Morbidity and mortality in
Cushing's disease (CD) patients are increased if patients are not appropriately treated. Surgery remains the first line
therapy, however the role of medical
therapy has become more prominent in patients when biochemical remission is not achieved/or recurs after surgery, while waiting effects of
radiation therapy or when surgery is contraindicated. Furthermore, use of preoperative medical
therapy has been also recognized. In addition to centrally acting
therapies (reviewed elsewhere in this special issue), adrenal steroidogenesis inhibitors, and
glucocorticoid receptor antagonists are frequently used. A PubMed search of all original articles or abstracts detailing medical
therapy in CD, published within 12 months (2013-2014), were identified and pertinent data extracted. Although not prospectively studied,
ketoconazole and
metyrapone have been the most frequently used medical
therapies. A large retrospective
ketoconazole study showed that almost half of patients who continued on
ketoconazole therapy achieved biochemical control and clinical improvement; however almost 20% discontinued
ketoconazole due to poor tolerability. Notably, hepatotoxicity was usually mild and resolved after
drug withdrawal.
Etomidate remains the only
drug available for intravenous use. A new potent inhibitor of both
aldosterone synthase and 11β-hydroxylase, following the completion of a phase II study
LCI699 is being studied in a large phase III with promising results.
Mifepristone, a
glucocorticoid receptor antagonist, has been approved for
hyperglycemia associated with
Cushing's syndrome based on the results of a prospective study where it produced in the majority of patients' significant clinical and metabolic improvement. Absence of both a
biochemical marker for remission and/or diagnosis of
adrenal insufficiency remain, however, a limiting factor. Patient characteristics and preference should guide the choice between different medications in the absence of clinical trials comparing any of these
therapies. Despite significant progress, there is still a need for a medical
therapy that is more effective and with less adverse effects for patients with CD.