Advances in Molecular Pathophysiology and Targeted Therapy for Cushing’s Disease

SIMPLE SUMMARY: Cushing’s disease is caused by autonomous adrenocorticotropic hormone (ACTH) produced by corticotroph pituitary neuroendocrine tumors, leading to cortisol over-production in the adrenal glands. Cushing’s disease presents with a variety of clinical features, ranging from overt to subtle, which are caused by hormonal activities. To treat the disease adequately, the molecular and genetic causes of Cushing’s disease need to be understood. This review discusses recent advances in molecular insights and targeted therapy for Cushing’s disease. ABSTRACT: Cushing’s disease is caused by autonomous secretion of adrenocorticotropic hormone (ACTH) from corticotroph pituitary neuroendocrine tumors. As a result, excess cortisol production leads to the overt manifestation of the clinical features of Cushing’s syndrome. Severe complications have been reported in patients with Cushing’s disease, including hypertension, menstrual disorders, hyperglycemia, osteoporosis, atherosclerosis, infections, and mental disorders. Cushing’s disease presents with a variety of clinical features, ranging from overt to subtle. In this review, we explain recent advances in molecular insights and targeted therapy for Cushing’s disease. The pathophysiological characteristics of hormone production and pituitary tumor cells are also explained. Therapies to treat the tumor growth in the pituitary gland and the autonomous hypersecretion of ACTH are discussed. Drugs that target corticotroph pituitary neuroendocrine tumors have been effective, including cabergoline, a dopamine receptor type 2 agonist, and pasireotide, a multi-receptor-targeted somatostatin analog. Some of the drugs that target adrenal hormones have shown potential therapeutic benefits. Advances in potential novel therapies for Cushing’s disease are also introduced.