Management of Persistent Cushing’s Disease Despite Prior Pituitary Adenoma Resection in a Pregnant Patient

Introduction: Cushing’s Disease (CD) in pregnancy is a rare, but serious disease that adversely impacts maternal and fetal outcomes. As the sole use of metyrapone in the management of CD has been rarely reported, we describe our experience using it to treat a pregnant patient with pre-existing CD. Clinical Case: The patient is a 29-year-old woman with a history of hypertension (HTN), who was diagnosed with CD a year prior to becoming pregnant based on elevated urinary free cortisol (UFC) 209 ug/24h (Reference Range (RR) 6 - 42), positive 1 mg dexamethasone suppression test, elevated ACTH 61 pg/mL (RR 0-46). and an 8 x 8 x 8 mm pituitary adenoma on magnetic resonance imaging (MRI). She underwent trans-sphenoidal adenoma resection 3 months prior to becoming pregnant; however, was found to have persistent disease based on a repeat MRI showing a residual 8 x 8 x 9 mm adenoma extending into the cavernous sinus and UFC 290 ug/24h. The patient discovered 6 weeks later that she was pregnant. She was referred to endocrinology at 12 weeks’ gestation, where she was experiencing easy bruising and taking labetalol 400 mg twice daily for HTN. UFC was 768 ug/24h and midnight salivary cortisols were 0.175 and 0.625 ug/dL (RR <0.010 - 0.090). Surgery was deemed to be high risk given the proximity of the tumor to the cavernous sinus and likelihood of residual disease. She was started on metyrapone 250 mg twice a day, and was uptitrated to 1000mg three times daily by the time of delivery with a UFC of 120 ug/24h (goal < 150 ug/24h). Her pregnancy was also complicated by diet-controlled gestational diabetes and cervical insufficiency requiring cerclage. Otherwise, her HTN was well controlled on labetolol and she remained normokalemic. The patient was induced at 37 weeks gestation and was given stress dose steroids along with metyrapone. She delivered a healthy baby boy without any complications. Discussion: CD during pregnancy is a rare disease, with the best outcomes in published cases seen with surgical intervention. This case highlights the use of metyrapone, a steroidogenesis inhibitor, as a sole therapy in cases where surgery is deemed to be high risk and unlikely curative due to location of the tumor. While it is effective in reducing cortisol levels, close surveillance of patients is required for worsening HTN, hypokalemia, and potential adrenal insufficiency. Though no fetal adverse events have been reported, the medication does cross the placenta and longterm effects are unknown.