SUN-383 Sustained Clinical Improvement after Discontinuation of Mifepristone: Unexpected Remission of Hypercortisolism

Background: The competitive GR antagonist mifepristone (MIFE, Korlym®, Corcept Therapeutics) has been used in the treatment of patients with hypercortisolism of unknown origin. In most patients, symptoms (e.g., hyperglycemia, weight gain, or psychiatric symptoms) return within several weeks if MIFE is discontinued in patients whose symptoms have improved. Here we describe a case of a patient who experienced clinical improvement in symptoms attributed to her excess cortisol for 4+ months after discontinuation of MIFE. Case Presentation: A 39-year-old woman presented with a history of significant increase in weight as well as hyperglycemia, migraines, poor sleep, and fatigue. Onset of conditions occurred 3 years prior when pt was diagnosed with thyroid cancer, which was treated with total thyroidectomy and iodine ablation leading to hypothyroidism. Despite being euthyroid and in cancer remission, her comorbidities did not improve. Before cancer diagnosis, patient’s weight was 160 lbs (BMI 26.6), but, after cancer diagnosis, increased to a max of 210 lbs (BMI 34.9), despite strenuous exercise and modifications to diet. Phentermine (phen) (37.5 mg) was prescribed daily, but pt lost only 8 lbs in 2 months. With unsuccessful attempts at weight loss, history of psychological stress due to cancer diagnosis, fatigue, poor sleep, and hypokalemia possibly attributed to mineralcorticoid receptor activation, hypercortisolism was suspected. Dexamethasone suppression test (DST) 1 mg revealed cortisol level of 2.6 µg/dL. Because of the unknown origin of hypercortisolism (the patient refused imaging), MIFE 300 mg QD and spironolactone 25 mg QD (for hypokalemia) were initiated. Lower limb edema and hypokalemia were observed at 4 months, and both were corrected by restarting spironolactone and with potassium supplementation. At month 6, weight had decreased 37 lbs, and fasting blood glucose (FBG) decreased from 118 to 89 mg/dL. Sleep quality and fatigue improved, and migraines ceased. After weight and FBG normalized, MIFE was stopped at month 6 to repeat DST. Unexpectedly, a repeat DST was normal at 0.4 µg/dL. Clinical benefit has been maintained for 4+ months. Pituitary and adrenal imaging was ordered again but pt refused citing that her life has improved dramatically and that she didn’t want any more testing for now. Conclusion: Four months after discontinuation of MIFE, hypercortisolism, obesity, migraines, poor sleep, and hyperglycemia remain resolved. We hypothesize that the patient’s sustained clinical improvements could be the result of an HPA axis reset, decreased stress, and/or spontaneous remission of disease.