Cushing disease is a genetic disease characterised by hypersecretion of adrenocorticotropic hormone (ACTH) by pituitary tumors that are resistant to glucocorticoid negative feedback. The pituitary tumors generate a range of clinical traits of chronic hypercortisolism such as, obesity, hypertension, hirsutism, cutaneous striae, diabetes mellitus, muscle loss, psychosis, menstrual irregularity, widened face with acne, and fatigue. ACTH is produced as a precursor from the POMC gene product. Microadenomas in Cushing's disease are identified through magnetic resonance imaging (MRI) and mandatory pre-operative localization of pituitary adenomas is performed through trans-sphenoid microsurgical method.

Pituitary Adenoma 4, ACTH-Secreting (Cushing Disease, Pituitary) is associated with mutations in USP8 gene.