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Medical management of Cushing’s disease

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Abstract

Cushing’s disease (CD), caused by excess adrenocorticotropin secretion from tumorous pituitary corticotrophs, is associated with substantial morbidity and mortality. The primary, definitive therapy for patients with CD is selective pituitary adenomectomy, generally performed via a transsphenoidal approach. Medical therapy has an important adjunctive role in the management of patients with CD, including preoperative patient preparation in patients with severe disease, and temporizing management of hypercortisolism while awaiting the effects of radiation therapy to occur in patients who are not in remission postoperatively. Medical therapy can also be used in patients with hypercortisolism of unclear origin or in the few patients who decline or are unfit for surgery. Available medical options for patients with CD include centrally acting agents (cabergoline and pasireotide), steroidogenesis inhibitors (ketoconazole, metyrapone, mitotane and etomidate) and a glucocorticoid receptor antagonist (mifepristone). Pasireotide and mifepristone have been recently granted regulatory approval in some countries for use in patients with CD, whereas other medications are used “off label” in this patient population. As clinical trials using comparator agents have not been reported, the choice between different medications is based on patient characteristics and preference. Despite impressive advances in pharmacotherapy for patients with CD, much remains to be done. The long term efficacy and safety of medical therapies for hypercortisolism need to be evaluated and the role of combination therapy must be further characterized. As the pathogenesis of CD becomes better understood at the molecular level, it is likely that novel, targeted medical therapies will be developed to treat CD.

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Abbreviations

ACTH:

Adrenocorticotropin

CD:

Cushing’s disease

CRH:

Corticotropin releasing hormone

CS:

Cushing’s syndrome

RXR:

Retinoid acid receptor X

TSS:

Transsphenoidal surgery

UFC:

Urine free cortisol

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Acknowledgments

Dr. Tritos has served as the principal investigator of research sponsored by Pfizer and Ipsen, has consulted for Pfizer and participated in scientific advisory board meetings organized by Pfizer and Corcept Therapeutics. Dr. Biller has served as the principal investigator of Grants to the MGH Neuroendocrine Clinical Center from Novartis and Corcept and as an occasional consultant to Novartis and HRA Pharma.

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Authors and Affiliations

  1. Neuroendocrine Unit, Massachusetts General Hospital, Zero Emerson Place # 112, Boston, MA, 02114, USA

    Nicholas A. Tritos & Beverly M. K. Biller

  2. Harvard Medical School, Boston, MA, USA

    Nicholas A. Tritos & Beverly M. K. Biller

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  1. Nicholas A. Tritos
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  2. Beverly M. K. Biller
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Correspondence to Nicholas A. Tritos.

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Tritos, N.A., Biller, B.M.K. Medical management of Cushing’s disease. J Neurooncol 117, 407–414 (2014). https://doi.org/10.1007/s11060-013-1269-1

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