Title:Current and Emerging Pharmacological Therapies for Cushing's Disease
Volume: 30
Issue: 10
Author(s): Efstathios Divaris, Georgios Kostopoulos and Zoe A. Efstathiadou*
Affiliation:
- Department of Endocrinology, "Hippokration" General Hospital of Thessaloniki, Thessaloniki, Greece
Keywords:
Pituitary, pituitary hormone excess, Cushing’s disease, hypercortisolism, pharmacological therapies, neurosurgery.
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.
