Portal de investigación
Urinary-free cortisol-based thresholds for differentiating ACTH-dependent Cushing: a Spanish validation study.
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Biagetti B
- Soto-Moreno A
- García-Centeno R
- González-Fernández L
- Ollero García MD
- Irigaray Echarri A
- Cardona-Arias A
- Moure Rodríguez MD
- Paja M
- Castro A
- Manzano Valero L
- Guerrero-Pérez F
- Lamas C
- Alcázar Lázaro V
- Gracía P
- Álvarez-Escolá C
- Lozano-Aida C
- Hanzu FA
- Araujo-Castro M
- Neuroendocrinology Task Force of Spanish Society of Endocrinology (SEEN)
Grupos
Abstract
CONTEXT: Differentiating ectopic ACTH secretion (EAS) from Cushing disease (CD) remains one of the most challenging steps in the diagnostic workup of ACTH-dependent Cushing syndrome (CS). Urinary-free cortisol (UFC) expressed as times above the upper limit of normal (ULN) has been proposed as a simple, noninvasive discriminator, but external validation in independent populations is lacking. OBJECTIVE: To validate the diagnostic performance of UFC × ULN for distinguishing EAS from CD and explore complementary biochemical markers, including late-night salivary cortisol (LNSC × ULN) and hypokalemia. DESIGN, SETTING, AND PARTICIPANTS: Multicenter retrospective study from the Spanish Cushing Registry including 269 patients with ACTH-dependent Cushing's syndrome (208 CD, 61 EAS) diagnosed and managed in tertiary referral centers. MAIN OUTCOME MEASURES: Diagnostic accuracy of UFC × ULN and LNSC × ULN for discriminating EAS from CD, expressed as area under the ROC curve (AUC), sensitivity, specificity, and predictive value. RESULTS: EAS patients were older (median 59.0 vs 44.9 years; P < .001) and showed higher UFC × ULN (16.6 vs 3.6; P < .001) and LNSC × ULN (9.3 vs 1.5; P < .001). UFC × ULN and LNSC × ULN achieved excellent discriminative performance (AUC 0.90 and 0.92). No EAS occurred with UFC × ULN < 3 × ULN, while 40.5% of patients with UFC = 10 × ULN had EAS. The combination of severe hypercortisolism (UFC = 10 × ULN and LNSC = 9 × ULN) plus hypokalemia identified 75% of EAS with 98% specificity. CONCLUSION: UFC × ULN thresholds reliably stratify the probability of EAS vs CD. Severe hypercortisolism and hypokalemia strongly predict EAS, supporting a pragmatic diagnostic approach that prioritizes whole-body imaging in high-risk patients and pituitary-centered evaluation in mild cases.
© The Author(s) 2026. Published by Oxford University Press on behalf of the Endocrine Society.
Datos de la publicación
- ISSN/ISSNe:
- 0021-972X, 1945-7197
- Tipo:
- Article
- Páginas:
- 2785-2795
- PubMed:
- 42063386
- Factor de Impacto:
- 1,746 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM ENDOCRINE SOC
Documentos
- No hay documentos
Filiaciones
Keywords
- Cushing disease; Cushing syndrome; ectopic Cushing; hypercortisolism; urinary-free cortisol
Cita
Biagetti B,MARQUES P,Soto A,García R,González L,Ollero MD,Irigaray A,Cardona A,Moure MD,Paja M,Castro A,Manzano L,Guerrero F,Lamas C,Alcázar V,Gracía P,SANCHIS D,Álvarez C,Lozano C,Hanzu FA,Araujo M,Neuroendocrinology Task Force of Spanish Society of Endocrinology (. Urinary-free cortisol-based thresholds for differentiating ACTH-dependent Cushing: a Spanish validation study. J. Clin. Endocrinol. Metab. 2026. 111. (10):p. 2785-2795. IF:5,400. (1).