Pre-Surgical Use of Mifepristone for Ectopic Cushing's in a High-Risk Bilateral Adrenalectomy Candidate

Presentation Number: SAT-391
Date of Presentation: March 7th, 2015

Ivy-Joan Madu1 and Dat Nguyen*2
1Diabetes Associates Medical Group, Orange, CA, 2Corcept Therapeutics, Menlo Park, CA

Abstract

Background: Surgical resection of the underlying tumor remains the definitive therapy for Cushing’s syndrome (CS).  Hypertension (HTN), obesity, hyperglycemia, and other cardiometabolic manifestations of CS can increase surgical risk. Preoperative intervention to improve metabolic control in a patient scheduled for a BLA is described.

Case: A 42yo female with CS due ACTH producing carcinoid with lung metastasis was referred for preoperative optimization prior to a scheduled BLA. Chest CT showed numerous bilateral pulmonary nodules (largest up to 3.6 cm).

She presented with moon facies, purple striae, and weakness requiring a cane for ambulation.

Co-morbid conditions included obesity (BMI 44), HTN (152/114 mmHg), Diabetes (A1c 8.8%, blood glucose=266 mg/dL). She was treated with: octreotide LAR injection, levemir insulin 10units/d, metformin 1000mg BID, glipizide 10mg BID, amlodipine 10mg/d, hydrochlorothiazide 12.5mg/d, metoprolol 50mg BID, losartan 100mg/d.

Due to the progressive nature of the lung masses and the uncontrolled cortisol secretion, a BLA was scheduled.  Preoperative evaluation categorized the patient as high risk due to her co-morbid conditions, high probability of frail tissues and poor wound healing due to prolonged hypercortisolism.  Preoperative optimization goals were to reduce blood sugars, BP, and the effects of hypercortisolism in order to improve wound healing, reduce the peri-operative complications such as DVT and electrolyte imbalance.

Mifepristone (Korlym®, Corcept Therapeutics) 300mg/d, a competitive glucocorticoid receptor antagonist, was utilized for a total of 2 months, terminating right before surgery. After one month of mifepristone therapy, blood glucose ranged between 90-150 mg/dL and levemir insulin was discontinued. Two months later and just prior to surgery, BMI decreased (42.5), improvements were documented in BP (143/101 mmHg), A1c (8.0%), and glucose (149 mg/dL). No adrenal insufficiency was observed.

Despite her high risk, there were no major postoperative complications requiring extended hospitalization after the BLA (via the posterior approach). Only episodes of nausea and vomiting were observed.  BP and blood glucose improved, allowing amlodipine and glipizide to be discontinued. Metformin was reduced to 500mg/d and eventually discontinued. Patient was placed on steroid replacement therapy with hydrocortisone 20 mg BID and fludrocortisone 0.1 mg daily. 

Nine months post-surgery, BMI 43.8, BP (135/80 mmHg), A1c 6.8%, glucose 118 mg/dL, Na 142 mEq/L, K 4.4 mEq/L.

Conclusion: Two months therapy with mifepristone improved pre-operative clinical status in a high-risk BLA patient by reducing weight and improving diabetic control. Clinical trials with longer duration of therapy are needed to evaluate the impact of mifepristone on surgical risks, outcomes and length of hospitalization.

 

Disclosure: IJM: Clinical Researcher, Novo Nordisk, Clinical Researcher, Sanofi, Clinical Researcher, Astra Zeneca, Clinical Researcher, Mylan, Clinical Researcher, Amylin Pharmaceuticals, Clinical Researcher, Andromeda, Clinical Researcher, Merck & Co., Clinical Researcher, Takeda, Clinical Researcher, Grifols, Clinical Researcher, Jansen Pharmaceuticals. DN: Employee, Corcept.