Ceccato Filippo, Bavaresco Alessandro, Ragazzi Eugenio, Barbot Mattia, Boscaro Marco, Basso Daniela, Scaroni Carla, Antonelli Giorgia
Department of Medicine DIMED, University of Padova, 35128 Padua, Italy.
Endocrine Disease Unit, University Hospital of Padova, 35128 Padua, Italy.
J Clin Endocrinol Metab. 2025 Jan 21;110(2):396-405. doi: 10.1210/clinem/dgae517.
The clinical presentation of Cushing syndrome (CS) overlaps with common conditions. Recommended screening tests are serum cortisol after 1-mg overnight dexamethasone suppression test (DST), urinary free cortisol (UFC), and late-night salivary cortisol (LNSC).
We analyzed the diagnostic accuracy of screening tests in 615 patients without CS (263 suspected CS, 319 adrenal and 33 pituitary incidentaloma) and 40 with CS.
Principal component analysis, K-means clustering, and neural network were used to compute an integrated analysis among tests, comorbidities, and signs/symptoms of hypercortisolism.
The diagnostic accuracy of screening tests for CS was high; DST and UFC were slightly superior to LNSC. The threshold of DST should be adapted to the population considered, especially in adrenal incidentaloma (AI) with mild autonomous cortisol secretion: The cutoff to differentiate CS should be increased to 196 nmol/L. Diabetes, hypertension, and obesity were more common in patients without CS: The direction of their vectors was not aligned and their correlation with screening tests was poor. Clustering allowed us to differentiate those patients without CS into cluster 1 (aged osteoporotic patients with impaired screening tests), cluster 2 (hypertensive and metabolic phenotype), and cluster 3 (young individuals with a low likelihood of overt CS). A neural network model that combined screening tests and clinical presentation was able to predict the CS diagnosis in the validation cohort with 99% precision and 86% accuracy.
Despite the high diagnostic accuracy of screening tests to detect CS, cortisol-related comorbidities or AI should be considered when interpreting a positive test.
库欣综合征（CS）的临床表现与常见病症重叠。推荐的筛查试验包括1毫克过夜地塞米松抑制试验（DST）后的血清皮质醇、尿游离皮质醇（UFC）和午夜唾液皮质醇（LNSC）。
我们分析了615例无CS患者（263例疑似CS、319例肾上腺和33例垂体偶发瘤）和40例CS患者筛查试验的诊断准确性。
采用主成分分析、K均值聚类和神经网络对试验、合并症以及皮质醇增多症的体征/症状进行综合分析。
CS筛查试验的诊断准确性较高；DST和UFC略优于LNSC。DST的阈值应根据所考虑的人群进行调整，尤其是在肾上腺偶发瘤（AI）伴轻度自主性皮质醇分泌的情况下：区分CS的临界值应提高至196 nmol/L。糖尿病、高血压和肥胖在无CS患者中更为常见：它们的向量方向不一致，与筛查试验的相关性较差。聚类使我们能够将无CS患者分为1组（老年骨质疏松症患者，筛查试验受损）、2组（高血压和代谢表型）和3组（明显CS可能性低的年轻个体）。结合筛查试验和临床表现的神经网络模型能够在验证队列中以99%的精度和86%的准确性预测CS诊断。
尽管筛查试验检测CS的诊断准确性较高，但在解释阳性试验结果时应考虑与皮质醇相关的合并症或AI。
