Aix-Marseille Université, Institut National de la Santé et de la Recherche Médicale (INSERM), U1251, Marseille Medical Genetics, Marseille, France.
Assistance Publique - Hôpitaux de Marseille (AP-HM), Department of Endocrinology, Hôpital de la Conception, Centre de Référence des Maladies Rares Hypophysaires HYPO, Marseille, France.
Eur J Endocrinol. 2018 Jun;178(6):R259-R266. doi: 10.1530/EJE-17-1058. Epub 2018 Mar 9.
With fewer than 200 reported cases, Cushing's syndrome (CS) in pregnancy remains a diagnostic and therapeutic challenge. In normal pregnancies, misleading signs may be observed such as striae or hypokalemia, while plasma cortisol and urinary free cortisol may rise up to 2- to 3-fold. While the dexamethasone suppression test is difficult to use, reference values for salivary cortisol appear valid. Apart from gestational hypertension, differential diagnosis includes pheochromocytoma and primary aldosteronism. The predominant cause is adrenal adenoma (sometimes without decreased ACTH), rather than Cushing's disease. There are considerable imaging pitfalls in Cushing's disease. Aberrant receptors may, in rare cases, lead to increased cortisol production during pregnancy in response to HCG, LHRH, glucagon, vasopressin or after a meal. Adrenocortical carcinoma (ACC) is rare and has poor prognosis. Active CS during pregnancy is associated with a high rate of maternal complications: hypertension or preeclampsia, diabetes, fractures; more rarely, cardiac failure, psychiatric disorders, infection and maternal death. Increased fetal morbidity includes prematurity, intrauterine growth retardation and less prevalently stillbirth, spontaneous abortion, intrauterine death and hypoadrenalism. Therapy is also challenging. Milder cases can be managed conservatively by controlling comorbidities. Pituitary or adrenal surgery should ideally be performed during the second trimester and patients should then be treated for adrenal insufficiency. Experience with anticortisolic drugs is limited. Metyrapone was found to allow control of hypercortisolism, with a risk of worsening hypertension. Cabergoline may be an alternative option. The use of other drugs is not advised because of potential teratogenicity and/or lack of information. Non-hormonal (mechanical) contraception is recommended until sustained biological remission is obtained.
库欣综合征（CS）在妊娠中病例少于 200 例，仍然是一个诊断和治疗上的挑战。在正常妊娠中，可能会出现误导性的迹象，如妊娠纹或低钾血症，而血浆皮质醇和尿游离皮质醇可能会升高 2-3 倍。虽然地塞米松抑制试验难以使用，但唾液皮质醇的参考值似乎是有效的。除了妊娠高血压外，鉴别诊断还包括嗜铬细胞瘤和原发性醛固酮增多症。主要原因是肾上腺腺瘤（有时 ACTH 不减少），而不是库欣病。库欣病在影像学上有很大的陷阱。异常受体在极少数情况下可能会导致妊娠期间皮质醇产生增加，这是对 HCG、LHRH、胰高血糖素、血管加压素或餐后的反应。肾上腺皮质癌（ACC）很少见，预后不良。妊娠期间活动性 CS 与母亲并发症的高发生率相关：高血压或先兆子痫、糖尿病、骨折；更罕见的是，心力衰竭、精神障碍、感染和母亲死亡。胎儿发病率增加包括早产、宫内生长受限，以及更罕见的死产、自然流产、宫内死亡和肾上腺功能减退。治疗也具有挑战性。轻度病例可通过控制合并症进行保守治疗。理想情况下，应在妊娠中期进行垂体或肾上腺手术，然后对患者进行肾上腺功能减退治疗。皮质醇抑制剂的经验有限。发现美替拉酮可以控制皮质醇过多症，但会增加高血压恶化的风险。卡麦角林可能是另一种选择。由于潜在的致畸性和/或缺乏信息，不建议使用其他药物。建议使用非激素（机械）避孕，直到获得持续的生物学缓解。
