自身免疫性艾迪生病患者的卵巢早衰：临床、遗传和免疫学评估。

Premature ovarian failure in patients with autoimmune Addison's disease: clinical, genetic, and immunological evaluation.

机构信息

Endocrine Unit, Department of Medical and Surgical Sciences, University of Padua School of Medicin, Padua; Italy.

出版信息

J Clin Endocrinol Metab. 2011 Aug;96(8):E1255-61. doi: 10.1210/jc.2011-0414. Epub 2011 Jun 15.

DOI:10.1210/jc.2011-0414

PMID:21677034

Abstract

DESIGN

The design of the study was to investigate the prevalence of the following: 1) premature ovarian failure (POF) in patients with autoimmune Addison's disease (AD); 2) steroid-producing cell antibodies (StCA) and steroidogenic enzymes (17α-hydroxylase autoantibodies and P450 side-chain cleavage enzyme autoantibodies) in patients with or without POF; and 3) the value of these autoantibodies to predict POF.

PATIENTS

The study included 258 women: 163 with autoimmune polyendocrine syndrome type 2 (APS-2), 49 with APS-1, 18 with APS-4, and 28 with isolated AD.

METHODS

StCA were measured by an immunofluorescence technique and 17α-hydroxylase autoantibodies and P450 side-chain cleavage enzyme autoantibodies by immunoprecipitation assays.

RESULTS

Fifty-two of 258 women with AD (20.2%) had POF. POF was diagnosed in 20 of 49 (40.8%) with APS-1, six of 18 (33.3%) with APS-4, 26 of 163 (16%) with APS-2, and none of 28 with isolated AD. In patients with APS-1 and APS-4, POF developed after AD, whereas it preceded AD in patients with APS-2. StCA were detected in 31 of 43 with POF (72%) and 51 of 198 without POF (25.7%). StCA were present in 22 of 38 with APS-1 (57.9%) (11 of 13 with POF); in five of 13 with APS-4 (38.5%) (three of four with POF); in 53 of 162 with APS-2 (32.7%) (17 of 26 with POF), and in one of 28 isolated AD patients (3.6%). Twelve of 13 patients with POF with a duration less than 5 yr (92.3%) and 18 of 25 with duration longer than 5 yr (72%) were StCA positive. Twenty-eight of 31 with POF (90.3%) were positive for at least one steroidogenic antibody. Forty-one women with AD less than 40 yr were followed up for a mean period of 9 yr. Eight of 21 women (38%) positive or seroconverted for steroidogenic autoantibodies developed POF at a mean age of 23 yr (six with APS-1, one with APS-2, and one with APS-4), and none of the 20 patients negative for steroidogenic autoantibodies developed POF.

CONCLUSIONS

This study indicates that AD is frequently associated with POF and that steroidogenic antibodies are markers of patients with POF. Steroidogenic autoantibodies are predictive markers of POF in patients with AD.

摘要

设计

本研究旨在调查以下情况的患病率：1）自身免疫性阿狄森病（AD）患者的卵巢早衰（POF）；2）产生甾体的细胞抗体（StCA）和甾体生成酶（17α-羟化酶自身抗体和 P450 侧链裂解酶自身抗体）在有或没有 POF 的患者中的存在情况；3）这些自身抗体对预测 POF 的价值。

患者

该研究纳入了 258 名女性：163 名患有自身免疫性多内分泌腺综合征 2 型（APS-2），49 名患有 APS-1，18 名患有 APS-4，28 名患有孤立性 AD。

方法

采用免疫荧光技术检测 StCA，采用免疫沉淀法检测 17α-羟化酶自身抗体和 P450 侧链裂解酶自身抗体。

结果

258 名 AD 患者中有 52 名（20.2%）患有 POF。在 49 名 APS-1 患者中，20 名（40.8%）诊断为 POF，18 名 APS-4 患者中有 6 名（33.3%），163 名 APS-2 患者中有 26 名（16%），28 名孤立性 AD 患者中无 POF。在 APS-1 和 APS-4 患者中，POF 发生在 AD 之后，而在 APS-2 患者中，POF 发生在 AD 之前。在 43 名 POF 患者中有 31 名（72%）检测到 StCA，在 198 名无 POF 患者中有 51 名（25.7%）。在 38 名 APS-1 患者中有 22 名（57.9%）（13 名中有 11 名 POF）；在 13 名 APS-4 患者中有 5 名（38.5%）（4 名中有 3 名 POF）；在 162 名 APS-2 患者中有 53 名（32.7%）（26 名中有 17 名 POF），在 28 名孤立性 AD 患者中有 1 名（3.6%）。13 名 POF 患者中，病程小于 5 年的 12 名（92.3%）和病程大于 5 年的 18 名（72%）为 StCA 阳性。在 31 名 POF 患者中，有 28 名（90.3%）至少有一种甾体生成抗体阳性。21 名甾体生成自身抗体阳性或血清转化的小于 40 岁的 AD 女性随访平均 9 年。8 名（38%）甾体生成自身抗体阳性或血清转化的患者发生 POF，平均年龄为 23 岁（6 名患有 APS-1，1 名患有 APS-2，1 名患有 APS-4），而 20 名甾体生成自身抗体阴性的患者均未发生 POF。