Severity and management of hypercortisolism in patients with adrenocortical carcinoma and overt Cushing´s syndrome.
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Araujo-Castro Marta, Bancos Irina, Detomas Mario, Reincke Martin, Kastelan Darko, Naglic Melani, Nekic Anja Barac, Biagetti Betina, Casteras Roman Anna, Cardona Andrés, Carrerra Concepción Blanco, Fano Miguel Paja, Lu Haibo, Kimpel Otilia, Kroiss Markus, Oettle Matthias, Pascual-Corrales Eider, Guerrero-Pérez Fernando, Hanzu Felicia Alexandra, Rodrigo-Calvo Maria Teresa, Aida Claudia Lozano, Menendez Edelmiro, García-Centeno Rogelio, Fernández Laura Gónzalez, Pasarón María, Gimeno Paola Gracia, Morreli Valentina, Restrepo Johnayro Gutiérrez, Pompey Néstor López, García Ramos Andrés Felipe, Alvarez Mauricio, Iglesias Pedro, Valdes Nuria, Moure Rodriguez María Dolores, Rodríguez-Jiménez Beatriz, Rodríguez Rosario Oliva, Recio José María, Iriarte Durán María Bernarda, Calderón Stefanía Cruz, Tapia Francisco González, Herrera-Martínez Aura D, Builes Montaño Carlos E, Terzolo Massimo, Torchio Marianna, Serra Guillermo, Rivera-Martínez Wilfredo Antonio
Аннотация
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.