Development of diagnostic algorithm for Cushing's syndrome: a tertiary centre experience.

Area of Science:

• Endocrinology
• Clinical Diagnostics
• Biochemistry

Background:

• Cushing's Syndrome (CS) diagnosis lacks a universally accepted gold standard screening method.
• Accurate screening is crucial for timely intervention and management of CS.

Purpose of the Study:

• To evaluate the diagnostic accuracy of late-night salivary cortisol (LNSC), late-night salivary cortisone (LNSE), and overnight dexamethasone suppression test (ODST) for CS screening.
• To develop an improved screening algorithm for CS by assessing the utility of these tests individually and in combination.
• To compare the effectiveness of LNSC, LNSE, and ODST in differentiating subtypes of CS, specifically CD and MACS.

Main Methods:

• A retrospective analysis of 93 adult patients evaluated for CS between 2017 and 2022.
• Statistical analysis using binomial logistic regression and receiver-operating characteristic (ROC) curves to determine diagnostic accuracy (Area Under the Curve - AUC).
• Evaluation of individual test performance, combined test performance, and the impact of pre-test clinical symptoms and ACTH levels on diagnostic utility.

Main Results:

• LNSC (AUC 0.76), LNSE (AUC 0.79), and ODST (AUC 0.74) showed comparable diagnostic effectiveness for CS.
• Combined use of LNSC, LNSE, and ODST significantly increased diagnostic accuracy (AUC 0.91).
• LNSE combined with LNSC (AUC 0.95) was superior for diagnosing Cushing's Disease (CD), while ODST (AUC 0.76) was better for detecting Macronodular Adrenal Hyperplasia (MACS).
• Inclusion of pre-test clinical symptoms improved screening performance for all tested methods.
• Combining LNSC, LNSE, and ODST with ACTH levels < 12.6 pmol/L perfectly differentiated CD and MACS (AUC 1.00).
• Urinary free cortisol (UFC) did not show statistically significant diagnostic utility.

Conclusions:

• LNSC, LNSE, and ODST are reliable screening tools for Cushing's Syndrome, with their combined application yielding the highest diagnostic precision.
• LNSE, particularly when used with LNSC, demonstrates high efficacy for CD diagnosis, surpassing ODST.
• ODST is the preferred test for MACS detection.
• Integrating ACTH levels significantly enhances the differentiation between CD and MACS.
• UFC has limited value in the diagnostic workup of CS.