Lo J C, Schwitzgebel V M, Tyrrell J B, Fitzgerald P A, Kaplan S L, Conte F A, Grumbach M M
Department of Medicine, University of California, San Francisco 94143, USA.
J Clin Endocrinol Metab. 1999 Mar;84(3):930-6. doi: 10.1210/jcem.84.3.5565.
Women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency, especially those patients with the salt-losing form, have decreased fertility rates. Pregnancy experience in this population is limited. We report the pregnancy outcomes and serial measurements of maternal serum steroid levels in four women with classic 21-hydroxylase deficiency, three of whom were female pseudohermaphrodites with the salt-losing form. These glucocorticoid-treated women gave birth to four healthy female newborns with normal female external genitalia, none of whom were affected with 21-hydroxylase deficiency. In three women, circulating androgen levels increased during gestation, but remained within the normal range for pregnancy during glucocorticoid therapy. In the fourth patient, androgen levels were strikingly elevated during gestation despite increasing the dose of oral prednisone from 5 to 15 mg/day (two divided doses). Notwithstanding the high maternal serum concentration of androgens, however, placental aromatase activity was sufficient to prevent masculinization of the external genitalia of the female fetus and quite likely the fetal brain, consistent with the idea that placental aromatization of androgens to estrogens is the principal mechanism that protects the female fetus from the masculinizing effects of maternal hyperandrogenism. These four patients highlight key issues in the management of pregnancy in women with 21-hydroxylase deficiency, particularly the use of endocrine monitoring to assess adrenal androgen suppression in the mother, especially when the fetus is female. Recommendations for the management of pregnancy and delivery in these patients are discussed.
患有因21-羟化酶缺乏所致先天性肾上腺皮质增生症的女性，尤其是那些失盐型患者，生育率降低。该人群的妊娠经历有限。我们报告了4例典型21-羟化酶缺乏症女性的妊娠结局及母体血清类固醇水平的系列测量结果，其中3例为失盐型女性假两性畸形患者。这些接受糖皮质激素治疗的女性产下了4名健康的女婴，其外生殖器为正常女性特征，无一例患有21-羟化酶缺乏症。在3名女性中，妊娠期循环雄激素水平升高，但在糖皮质激素治疗期间仍处于妊娠正常范围内。在第4例患者中，尽管口服泼尼松剂量从5毫克/天增加至15毫克/天（分两次服用），但其妊娠期雄激素水平仍显著升高。然而，尽管母体血清雄激素浓度很高，但胎盘芳香化酶活性足以防止女性胎儿外生殖器男性化，很可能也能防止胎儿大脑男性化，这与雄激素经胎盘芳香化转化为雌激素是保护女性胎儿免受母体高雄激素血症男性化影响的主要机制这一观点相符。这4例患者凸显了21-羟化酶缺乏症女性妊娠管理中的关键问题，尤其是利用内分泌监测来评估母亲肾上腺雄激素抑制情况，特别是当胎儿为女性时。文中讨论了这些患者妊娠及分娩管理的建议。
