Barnes R B, Ehrmann D A, Brigell D F, Rosenfield R L
Department of Obstetrics/Gynecology, University of Chicago, Pritzker School of Medicine, Illinois 60637.
J Clin Endocrinol Metab. 1993 Feb;76(2):450-5. doi: 10.1210/jcem.76.2.8381802.
Nonclassical 3 beta-hydroxy-delta 5-steroid dehydrogenase (3 beta-HSD) deficiency type of congenital adrenal hyperplasia has been hypothesized to occur in as many as 10-40% of hirsute women, based on the adrenal steroidogenic responses to ACTH. However, diagnostic criteria for this "late-onset" 3 beta-HSD deficiency are not clearly established. Among 40 successive hyperandrogenic women undergoing evaluation of adrenal steroidogenic responses to ACTH, 8 had responses suggestive of 3 beta-HSD deficiency. Since 3 beta-HSD is present in both the ovary and adrenal, we attempted to document the defect in the ovary by stimulating their ovarian function with a gonadotropin-releasing hormone agonist test using nafarelin (6-D-[2-naphthyl]alanine-gonadotropin-releasing hormone). The eight hirsute women had steroid responses to ACTH suggestive of 3 beta-HSD deficiency, namely, the values of the delta 5-steroids, 17-hydroxypregnenolone and dehydroepiandrosterone, 30 and 60 min after ACTH in each hirsute woman were greater than 2 SD above the normal mean. Seven of the eight hirsute women had at least one elevated delta 5/delta 4-steroid ratio; however, only three of the hirsute women had two abnormal ratios. Furthermore, the response of the delta 4-steroid androstenedione and the ratio of androstenedione to cortisol after ACTH were significantly increased in the hirsute women, findings not consistent with 3 beta-HSD deficiency. After nafarelin, five and six hirsute patients had elevated values of the delta 4-steroids androstenedione and 17-hydroxyprogesterone, respectively. No patient had an elevated delta 5/delta 4-steroid ratio after nafarelin. Thus, ovarian steroidogenic responses to nafarelin did not support the diagnosis of 3 beta-HSD deficiency. Rather, they are consistent in most cases with polycystic ovary syndrome due to dysregulation of 17-hydroxylase and 17,20-lyase activities. We propose that increased activity of the enzyme P450c17 alpha in the adrenal cortex is responsible for most of what is often termed late-onset 3 beta-HSD deficiency.
基于肾上腺类固醇对促肾上腺皮质激素（ACTH）的反应，有人推测先天性肾上腺皮质增生症的非经典3β-羟基-δ5-类固醇脱氢酶（3β-HSD）缺乏型在多达10%至40%的多毛女性中存在。然而，这种“迟发性”3β-HSD缺乏症的诊断标准尚未明确确立。在40例连续接受肾上腺类固醇对ACTH反应评估的高雄激素血症女性中，有8例的反应提示存在3β-HSD缺乏。由于3β-HSD在卵巢和肾上腺中均有表达，我们试图通过使用那法瑞林（6-D-[2-萘基]丙氨酸-促性腺激素释放激素）进行促性腺激素释放激素激动剂试验来刺激她们的卵巢功能，从而证实卵巢中的缺陷。这8例多毛女性对ACTH的类固醇反应提示存在3β-HSD缺乏，即每例多毛女性在ACTH注射后30分钟和60分钟时，δ5-类固醇、17-羟孕烯醇酮和脱氢表雄酮的值均高于正常均值2个标准差以上。这8例多毛女性中有7例至少有一个升高的δ5/δ4-类固醇比值；然而，只有3例多毛女性有两个异常比值。此外，多毛女性在ACTH注射后，δ4-类固醇雄烯二酮的反应以及雄烯二酮与皮质醇的比值均显著升高，这些结果与3β-HSD缺乏不一致。在使用那法瑞林后，分别有5例和6例多毛患者的δ4-类固醇雄烯二酮和17-羟孕酮值升高。使用那法瑞林后，没有患者的δ5/δ4-类固醇比值升高。因此，卵巢对那法瑞林的类固醇反应不支持3β-HSD缺乏的诊断。相反，在大多数情况下，它们与因17-羟化酶和17,20-裂解酶活性失调导致的多囊卵巢综合征一致。我们提出，肾上腺皮质中P450c17α酶活性增加是导致大多数通常被称为迟发性3β-HSD缺乏的原因。
