Miura K, Yasuda K, Yanase T, Yamakita N, Sasano H, Nawata H, Inoue M, Fukaya T, Shizuta Y
Department of Internal Medicine/Clinical Research Center of Endocrinology and Metabolism, Matsunami General Hospital, Gifu, Japan.
J Clin Endocrinol Metab. 1996 Oct;81(10):3797-801. doi: 10.1210/jcem.81.10.8855840.
A 17-yr-old female Japanese patient, who was reported in 1968 as having glucocorticoid-responsive hyperaldosteronism but was presumed to have a defect of 17 alpha-hydroxylation mainly in the adrenal glands as the etiology of her illness, was followed. The relationship between clinical manifestations and molecular abnormalities in cytochrome P-45017 alpha gene (CYP17) was also reviewed based on the literature on Japanese patients with 17 alpha-hydroxylase deficiency. She has been treated with dexamethasone, resulting in normal blood pressure and normokalemia for 28 yr. She had almost normal gonadal function with regular menstruation on her first admission. Because of sustained genital bleeding, however, she underwent total hysterectomy with an ovarian biopsy at the age of 42 yr. No follicles or corpus luteum were detected in the ovarian specimen. At the age of 45 yr, the basal levels of sex steroids were decreased, while those of gonadotropins were increased. A genetic study on CYP17 revealed a homozygous deletion of phenylalanine (Phe) codon (TTC) at either amino acid position 53 or 54 in exon 1. A review of the literature revealed 4 patients with this type of CYP17 mutation, including the present patient, out of a total of 11 young adult Japanese patients. The clinical manifestations caused by congenitally deficient gonadal function were not marked in any of these 4 patients, but were marked in 5 of the 7 patients with different mutations of CYP17. The remaining 2 female patients had irregular menstruation. The pretreatment urine/plasma values of aldosterone were variable, normal to high, in individual patients, regardless of the structural abnormalities of CYP17. The following conclusions were suggested: 1) this type of CYP17 mutation is associated with well preserved gonadal function in young adult patients, but it likely causes early reduction of gonadal function with increasing age in these patients; 2) the prevalence of this type of CYP17 mutation is quite high in Japanese patients; and 3) the pretreatment hyperaldosteronism observed in the present patient seems not to be related to the mutation of CYP17.
一名17岁的日本女性患者，1968年报告患有糖皮质激素反应性醛固酮增多症，但推测其病因主要是肾上腺17α-羟化缺陷。对其进行了随访。还根据日本17α-羟化酶缺乏症患者的文献，综述了细胞色素P-45017α基因（CYP17）的临床表现与分子异常之间的关系。她接受了地塞米松治疗，28年来血压正常且血钾正常。首次入院时她的性腺功能几乎正常，月经规律。然而，由于持续性生殖器出血，她在42岁时接受了全子宫切除术及卵巢活检。卵巢标本中未检测到卵泡或黄体。45岁时，性类固醇的基础水平降低，而促性腺激素水平升高。对CYP17的基因研究显示，外显子1中氨基酸位置53或54处苯丙氨酸（Phe）密码子（TTC）纯合缺失。文献综述显示，在11名日本年轻成年患者中，共有4名患者（包括本例患者）存在这种类型的CYP17突变。这4名患者中，先天性性腺功能缺陷引起的临床表现均不明显，但7名CYP17不同突变的患者中有5名临床表现明显。其余2名女性患者月经不规律。无论CYP17的结构异常如何，各患者醛固酮的治疗前尿/血浆值各不相同，从正常到升高。得出以下结论：1）这种类型的CYP17突变与年轻成年患者性腺功能良好保存有关，但随着年龄增长，这些患者的性腺功能可能会早期降低；2）这种类型的CYP17突变在日本患者中的患病率相当高；3）本例患者观察到的治疗前醛固酮增多症似乎与CYP17突变无关。
