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Medical Therapies in Cushing’s Syndrome

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The Hypothalamic-Pituitary-Adrenal Axis in Health and Disease

Abstract

Medical therapy has an important, albeit secondary, role in patients with Cushing’s syndrome. While medications are not currently used as definitive therapy of this condition, they can be very effective in controlling hypercortisolism in patients who fail surgery, those who are not surgical candidates, or those whose tumor location is unknown. Medical therapies can be particularly helpful to control hypercortisolism in patients with Cushing’s disease who underwent radiation therapy and are awaiting its salutary effects.

Currently available treatment options include several steroidogenesis inhibitors (ketoconazole, metyrapone, mitotane, etomidate), which block one or several steps in cortisol synthesis in the adrenal glands, centrally acting agents (cabergoline, pasireotide), which decrease ACTH secretion, and glucocorticoid receptor antagonists, which are represented by a single agent (mifepristone). With the exception of pasireotide and mifepristone, available agents are used “off-label” to manage hypercortisolism. Several other medications are at various stages of development and may offer additional options for the management of this serious condition.

As more potential molecular targets become known and our understanding of the pathogenesis of Cushing’s syndrome improves, it is anticipated that novel, rationally designed medical therapies may emerge. Clinical trials are needed to further investigate the relative risks and benefits of currently available and novel medical therapies and examine the potential role of combination therapy in the management of Cushing’s syndrome.

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Disclosures 

BMKB has received research grants (to MGH) from Cortendo and Novartis, and has consulted for Cortendo, HRA Pharma, Ipsen and Novartis. NAT has received research grants (to MGH) from Ipsen, Novartis, Novo Nordisk and Pfizer.

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  1. Neuroendocrine Unit/Neuroendocrine Clinical Center, Massachusetts General Hospital, Zero Emerson Place, Suite 112, Boston, MA, 02114, USA

    Nicholas A. Tritos M.D., D.Sc. & Beverly M. K. Biller M.D.

  2. Harvard Medical School, Boston, MA, USA

    Nicholas A. Tritos M.D., D.Sc. & Beverly M. K. Biller M.D.

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  1. Nicholas A. Tritos M.D., D.Sc.
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Correspondence to Nicholas A. Tritos M.D., D.Sc. .

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  1. Division of Endocrinology, Multidisciplinary Pituitary and Skull Base Tumor Center, Memorial Sloan Kettering Cancer Center, New York, New York, USA

    Eliza B. Geer

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Tritos, N.A., Biller, B.M.K. (2017). Medical Therapies in Cushing’s Syndrome. In: Geer, E. (eds) The Hypothalamic-Pituitary-Adrenal Axis in Health and Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-45950-9_9

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