Purpose: Erdheim–Chester disease (ECD) is an L Group Langerhans histiocytosis associated with pathogenic variants within the MAPK pathways, most commonly theBRAFgene. We analyzed prevalence, genetic, biochemical, and pituitary imaging features associated with arginine vasopressin deficiency (AVP-D), one of the most common endocrinopathies in ECD. Methods: A cross-sectional descriptive study of 61 subjects with ECD was conducted at a clinical research center from January 2011 to December 2018, with molecular genetics, baseline biochemical and pituitary endocrine function studies, and dedicated pituitary MRI (or CT) studies. AVP-D and anterior pituitary endocrinopathies (hypothyroidism, hypogonadism, adrenal insufficiency and panhypopituitarism) were assessed. Students’t-tests, nonparametric tests, Fisher’s exact tests, and logistic regression were employed for analysis. Results: In total, 22 out of 61 subjects (36%; 19 males and 3 females) had AVP-D; 18 subjects with AVP-D were in active treatment with desmopressin. Those with versus without AVP-D were younger [mean (±SD): 50.00 (±10.45) vs. 56.72 (±10.45) years], had higher prevalence ofBRAFV600E pathogenic variants [68% vs. 43%], lower IGF-1 [mean (±SD): 137.05 (±67.97) vs. 175.92 (±61.89) ng/mL], lower urine osmolality [416.00 (250.00–690.00) vs. 644.50 (538.75–757.75)) mOsm/kg], and a higher burden of central hypogonadism [81.82% vs. 36.00%], central hypothyroidism [23% vs. 2.5%], panhypopituitarism [41% vs. 0%], anterior pituitary endocrine deficits, absent posterior pituitary bright spots [63.64% vs. 20.51%], and abnormal pituitary imaging. In adjusted models, [OR (95%CI)]BRAFV600E mutation [7.38 (1.84–39.01)], central hypogonadism [6.193 (1.44–34.80)], primary hypothyroidism [13.89 (1.401–406.5)], absent posterior pituitary bright spot [12.84 (3.275–65.04)], and abnormal pituitary imaging [10.60 (2.844–48.29)] were associated with higher odds of having AVP-D. Conclusions: AVP-D is common in ECD and accompanied by a higher burden of pituitary endocrinopathies,BRAFV600E pathogenic variants, abnormal pituitary imaging, and absent posterior pituitary bright spots.
目的：埃尔德海姆-切斯特病（ECD）是一种与MAPK通路（最常见为BRAF基因）致病性变异相关的L组朗格汉斯细胞组织细胞增生症。本研究旨在分析ECD中最常见的内分泌疾病之一——精氨酸加压素缺乏症（AVP-D）的患病率及其相关的遗传学、生化学和垂体影像学特征。方法：于2011年1月至2018年12月在临床研究中心对61例ECD患者进行横断面描述性研究，内容包括分子遗传学检测、基线生化及垂体内分泌功能评估、以及专用垂体MRI（或CT）检查。评估指标包括AVP-D及前叶垂体功能减退（甲状腺功能减退、性腺功能减退、肾上腺功能不全及全垂体功能减退）。采用t检验、非参数检验、Fisher精确检验和逻辑回归进行分析。结果：61例患者中22例（36%；男性19例，女性3例）存在AVP-D，其中18例正在接受去氨加压素治疗。与无AVP-D组相比，AVP-D组患者年龄更轻[均值（±标准差）：50.00（±10.45）岁 vs. 56.72（±10.45）岁]，BRAFV600E致病性变异发生率更高[68% vs. 43%]，IGF-1水平更低[均值（±标准差）：137.05（±67.97） ng/mL vs. 175.92（±61.89） ng/mL]，尿渗透压更低[416.00（250.00–690.00） mOsm/kg vs. 644.50（538.75–757.75） mOsm/kg]，且中枢性性腺功能减退[81.82% vs. 36.00%]、中枢性甲状腺功能减退[23% vs. 2.5%]、全垂体功能减退[41% vs. 0%]等前叶垂体内分泌缺陷发生率更高，垂体后叶高信号消失[63.64% vs. 20.51%]及垂体影像异常比例更高。校正模型显示，BRAFV600E突变[OR（95%CI）：7.38（1.84–39.01）]、中枢性性腺功能减退[6.193（1.44–34.80）]、原发性甲状腺功能减退[13.89（1.401–406.5）]、垂体后叶高信号消失[12.84（3.275–65.04）]及垂体影像异常[10.60（2.844–48.29）]与AVP-D发生风险显著相关。结论：AVP-D在ECD中较为常见，常伴随更高负荷的垂体内分泌疾病、BRAFV600E致病性变异、垂体影像异常及垂体后叶高信号消失。
肿瘤(癌症)患者之家