Abstract
Cushing’s disease (CD) is caused by a pituitary corticotroph neuroendocrine tumor inducing uncontrolled hypercortisolism. Transsphenoidal surgery is the first-line treatment in most cases. Nonetheless, some patients will not achieve cure even in expert hands, others may not be surgical candidates and a significant percentage will experience recurrence. Many patients will thus require medical therapy to achieve disease control. Pharmacologic options to treat CD have increased in recent years, with an explosion in knowledge related to pathophysiology at the molecular level. In this review, we focus on medications targeting specifically pituitary adrenocorticotropic hormone-secreting tumors. The only medication in this group approved for the treatment of CD is pasireotide, a somatostatin receptor ligand. Cabergoline and temozolomide may also be used in select cases. Previously studied and abandoned medical options are briefly discussed, and emphasis is made on upcoming medications. Mechanism of action and available data on efficacy and safety of cell cycle inhibitor roscovitine, epidermal growth factor receptor inhibitor gefitinib, retinoic acid, and silibinin, a heat shock protein 90 inhibitor are also presented.
Highlights
Clinical hypercortisolism is associated with significant morbidity and mortality [1]
20–40% of patients, depending on tumor size and surgeon expertise, will not be cured by transsphenoidal surgery, and for patients in remission, 20–35% will relapse within 10 years [3,4,5]
Today, accumulated Cushing’s disease (CD) knowledge allows for development of precise molecular targeting for adrenocorticotropic hormone (ACTH) secretion and cell proliferation
Summary
Clinical hypercortisolism is associated with significant morbidity and mortality [1]. Most corticotroph adenomas co-express SSTR5 and D2 receptors, and combining pasireotide and cabergoline could have additive or even synergistic effects [21, 64]. The study did demonstrate improvement in UFC normalization with the addition of cabergoline to pasireotide (from 29 to 53%), the patients included in the study had significantly lower mean baseline UFC levels compared with the phase III subcutaneous pasireotide trial, possibly underrepresenting the potential added therapeutic effects of cabergoline to pasireotide.
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