Abstract
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.
Highlights
Pituitary adenoma size was significantly reduced at the end of retinoic acid treatment
In this study we show that retinoic acid is at least as effective as ketoconazole, if not more so, but the fall in cortisol excretion is accompanied by a reduction in circulating ACTH and ␣-MSH and a reduction in size of the pituitary tumor
This supports the concept that retinoic acid may improve the clinical and biochemical signs of Cushing’s disease by a direct action on the tumorous corticotroph, as suggested by earlier studies in rodents [25]
Summary
Pituitary adenoma size was significantly reduced at the end of retinoic acid treatment. 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. For ACTH-secreting pituitary tumors causing pituitary-dependent Cushing’s syndrome, Cushing’s disease, only a minority respond to treatment with dopamine agonists or somatostatin analogs (4 – 6), and the primary mode of therapy remains transsphenoidal surgery. Such corticotroph cell adenomas, or corticotrophinomas, account for approximately 8% of all clinically recognized pituitary adenomas, possibly more when considering silent corticotroph. Several adrenal target drugs, such as ketoconazole, have been used [5, 13, 14], but they control the excessive glucocorticoid secretion in some patients, they do not inhibit corticotrophinoma growth and its consequent effects and are not a real alternative to the established procedures
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
