7533 Mifepristone For Primary Hypercortisolism Contributing To Profound Hypokalemia

Abstract Disclosure: J. Watkins: None. J.G. Melendez-Rivera: None. E. Florin: None. K.B. Rivera: None. Background: Primary hypercortisolism is typically treated surgically, but when adrenalectomy is not pursued, medical therapy can be effective. Adrenal enzyme inhibitors or glucocorticoid antagonists can be used. Mifepristone is the only available glucocorticoid antagonist at this time. Mifepristone is approved specifically for glucose control in Cushing’s syndrome. Because mifepristone blocks cortisol action rather than production, hormone levels may increase and are unhelpful in titrating the mifepristone dose. Rather, titration is based on clinical manifestations of Cushing’s syndrome. Further, the increased hormone levels can lead to increased activation of mineralocorticoid receptor, in addition to the increased activation caused by hypercortisolism, which can cause hypokalemia. Clinical Case: An 82-year-old woman had been following with endocrinology for hypercortisolism found to be secondary to bilateral adrenal adenomas. She preferred medical therapy rather than surgery given her age, and she was started on mifepristone 300 mg/day. Within a few weeks, she developed leg swelling and was started on a low dose of chlorthalidone by her primary care doctor. She then presented to the emergency department after five days of nausea, abdominal pain, palpitations, and reduced oral intake. She was found to have severe hypokalemia (potassium 1.8 mEq/L, normal 3.5 - 5.0 mEq/L), and her creatinine was 0.97 µmol/L (baseline 0.6-0.75 µmol/L). Physical exam was unremarkable. CT abdomen/pelvis revealed three adrenal lesions, similar to a study from one year prior. Her mifepristone was stopped, and she was given potassium supplementation and started on spironolactone with eventual stabilization of her potassium level. She was also started on ketoconazole for management of her hypercortisolism. It was discussed that she might now consider adrenal vein sampling to pursue adrenalectomy. Severe hypokalemia and borderline metabolic alkalosis were most likely multifactorial in etiology. Hypercortisolism predisposed the patient to hypokalemia. She was then started on mifepristone, which inhibits the glucocorticoid receptor thereby increasing activation of the mineralocorticoid receptor, which likely further contributed to hypokalemia. The leg swelling that she developed and saw her primary doctor for may have been a sign of over-activation of the mineralocorticoid receptor due to the mifepristone, and prescription of chlorthalidone at that time would have worsened the hypokalemia that was likely present at that time. Conclusion: It is important to be aware of the possible severity of side effects of medical therapy for hypercortisolism, such as severe hypokalemia. There is a role for increased awareness of routine monitoring of potassium levels, as well as considering spironolactone in many patients even prior to onset of hypokalemia. Presentation: 6/3/2024