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

Abstract

CONTEXT:

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.

OBJECTIVES:

This work aimed to identify clinical, biochemical, and molecular markers for predicting long-term clinical outcome and remission in ACTHomas.

METHODS:

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.

RESULTS:

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 < .001).

CONCLUSION:

This study demonstrates that the combination of a set of clinical and molecular biomarkers in ACTHomas is able to accurately predict the clinical evolution and remission of patients. Consequently, the postsurgery molecular profile represents a valuable tool for clinical evaluation and follow-up of patients with ACTHomas.

• Authors: Paloma Moreno-Moreno, Alejandro Ibáñez-Costa, Eva Venegas-Moreno, Antonio C Fuentes-Fayos, María R Alhambra-Expósito, Carmen Fajardo-Montañana, Araceli García-Martínez, Elena Dios, Mari C Vázquez-Borrego, Pablo Remón-Ruiz, Rosa Cámara, Cristina Lamas, José Carlos Padillo-Cuenca, Juan Solivera, David A Cano, Manuel D Gahete, Aura D Herrera-Martínez, Antonio Picó, Alfonso Soto-Moreno, María Ángeles Gálvez-Moreno, Justo P Castaño, Raúl M Luque
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 107 Issue 7 Pg. e2938-e2951 (06 16 2022) ISSN: 1945-7197 [Electronic] United States
• PMID: 35312002 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Hydrocortisone

Topics

• Humans
• Hydrocortisone
• Pituitary ACTH Hypersecretion (diagnosis, genetics, surgery)
• Pituitary Diseases
• Pituitary Gland (pathology)
• Pituitary Neoplasms (diagnosis, genetics, surgery)
• Recurrence
• Remission Induction
• Retrospective Studies
• Treatment Outcome