Adrenal Cushing’s in Pregnancy, Managed with Metyrapone to Optimize for Adrenalectomy at 27 Weeks Gestation

Abstract

Background: Cushing’s syndrome in pregnancy is associated with increased fetal and maternal morbidity and mortality. Prompt diagnosis and management during pregnancy is critical to improving these outcomes. Clinical Case: Patient is a 28-year-old female who presented to our hospital at 25 weeks of pregnancy with severe striae, high blood pressure, mildly elevated blood sugars and hypokalemia. Striae began in the 6th week of her pregnancy but progressed in the 2nd trimester to encompass multiple sections of skin. Blood pressure on presentation was 146/100 mmHg (on labetalol) and fasting glucose 113 mg/dL (goal <95 mg/dL in pregnancy). Labs were consistent with ACTH-independent Cushing’s Syndrome: AM serum cortisol of 42.3 mcg/dL (n < 22.6 mcg/dL), PM serum cortisol of 46 mcg/dL (n < 11.9 mcg/dL), ACTH of <1 pg/mL (normal 7–63 pg/mL), 24-hour urinary free cortisol of 1388 mcg/day (n <45 mcg/day), and salivary midnight cortisol of 2.2 mcg/dL (n <0.3 mcg/dL). An abdominal MRI scan without contrast showed a 3.2 cm fat-containing right adrenal lesion consistent with an adenoma. The fetus was large for gestational age at 98th percentile. Patient was started on metyrapone 250 mg twice daily, which was titrated up to 250 mg three times daily. Her blood pressure and glucose levels, treated with labetalol and insulin respectively, improved on metyrapone. Surgery, Maternal Fetal Medicine, Endocrine, Anesthesia, and Neonatal physicians reviewed her case at an interdisciplinary meeting. She received metyrapone for 1 week pre-operatively. AM serum cortisol improved to 21.4 mcg/dL and 24-hour urinary free cortisol improved to 139 mcg/day. She underwent laparoscopic right adrenalectomy at 27 weeks of pregnancy. Betamethasone was given 2 days prior to ensure fetal lung maturity in case of preterm labor. Stress dose hydrocortisone 100 mg was given intra-operatively. Fetal heart monitoring was normal throughout the surgery and post-operatively. After surgery, metyrapone was stopped and hydrocortisone was tapered to 20 mg and 10 mg. Five weeks after her adrenalectomy, striae decreased in size and glucoses normalized. Remarkably, fetal size is now appropriate for gestational age in the 62th percentile at 34 weeks. However, blood pressure remains elevated and is being treated with labetalol. She is planned for induction of labor at 37 weeks due to her elevated blood pressures and will be given stress dose steroids intraoperatively. Conclusion: Medical management of adrenal Cushing’s in pregnancy with metyrapone followed by adrenalectomy required a multidisciplinary team approach. Patient underwent successful adrenalectomy without complications of severe hypercortisolism, including infection, thromboembolism, pre-eclampsia, preterm labor and pregnancy loss. After surgery, there was normalization of maternal blood sugars as well as fetal size, and persistent, but improved, elevated blood pressure.