In the realm of endocrine diagnostics, Professor Brian Keevil is a beacon of innovation, leading the charge in revolutionizing the way we detect and monitor adrenal disorders. As the Clinical Lead for Biochemistry at Manchester University NHS Foundation Trust, Keevil's expertise lies in harnessing the power of salivary cortisone testing to advance the diagnosis and management of Cushing's syndrome and adrenal insufficiency. This interview delves into the fascinating world of non-invasive testing, where saliva becomes a window into the body's hormonal secrets.
A Salivary Revolution
What sparked Keevil's interest in salivary cortisol and cortisone? The answer lies in the quest for simplicity and patient-friendliness. Traditional blood-based testing, while effective, often requires hospital visits and venepuncture, burdening both patients and healthcare services. Saliva, on the other hand, offers a convenient and accessible alternative. It's easy to collect, and its free fraction of cortisol, the biologically active component, makes it an ideal biomarker for adrenal function assessment.
The advantages of salivary cortisone over cortisol are particularly intriguing. Concentrations of cortisone in saliva are around four times higher, making them easier to measure accurately. Moreover, salivary cortisone shows a more linear relationship with serum cortisol levels, reflecting physiological cortisol exposure more reliably. This is especially valuable in diagnosing adrenal insufficiency, a potentially life-threatening condition often underdiagnosed due to nonspecific symptoms and resource-intensive screening tests.
Diagnosing Adrenal Insufficiency
Keevil's research has shown that waking salivary cortisone collected at home can act as an effective first-line screening test for adrenal insufficiency. This non-invasive approach is safe, practical, and reduces the need for more invasive investigations. Several UK hospitals are now implementing or evaluating this method, and Manchester University NHS Foundation Trust has already embraced routine use of the test.
Cushing's Syndrome: A Complex Diagnosis
Cushing's syndrome, a challenging endocrine disorder, lacks a single definitive test. Current investigations include urinary free cortisol measurements, late-night salivary cortisol, and overnight dexamethasone suppression testing. Keevil's studies have revealed that late-night salivary cortisone performs exceptionally well, especially in patients with pituitary-dependent Cushing's disease. In one tertiary referral study, late-night salivary cortisone emerged as the top performer, achieving impressive sensitivity and specificity.
Salivary Cortisone and Dexamethasone Suppression Testing
The overnight dexamethasone suppression test is a widely used diagnostic tool. Keevil's research has explored whether saliva samples can replace serum measurements in this setting. The results are promising, with strong correlations between serum cortisol and post-dexamethasone salivary cortisone concentrations. This approach not only removes the need for hospital visits but also enhances diagnostic performance, making it a more convenient and effective tool.
Metabolites and Their Role
Keevil's research has also delved into salivary dexamethasone metabolites. Measuring salivary 11-dehydrodexamethasone, a metabolite produced through similar enzymatic pathways to cortisone, provides better correlation with serum dexamethasone concentrations. This could become a valuable addition to future saliva-based diagnostic pathways, helping identify patients with altered dexamethasone metabolism or absorption.
Mild Cortisol Excess: A Hidden Challenge
One area of interest is mild autonomous cortisol secretion, which can be difficult to identify using conventional approaches. Keevil's recent work suggests that late-night salivary cortisone may offer excellent discrimination between affected patients and controls. This highlights the potential of salivary cortisone as a screening tool for identifying subtle cortisol excess before more severe disease develops.
Future Horizons
Looking ahead, Keevil envisions a bright future for salivary cortisone testing in endocrine medicine. Multicenter studies are investigating cyclical Cushing's syndrome, where cortisol excess fluctuates over time. By collecting repeated late-night saliva samples, researchers hope to gain deeper insights into disease patterns. Keevil believes that salivary cortisone will continue to gain traction as a routine outpatient and home-based test, offering excellent diagnostic performance, convenience, and cost-effectiveness.
In conclusion, Professor Brian Keevil's work is a testament to the power of innovation in healthcare. By harnessing the potential of salivary cortisone testing, he is not only advancing the diagnosis and management of adrenal disorders but also improving patient care and access to endocrine testing. As more centers adopt LC-MS/MS methodologies, the future of endocrine diagnostics looks brighter, with saliva-based steroid testing playing a pivotal role.
