Severity and management of hypercortisolism in patients with adrenocortical carcinoma and overt Cushing´s syndrome
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ID: 328084
2026
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Abstract
OBJECTIVE: To analyze the association between the degree of hypercortisolism and survival outcomes of patients with Cushing´s syndrome (CS) due to adrenocortical carcinoma (ACC). METHODS: An international retrospective of patients with CS due to ACC. The primary outcomes were to evaluate the prognostic role of baseline hypercortisolism on survival outcomes, including progression-free survival (PFS), disease-free survival (DFS), and overall survival (OS). RESULTS: A total of 101 patients with ACC were included. The median urinary free cortisol (UFC) levels at the time of CS diagnosis were 6.4 times above the upper limit of normal (ULN) (IQR 2.9-14) and 53.5% (n = 54) of the cases had metastatic ACC. Maximum adrenal tumor size (OR 1.02, 95%CI 1.01-1.03) and UFC levels (1.62, 95%CI 1.03-2.57) were independent predictors of metastatic ACC. The median OS was 19.4 (range 1-176) months, the median DFS was 12.3 months (range 2.6-143), and PFS was 5.6 months (range 1.1-43.7). The risk of recurrence/progression increased as the severity of CS increased (21% in mild hypercortisolism (UFC <2xULN), 52% in moderate (2-5xULN) and 57% in severe CS (>5xULN), P = 0.035). UFC levels (HR 1.48; 95%CI 0.97-2.24, P = 0.057) tended to be associated with the risk of progression (metastatic ACC). When we considered a combined outcome (progression in metastatic ACC and recurrence in localized ACC), age, UFC, hypokalemia, R0 after surgery, and Ki-67 were independent predictors of recurrence/progression. CONCLUSION: Adrenal tumor size and the severity of cortisol excess are associated with a higher probability of metastatic disease at diagnosis. Our study suggests that the severity of cortisol excess appears to be associated with an increased risk of tumor recurrence/progression, suggesting that hypercortisolism intensity may serve as a marker of aggressive disease.
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| Authors | Marta Araujo‐Castro, Irina Bancos, Mario Detomas, Martín Reincke, Darko Kaštelan, Melani Naglic, Anja Barač Nekić, Betina Biagetti, Anna Casteràs, Andrés Cardona, Concepción Blanco Carrerra, Miguel Paja Fano, Haibo Lu, Otilia Kimpel, Markus Kroiss, Matthias Oettle, Eider Pascual‐Corrales, Fernando Guerrero-Pérez, Felicia Alexandra Hanzu, Maria Teresa Rodrigo‐Calvo, Claudia Lozano Aida, Edelmiro Menéndez, Rogelio García-Centeno, Laura Gónzalez Fernández, María Pasarón, Paola Gracia Gimeno, Valentina Morreli, Johnayro Gutiérrez Restrepo, Néstor López Pompey, Andrés Felipe García Ramos, Mauricio Alvarez, Pedro Iglesias, Nuria Valdes, María Dolores Moure Rodríguez, B Rodríguez-Jiménez, Rosario Oliva Rodríguez, José María Recio, María Bernarda Iriarte-Durán, Stefania Cruz Calderón, Francisco Gonzalez Tapia, Aura D Herrera-Martínez, Carlos E Builes Montaño, Massimo Terzolo, Marianna Torchio, Guillermo Serra, Wilfredo Antonio Rivera-Martínez |
| Journal | the journal of clinical endocrinology & metabolism |
| Year | 2026 |
| DOI |
10.1210/clinem/dgag373
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| URL | |
| Keywords | Keywords not found |
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