De Bellis A, Bizzarro A, Rossi R, Paglionico V A, Criscuolo T, Lombardi G, Bellastella A
Institute of Endocrinology, First Faculty of Medicine and Surgery, University of Naples, Italy.
J Clin Endocrinol Metab. 1993 Apr;76(4):1002-7. doi: 10.1210/jcem.76.4.8473373.
Idiopathic Addison's disease is a chronic organ-specific autoimmune disorder with a long subclinical period characterized only by the presence of adrenal autoantibodies (AA) with or without adrenal function failure. The aim of this longitudinal study was to evaluate the behavior of AA using, an indirect fluorescence method, and adrenal function in 20 AA-positive and 50 AA-negative patients screened by an investigation of a large population of organ-specific autoimmune disease patients without clinical Addison's disease. As controls, 100 normal age-matched subjects were tested only once. In the 20 AA-positive and 50 negative patients, AA and adrenal functional tests were evaluated every 4 months for 5 yr. The AA-positive patients were grouped into 5 adrenal functional stages, specifically: stage 0, normal adrenal function; stage 1, high PRA and low (or normal) aldosterone levels alone; stage 2, along with impaired cortisol response to ACTH, stage 3, along with increased ACTH levels; and stage 4, clinically overt Addison's disease. On the basis of the behavior of AA, the 20 positive patients were grouped as follows: group A, 11 patients with AA titer of 1:8 or higher at the first observation and persistently AA positive in subsequent observations, with titers ranging from 1:8 to 1:64; group B, 6 patients with initial AA titers of 1:8 or lower and AA disappearance in subsequent observations; and group C, 3 patients with AA titer of 1:32 or higher, undergoing corticosteroid therapy after the start of the study and showing AA disappearance in subsequent observations. With respect to adrenal function in group A, 2 patients initially in stage 1 and 1 patient initially in stage 2 did not progress to the upper stages, whereas 5 patients initially in stage 0 and 3 initially in stage 1 progressed subsequently to the upper stages, in 2 cases reaching overt clinical Addison's disease (stage 4). On the other hand, all of the patients of group B showed both a spontaneous disappearance of AA and recovery of adrenal function during the study span. Also, the 3 patients of group C showed disappearance of AA after corticosteroid therapy with recovery of adrenal function. None of the 50 patients who were initially AA negative became AA positive subsequently or showed impairment of adrenal function. We reached the following conclusions. 1) AA, even if present initially in some subjects without clinical Addison's disease, can subsequently disappear. 2) Restoration of adrenal function after disappearance of AA indicates that a spontaneous remission of subclinical adrenocortical failure can occur.(ABSTRACT TRUNCATED AT 400 WORDS)
特发性Addison病是一种慢性器官特异性自身免疫性疾病,亚临床期较长,其特征仅为存在肾上腺自身抗体(AA),伴或不伴有肾上腺功能衰竭。本纵向研究的目的是,通过间接荧光法评估20例AA阳性和50例AA阴性患者的AA行为,并评估肾上腺功能,这些患者是从大量无临床Addison病的器官特异性自身免疫性疾病患者中筛查出来的。作为对照,对100名年龄匹配的正常受试者仅进行一次检测。在20例AA阳性和50例阴性患者中,每4个月评估一次AA和肾上腺功能测试,持续5年。AA阳性患者被分为5个肾上腺功能阶段,具体如下:0期,肾上腺功能正常;1期,仅肾素活性(PRA)高,醛固酮水平低(或正常);2期,伴有皮质醇对促肾上腺皮质激素(ACTH)反应受损;3期,伴有ACTH水平升高;4期,临床显性Addison病。根据AA的行为,将20例阳性患者分为以下几组:A组,11例患者在首次观察时AA滴度为1:8或更高,在随后的观察中持续AA阳性,滴度范围为1:8至1:64;B组,6例患者初始AA滴度为1:8或更低,在随后的观察中AA消失;C组,3例患者AA滴度为1:32或更高,在研究开始后接受皮质类固醇治疗,在随后的观察中AA消失。关于A组的肾上腺功能,最初处于1期的2例患者和最初处于2期的1例患者未进展到更高阶段,而最初处于0期的5例患者和最初处于1期的3例患者随后进展到更高阶段,2例发展为显性临床Addison病(4期)。另一方面,B组所有患者在研究期间均出现AA自发消失和肾上腺功能恢复。此外,C组的3例患者在皮质类固醇治疗后AA消失,肾上腺功能恢复。最初AA阴性的50例患者中,没有一例随后变为AA阳性或出现肾上腺功能损害。我们得出以下结论。1)AA即使最初存在于一些无临床Addison病的受试者中,随后也可能消失。2)AA消失后肾上腺功能的恢复表明亚临床肾上腺皮质功能衰竭可自发缓解。(摘要截断于400字)