NE07 A simple clinical and biochemical prediction score for distinguishing ectopic ACTH syndrome from Cushing disease
TL;DR
The Ectopic Cushing Prediction Score (ECPS) accurately differentiates EAS from CD using routine clinical and biochemical parameters and may guide the diagnostic evaluation of ACTH-dependent Cushing syndrome.
Abstract
Differentiating ectopic ACTH syndrome (EAS) from Cushing disease (CD) remains challenging in ACTH-dependent Cushing syndrome. We aimed to evaluate routinely available markers and develop a simple prediction score for distinguishing EAS from CD. This retrospective single-center study included 85 patients with ACTH-dependent Cushing syndrome: 77 with CD and 8 with EAS. Clinical, biochemical, and imaging findings were compared. Receiver operating characteristic analyses were used to assess marker performance, and the most discriminative variables were incorporated into the Ectopic Cushing Prediction Score (ECPS). Patients with EAS had a more severe phenotype, with higher rates of hypertension, proximal muscle weakness, hypokalemia, and opportunistic infections. ACTH, serum cortisol, midnight cortisol, late-night salivary cortisol (LNSC), and 24-hour urinary free cortisol (UFC) were significantly higher in EAS than in CD. Among individual markers, hypokalemia showed the highest diagnostic accuracy (AUC=0.967; sensitivity 100%; specificity 93.3%), followed by UFC >10× ULN (AUC=0.950) and ACTH (AUC=0.891). Optimal cut-offs were 467.5 μg/24 h for UFC and 149.5 pg/mL for ACTH. The ECPS included hypokalemia, UFC >10× ULN, ACTH ≥149.5 pg/mL, LNSC ≥1.4× ULN, and post–1 mg dexamethasone suppression test cortisol ≥14.85 μg/dL. The ECPS showed excellent performance (AUC=0.994), and a score ≥5 yielded 87.5% sensitivity and 98.6% specificity. The ECPS accurately differentiates EAS from CD using routine clinical and biochemical parameters and may guide the diagnostic evaluation of ACTH-dependent Cushing syndrome.