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Review Article

Current and Emerging Pharmacological Therapies for Cushing's Disease

Author(s): Efstathios Divaris, Georgios Kostopoulos and Zoe A. Efstathiadou*

Volume 30, Issue 10, 2024

Published on: 28 February, 2024

Page: [757 - 777] Pages: 21

DOI: 10.2174/0113816128290025240216110928

Price: $65

Abstract

Cushing’s Disease (CD), hypercortisolism due to pituitary ACTH secreting neuroendocrine neoplasm, is associated with increased morbidity and, if untreated, mortality in about half of the affected individuals. Consequently, the timely initiation of effective treatment is mandatory. Neurosurgery is the first line and the only potentially curative treatment; however, 30% of patients will have persistent disease post-surgery. Furthermore, a small percentage of those initially controlled will develop hypercortisolism during long-term follow- up. Therefore, patients with persistent or recurrent disease, as well as those considered non-eligible for surgery, will need a second-line therapeutic approach, i.e., pharmacotherapy. Radiation therapy is reserved as a third-line therapeutic option due to its slower onset of action and its unfavorable profile regarding complications. During the past few years, the understanding of molecular mechanisms implicated in the physiology of the hypothalamus-pituitary-adrenal axis has evolved, and new therapeutic targets for CD have emerged. In the present review, currently available treatments, compounds currently tested in ongoing clinical trials, and interesting, potentially new targets emerging from unraveling molecular mechanisms involved in the pathophysiology of Cushing’s disease are discussed.

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