Treatment of Cushing's disease: a mechanistic update.

Abstract

Cushing's disease (CD) is characterized by an ACTH-producing anterior corticotrope pituitary adenoma. If hypothalamus-pituitary-adrenal (HPA) axis physiology is disrupted, ACTH secretion increases, which in turn stimulates adrenocortical steroidogenesis and cortisol production. Medical treatment plays an important role for patients with persistent disease after surgery, for those in whom surgery is not feasible, or while awaiting effects of radiation. Multiple drugs, with different mechanisms of action and variable efficacy and tolerability for controlling the deleterious effects of chronic glucocorticoid excess, are available. The molecular basis and clinical data for centrally acting drugs, adrenal steroidogenesis inhibitors, and glucocorticoid receptor antagonists are reviewed, as are potential novel molecules and future possible targets for CD treatment. Although progress has been made in the understanding of specific corticotrope adenoma receptor physiology and recent clinical studies have detected improved effects with a combined medical therapy approach, there is a clear need for a more efficacious and better-tolerated medical therapy for patients with CD. A better understanding of the molecular mechanisms in CD and of HPA axis physiology should advance the development of new drugs in the future.

• Authors: Daniel Cuevas-Ramos, Maria Fleseriu
• Journal: The Journal of endocrinology (J Endocrinol) Vol. 223 Issue 2 Pg. R19-39 (Nov 2014) ISSN: 1479-6805 [Electronic] England
• PMID: 25134660 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: © 2014 Society for Endocrinology.

Chemical References

• Ligands
• Receptors, Somatostatin
• Steroid Synthesis Inhibitors
• Somatostatin

Topics

• Animals
• Humans
• Hypothalamo-Hypophyseal System (drug effects)
• Ligands
• Molecular Targeted Therapy (methods)
• Pituitary ACTH Hypersecretion (drug therapy)
• Pituitary-Adrenal System (drug effects)
• Receptors, Somatostatin (agonists, metabolism)
• Signal Transduction (drug effects)
• Somatostatin (analogs & derivatives, therapeutic use)
• Steroid Synthesis Inhibitors (therapeutic use)