SAT-418 - A Rare Etiology of Cushing Syndrome Highlighted by Mifepristone-Related Adverse Effects

Introduction:
ACTH-independent Cushing syndrome is most commonly caused by a unilateral cortisol-secreting adrenal adenoma, whereas bilateral adrenal adenomas causing hypercortisolism are rare and present unique diagnostic and therapeutic challenges. Mifepristone, a glucocorticoid receptor antagonist, is an effective medical therapy but may cause severe electrolyte disturbances due to unopposed mineralocorticoid receptor activation by elevated cortisol levels.

Case Presentation:
A 63-year-old woman with ACTH-independent Cushing syndrome attributed to bilateral adrenal adenomas, type 2 diabetes mellitus, hypertension, and coronary artery disease status post PCI presented with progressive dizziness, generalized weakness, and lower extremity edema. She had been managed medically with high-dose mifepristone (300 mg three times daily) and spironolactone outpatient. Laboratory evaluation revealed severe hypokalemia (2.0 mmol/L), metabolic alkalosis (bicarbonate >50 mmol/L) with venous pH 7.61, hypochloremia (82 mmol/L), mild hypomagnesemia (1.7 mg/dL), and preserved renal function (creatinine 1.1 mg/dL) on admission. Urine studies showed potassium 17.6 mmol/L, chloride 95 mmol/L, sodium 104 mmol/L, and osmolality 298 mOsm/kg, consistent with renal electrolyte wasting. Mifepristone was held, aggressive electrolyte repletion was initiated, and spironolactone was continued, resulting in clinical and biochemical improvement. She was discharged on a reduced dose of mifepristone with close endocrinology follow-up.
Prior endocrine evaluation demonstrated elevated late-night salivary cortisol levels (0.218, 0.384, 0.227), normal 24-hour urinary free cortisol (16), incomplete suppression on dexamethasone testing (cortisol 6), and a fasting ACTH of 8 pg/mL. CT imaging revealed bilateral lipid-rich adrenal nodules (right 16 mm, −34 HU; left 11 mm, −25 HU), supporting the diagnosis of bilateral adrenal adenoma–related Cushing syndrome.

Conclusion:
This case highlights bilateral adrenal adenomas as an uncommon cause of Cushing syndrome and illustrates a serious complication of mifepristone therapy. Bilateral adrenalectomy is the standard treatment of choice for overt Cushing’s syndrome. Medical management options include osilodrostat, ketoconazole, metyrapone, and mifepristone. Clinicians should remain vigilant for severe electrolyte abnormalities in patients treated with mifepristone and recognize the challenges of managing hypercortisolism when surgical options are limited.

Gadelha M, Gatto F, Wildemberg LE, Fleseriu M. Cushing’s syndrome. Lancet. 2023;402(10418):2237–2252. doi:10.1016/S0140-6736(23)01961-X.

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