Advances in pharmacological treatment of Cushing's disease.

Cushing's disease is a rare endocrine disorder characterized by hypercortisolism. Chronic elevated cortisol levels can lead to dysfunction or complications in multiple organs of systems, including cardiovascular, glucose, and bone metabolism, severely impacting patients' quality of life and posing life-threatening risks. Surgery is the first-line treatment for Cushing's disease. However, in cases of delayed diagnosis, surgical contraindications, or suboptimal surgical outcomes, pharmacological therapy is often required. Currently, three categories of medications are commonly used: 1) Drugs targeting somatostatin and/or dopamine receptors to inhibit pituitary adrenocorticotropic hormone (ACTH) synthesis (e.g., pasireotide, cabergoline); 2) drugs targeting adrenal cortex-related receptors to suppress steroid synthesis (e.g., ketoconazole, metyrapone, mitotane, and osilodrostat); 3) drugs acting on glucocorticoid receptors (e.g., mifepristone). Research on pharmacological treatments for Cushing's disease is ongoing, with new drugs such as seliciclib, CRN04894, fimepinostat, vorinostat, and SPI-62 currently in phase II clinical trial. The development of novel drugs holds promise for more precise and effective treatment for Cushing's disease patients.