Endocrine Abstracts

A personalized patient treatment regimen for endogenous Cushing’s syndrome (CS) should be developed by a specialized multidisciplinary team, taking patient values and preferences into consideration. Comorbidities, which may compromise patient health and QoL need to be addressed, in many cases concomitant with or even before CS-specific treatments to restore eucortisolemia. Treatment of endogenous CS is initially primarily surgical and aims at complete resection of the underlying tumor source. Medical therapy for CS is mostly used as second-line treatment after failed surgery or recurrence and comprises several pituitary-directed drugs (for Cushing’s disease), adrenal steroidogenesis inhibitors and glucocorticoid receptor blockers for CS. Medical therapy should be individualized for all patients, based on the clinical scenario, including severity of hypercortisolism. Adrenal steroidogenesis inhibitors are usually used first, given their reliable effectiveness. Long-term data from new prospective (osilodrostat, levoketoconazole) and retrospective studies with ketoconazole and metyrapone has been recently added. In patients with severe disease, the primary goal is to treat aggressively to normalize cortisol levels (or cortisol action if using mifepristone). There are few rigorous data supporting specific regimens for combination therapy, but several have been described. For all patients, regular monitoring for treatment efficacy is required, including cortisol measurements, symptoms and comorbidities, especially weight, glycemia, and blood pressure. In addition, QoL is important to take into account, preferably through patient-reported outcomes. Multiple serial tests of both UFC and LNSC are used to monitor biochemical treatment outcomes. There are no rigorous data supporting use of primary or preoperative medical therapy, though is frequently done if surgery is delayed. Patients who have potentially life-threatening metabolic, psychiatric, infectious, or cardiovascular/thromboembolic complications also may benefit from preoperative medical therapy in select cases. Guidelines recommendations for use in clinical practice should be considered alongside patient- and disease-specific factors for individualized care and improved patients’ outcome.