THU020 Bilateral Adrenal Hyperplasia (BAH): Undesirable Effect Of Glucocorticoid Receptor Competitive Antagonist (GRCAnt) In Cushing’s Disease

Disclosure: A. Canturk: None. C. Villabona: None. A. Kargi: None. We present a case of a complicated ACTH (adrenocorticotropic hormone)-dependent tumor and hypercortisolism, we discuss the potential side effects of mifepristone, a GRCAnt potentially causing bilateral adrenal hyperplasia and we discuss potential pathophysiologic mechanisms. This is a 73 years old male who presents to the clinic for a follow-up of Cushing’s Disease (CD). He has a pmh of osteoporosis, hypopituitarism, and secondary DM in the setting of an aggressive and medication-resistant Corticotroph Pituitary Neuroendocrine Tumor (cPNET). He has undergone a total of four transsphenoidal surgeries since 2013 and two treatments with external beam radiations. He still has residual tissue invading his cavernous sinus, thus another surgery was not an option, so Gamma Knife (GK) therapy was given. In the past, he has received a trial of ketoconazole for a period of 2-3 years, temozolomide, and octreotide, and is currently on mifepristone for the past four years. He underwent Bilateral Adrenalectomy in 2016 and had a small adrenal residual. It is demonstrated in a PET scan from 2018 that he had BAH and confirmed in a recent CT abdomen on 12/2022. While on mifepristone his ACTH was 1173pg/mL (nl:10 and 60 pg/mL), and cortisol 92.7 mcg/dL (nl:5 to 25 mcg/dL). Cortisol urine was 1627.2 mcg/24hr (nl:4 to 40 mcg/24hr). For treatment of his cPNET, we discontinued mifepristone and started on ketoconazole, and referred him to surgery for a second adrenalectomy. We reordered IHC on pathology specimens obtained in 2019 for SSTRs 1-5 and might consider starting synthetic somatostatin analog. We illustrate the potential negative effect of the long-term use of mifepristone. This is a GRCAnt that increases ACTH levels (8-10 fold in some cases) and will potentially cause BAH. This is an aggressive cPNET with hypercortisolism, who has been on long-standing medical therapy with mifepristone. He has developed BAH which has been potentially caused or exacerbated by GRCAnt. Reviewing the literature, there is limited data on this topic. This effect appears not to occur in all patients with Cushing’s disease. We propose potential pathophysiologic mechanisms of the indirect or direct effect of mifepristone causing BAH and potential factors explaining why this phenomenon might only occur in selected patients, we also propose management of patients on long therapy with GRCAnts. Presentation: Thursday, June 15, 2023