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Medical therapy of Cushing's disease: where are we now?

Abstract
The goals of ideal medical therapy for Cushing's disease should be to target the aetiology of the disorder, and thus surgery is the current 'gold standard' treatment. However, no effective drug that directly and effectively targets the adrenocorticotropin-secreting pituitary adenoma has been found to date, and treatments to control the hypercortisolaemic state by adrenal-based therapy are frequently used. Inhibitors of adrenal steroidogenesis, adrenolytic agents, compounds with neuromodulatory properties, and ligands of different nuclear hormone receptors involved in hypothalamo-pituitary regulation currently used have been reviewed. Ketoconazole and metyrapone can control hypercortisolaemicstates, as well as mitotane in selective cases, depending on their side effects and frequent monitoring. The somatostatin analogue pasireotide and the dopamine agonist cabergoline, as well as their combination, show some therapeutic promise, while retinoic acid analogues should be further investigated in the pituitary-targeted medical therapy of Cushing's disease. Since a percentage of patients treated with surgery are not cured, or improve and subsequently relapse, there is an urgent need for effective medical therapies for this disorder. At present, only cabergoline and pasireotide are under active investigation, while adrenal steroidogenesis inhibitors are still the mainstay treatments for the control of the hypercortisolaemic state.
AuthorsKrystallenia I Alexandraki, Ashley B Grossman
JournalFrontiers of hormone research (Front Horm Res) Vol. 38 Pg. 165-173 ( 2010) ISSN: 0301-3073 [Print] Switzerland
PMID20616508 (Publication Type: Journal Article, Review)
CopyrightCopyright (c) 2010 S. Karger AG, Basel.
Chemical References
  • Dopamine Agonists
  • Mifepristone
  • Somatostatin
  • Mitotane
  • Ketoconazole
  • Hydrocortisone
  • Metyrapone
Topics
  • Dopamine Agonists (therapeutic use)
  • Humans
  • Hydrocortisone (antagonists & inhibitors)
  • Ketoconazole (therapeutic use)
  • Metyrapone (therapeutic use)
  • Mifepristone (therapeutic use)
  • Mitotane (therapeutic use)
  • Pituitary ACTH Hypersecretion (drug therapy)
  • Somatostatin (analogs & derivatives)

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