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.