SUN-437 A Case of Cortisol and Aldosterone Co-secretion in Metastatic Adrenocortical Carcinoma

Abstract Disclosure: N.A. Musacchio: None. C.A. Zmijewski: None. A. Kirschenbaum: None. N. Cohen: None. C. Ang: None. A.C. Levine: None. Background: Adrenocortical carcinoma (ACC) is a rare and aggressive cancer with an incidence of 1-2 cases per million people per year. Less than 10% of hormonally active ACCs secrete aldosterone. Here, we present a rare case of metastatic ACC presenting with both hypercortisolism and hyperaldosteronism. Case Report: A 55-year-old female presented for management of metastatic ACC. She was diagnosed three years earlier when she underwent a left adrenalectomy for an 8.9 cm left adrenal mass, with pathology showing stage II ACC and Ki-67 60%. Pre-operative workup was suggestive of hypercortisolism with mild hyperaldosteronism, including an abnormal dexamethasone suppression test, aldosterone of 10-13 ng/dL, suppressed renin, and low-normal potassium in the setting of hypertension. She declined adjuvant mitotane. One year later, surveillance imaging showed new right lung and hepatic lesions, with subsequent liver biopsy confirming metastatic ACC. Her course was complicated by multiple admissions for hypokalemia, at which time she presented to our care. Workup was notable for suppressed renin, markedly elevated serum aldosterone levels (10x ULN), elevated 11-deoxycorticosterone (DOC), and moderately elevated 24-hour urine free cortisol (2x ULN). Her hypokalemia was refractory to mineralocorticoid receptor antagonists and potassium supplementation, and the patient ultimately required partial hepatectomy to control her endocrinopathy (mainly hyperaldosteronism). Aldosterone normalized post-operatively. Immunohistochemical (IHC) staining of her original tumor was positive for synaptophysin, CYP11B1, DLK1 and COX-2 expression with only small tumor clones positive for CYP11B2 and no expression of LH/HCGR. In contrast, her liver metastases demonstrated strong expression of CYP11B2, in addition to CYP11B1, CYPB5, LH/HCG receptor, COX-2, and DLK1 expression. Discussion: This case shows rare co-secretion of aldosterone and cortisol by metastatic ACC. On initial presentation, the predominant endocrinopathy noted was hypercortisolism, and IHC confirmed strong expression of CYP11B1 with only one or two clones expressing CYP11B2. In contrast, when presenting with ACC liver metastases, her predominant, life-threatening endocrinopathy was hyperaldosteronism, and IHC investigation revealed strong CYP11B2 staining in addition to CYP11B1, LH/HCGR, COX-2, DLK1, and CYPB5. This tumor evolved with time and in the metastatic site demonstrating either tumor plasticity and/or selection in the liver metastatic site, without any significant medical therapy. Conclusion: This is a rare case of hypercortisolism and hyperaldosteronism in metastatic ACC, evidenced by both biochemical data and tissue staining that evolved over time and in the metastatic site. Additionally, this case may give insights into cancer stem cells and possible new therapeutic targets in metastatic ACC. Presentation: Sunday, July 13, 2025