Category: Pituitary Disorders/Neuroendocrinology
Objective : Cushing disease (CD) has been associated with cardiovascular complications and psychiatric disease. These 2 cases describe the use of the competitive glucocorticoid receptor antagonist, mifepristone (MIFE, Korlym®, Corcept Therapeutics) in a community endocrinology practice.
Methods : n/a
Results : n/a
Case 1: 50-year-old woman presented with a history of diabetes and hypertension managed with insulin glargine, metformin, glimepiride, losartan, and labetalol. Hypercortisolism was confirmed with biochemical testing (1-mg DST 17.6 µg/dL and ACTH 104.9 pg/mL) and CT, which revealed a 1.8 cm nodule in the left adrenal gland that a previous endocrinologist considered stable and nonsecreting. Pituitary MRI was normal; IPSS confirmed right lateralization, but she was not a surgical candidate (tumor not visible). Two years later, pasireotide (PASI) was initiated, but her HbA1c increased from 7.1% to 8.5%, requiring modifications to her diabetes therapies. PASI therapy was stopped after patient experienced weight gain and uncontrolled fasting glucose. Twenty-one months after PASI, she gained 70 lbs and hypertension worsened. Glucose levels remained uncontrolled despite several medication adjustments. MIFE was initiated at 300 mg QD. Patient experienced hypokalemia prompting the discontinuation of hydralazine and addition of spironolactone. After 9 months, potassium levels stabilized, and the patient took a drug holiday and restarted mifepristone 300 mg QD. At month 9, the patient lost 50 lbs. HbA1c decreased from 8.0% to 5.5% with discontinuation of glimepiride and reduction of dapagliflozin-metformin.
Case 2: A 26-year-old woman with hypercortisolism, previously treated with PASI, presented to community practice with depression and social withdrawal (severe enough to require parental care). She weighed 176 lbs, her fasting glucose was 87 mg/dL, and her fasting insulin was 15 IU/mL. Her HOMA-IR level was 3.2, indicative of insulin resistance. MIFE therapy was initiated. After 6 months taking MIFE, she experienced a weight loss of 37 lbs, and her HOMA-IR improved to 1.0. Additionally, after a year on MIFE this patient’s mood and social behavior improved. This patient now has a job, lives on her own, is engaged to be married, and is no longer accompanied by her mother to her appointments.
These 2 cases demonstrate that MIFE treatment for the signs and symptoms of hypercortisolism resulted in improved clinical outcomes and improvement in quality of life.