SAT-014 - When Medical Therapy Backfires: Bilateral Adrenal Hemorrhage in Cushing Disease

Cushing disease is characterized by inappropriate pituitary adrenocorticotropic hormone (ACTH) excess with clinical consequences of hypercortisolism. Excessive ACTH frequently leads to bilateral adrenocortical hyperplasia and increased adrenal vascularity. Despite these changes, adrenal hemorrhage is exceedingly rare. We report the case of a 32-year-old male with refractory ACTH-dependent Cushing disease and new-onset diabetes treated unsuccessfully with two transsphenoidal resections, stereotactic radiosurgery, and levo-ketoconazole, who was started on osilodrostat at 1 mg twice daily. The dose was increased to 2 mg twice daily after one week and 5 mg twice daily two weeks later, producing the first documented normalization of 24-hour urinary free cortisol and significant improvement in his diabetes control. One week after escalating to 5 mg twice daily, he presented with acute abdominal pain. CT imaging revealed an acute 6.2 cm right adrenal hematoma and stable diffuse left adrenal hyperplasia. Osilodrostat was temporarily discontinued; adrenal insufficiency was excluded, and therapy cautiously resumed at 4 mg twice daily. One week after restarting osilodrostat, recurrent abdominal pain prompted repeat imaging, which demonstrated an acute 5.3 cm left adrenal hematoma and stable right adrenal hematoma. Osilodrostat was discontinued indefinitely. Serial testing excluded glucocorticoid and mineralocorticoid insufficiency, and 24-hour urinary free cortisol remained normal one month after stopping osilodrostat. This is the first reported case of bilateral adrenal hemorrhage temporally associated with osilodrostat escalation in the absence of alternative etiologies such as anticoagulation, thrombocytopenia, sepsis, critical illness, or trauma. Steroidogenesis inhibitors, including osilodrostat, induce compensatory surges in ACTH secretion, which we propose may lead to augmented adrenal blood flow thereby predisposing to adrenal hemorrhage in patients with pre-existing adrenal hyperplasia. Clinicians should maintain heightened awareness and initiate prompt evaluation for adrenal hemorrhage during titration of steroidogenesis inhibitors, particularly in patients with longstanding ACTH excess and adrenal hyperplasia.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*