Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Department of Endocrinology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium.
Eur J Endocrinol. 2017 Nov;177(5):K13-K20. doi: 10.1530/EJE-17-0263. Epub 2017 Aug 17.
Cushing syndrome (CS) during pregnancy is a rare condition with only a few cases reported in the literature. Misdiagnosis of CS is common because of overlapping features like fatigue, weight gain, striae and emotional changes that can occur during normal pregnancy. Changes in maternal hormones and their binding proteins complicate assessment of glucocorticoid hormone levels during gestation. CS during pregnancy is most frequently due to an adrenal adenoma and to a lesser degree to adrenocorticotropic hormone (ACTH) hypersecretion by a pituitary adenoma. Furthermore, aberrant expression of luteinizing hormone (LH) receptors in the adrenal cortex has been suggested to be involved in the pathogenesis of adrenal CS during pregnancy. We report three pregnant women with ACTH-independent Cushing's syndrome and an adrenal tumor. After uncomplicated delivery, patient 1 underwent testing for aberrant hormone receptor expression by the adenoma. Cortisol responses were found after administration of luteinizing hormone-releasing hormone (LHRH), human chorionic gonadotropin (hCG), glucagon, vasopressin and a standard mixed meal. All patients were treated with laparoscopic adrenalectomy. Adrenal tumor tissue of two patients showed positive immunohistochemical staining of LH receptors. Considering the cortisol responses to LHRH and hCG, and the development of CS during pregnancy in these patients, it is likely that ACTH-independent hypercortisolism was induced by the pregnancy-associated rise in hCG levels that activated aberrantly expressed LH receptors in the adrenal adenoma. Remarkably, adrenal adenomas may simultaneously express multiple aberrant receptors and individual ligands may play a role in the regulation of cortisol production in CS during pregnancy.
妊娠合并库欣综合征（CS）是一种罕见的疾病，文献中仅有少数病例报道。由于正常妊娠期间也会出现疲劳、体重增加、妊娠纹和情绪变化等重叠症状，因此 CS 常被误诊。母体激素及其结合蛋白的变化使妊娠期糖皮质激素水平的评估变得复杂。妊娠期间 CS 最常见的原因是肾上腺腺瘤，其次是垂体腺瘤促肾上腺皮质激素（ACTH）分泌过多。此外，还提示黄体生成素（LH）受体在肾上腺皮质中的异常表达与妊娠期间肾上腺 CS 的发病机制有关。我们报告了 3 例 ACTH 非依赖性库欣综合征合并肾上腺肿瘤的孕妇。分娩顺利后，患者 1 接受了对腺瘤中异常激素受体表达的检测。给予黄体生成素释放激素（LHRH）、人绒毛膜促性腺激素（hCG）、胰高血糖素、血管加压素和标准混合餐刺激后，发现皮质醇有反应。所有患者均接受腹腔镜肾上腺切除术。两名患者的肾上腺肿瘤组织显示 LH 受体的免疫组化染色阳性。考虑到对 LHRH 和 hCG 的皮质醇反应，以及这些患者在妊娠期间发生 CS，很可能是妊娠相关 hCG 水平升高激活了肾上腺腺瘤中异常表达的 LH 受体，导致 ACTH 非依赖性高皮质醇血症。值得注意的是，肾上腺腺瘤可能同时表达多种异常受体，并且个体配体可能在妊娠期间 CS 中皮质醇产生的调节中发挥作用。
