Department of Clinical and Experimental Medicine and Surgery, F. Magrassi, A. Lanzara, Second University of Naples, via Pansini N. 5, 80131 Naples, Italy.
J Clin Endocrinol Metab. 2010 Aug;95(8):3750-7. doi: 10.1210/jc.2010-0551. Epub 2010 May 25.
Antipituitary antibodies (APA) are frequently present in patients with autoimmune polyendocrine syndrome (APS).
The aim was to evaluate the predictive value of APA for the occurrence of hypopituitarism. A total of 149 APA-positive and 50 APA-negative patients with APS and normal pituitary function were longitudinally studied for 5 yr.
APA, by indirect immunofluorescence, and anterior pituitary function were assessed yearly in all patients. The risk for developing autoimmune pituitary dysfunction was calculated using survival and multivariate analysis.
Hypopituitarism occurred in 28 of 149 (18.8%) APA-positive patients but in none of the 50 APA-negative patients. The immunostaining pattern in APA-positive patients involved either isolated pituitary cells [type 1 pattern; n=99 (66.4%)] or all pituitary cells [type 2 pattern; n=50 (33.6%)]. All patients developing pituitary dysfunction throughout the study span had a type 1 pattern. Kaplan-Meier curves for cumulative survival showed a significantly higher rate for developing hypopituitarism in relation to positive APA tests (P<0.005), pattern of immunostaining (P<0.0001), and APA titers (P<0.000001). Cox regression analysis in APA-positive patients with a type 1 pattern demonstrated a significantly (P<0.0001) higher risk for the onset of hypopituitarism in relation to increasing titers of APA.
APA measurement by immunofluorescence may help to predict the occurrence of hypopituitarism but only when considering the immunostaining pattern and their titers. Combined evaluation of these parameters allows identifying patients at higher risk for pituitary autoimmune dysfunction, thus requiring a strict pituitary surveillance to disclose a preclinical phase of hypopituitarism and possibly interrupt therapeutically the progression to clinically overt disease.
抗垂体抗体（APA）在自身免疫性多内分泌综合征（APS）患者中经常存在。
本研究旨在评估 APA 对垂体功能减退症发生的预测价值。共对 149 例 APA 阳性和 50 例 APA 阴性的 APS 合并正常垂体功能患者进行了 5 年的纵向研究。
所有患者每年通过间接免疫荧光法评估 APA 和前垂体功能。采用生存和多因素分析计算发生自身免疫性垂体功能障碍的风险。
149 例 APA 阳性患者中有 28 例（18.8%）发生垂体功能减退症，但 50 例 APA 阴性患者中无一例发生。APA 阳性患者的免疫染色模式涉及孤立的垂体细胞[1 型模式；n=99（66.4%）]或所有垂体细胞[2 型模式；n=50（33.6%）]。整个研究期间发生垂体功能障碍的所有患者均为 1 型模式。累积生存的 Kaplan-Meier 曲线显示，与 APA 检测阳性（P<0.005）、免疫染色模式（P<0.0001）和 APA 滴度（P<0.000001）相关，发生垂体功能减退症的累积生存率明显较高。在 1 型模式的 APA 阳性患者中，Cox 回归分析显示，与 APA 滴度增加相关，发生垂体功能减退症的风险显著增加（P<0.0001）。
通过免疫荧光法测量 APA 可能有助于预测垂体功能减退症的发生，但仅当考虑免疫染色模式及其滴度时。联合评估这些参数可以识别出发生垂体自身免疫功能障碍风险较高的患者，从而需要进行严格的垂体监测，以发现亚临床垂体功能减退症，并可能在临床上中断疾病的进展。
