Case Presentation: A 55-year-old woman with hypertension and diabetes presented with hypertensive emergency, chest pain, severe hyperglycemia (glucose >600 mg/dL), hypokalemia (serum potassium 2.6 mmol/L), Cushingoid features, anasarca, and proteinuria (urine protein to creatinine ratio 4.3). Imaging demonstrated a heterogenous 4 cm left adrenal mass, as well as adenopathy above and below the diaphragm. Biochemical evaluation confirmed adrenocorticotropic hormone (ACTH)-independent hypercortisolism (cortisol 53.7 mcg/dL after dexamethasone suppression; ACTH < 5 pg/mL) and elevated dehydroepiandrosterone sulfate and testosterone, but aldosterone was appropriately suppressed (< 4 ng/dL). After plasma and urine metanephrines were negative (to rule out pheochromocytoma), core biopsy of a para-aortic lymph node revealed high-grade, poorly differentiated adrenocortical carcinoma (ACC). She concurrently underwent evaluation of nephrotic-range proteinuria, which nephrology considered inconsistent with her relatively short duration (~5 years) of diabetes alone, and renal biopsy confirmed focal segmental glomerulosclerosis (FSGS).Initial management included intensive blood pressure control (including high-dose spironolactone), potassium repletion, and insulin titration. Persistent hypokalemia was compounded by loop diuretic use for volume overload. Ketoconazole was initiated to control hypercortisolism. Given her poor performance status and extensive metastatic disease, she was not a candidate for adrenalectomy, systemic chemotherapy, or mitotane, and a palliative approach to care was recommended.
Discussion: ACC is a rare and aggressive neoplasm, usually hormonally functional, with cortisol excess being the most common clinical presentation, though sometimes diagnosed after incidental discovery on imaging. ACC can produce any cortical steroid hormones or their intermediates (1,2). Although aldosterone is not the only mineralocorticoid produced by the adrenal gland, in this case, hypokalemia and apparent mineralocorticoid excess were most likely mediated by cortisol, which, at supraphysiologic concentrations, can overwhelm 11β-hydroxysteroid dehydrogenase type 2 activity in the distal nephron, permitting cortisol activation of mineralocorticoid receptors (3,4). The concomitant diagnosis of FSGS is notable. Although the association between hypercortisolism and glomerular disease remains poorly defined, a prior report describes remission of FSGS following resolution of hypercortisolism in a patient Cushing disease, suggesting a potential pathophysiologic relationship (5).
Conclusions: This case emphasizes the necessity of comprehensive hormonal evaluation in all adrenal tumors, as management of endocrine excess is essential regardless of oncologic treatment candidacy. Profound hypercortisolism can induce apparent mineralocorticoid excess, manifesting as severe hypertension and hypokalemia. The coexistence of hypercortisolism and FSGS, though rarely reported, warrants further investigation into a possible causal association.