In the realm of endocrine diagnostics, Professor Brian Keevil is a beacon of innovation, shedding light on the transformative potential of salivary cortisone testing. As the Clinical Lead for Biochemistry at Manchester University NHS Foundation Trust, Keevil's expertise lies in the development and implementation of advanced mass spectrometry methods for clinical diagnostics, particularly in endocrinology. His passion for salivary cortisol and cortisone testing is rooted in the desire to simplify and enhance the diagnosis and monitoring of adrenal disorders, such as Cushing's syndrome and adrenal insufficiency.
The Power of Salivary Cortisone
Keevil's interest in salivary cortisol and cortisone stems from the need for a simpler, more patient-friendly alternative to traditional blood-based testing. Saliva, he explains, is easy to collect and convenient for patients, avoiding the burden of venepuncture and reducing the strain on healthcare services. From an analytical perspective, saliva contains the free fraction of cortisol, which is the biologically active component, making it ideal for assessing adrenal function.
What sets salivary cortisone apart is its superior sensitivity and correlation with serum cortisol levels. Keevil notes, "We found that measuring salivary cortisone offered several advantages over salivary cortisol, particularly in terms of sensitivity and correlation with serum cortisol concentrations." This makes it a more reliable biomarker, reflecting physiological cortisol exposure across a wider concentration range.
Diagnosing Adrenal Insufficiency
Adrenal insufficiency, a potentially life-threatening condition, is often underdiagnosed due to nonspecific symptoms and the inconvenience of existing screening tests. Keevil's research has shown that waking salivary cortisone collected at home can act as an effective first-line screening test. He emphasizes, "We have demonstrated that the test is safe, practical, and capable of reducing the number of patients requiring more invasive investigations."
Cushing's Syndrome: A Complex Diagnosis
Cushing's syndrome, another challenging endocrine disorder, lacks a single definitive test. Keevil's studies have shown that late-night salivary cortisone performs exceptionally well, especially in patients with pituitary-dependent Cushing's disease. He highlights, "In one tertiary referral study, late-night salivary cortisone was the single best-performing test, achieving sensitivity of 95% and specificity of 100% using an optimized cutoff value."
Salivary Cortisone and Dexamethasone Suppression Testing
Keevil's research has also explored the use of salivary cortisone alongside the overnight dexamethasone suppression test. He explains, "The overnight dexamethasone suppression test is widely used because dexamethasone should suppress cortisol production in healthy individuals. We investigated whether saliva samples could replace serum measurements in this setting."
The results were promising, with strong correlations between serum cortisol and post-dexamethasone salivary cortisone concentrations. Keevil notes, "Using a salivary cortisone cutoff of less than 2.7 nmol/L produced excellent diagnostic performance, with sensitivity around 85% and specificity around 92% for detecting cortisol excess."
Salivary Dexamethasone Metabolites: Unlocking New Insights
Keevil's research has also delved into salivary dexamethasone metabolites, aiming to confirm medication absorption. He explains, "Direct measurement of salivary dexamethasone has not performed particularly well. However, we found that measuring salivary 11-dehydrodexamethasone, a metabolite produced through similar enzymatic pathways to cortisone, provides much better correlation with serum dexamethasone concentrations."
This could become a valuable addition to future saliva-based diagnostic pathways, helping identify patients whose suppression tests fail due to altered dexamethasone metabolism or absorption.
Mild Cortisol Excess: A Hidden Challenge
Keevil's interest extends to mild autonomous cortisol secretion, a subtle yet significant challenge. He notes, "One of the areas generating considerable interest is mild autonomous cortisol secretion, which can be difficult to identify using conventional approaches."
Recent work suggests that late-night salivary cortisone may offer excellent discrimination between affected patients and controls. Keevil speculates, "Late-night salivary cortisone may offer excellent discrimination between affected patients and controls, suggesting that salivary cortisone could become an important screening tool for identifying subtle cortisol excess before more severe disease develops."
The Future of Salivary Cortisone Testing
Looking ahead, Keevil envisions a bright future for salivary cortisone testing in endocrine medicine. He predicts, "I believe salivary cortisone will continue to gain traction as a routine outpatient and home-based test. It offers excellent diagnostic performance, is highly convenient for patients, and has the potential to reduce healthcare costs while improving access to endocrine testing."
Keevil's work, supported by multicenter studies across the UK and Germany, is paving the way for a new era in adrenal disease diagnosis. He concludes, "As more centers adopt LC-MS/MS methodologies, I expect saliva-based steroid testing to become an increasingly important part of clinical practice."
In conclusion, Professor Brian Keevil's insights into salivary cortisone testing offer a glimpse into the future of endocrine diagnostics. His passion for innovation and patient-centric care is transforming the way we approach adrenal disorders, offering hope for improved diagnosis and management.
