PREMATURE OVARIAN FAILURE - AUTOIMMUNITY AND NATURAL-HISTORY
PREMATURE OVARIAN FAILURE - AUTOIMMUNITY AND NATURAL-HISTORY
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DOI：
10.1111/j.1365-2265.1993.tb01748.x
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发表时间：
1993-07-01
影响因子：
3.2
通讯作者：
CARETTO, A
中科院分区：
文献类型：
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作者：
BETTERLE, C;ROSSI, A;CARETTO, A
目的研究卵巢早衰（I组）患者的临床和隐匿性自身免疫性疾病与循环类固醇产生细胞自身抗体（SCA）的关系。我们研究了SCA的存在，在器官特异性自身免疫性疾病，但没有性腺功能减退症（组II）的患者。我们评估SCA是否可以被认为是高促性腺激素性腺功能减退症的标志物。设计在组I和II的血液样本在诊断。在一组无性腺功能减退的SCA患者中，至少每年采集一次血液样本进行免疫学和功能检查，共6年。第二组包括3677名患者，年龄6-79岁，分为IIA亚组（99例为单独的Addison病或与其他内分泌疾病或甲状旁腺功能减退相关的疾病）和IIB亚组（3578例为胰岛素依赖型糖尿病或甲状腺自身免疫性疾病）。随访组包括9名受试者，年龄5-31岁（7名女性和2名男性）。测量SCA和其他器官特异性自身抗体通过使用正常人体组织或被动血凝试验的标准间接免疫荧光法检测。性腺功能测试包括评价FSH和LH水平的RIA方法;肾上腺皮质功能包括评价皮质醇和ACTH血浆水平的RIA method.Results三个亚组确定在组I的基础上的临床自身免疫性疾病。发现9/50（18%）例患者患有阿狄森病（亚组IA），在该亚组中，SCA存在于7/9（78%）中; 10/50（20%）患有其他自身免疫性疾病10例患者中1例（10%）有自身免疫性疾病（IB亚组）和SCA，31例（62%）无其他临床自身免疫性疾病（IC亚组），1例（3%）有SCA。IA亚组与IB亚组（P=0.017）和IC亚组（P = 0.00002）相比SCA显著增加，在II组中，20/3677例（0.5%）发现SCA，特别是IIA亚组中18/99例（18%）和IIB亚组中2/3578例（0.06%）发现SCA。IIA亚组SCA发生率显著高于IIB亚组（P = 0.001 × 10（-5））。随访期间，3/7名女性（42.8%）和0/2名男性发生高促性腺激素性性腺功能减退症，潜伏期分别为10、13和15年。3名女性和2名男性在研究开始时缺乏临床Addison病，但在随访期间，13的女性和2/2的男性发展为临床Addison病，平均潜伏期为13 months.CONCLUSIONS结果证实了卵巢早衰与其他临床自身免疫性疾病之间的密切关系，以及原发性卵巢功能衰竭，阿狄森氏病和类固醇产生细胞抗体。这项研究还表明，在女性中，类固醇产生细胞的抗体是潜在的高促性腺激素性性腺功能减退症和阿狄森氏病的血清学标志物;然而，在男性中，这些抗体可能仅被认为是潜在的阿狄森氏病的标志物。
OBJECTIVE We studied the association of clinical and latent autoimmune diseases with circulating steroid-producing cells autoantibodies (SCA) in patients with premature ovarian failure (Group I). We investigated the presence of SCA in patients with organ-specific autoimmune diseases but without hypogonadism (Group II). We assessed whether SCA can be considered markers of hypergonadotrophic hypogonadism.DESIGN In Groups I and II blood samples were taken at diagnosis. In a subset of patients with SCA without hypogonadism blood samples were taken at least yearly for 6 years for immunological and functional tests.PATIENTS Group I included 50 females, aged 16-39 years; Group II included 3677 patients, aged 6-79 years, divided into Subgroup IIA (99 with Addison's disease alone or associated with other endocrinopathies or with hypoparathyroidism) and Subgroup IIB (3578 with insulin-dependent diabetes mellitus or thyroid autoimmune diseases). The follow-up group included nine subjects, aged 5-31 years (seven females and two males).MEASUREMENTS SCA and other organ-specific autoantibodies were detected by standard indirect immunofluorescence using normal human tissues or passive haemagglutination tests. Gonadal functional tests included evaluation of FSH and LH levels by a RIA method; adrenocortical function included evaluation of cortisol and ACTH plasma levels by a RIA method.RESULTS Three subgroups were identified in Group I on the basis of clinical autoimmune disease. 9/50 (18%) patients were found to have an Addison's disease (Subgroup IA) and in this subgroup SCA were present in 7/9 (78%); 10/50 (20%) had other autoimmune diseases (Subgroup IB) and SCA were found in 1/10 (10%); 31/50 (62%) did not have other clinical autoimmune diseases (Subgroup IC) and 1/31 (3%) had SCA. SCA were significantly increased in Subgroup IA vs IB (P=0.017) and vs IC (P = 0.00002).In Group II, SCA were found in 20/3677 (0.5%); in particular, SCA were detected in 18/99 (18%) of the patients in Subgroup IIA and in 2/3578 (0.06%) of the patients in Subgroup IIB. The frequency of SCA in Subgroup IIA was found to be significantly increased with respect to that found in Subgroup IIB (P = 0.001 x 10(-5)).During follow-up, 3/7 females (42.8%) but 0/2 males developed hypergonadotrophic hypogonadism with a latency period of 10, 13 and 15 years, respectively. Three females and two males lacked clinical Addison's disease at the beginning of the study, but during follow-up 1/3 female and 2/2 males developed clinical Addison's disease with a mean latency period of 13 months.CONCLUSIONS The results confirm the strong relationship between premature ovarian failure and other clinical autoimmune diseases, as well as the strong link existing between primary ovarian failure, Addison's disease and antibodies to steroid-producing cells. The study also suggests that in females antibodies to steroid-producing cells are serological markers of both potential hypergonadotrophic hypogonadism, and Addison's disease; however, in males these antibodies may be considered only as markers of potential Addison's disease.