Professor Brian Keevil, a Consultant Clinical Scientist at Manchester University NHS Foundation Trust, discusses the growing role of salivary cortisol and cortisone testing in the diagnosis and monitoring of adrenal disorders, including Cushing's syndrome and adrenal insufficiency. He highlights how non-invasive saliva-based testing, combined with LC-MS/MS analysis, could improve diagnostic accuracy, reduce the need for hospital visits, and support earlier intervention for patients with endocrine disorders.
Keevil's interest in salivary cortisol and cortisone stems from the desire to find a simpler, more patient-friendly alternative to traditional blood-based testing. Saliva collection is easy, convenient, and can be done at home, avoiding the burden of venepuncture. Additionally, saliva contains the free fraction of cortisol, which is biologically active, making it particularly useful for assessing adrenal function.
One key advantage of salivary cortisone over salivary cortisol is its higher sensitivity and correlation with serum cortisol concentrations. This is because salivary cortisone concentrations are around four times higher than salivary cortisol concentrations, making it easier to measure accurately. Moreover, salivary cortisone shows a more linear relationship with serum cortisol levels, reflecting physiological cortisol exposure and providing a more reliable marker across a wider concentration range.
Late-night salivary cortisone has emerged as a valuable biomarker for diagnosing Cushing's syndrome, particularly in patients with pituitary-dependent Cushing's disease. In a tertiary referral study, late-night salivary cortisone achieved high sensitivity and specificity, outperforming other tests like urinary free cortisol and standard late-night salivary cortisol measurements.
Salivary cortisone has also shown promise in diagnosing adrenal insufficiency, a potentially life-threatening condition often underdiagnosed due to nonspecific symptoms and resource-intensive screening tests. Waking salivary cortisone collected at home can act as an effective first-line screening test, reducing the need for more invasive investigations.
Furthermore, salivary cortisone testing can help identify milder forms of cortisol excess, such as mild autonomous cortisol secretion, which is difficult to detect using conventional approaches. Recent studies suggest that late-night salivary cortisone may offer excellent discrimination between affected patients and controls, making it a valuable screening tool for subtle cortisol excess.
Looking ahead, Keevil anticipates the continued growth of salivary cortisone testing in endocrine medicine. Multicenter studies are investigating cyclical Cushing's syndrome, and he believes that saliva-based steroid testing will become an increasingly important part of clinical practice, offering convenience, diagnostic accuracy, and cost-effectiveness.
