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. 2025 Sep;138(9):1296-1303.
doi: 10.1016/j.amjmed.2025.04.035. Epub 2025 May 23.

The Combination of Afternoon and Midnight Salivary Cortisol Improves the Diagnosis of Cushing Syndrome

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Free article

The Combination of Afternoon and Midnight Salivary Cortisol Improves the Diagnosis of Cushing Syndrome

Luana Lionetto et al. Am J Med. 2025 Sep.
Free article

Abstract

Background: The diagnosis of Cushing syndrome is challenging and often fraught with many pitfalls depending on several factors. We compare the diagnostic performance of AM serum cortisol; 24-hour urinary free cortisol; and 0800 h, 1400 h, and 2400 h salivary cortisol curve (SCC) in 1 mg dexamethasone suppression test positive and negative patients.

Methods: Eighty-three subjects performed measurements of SCC by the liquid chromatography tandem mass spectrometry method, exploiting the circadian rhythm of cortisol.

Results: The reproducibility and specificity of the test identify patients with hypercortisolism in 95% of cases at midnight. Interestingly, when considering 2 specific points (1400 h and 2400 h) on the SCC, the success rate rises to 100%.

Conclusion: The evaluation of the 1400 h and 2400 h assays led to detection of the total number of patients with Cushing syndrome. Salivary cortisol curve analysis is a non-invasive diagnostic strategy associated with elevated positive predictive value for hypercortisolism capable of enabling diagnosis. In addition, it can be considered for management of patient outcomes and monitoring of Cushing syndrome pharmacological treatment.

Keywords: 1 mg dexamethasone suppression test; Cushing syndrome; Liquid chromatography tandem mass spectrometry; Salivary cortisol curve; Urinary free cortisol.

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