Azzola Alescia, Eastabrook Genevieve, Matsui Doreen, Berberich Amanda, Tirona Rommel G, Gray Daryl, Gallego Patricia, Van Uum Stan
Department of Medicine, Schulich School of Medicine, Western University, London, Ontario, Canada.
Obstetrics and Gynaecology, Schulich School of Medicine, Western University, London, Ontario, Canada.
J Endocr Soc. 2020 Nov 5;5(1):bvaa167. doi: 10.1210/jendso/bvaa167. eCollection 2021 Jan 1.
Adrenal Cushing syndrome during pregnancy is rare, and there is limited information on the effect and safety of metyrapone treatment both for mother and fetus. We present a 24-year-old woman diagnosed with adrenal Cushing syndrome at the end of the second trimester. We elected treatment with metyrapone titrated to 250 mg 3 times daily, resulting in good clinical response and maternal serum and saliva cortisol levels in the upper half of the normal pregnancy range. A healthy male infant was born at 35 weeks' gestation, with no clinical signs of adrenal insufficiency, this despite a low cortisol of 5 nmol/L on the first day of life. We measured metyrapone in maternal and umbilical cord blood samples, demonstrating fetal venous metyrapone levels similar to maternal venous concentration, and a fetal arterial cord concentration at about 60% of the fetal venous cord concentration. This case demonstrates that salivary cortisol levels may be used to monitor the effect of metyrapone on adrenal Cushing syndrome during pregnancy. We show, for the first time in humans, that metyrapone does cross the placenta and may suppress fetal cortisol production without necessarily causing clinical signs of adrenal insufficiency.
妊娠期肾上腺皮质醇增多症较为罕见，关于甲吡酮治疗对母亲和胎儿的疗效及安全性的信息有限。我们报告了一名24岁女性，在孕中期末被诊断为肾上腺皮质醇增多症。我们选择使用甲吡酮进行治疗，滴定至每日3次，每次250毫克，临床反应良好，母亲血清和唾液皮质醇水平处于正常孕期范围的上半部分。一名健康男婴在孕35周出生，出生时无肾上腺功能不全的临床体征，尽管出生第一天皮质醇水平低至5纳摩尔/升。我们检测了母亲和脐带血样本中的甲吡酮，结果显示胎儿静脉中甲吡酮水平与母亲静脉浓度相似，胎儿动脉血中浓度约为胎儿静脉血浓度的60%。该病例表明，唾液皮质醇水平可用于监测孕期甲吡酮对肾上腺皮质醇增多症的治疗效果。我们首次在人体中证明，甲吡酮确实可穿过胎盘，可能抑制胎儿皮质醇生成，但不一定会导致肾上腺功能不全的临床体征。
