Hána V, Dokoupilová M, Marek J, Plavka R
3rd Department of Medicine, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
Clin Endocrinol (Oxf). 2001 Feb;54(2):277-81. doi: 10.1046/j.1365-2265.2001.01055.x.
A 17-year-old primigravid woman presented with Cushing's syndrome. Typical clinical symptoms and signs developed at the beginning of pregnancy. By week 17 of gestation, plasma cortisol diurnal rhythm was absent and there was a paradoxical increase in plasma cortisol after a 1-mg dexamethasone overnight suppression test. Basal urinary free cortisol was 10 times above the upper limit (in pregnancy) and ACTH levels were suppressed. The diagnosis of ACTH--independent Cushing's syndrome was established. MRI scans revealed normal adrenal and pituitary glands. To control hypercortisolism, the patient was treated with metyrapone. At 34 weeks of gestation, the patient developed preeclampsia and underwent caesarean section. A female infant weighing 1070 g was delivered. No apparent metyrapone-induced teratogenic effects were observed. Cushing's syndrome in the patient resolved within three weeks of delivery. No corticosteroid replacement therapy either for child or mother was needed. Eight months after delivery the patient became pregnant again and rapidly developed Cushing's syndrome with typical clinical symptoms and signs and laboratory results (urinary free cortisol 6464 nmol/24 h). This second pregnancy was unwanted and terminated by artificial abortion that was followed by rapid resolution of hypercortisolism. A third pregnancy, 12 months after delivery was also accompanied by the rapid development of hypercortisolism which recovered after artificial termination. The mechanisms by which pregnancy-induced Cushing's syndrome occurred in this patient are unclear. Aberrant responsiveness or hyperresponsiveness of adrenocortical cells to a non-ACTH and non-CRH substance produced in excess in pregnancy should be considered. Metyrapone suppression of hypercortisolism currently represents the best treatment for these rare cases.
一名17岁的初孕妇出现库欣综合征。典型的临床症状和体征在妊娠初期出现。妊娠17周时，血浆皮质醇昼夜节律消失，过夜1毫克地塞米松抑制试验后血浆皮质醇出现反常升高。基础尿游离皮质醇高于（妊娠时）上限10倍，促肾上腺皮质激素（ACTH）水平被抑制。确诊为非ACTH依赖性库欣综合征。磁共振成像（MRI）扫描显示肾上腺和垂体正常。为控制高皮质醇血症，患者接受了甲吡酮治疗。妊娠34周时，患者发生子痫前期并接受剖宫产。娩出一名体重1070克的女婴。未观察到明显的甲吡酮诱导的致畸作用。患者的库欣综合征在分娩后三周内缓解。无需对婴儿或母亲进行皮质类固醇替代治疗。分娩八个月后患者再次怀孕，并迅速出现具有典型临床症状、体征及实验室检查结果（尿游离皮质醇6464纳摩尔/24小时）的库欣综合征。此次妊娠为意外妊娠，通过人工流产终止妊娠，随后高皮质醇血症迅速缓解。分娩12个月后的第三次妊娠也伴有高皮质醇血症的迅速发展，人工终止妊娠后恢复。该患者妊娠诱导的库欣综合征发生机制尚不清楚。应考虑肾上腺皮质细胞对妊娠时过量产生的非ACTH和非促肾上腺皮质激素释放激素（CRH）物质的异常反应性或高反应性。目前，甲吡酮抑制高皮质醇血症是这些罕见病例的最佳治疗方法。
