Retinoic Acid as a Novel Medical Therapy for Cushing’s Disease in Dogs

Authors
Castillo, Victor Alejandro; Giacomini, Damiana Paula; Páez Pereda, Marcelo; Stalla, Johanna; Labeur, Marta; Theodoropoulou, Marily; Holsboer, Florian; Grossman, Ashley B.; Stalla, Günter K.; Arzt, Eduardo Simon
Publication Year
2006
Language
English
Format
article
Status
Published version
Description
Cushing's disease is almost always caused by an ACTH-secreting pituitary tumor, but effective medical therapy is currently limited. Because retinoic acid has been shown to be potentially useful in decreasing corticotroph secretion and proliferation in rodent models, we have studied its action in dogs with Cushing's disease. A randomized treatment with retinoic acid (n = 22) vs. ketoconazole (n = 20) in dogs with Cushing's disease was assigned for a period of 180 d. Clinical signs, plasma ACTH and alpha-MSH, the cortisol/creatinine urine ratio, and pituitary magnetic resonance imaging were assessed and compared at different time points. We recorded a significant reduction in plasma ACTH and alpha-MSH, and also in the cortisol/creatinine urine ratio, of the dogs treated with retinoic acid. Pituitary adenoma size was also significantly reduced at the end of retinoic acid treatment. Survival time and all the clinical signs evaluated showed an improvement in the retinoic-acid-treated dogs. No adverse events or signs of hepatotoxicity were observed, suggesting that the drug is not only effective but also safe. Retinoic acid treatment controls ACTH and cortisol hyperactivity and tumor size in dogs with ACTH-secreting tumors, leading to resolution of the clinical phenotype. This study highlights the possibility of using retinoic acid as a novel therapy in the treatment of ACTH-secreting tumors in humans with Cushing's disease.
Fil: Castillo, Victor Alejandro. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina
Fil: Giacomini, Damiana Paula. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Páez Pereda, Marcelo. Max Planck Institute of Psychiatry; Alemania
Fil: Stalla, Johanna. Max Planck Institute of Psychiatry; Alemania
Fil: Labeur, Marta. Max Planck Institute of Psychiatry; Alemania
Fil: Theodoropoulou, Marily. Max Planck Institute of Psychiatry; Alemania
Fil: Holsboer, Florian. Max Planck Institute of Psychiatry; Alemania
Fil: Grossman, Ashley B.. Max Planck Institute of Psychiatry; Alemania
Fil: Stalla, Günter K.. Max Planck Institute of Psychiatry; Alemania
Fil: Arzt, Eduardo Simon. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina
Subject
.RETINOIC ACID
CUSHING'S DISEASE
Access level
Restricted access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/44644