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Limitations of nocturnal salivary cortisol and urine free cortisol in the diagnosis of mild Cushing's syndrome. Eur J Endocrinol 2007 Dec;157(6):725-31



Pubmed ID




Scopus ID

2-s2.0-38349025604   89 Citations


OBJECTIVE: Cushing's syndrome (CS) is difficult to diagnose due to its nonspecific presentation. Diagnostic tests like 24-h urine free cortisol (UFC) and the overnight 1 mg dexamethasone suppression test (DST) lack sufficient sensitivity and specificity. Measurement of nocturnal salivary cortisol (NSC) is an accurate and reproducible test with a high sensitivity for CS. However, its performance in mild CS has not been reported. We present 11 cases of CS with normal or mildly elevated UFC in whom NSC was helpful in making a diagnosis.

DESIGN AND METHODS: All patients had at least one collection of 24-h UFC and NSC and eight had an overnight 1 mg DST. The number of NSC measurements per patient was determined by the clinical index of suspicion and the results of initial testing. Imaging studies included magnetic resonance imaging (MRI) of pituitary or computer tomography scan of abdomen.

RESULTS: Only four out of eleven patients had elevations in UFC and none were >2 times the upper limit of normal. Seven out of eight had an abnormal DST. All patients had some elevated NSCs (14-100%). Out of eleven patients, six had an abnormality in the pituitary gland found by MRI and two out of eleven had adrenal masses. The remaining three had normal pituitary MRI but had inferior petrosal sinus (IPS) sampling indicating Cushing's disease. All patients had appropriate surgery, and histopathology of all except one was suggestive of either a cortisol-producing adrenal adenoma or an ACTH-secreting pituitary adenoma.

CONCLUSION: Neither a normal UFC nor a normal NSC excludes mild CS. Multiple samples (urine/saliva) and DST are needed to make the diagnosis of mild CS.

Author List

Kidambi S, Raff H, Findling JW


James W. Findling MD Staff Physician in the Multi-Specialty department at Medical College of Wisconsin
Srividya Kidambi MD Chief, Associate Professor in the Medicine department at Medical College of Wisconsin
Hershel Raff PhD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cushing Syndrome
Middle Aged
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d