Ceccato, Filippo
(2023)
Clinical and biochemical data for the diagnosis of endogenous hypercortisolism: the “Cushingomic” approach.
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Clinical and biochemical data for the diagnosis of endogenous hypercortisolism: the “Cushingomic” approach. (deposited 30 Oct 2023 09:47)
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Background: The recommended first-line screening tests for Cushing’s syndrome (CS) are cortisol after dexamethasone suppression test (DS), 24h urinary free cortisol (UFC), and late night salivary cortisol (LNSC). We collected them and evaluated in combination with the clinical presentation of suspected CS.
Methods: We analysed 1-mg DST (with dexamethasone levels), UFC and LNSC (with tandem-mass spectrometry) in patients without CS (263 suspected CS, 319 adrenal and 33 pituitary incidentalomas) and 40 confirmed CS. Non-parametric multivariate methods (principal component analysis, K-means clustering, random forest, and supervised learning algorithm) were used to compute an integrated analysis among screening tests (1-mg DST, UFC, LNSC), cortisol-related comorbidities and signs/symptoms of CS.
Findings: The three tests were able to individuate CS, cortisol after DST and UFC were slightly superior to LNSC. The threshold of 1-mg DST should be adapted to the population considered, especially in adrenal incidentaloma with mild autonomous cortisol secretion, the results of UFC and LNSC were independent of the group or high-risk condition considered. Some cortisol-related comorbidities were more common in patients without CS (diabetes, hypertension, and obesity), their correlation with screening tests was poor: the direction of their vectors was not aligned. A neural network model that combined screening tests and clinical presentation was able to predict the CS diagnosis in the validation cohort with 99% sensitivity, 86% specificity, 99% precision and 86% accuracy.
Interpretation: Screening tests for CS performed adequately. The presence of cortisol-related comorbidities and mild autonomous cortisol secretion in adrenal incidentalomas should be interpreted carefully.
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