal glands in response to stress. It's released through the hypothalamic-pituitary-adrenal (HPA) axis — a three-part neuroendocrine system that coordinates stress response and metabolic homeostasis.
In the short term, cortisol is essential: it increases blood glucose for energy, enhances mental alertness, and suppresses inflammation. But chronic elevation from sustained stress has profound health consequences, affecting mood, immunity, metabolism, and longevity.
Diurnal cortisol rhythm and its significance
Cortisol doesn't stay constant throughout the day. It follows a predictable 24-hour rhythm (diurnal pattern): highest in the early morning hours (awakening response), gradually declining through the afternoon, and reaching its lowest point around midnight. This rhythm is crucial for sleep quality, energy availability, and immune function.
Chronic psychological or physical stress can flatten this rhythm, causing morning fatigue, afternoon crashes, or middle-of-the-night awakening. A flattened cortisol curve is associated with exhaustion, impaired recovery, and increased infection susceptibility.
Cushing's syndrome vs. Addison's disease
Cushing's syndrome occurs when cortisol is persistently too high, either from a pituitary tumour or ectopic source. Symptoms include central weight gain, purple stretch marks, easy bruising, muscle weakness, and mood disturbance. Conversely, Addison's disease results from adrenal failure or autoimmune destruction, causing low cortisol and presenting with fatigue, weight loss, and hypotension.
While these are rare conditions, subclinical cortisol dysregulation is common. Salivary testing can detect early warning patterns that blood testing might miss, particularly when a diurnal rhythm is measured.
Chronic stress and HPA axis dysregulation
Prolonged psychological stress (work burnout, relationship difficulties, grief) or physical stress (overtraining, chronic illness, poor sleep) can dysregulate the HPA axis. The result is often not frank Cushing's or Addison's, but rather a blunted cortisol response — where the body can no longer mount appropriate physiological responses to new stressors.
This dysregulation is associated with chronic fatigue, recurrent infections, mood disorders, and slow recovery from exercise. It's one of the most common functional imbalances observed in clinical practice.
Why salivary cortisol and cortisone testing matters
Saliva contains only the free, biologically active fraction of cortisol — not the protein-bound form measured in serum. This makes salivary testing more physiologically relevant to actual HPA axis function and tissue-level stress response.
Masdiag measures both cortisol and cortisone from saliva using liquid chromatography-mass spectrometry (LC-MS/MS). Cortisone is the inactive metabolite of cortisol, and the cortisol-to-cortisone ratio provides insight into 11-beta-hydroxysteroid dehydrogenase (11-HSD) activity — an enzyme central to tissue-specific cortisol regulation.
Who benefits from salivary cortisol testing?
People with symptoms of chronic fatigue, burnout, or poor recovery from training should consider testing. Those with suspected adrenal dysfunction, unexplained mood disturbance, or sleep dysregulation may also benefit. Additionally, athletes and high-performing professionals undergoing intense training or demanding schedules can use cortisol patterns to optimise recovery and prevent overtraining.
The non-invasive nature of saliva collection makes it practical for repeated sampling across a day or over weeks, allowing practitioners to assess true patterns rather than single-point measurements.
Frequently asked questions
What is the HPA axis and why does it matter?
The hypothalamic-pituitary-adrenal (HPA) axis is a three-part neuroendocrine system that controls cortisol production in response to stress. The hypothalamus signals the pituitary gland, which in turn signals the adrenal glands to release cortisol. This system coordinates the body's stress response and maintains homeostasis.
What is diurnal cortisol rhythm?
Cortisol follows a predictable 24-hour pattern: highest in the early morning (to wake you up) and gradually declining through the day, with lowest levels at night. This rhythm is crucial for sleep quality, energy, and immune function. Chronic stress can flatten or reverse this pattern, causing fatigue and sleep disruption.
How is salivary cortisol different from blood cortisol?
Saliva contains only the free, biologically active form of cortisol — not the protein-bound form measured in blood. This makes salivary testing more physiologically relevant for assessing HPA axis function and stress-related symptoms. Saliva collection is also non-invasive, making it ideal for frequent sampling across the day.
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View the full method details, sample requirements, and analytical specifications for our salivary cortisol and cortisone test.
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