Treatment of Cushing's disease: a mechanistic update

    1. Maria Fleseriu3
    1. 1Department of Medicine, Pituitary Center, Cedars-Sinai Medical Center, Los Angeles, California, USA
      2Neuroendocrinology Clinic, Department of Endocrinology and Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
      3Departments of Medicine and Neurological Surgery, and Northwest Pituitary Center, Oregon Health & Science University, 3181 SW Sam Jackson Park Road (BTE 472), Portland, Oregon 97239, USA
    1. Correspondence should be addressed to M Fleseriu; Email: fleseriu{at}


    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.

    • Received in final form 31 July 2014
    • Accepted 18 August 2014
    • Made available online as an Accepted Preprint 18 August 2014
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