System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Ahead of print

PubMed: 42717378 DOI: 10.1210/clinem/dgag373

Severity and management of hypercortisolism in patients with adrenocortical carcinoma and overt Cushing´s syndrome.

J Clin Endocrinol Metab

Authors: Marta Araujo-Castro, Irina Bancos, Mario Detomas, Martin Reincke, Darko Kastelan, Melani Naglic, Anja Barac Nekic, Betina Biagetti, Anna Casteras Roman, 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 Menendez, 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 Rodriguez, Beatriz Rodríguez-Jiménez, Rosario Oliva Rodríguez, José María Recio, María Bernarda Iriarte Durán, Stefanía Cruz Calderón, Francisco González Tapia, Aura D Herrera-Martínez, Carlos E Builes Montaño, Massimo Terzolo, Marianna Torchio, Guillermo Serra, Wilfredo Antonio Rivera-Martínez

Affiliations

  • Endocrinology & Nutrition Department. Hospital Universitario Ramón y Cajal Madrid, Spain.
  • Instituto de Investigación Biomédica Ramón y Cajal (IRYCIS), Madrid, Spain.
  • Division of Endocrinology, Diabetes, and Nutrition, Mayo Clinic, Rochester, MN, USA.
  • Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Würzburg, Germany.
  • Department of Medicine IV, LMU University Hospital, LMU Munich, Munich, Germany.
  • Department of Endocrinology and Diabetes, University Hospital Zagreb, Zagreb, Croatia.
  • Endocrinology & Nutrition Department. Hospital Universitario Vall d'Hebron, Barcelona, Spain.
  • Endocrinology & Nutrition Department. Hospital Principe de Asturias, Madrid, Spain.
  • Endocrinology & Nutrition, Biobizkaia Health Research Institute; Osakidetza, Basurto University Hospital; EHU, University of the Basque Country, Bilbao, Bizkaia, Spain.
  • Luoyang Key Laboratory of Clinical Multiomics and Translational Medicine, Key Laboratory of Hereditary Rare Diseases of Health Commission of Henan Province, Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China, 471003.
  • Endocrinology & Nutrition Department, Hospital Universitario de Bellvitge. Biomedical Research Institute of Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
  • Endocrinology and Nutrition Department and Institut de Investigacions Biomediques Pi I Sunyer Barcelona, Hospital Clínic of Barcelona, University Barcelona, Barcelona, Spain.
  • Endocrinology & Nutrition Department. Hospital Universitario Central de Asturias, Asturias, Spain & l Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Asturias, Spain.
  • Endocrinology & Nutrition Department. Hospital Universitario Gregorio Marañón, Madrid, Spain.
  • Endocrinology & Nutrition Department. Hospital Universitario de Cabueñes, Gijón (Asturias), Spain.
  • Endocrinology & Nutrition Department. Hospital Universitario Royo Villanova, Zaragoza, Spain.
  • Endocrinology & Nutrition Department. Instituto Auxologico Italiano - IRCCS - Italy.
  • Endocrinology & Nutrition Department. Clínica Somer, Rionegro, Colombia.
  • Endocrinology & Nutrition Department. Universidad del Valle, Cali, Colombia.
  • Endocrinology & Nutrition Department. Clínica Imbanaco, Cali, Colombia.
  • Endocrinology & Nutrition Department. Hospital Militar Central, Bogotá, Colombia.
  • Endocrinology & Nutrition Department. Hospital Puerta de Hierro, Madrid, Spain.
  • Endocrinology and Nutrition Department, Hospital Universitario Cruces, Barakaldo, Bizkaia, Spain; Biobizkaia Health Research Institute, University of the Basque Country, CIBERDEM, CIBERER, Endo-ERN.
  • Endocrinology & Nutrition Department. Hospital Virgen del Macarena, Sevilla, Spain.
  • Endocrinology & Nutrition Department. Hospital Universitario Salamanca, Salamanca, Spain.
  • Endocrinology & Nutrition Department. Hospital Universitario Fundación Valle de Lili, Cali, Colombia.
  • Endocrinology & Nutrition Department. Universidad UPB, Medellín, Colombia.
  • Endocrinology & Nutrition Department. Hospital Reina Sofía, Córdoba, Spain.
  • Internal Medicine department, Hospital Pablo Tobón Uribe, Medellín, Colombia.
  • Division of Internal Medicine, University of Turin, San Luigi Hospital, Orbassano, Italy.
  • Endocrinology department, Hospital Universitario Son Espases, Palma de Mallorca, Spain.

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.

MeSH

Disease-Free Survival, Neoplasms, Adrenalectomy, Adrenocortical Carcinoma, Diagnosis, Hydrocortisone, Mitotane, Cushing Syndrome