Mifepristone Treatment Effectively Improved Clinical Symptoms of Severe Hypercortisolism in a Patient with Primary Macronodular Adrenal Hyperplasia (PMAH) Allowing Surgical Treatment and Subsequent Conception

Presentation Number: MON 402
Date of Presentation: April 3rd, 2017

Jennifer U Mercado1, Kelley Moloney1, Precious J. Lim2 and Kevin C.J. Yuen*1
1Swedish Neuroscience Institute, Seattle, WA, 2Corcept Therapeutics, Menlo Park, CA

Abstract

Background: Endocrine Society Guidelines recommend surgical resection of the causal lesion/s as the first-line treatment for Cushing’s syndrome (1). However, chronic severe hypercortisolism renders the patient high-risk for adverse surgical outcomes, and medical therapy could be considered for preoperative risk optimization. We present a patient with PMAH effectively treated with mifepristone (MIFE), a competitive glucocorticoid receptor antagonist, prior to undergoing bilateral adrenalectomy (BLA).

Case: A 27 yo woman presented with severe hypercortisolism: new onset hypertension (156/104 mmHg), pre-diabetes (A1C 6.3%), weight gain (30 kg in 2 yrs), secondary amenorrhea, dorsocervical and supraclavicular fat pads, abdominal striae, insomnia, depression, anxiety, proximal myopathy, easy bruising, hirsutism, acne, and facial plethora.

Hormonal testing showed multiple elevated 24hr UFC (729.3, 444.2, 292.3, 231.7 µg/24hr, ULN < 50 µg/24hr), late night salivary cortisol (5.7, 11.2, 11.8, 13.6, 14.9, 15.4, 15.5, 28.3 nmol/L, ULN < 4.1 nmol/L), and suppressed AM ACTH (< 1.1 pg/mL, normal 7.2-63.3 pg/mL). Abdominal CT revealed symmetrically enlarged adrenal glands with nodules measuring 1.5-2.9 cm.

Her comorbidities precluded immediate BLA, and MIFE was initiated to optimize the patient’s condition in preparation for surgery. After 2 weeks of MIFE (300 mg/d), improvements in blood pressure (122/94 mmHg), hyperglycemia and weight loss (10.83 kg) were noted. After 6 months of MIFE (900 mg/d), hypertension and pre-diabetes resolved, and BMI dropped from 32.43 to 25.26 kg/m2. Patient reported lightening of striae, reduction of supraclavicular and dorsocervical fat, and improved sleep, energy, headaches, cognitive function and mood. While on MIFE, the patient experienced transient cortisol withdrawal symptoms (nausea, fatigue), which resolved without intervention.

The patient subsequently underwent BLA. Given the substantial improvement in her symptoms post-BLA, the patient was treated on low dose hydrocortisone taper (20 mg BID) and did not report cortisol withdrawal symptoms. Her menstrual periods returned spontaneously within 1 month and she is currently 8 months post-BLA with no significant symptoms, detectable ACTH levels, and is 4 weeks pregnant.

Conclusion: Short-term MIFE therapy rapidly improved clinical symptoms and cardiometabolic derangements of a young woman with severe hypercortisolism due to PMAH, allowing successful BLA, and subsequent conception.

 

Disclosure: PJL: Employee, Corcept. KCJY: Researcher, Novartis Pharmaceuticals, Advisory Group Member, Novartis Pharmaceuticals, Researcher, Strongbridge Biopharma, Researcher, Corcept, Speaker Bureau Member, Corcept. Nothing to Disclose: JUM, KM