Medical therapy of hypercortisolism
Cushing syndrome (CS) is a state of chromic hypercortisolism associated with multi-system morbidity and an increased mortality, mainly due to cardiovascular disease. Only complete normalization of cortisol production can optimally reverse morbidity and mortality. Medical therapy is an important treatment modality in patients in whom surgery is not successful or not feasible. Medical therapy for CD can be classified into adrenal-blocking drugs, pituitary-targeting drugs, and glucocorticoid receptor antagonists. With respect to adrenal blocking drugs, ketoconazole and metyrapone are the most widely used to suppress adrenal steroidogenesis. Osilodrostat and levoketoconazole are recently developed inhibitors of steroidogenesis and are currently under investigation in multicenter trials. Dopamine and somatostatin receptors on the corticotroph adenoma are important targets for pituitary-directed drug therapy. Cabergoline and pasireotide, acting via dopamine receptor subtype-2 and somatostatin receptor subtype-5 respectively can normalize cortisol production in 30%-40% of patients. Combined treatment with cabergoline and pasireotide showed promising results, possibly pointing to synergistic effects. Potential new therapeutic targets in corticotroph adenomas include epidermal growth factor receptor, cyclin-dependent kinases, and heat shock protein 90. Mifepristone is currently the only available glucocorticoid receptor antagonist and was recently approved in the USA for treatment of hyperglycemia related to CS. Combined medical therapy is indicated in patients with moderate to severe hypercortisolism. Medical therapy for CS should always be given in a tailor-made approach.
|Keywords||Adrenal neoplasia, Corticotroph adenoma, Cushing disease, Cushing syndrome, Dopamine receptor, Ectopic ACTH production, Glucocorticoid receptor, Hypercortisolism, Somatostatin receptor, Steroidogenic enzymes|
|Persistent URL||dx.doi.org/10.1016/B978-0-12-801238-3.64356-8, hdl.handle.net/1765/124755|
Feelders, R.A. (2018). Medical therapy of hypercortisolism. In Encyclopedia of Endocrine Diseases (pp. 232–236). doi:10.1016/B978-0-12-801238-3.64356-8