Medical treatment of Cushing's disease: Overview and recent findings

Abstract

Cushing's disease, due to pituitary adrenocorticotropic hormone (ACTH) hypersecretion, is the most common etiology of spontaneous excess cortisol production. The majority of pituitary tumors causing Cushing's disease measure <1 cm and the excess morbidity associated with these tumors is mostly due to the effects of elevated, nonsuppressible, ACTH levels leading to adrenal steroid hypersecretion. Elevated circulating cortisol levels lead to abnormal fat deposition, hypertension, diabetes, coronary artery disease, osteoporosis, muscle weakness and psychological disturbances. At experienced centers, initial surgical remission rate via transnasal, transphenoidal resection approaches 80% for tumors less than 1 cm, but may be as low as 30% for larger lesions and long-term recurrence in all groups approaches 25%. Residual disease may be managed with more radical surgery, pituitary-directed radiation, bilateral adrenalectomy, or medical therapy. This paper addresses current and novel therapies in various stages of development for Cushing's disease.

Keywords: 11 β-hydroxysteroid dehydrogenase inhibitors; Cushing’s disease; PPAR-γ; dopamine agonists; pasireotide; treatment.

Figure 1

Schematic summarizing the sites of action of currently available and investigational medical therapies for Cushing’s disease.