Treatment Options in Cushing's Disease

Abstract

Endogenous Cushing’s syndrome is a grave disease that requires a multidisciplinary and individualized treatment approach for each patient. Approximately 80% of all patients harbour a corticotroph pituitary adenoma (Cushing’s disease) with excessive secretion of adrenocorticotropin-hormone (ACTH) and, consecutively, cortisol. The goals of treatment include normalization of hormone excess, long-term disease control and the reversal of comorbidities caused by the underlying pathology. The treatment of choice is neurosurgical tumour removal of the pituitary adenoma. Second-line treatments include medical therapy, bilateral adrenalectomy and radiation therapy. Drug treatment modalities target at the hypothalamic/pituitary level, the adrenal gland and at the glucocorticoid receptor level and are commonly used in patients in whom surgery has failed. Bilateral adrenalectomy is the second-line treatment for persistent hypercortisolism that offers immediate control of hypercortisolism. However, this treatment option requires a careful individualized evaluation, since it has the disadvantage of permanent hypoadrenalism which requires lifelong glucocorticoid and mineralocorticoid replacement therapy and bears the risk of developing Nelson’s syndrome. Although there are some very promising medical therapy options it clearly remains a second-line treatment option. However, there are numerous circumstances where medical management of CD is indicated. Medical therapy is frequently used in cases with severe hypercortisolism before surgery in order to control the metabolic effects and help reduce the anestesiological risk. Additionally, it can help to bridge the time gap until radiotherapy takes effect. The aim of this review is to analyze and present current treatment options in Cushing’s disease.

MANAGEMENT OF ENDOCRINE DISEASE: The burden of Cushing's disease: clinical and health-related quality of life aspects

“…The data reported by Bolland et al (29) also showed a relatively consistent elevated SMR over four time periods (1960-1980, 1980-1990, 1990-2000, and 2000-present) despite a general shift in pituitarydirected therapy from radiotherapy to TSS, which is at odds with the previously discussed UK data in which the majority of deaths occurred before 1985, before TSS was employed as the standard first-line therapy (36). Nonetheless, early detection and rapid intervention may be key in avoiding long-term sequelae of the disease (41). As CD is a rare disease and, thus, difficult to study, it is hoped that databases such as the ERCUSYN, which now includes more than 500 patients, could become a key resource to further research and aid collaboration (42).…”

Mifepristone for Management of Cushing's Syndrome

“…Other agents in this class include aminoglutethimide and etomidate (Table 2). 3,13,[16][17][18][19][20] Steroidogenesis inhibitors are considered adrenal-directed medical therapy because they control cortisol production by directly decreasing adrenal hormone production. Ketoconazole is the most commonly used steroidogenesis inhibitor because of its availability and relatively rapid onset of action.…”

Laparoscopic Bilateral Transperitoneal Adrenalectomy for Cushing Syndrome

“…2 The reasons for failure include large tumor and unidentifiable small microadenoma. Patients with Cushing disease are initially referred to the neurosurgeon for the transsphenoidal surgery.…”