From the Guidelines
The best way to test for elevated cortisol is through a combination of tests, including 24-hour urine collection, late-night salivary cortisol, and dexamethasone suppression testing, as recommended by the most recent guidelines 1. When suspecting Cushing's disease, it is advised to start with either urinary free cortisol (UFC) and/or late-night salivary cortisol (LNSC) tests, with the dexamethasone suppression test (DST) being an option if LNSC is not feasible 1. For confirming Cushing's disease, any of these tests can be used, with UFC averaging 2-3 collections, LNSC requiring ≥2 on consecutive days, and DST being useful in specific cases such as shift workers but not in women on estrogen-containing oral contraceptives 1. Measuring dexamethasone level along with cortisol the morning after 1 mg dexamethasone ingestion can improve test interpretability 1. In cases where Cushing's syndrome is due to an adrenal tumor, starting with DST is recommended, as LNSC has lower specificity in these patients 1. It's crucial to avoid factors that can temporarily elevate cortisol levels, such as strenuous exercise, acute illness, and significant stress, for 24 hours before testing, and to discontinue certain medications like oral contraceptives, estrogen, and glucocorticoids if possible, under physician guidance 1. Multiple tests are often necessary for an accurate diagnosis due to the natural fluctuations of cortisol levels and their susceptibility to various factors, including sleep patterns, stress, and medical conditions 1. The choice of test may also depend on patient-specific factors, such as the ability to collect samples and the presence of certain medications or conditions that could affect test results 1. Given the complexity and variability of cortisol testing, following the most recent and highest quality guidelines, such as those from 2024 1, is essential for optimal diagnosis and management. Key considerations include the sensitivity and specificity of each test, as outlined in guidelines, to ensure the most accurate diagnosis and appropriate management plan for patients with suspected elevated cortisol levels.
From the Research
Testing for Elevated Cortisol
To test for elevated cortisol, several methods can be employed, including:
- Midnight salivary cortisol (MSC) measurement
- Midnight serum cortisol (MNC) measurement
- Urinary free cortisol (UFC) measurement
Comparison of Testing Methods
A study published in 2003 2 compared the diagnostic performance of MSC, MNC, and UFC in differentiating patients with Cushing's syndrome from those with pseudo-Cushing states and simple obesity. The results showed that:
- MSC had a sensitivity of 92.7% and a diagnostic accuracy of 93%
- UFC had a diagnostic accuracy of 95.3%
- MNC had a diagnostic accuracy of 95.7% No statistically significant differences were observed among the tests, suggesting that MSC can be recommended as a first-line test for Cushing's syndrome.
Convenience and Recommendations
Given its convenience, MSC measurement can be added to tests traditionally used for this purpose, such as UFC and MNC 2. This is particularly useful in both low-risk and high-risk patients.
Note: The study published in 1976 3 is not relevant to the topic of testing for elevated cortisol.