Late-night cortisol saliva test not as accurate in real world: Study

But LNSaC test still found useful for diagnosing Cushing's syndrome

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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The accuracy of late-night testing of cortisol levels in saliva — a common test for diagnosing Cushing’s syndrome — may be lower in real-world clinical practice than in controlled experimental settings, according to a new study from Turkey.

The results showed the sensitivity, or true positive rate, of the late-night salivary cortisol (LNSaC) test was not as high as what’s been reported in research studies.

Still, the scientists found the LNSaC to have an acceptable and similar diagnostic value for identifying clinical Cushing’s, as well as subclinical forms of the disease in which overt symptoms may not be apparent.

“In order to correctly use this test, … each center should establish their own cut-off value depending on their in-house measurement method and then apply such values to decide on the diagnosis,” the team wrote.

The study, “Diagnostic Value of the Late-Night Salivary Cortisol in the Diagnosis of Clinical and Subclinical Cushing’s Syndrome: Results of a Single-Center 7-Year Experience,” was published in the Journal of Investigative Medicine.

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Cortisol saliva test can diagnose both clinical and subclinical disease

Cushing’s syndrome encompasses all disorders marked by excess levels of the hormone cortisol in the body. Cushing’s disease is a form of Cushing’s syndrome caused by tumors in the brain’s pituitary gland that ultimately lead to the overproduction of cortisol.

The diagnosis of Cushing’s syndrome typically involves measuring cortisol levels in the blood, urine, and/or saliva with various tests.

Normally, cortisol levels in the body change throughout the day, reaching a peak in the morning and a nadir in the middle of the night. But for patients with Cushing’s, these natural rhythms are disrupted, and cortisol might not decrease as expected during the night.

Thus, assessing nighttime cortisol levels in saliva — both easy to do and cost-effective — is often a first-line test for suspected Cushing’s. Such measurements, dubbed an LNSaC test, are used to help doctors understand if a person’s cortisol rhythms are altered.

Essentially, cortisol levels are measured from a saliva sample collected at night when cortisol is expected to be low. Higher than normal levels at that time might signal the presence of the disease.

However, there are no clearly defined LNSaC cut-off values for what is considered Cushing’s and what isn’t.

To learn more about LNSaC’s diagnostic performance, researchers from the School of Medicine at Akdeniz University, in Turkey, analyzed data from 324 people who underwent the test between 2010 and 2017.

Among them, 38% were tested with LNSaC for suspected Cushing’s. Other reasons for undergoing the test included conditions like obesity, high blood pressure, and osteoporosis — a disease that causes bones to become weaker and more prone to fractures. The test also was done to detect a tumor in the adrenal glands, known as adrenal incidentaloma.

Ultimately, 58 people were diagnosed with clinical Cushing’s and 53 had subclinical Cushing’s, meaning that biochemical signs of the disease were present, but patients did not have overt symptoms. The remaining 213 people did not have Cushing’s.

Saliva samples were collected from each patient at 11 p.m. and analyzed for cortisol levels.

Results showed that median LNSaC levels differed significantly between these three groups. Values were highest in those with clinical Cushing’s, who had a median of 0.724 micrograms of cortisol per deciliter of saliva (mcg/dL). Median values in those with subclinical disease were 0.398 mcg/dL, and in patients without Cushing’s were 0.18 mcg/dL.

With a clinical cut-off value of 0.2888 mcg/dL, LNSaC was found to have a sensitivity of 89.6% and a specificity of 81.6% for identifying Cushing’s. Sensitivity refers to a test’s ability to correctly identify a person with a disease as being positive, also called a true positive result, whereas specificity is its ability to correctly classify a person without the disease as being negative. Specificity also is known as a test’s true negative rate.

This [study] suggests that LNSaC can … be used in the diagnosis of [subclinical Cushing’s] and similar cut-off values can be used for both entities.

Researchers noted that some studies have found the test to have higher diagnostic accuracy than that observed here. However, those tests typically were performed in controlled experimental conditions and not in real-world clinical settings.

Taken together, data from the literature overall “suggest that LNSaC has a lower diagnostic performance than expected in the daily clinical practice,” the scientists wrote.

The test’s diagnostic performance, however, was found to be similar for patients with subclinical Cushing’s and those with clinical disease. At a cut-off value of 0.273 mcg/dL, LNSac had a sensitivity of 80.7% and a specificity of 85.1% at identifying subclinical Cushing’s.

“This suggests that LNSaC can … be used in the diagnosis of [subclinical Cushing’s] and similar cut-off values can be used for both entities,” the researchers wrote.

“In the event of an LNSaC value smaller than the determined cut-off value, and an ongoing suspicion of Cushing’s syndrome, the patients must be evaluated with other tests … as necessary,” the team wrote.