Patti Giuseppa, Calandra Erika, De Bellis Annamaria, Gallizia Annalisa, Crocco Marco, Napoli Flavia, Allegri Anna Maria Elsa, Thiabat Hanan F, Bellastella Giuseppe, Maiorino Maria Ida, Garrè Maria Luisa, Parodi Stefano, Maghnie Mohamad, di Iorgi Natascia
Department of Pediatrics, IRCCS Istituto Giannina Gaslini, University of Genova, Genova, Italy.
Department of Neuroscience, Rehabilitation, Ophtalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy.
Front Endocrinol (Lausanne). 2020 Feb 18;11:16. doi: 10.3389/fendo.2020.00016. eCollection 2020.
To detect the presence of antipituitary (APA) and antihypothalamus antibodies (AHA) in subjects treated for brain cancers, and to evaluate their potential association with pituitary dysfunction. We evaluated 63 patients with craniopharyngioma, glioma, and germinoma treated with surgery and/or radiotherapy and/or chemotherapy at a median age of 13 years. Forty-one had multiple pituitary hormone deficiencies (MPHD), six had a single pituitary defect. GH was the most common defect (65.1%), followed by AVP (61.9%), TSH (57.1%), ACTH (49.2%), and gonadotropin (38.1%). APA and AHA were evaluated by simple indirect immunofluorescence method indirect immunofluorescence in patients and in 50 healthy controls. Circulating APA and/or AHA were found in 31 subjects (49.2%) and in none of the healthy controls. In particular, 25 subjects out of 31 were APA (80.6%), 26 were AHA (83.90%), and 20 were both APA and AHA (64.5%). Nine patients APA and/or AHA have craniopharyngioma (29%), seven (22.6%) have glioma, and 15 (48.4%) have germinoma. Patients with craniopharyngioma were positive for at least one antibody in 39.1% compared to 33.3% of patients with glioma and to 78.9% of those with germinoma with an analogous distribution for APA and AHA between the three tumors. The presence of APA or AHA and of both APA and AHA was significantly increased in patients with germinoma. The presence of APA ( = 0.001) and their titers ( = 0.001) was significantly associated with the type of tumor in the following order: germinomas, craniopharyngiomas, and gliomas; an analogous distribution was observed for the presence of AHA ( = 0.002) and their titers ( = 0.012). In addition, we found a significant association between radiotherapy and APA ( = 0.03). Brain tumors especially germinoma are associated with the development of hypothalamic-pituitary antibodies and pituitary defects. The correct interpretation of APA/AHA antibodies is essential to avoid a misdiagnosis of an autoimmune infundibulo-neurohypophysitis or pituitary hypophysitis in patients with germinoma.
检测接受脑癌治疗的患者体内抗垂体抗体（APA）和抗下丘脑抗体（AHA）的存在情况，并评估它们与垂体功能障碍的潜在关联。我们评估了63例颅咽管瘤、胶质瘤和生殖细胞瘤患者，这些患者接受了手术和/或放疗和/或化疗，中位年龄为13岁。41例有多垂体激素缺乏（MPHD），6例有单一垂体缺陷。生长激素（GH）是最常见的缺陷（65.1%），其次是抗利尿激素（AVP，61.9%）、促甲状腺激素（TSH，57.1%）、促肾上腺皮质激素（ACTH，49.2%）和促性腺激素（38.1%）。通过简单间接免疫荧光法在患者和50名健康对照中评估APA和AHA。在31名受试者（49.2%）中发现循环APA和/或AHA，而在健康对照中均未发现。特别是，31名受试者中有25名是APA（80.6%），26名是AHA（83.90%），20名同时是APA和AHA（64.5%）。9例APA和/或AHA患者患有颅咽管瘤（29%），7例（22.6%）患有胶质瘤，15例（48.4%）患有生殖细胞瘤。颅咽管瘤患者中至少有一种抗体呈阳性的比例为39.1%，胶质瘤患者为33.3%，生殖细胞瘤患者为78.9%，三种肿瘤之间APA和AHA的分布类似。生殖细胞瘤患者中APA或AHA以及同时存在APA和AHA的情况显著增加。APA的存在（P = 0.001）及其滴度（P = 0.001）与肿瘤类型显著相关，顺序如下：生殖细胞瘤、颅咽管瘤和胶质瘤；AHA的存在（P = 0.002）及其滴度（P = 0.012）也观察到类似分布。此外，我们发现放疗与APA之间存在显著关联（P = 0.03）。脑肿瘤尤其是生殖细胞瘤与下丘脑 - 垂体抗体的产生和垂体缺陷有关。正确解读APA/AHA抗体对于避免误诊生殖细胞瘤患者的自身免疫性漏斗 - 神经垂体炎或垂体炎至关重要。
