Interpreting salivary cortisol thresholds in ectopic ACTH syndrome

This Perspective comments on a recent national cohort study of ectopic ACTH syndrome that identified late-night salivary cortisol (LNSC) ≥ 130 nmol/L as an independent predictor of mortality. The finding is clinically important because it supports the prognostic relevance of biochemical severity. However, its numerical interpretation should remain method-specific. LNSC is sensitive to sampling conditions and analytical platform, and absolute values are not necessarily interchangeable across immunoassays or between immunoassays and liquid chromatography-tandem mass spectrometry. In addition, dichotomizing a continuous biomarker can reduce information and overstate apparent separation at a data-derived cut point. Building on the original authors' own assay caveat, the threshold is best viewed as a Roche ECLIA-context signal of severe hypercortisolism, pending prospective multicenter validation using continuous biomarker modeling, assay harmonization, and subgroup analyses by tumor context and treatment era.