Integrative Clinical, Radiological, and Molecular Analysis for Predicting Remission and Recurrence of Cushing Disease

Adrenocorticotropin (ACTH)-secreting pituitary tumors (ACTHomas) are associated with severe comorbidities and increased mortality. Current treatments mainly focus on remission and prevention of persistent disease and recurrence. However, there are still no useful biomarkers to accurately predict the...

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Published in:The journal of clinical endocrinology and metabolism 2022-06, Vol.107 (7), p.e2938-e2951
Main Authors: Moreno-Moreno, Paloma, Ibáñez-Costa, Alejandro, Venegas-Moreno, Eva, Fuentes-Fayos, Antonio C, Alhambra-Expósito, María R, Fajardo-Montañana, Carmen, García-Martínez, Araceli, Dios, Elena, Vázquez-Borrego, Mari C, Remón-Ruiz, Pablo, Cámara, Rosa, Lamas, Cristina, Carlos Padillo-Cuenca, José, Solivera, Juan, Cano, David A, Gahete, Manuel D, Herrera-Martínez, Aura D, Picó, Antonio, Soto-Moreno, Alfonso, Gálvez-Moreno, María Ángeles, Castaño, Justo P, Luque, Raúl M
Format: Article
Language:English
Subjects:
Comorbidity
Corticosteroids
Diagnosis
Diseases
Health aspects
Medical research
Medicine, Experimental
Mortality
Pituitary hormones
Prevention
Prognosis
Relapse
RNA
Spain
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Summary:Adrenocorticotropin (ACTH)-secreting pituitary tumors (ACTHomas) are associated with severe comorbidities and increased mortality. Current treatments mainly focus on remission and prevention of persistent disease and recurrence. However, there are still no useful biomarkers to accurately predict the clinical outcome after surgery, long-term remission, or disease relapse. This work aimed to identify clinical, biochemical, and molecular markers for predicting long-term clinical outcome and remission in ACTHomas. A retrospective multicenter study was performed with 60 ACTHomas patients diagnosed between 2004 and 2018 with at least 2 years' follow-up. Clinical/biochemical variables were evaluated yearly. Molecular expression profile of the somatostatin/ghrelin/dopamine regulatory systems components and of key pituitary factors and proliferation markers were evaluated in tumor samples after the first surgery. Clinical variables including tumor size, time until diagnosis/first surgery, serum prolactin, and postsurgery cortisol levels were associated with tumor remission and relapsed disease. The molecular markers analyzed were distinctly expressed in ACTHomas, with some components (ie, SSTR1, CRHR1, and MKI67) showing instructive associations with recurrence and/or remission. Notably, an integrative model including selected clinical variables (tumor size/postsurgery serum cortisol), and molecular markers (SSTR1/CRHR1) can accurately predict the clinical evolution and remission of patients with ACTHomas, generating a receiver operating characteristic curve with an area under the curve of 1 (P 
ISSN:0021-972X
1945-7197
DOI:10.1210/clinem/dgac172