Conclusions and future directions
Medical therapies targeting the corticotroph adenoma represent a relatively new avenue in the long term treatment of patients with CD who are unsuitable for surgery, or who fail to achieve long-term disease control post-surgery [86, 87]. Drugs targeting adrenal steroid synthesis have been in use for many years, but have not been prospectively studied and do not target the underlying pituitary tumor. A glucocorticoid receptor blocker could be a valuable asset in selected patients, but is relatively complicated to use due to absence of a biochemical marker, and there are potential adverse reactions inherent to mechanism of action.
Pasireotide, a multiligand somatostatin analog is the first pituitary-directed agent shown to effectively reduce cortisol levels and improve disease symptoms in a large, prospective, phase 3 clinical trial. Further investigation is needed, however, to clarify optimal management approaches for pasireotide-associated hyperglycemia. The dopamine agonist cabergoline has shown some promise in a small, open-label trial (and one retrospective trial), but randomized, controlled trials with this agent have not been conducted. A combination of lower doses of pasireotide with dopamine agonists or adrenal steroidogenesis inhibitors (e.g., a combination of low-dose pasireotide/cabergoline/ketoconazole) may increase the proportion of patients whose disease can be controlled while minimizing adverse effects.
Finally, further research into patterns of receptor expression in corticotroph adenomas may lead to increased understanding of the pathogenesis of these tumors, and allow development of therapies specifically tailored to individual patients following analysis of surgical pathology.