Cushing’s syndrome: drug targets and therapeutic options

Abstract

Cushing’s syndrome is caused by endocrine and metabolic alterations produced by high levels of glucocorticoids. Glucocorticoid excess is usually a result of exogenous administration of glucocorticoids or alteration of the hypothalamus-pituitary-adrenal (HPA) axis. However, in the majority of patients it is due to an adrenocorticotrophic hormone (ACTH)-secreting pituitary adenoma. Other possible causes are ectopic ACTH-secreting tumours of the lung, glucocorticoid-producing adrenal tumours and other ectopic tumours. The symptoms include central fat deposition, altered energy and protein metabolism, hypertension and depression. The molecular mechanisms that regulate the HPA axis provide a rationale to correct the alterations observed in Cushing’s syndrome. Recent developments have identified possible targets and drugs for therapy at different levels of the HPA axis. This article reviews patents claiming novel targets and drugs for Cushing’s syndrome in the period 1997–2002.

• adrenocorticotrophic hormone (ACTH)
• Cushing’s syndrome
• glucocorticoids
• hypothalamus-pituitary adrenal (HPA) axis
• pro-opiomelanocortin (POMC)