Table_1_The Incidence of Pregnancy-Associated Cushing's Disease and Its Relation to Pregnancy: A Retrospective Study.DOCX

Purpose: Cushing's disease (CD) is one of the most severe endocrine disorders and primarily affects women of reproductive age. The peripartum period has been observed to be a common time to develop CD. This study aims to retrospectively analyze the clinical characteristics of CD potentially associated with pregnancy and to evaluate relevant pregnancy outcomes.
Methods: Patients who underwent surgery from January 2010 to May 2019 at Peking Union Medical College Hospital (PUMCH) with biochemically and pathologically confirmed CD were retrospectively analyzed. Pregnancy-associated CD was defined as CD onset during gestation or within 12 months after delivery or abortion. Data including demographics, biochemical tests, magnetic resonance imaging (MRI) findings, and disease outcomes were obtained from all patients by reviewing their medical records. Information regarding pregnancy was collected through a supplementary online questionnaire.
Results: In a series of female patients (n = 70) of reproductive age with childbearing desire, 27.1% (n = 19) met the criteria for pregnancy-associated CD. The timing of diagnosis of pregnancy-associated CD was 2.7 ± 3.4 years after symptom onset, and the overall remission rate for these women was 89.5%. Three patients with pregnancy-associated CD developed hypertension during pregnancy, two of whom had new-onset hypertension at 16 weeks of gestation and one of whom had a complication of severe diabetes. The rates of spontaneous abortion and preterm birth among the women with pregnancy-associated CD were 26.3 and 28.6%, respectively. The proportions of all low-birth-weight (LBW) newborns (p = 0.002) and term LBW newborns (p = 0.033) were significantly higher in the pregnancy-associated CD group than in the non-pregnancy-associated CD group.
Conclusions: In this study, a total of 27.1% of women of reproductive age with CD had pregnancy-associated CD, which might be induced by the hormonal milieu of pregnancy. An increased risk of having a LBW newborn was observed among mothers with pregnancy-associated CD. A high degree of clinical suspicion for CD may be warranted in the peripartum period. Patients with symptoms suspicious for CD throughout pregnancy and after childbirth, such as early-onset hypertension, severe hyperglycemia, and persistent weight gain, should be carefully diagnosed and closely monitored by clinicians.

研究目的：库欣病（Cushing's disease, CD）是最为严重的内分泌疾病之一，主要累及育龄期女性。临床观察显示，围产期是CD高发的常见时段。本研究旨在回顾性分析与妊娠相关的CD患者的临床特征，并评估相关妊娠结局。
研究方法：回顾性分析2010年1月至2019年5月于北京协和医院（PUMCH）接受手术治疗、经生化及病理证实为CD的育龄女性患者。妊娠相关性CD定义为妊娠期间、分娩或流产后12个月内出现CD发作。通过查阅患者病历资料，收集其人口统计学信息、生化检验结果、磁共振成像（magnetic resonance imaging, MRI）表现及疾病转归等数据；妊娠相关信息则通过补充线上问卷进行采集。
研究结果：本研究纳入70例有生育意愿的育龄女性CD患者，其中27.1%（n=19）符合妊娠相关性CD的诊断标准。妊娠相关性CD患者从症状发作至确诊的时间为2.7±3.4年，该人群的总体缓解率为89.5%。3例妊娠相关性CD患者在妊娠期间出现高血压，其中2例于妊娠16周时新发高血压，1例并发严重糖尿病。妊娠相关性CD患者的自然流产率与早产率分别为26.3%与28.6%。妊娠相关性CD组的低出生体重（low-birth-weight, LBW）新生儿总体占比（p=0.002）及足月低出生体重新生儿占比（p=0.033）均显著高于非妊娠相关性CD组。
研究结论：本研究中，27.1%的育龄期CD女性患有妊娠相关性CD，其发病可能与妊娠时期的激素环境相关。妊娠相关性CD患者产下低出生体重儿的风险升高。临床医师在围产期应高度警惕CD的发生。对于妊娠期间及产后出现疑似CD症状（如早发性高血压、严重高血糖及持续性体重增加）的患者，临床医师应予以细致诊断并密切监测。