De Bellis Annamaria, Bizzarro Antonio, Conte Marisa, Perrino Silvia, Coronella Concetta, Solimeno Stefano, Sinisi Antonia Maria, Stile Luisa Anna, Pisano Gustavo, Bellastella Antonio
Department of Clinical and Experimental Medicine and Surgery F. Magrassi, A. Lanzara, Second University of Naples, 80131 Naples, Italy.
J Clin Endocrinol Metab. 2003 Feb;88(2):650-4. doi: 10.1210/jc.2002-021054.
The role of antipituitary antibodies (APA) in autoimmune pituitary diseases still needs to be clarified. The aim of this study was 2-fold: first, to investigate the presence of APA in adults with idiopathic or acquired GH deficiency (GHD) and in adults with autoimmune endocrine diseases; and second, to evaluate whether in autoimmune endocrine patients APA titer is correlated to the pituitary function and particularly to GH secretion. We studied 12 adults with isolated and apparently idiopathic GHD who were treated with recombinant GH in childhood (group 1a), 14 patients with adult GHD secondary to surgery for pituitary and parasellar tumors (group 1b), and 180 patients with organ-specific autoimmune diseases (group 2). APA were evaluated by indirect immunofluorescence. In all APA-positive patients and in 20 APA-negative patients of group 2, GH secretion was investigated by testing its response to insulin-induced hypoglycemia (insulin tolerance test) and, when impaired, also to arginine. APA were found (at high titers) in 4 of 12 patients of group 1a (33.3%) but were absent in all patients in group 1b. APA were also found in 40 of 180 patients of group 2 (22.2%), 35 of them at low titers (group 2a) and 5 at high titers (group 2b). Twenty of the 140 autoimmune endocrine APA-negative patients studied (group 2c) and all APA-positive patients at low titers (group 2a) had normal pituitary function. Conversely, all APA-positive patients at high titers (groups 1a and 2b) had a severe isolated GHD. An inverse correlation between APA titers and GH peak serum response to insulin tolerance test in autoimmune endocrine patients was observed. Our results suggest that APA, when detected at high titers, may be considered a good diagnostic tool to highlight the possible occurrence of GHD in adults with autoimmune endocrine diseases. Moreover, they may indicate an autoimmune pituitary involvement in adults with apparently idiopathic GHD, suggesting that the prevalence of autoimmune GHD is much higher than that so far considered.
抗垂体抗体(APA)在自身免疫性垂体疾病中的作用仍有待阐明。本研究的目的有两个:第一,调查特发性或获得性生长激素缺乏症(GHD)成人患者以及自身免疫性内分泌疾病成人患者中APA的存在情况;第二,评估自身免疫性内分泌患者的APA滴度是否与垂体功能相关,特别是与生长激素分泌相关。我们研究了12名童年期接受重组生长激素治疗的孤立性且明显为特发性GHD成人患者(1a组),14名因垂体及鞍旁肿瘤手术继发成人GHD的患者(1b组),以及180名器官特异性自身免疫性疾病患者(2组)。通过间接免疫荧光法评估APA。在所有APA阳性患者以及2组的20名APA阴性患者中,通过检测生长激素对胰岛素诱导的低血糖反应(胰岛素耐量试验)来研究生长激素分泌,若反应受损,则还检测其对精氨酸的反应。在1a组的12名患者中有4名(33.3%)发现了APA(高滴度),但1b组所有患者中均未发现。2组的180名患者中有40名(22.2%)也发现了APA,其中35名滴度较低(2a组),5名滴度较高(2b组)。所研究的140名自身免疫性内分泌APA阴性患者中有20名(2c组)以及所有低滴度APA阳性患者(2a组)垂体功能正常。相反,所有高滴度APA阳性患者(1a组和2b组)均患有严重的孤立性GHD。在自身免疫性内分泌患者中观察到APA滴度与胰岛素耐量试验的生长激素血清峰值反应呈负相关。我们的结果表明,高滴度检测到的APA可能被视为一种良好的诊断工具,以突出自身免疫性内分泌疾病成人患者中可能出现的GHD。此外,它们可能表明明显特发性GHD成人患者存在自身免疫性垂体受累,提示自身免疫性GHD的患病率远高于目前所认为的。