The Use of Mifepristone in the Perioperative Management of a Patient with Cushing's Disease

Introduction: Mifepristone is a competitive antagonist of glucocorticoid receptors. Reversal of the clinical features of Cushing’s disease/syndrome is most prominent at higher doses with overall clinical benefit of treatment occurring in close to 90% of patients who are refractory to other treatments. Serum cortisol may increase during treatment, which can lead to a confounding clinical picture in the setting of patients presenting for pituitary adenectomy.

Case Report: A 59-year-old female presents with a history of osteoporosis, multiple pathologic fractures, hypertension and obesity. She was diagnosed with Cushing’s disease after confirmatory laboratory testing. Magnetic resonance imaging of her pituitary gland did not reveal a definitive sellar lesion and the patient was subsequently referred for inferior petrosal sinus sampling. The study suggested the presence of a pituitary adenoma with mild lateralization to the left side of the gland. She was maintained on 600 mg twice daily of mifepristone, which was discontinued one day prior to surgery. Intraoperatively, an adenoma was identified and removed with an extracapsular dissection. Her ACTH intraoperatively dropped to 5.6 pg/mL from 48 and the following morning was 5.3; her cortisol was 64.09 mcg/dL on the first post-operative morning and never went below 20. Clinically, the patient was complaining of nausea and headache and her blood pressure was trending below her baseline levels. Her nausea worsened, she became anorexic and vomited; her headache persisted and she remained bed-bound. In addition she developed hypo-osmolar hyponatremia based on her urine studies. Because of these findings, it was felt that overall she had a clinical picture of adrenal insufficiency and she was given stress dose steroids although at the time her cortisol level was 64.07 mcg/dL. She was started on 100 mg of hydrocortisone every six hours. She received six doses of high dose steroids and she clinically improved.

Conclusion: This patient had a complicated post-operative course, likely due to sudden changes of cortisol levels due to successful adenectomy. Approximately 11 months after surgery, her endocrinologist determined that she had a successful biochemical remission without any evidence of tumor on her imaging. Although published literature states that the hypothalamic-pituitary-adrenal (HPA) axis is maintained in the perioperative setting, this case underscores the potential confounding laboratory results that emerge when patients do not discontinue the drug prior to surgery.