Clinical and Hormonal Response to Mifepristone Therapy in 2 Patients with ACTH-Independent Cushing Syndrome

Abstract

ABSTRACT Objective: Cushing syndrome is an endocrine disorder resulting from prolonged exposure to excess cortisol that can lead to significant morbidity and mortality. Surgery is the first-line treatment for Cushing syndrome. Mifepristone is a glucocorticoid receptor (GR) antagonist that is used in the medical treatment of Cushing syndrome. Methods: We describe the clinical and hormonal responses of 2 patients with adrenal (adrenocorticotropic hormone lACTH]-independent) Cushing syndrome who were treated with mifepristone. The first case was a 41-year-old male with Cushing syndrome secondary to primary pigmented nodular adrenocortical disease associated with Carney complex. He was treated with mifepristone prior to definitive surgical management. During medical treatment with mifepristone, he lost 44 pounds, and his Cushingoid features resolved. The second case was a 65-year-old male with Cushing syndrome secondary to ACTH-independent macronodular adrenal hyperplasia (AIMAD). Cushing syndrome persisted after unilateral adrenalectomy, but medical comorbidities precluded a second surgery. Ketoconazole failed to adequately control his symptoms, and he was treated with mifepristone. During medical treatment with mifepristone, he lost 12 pounds, and his Cushingoid features and cortisol excessrelated comorbidities improved. In both cases, ACTH was suppressed prior to treatment and rose into the normal range within 3 months of initiating pharmacologic therapy. Conclusions: Mifepristone is a GR antagonist that can be used in the medical management of cortisol excess due to ACTH-independent Cushing syndrome. Hormonal responses indicating recovery of the hypothalamus-pituitary adrenal (HPA) axis can be seen within 3 months of therapy. Abbreviations: ACTH adrenocorticotropin hormone CT computed tomography DHEAS dehydroepiandrosterone sulfate GR glucocorticoid receptors HPA hypothalamic-pituitary adrenal axis MR mineralocorticoid receptors UFC urinary free cortisol