Vaid Sonal, Estrada-Veras Juvianee, Gahl William A, Patronas Nicholas, Dave Rahul H, Hannah-Shmouni Fady, O'Brien Kevin, Shekhar Skand
Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health (NIH), Research Triangle Park, NC 27709, USA.
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Cancers (Basel). 2025 Feb 27;17(5):824. doi: 10.3390/cancers17050824.
Erdheim-Chester disease (ECD) is an L Group Langerhans histiocytosis associated with pathogenic variants within the MAPK pathways, most commonly the gene. We analyzed prevalence, genetic, biochemical, and pituitary imaging features associated with arginine vasopressin deficiency (AVP-D), one of the most common endocrinopathies in ECD.
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' -tests, nonparametric tests, Fisher's exact tests, and logistic regression were employed for analysis.
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 of V600E 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)] V600E 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.
AVP-D is common in ECD and accompanied by a higher burden of pituitary endocrinopathies, V600E pathogenic variants, abnormal pituitary imaging, and absent posterior pituitary bright spots.
Erdheim-Chester病（ECD）是一种L组朗格汉斯细胞组织细胞增多症，与MAPK通路中的致病变异有关，最常见的是 基因。我们分析了与精氨酸加压素缺乏症（AVP-D）相关的患病率、遗传学、生物化学和垂体影像学特征，AVP-D是ECD中最常见的内分泌疾病之一。
2011年1月至2018年12月在一个临床研究中心对61例ECD患者进行了横断面描述性研究，包括分子遗传学、基线生物化学和垂体内分泌功能研究，以及专门的垂体MRI（或CT）研究。评估了AVP-D和垂体前叶内分泌疾病（甲状腺功能减退、性腺功能减退、肾上腺功能不全和全垂体功能减退）。采用学生t检验、非参数检验、Fisher精确检验和逻辑回归进行分析。
61例患者中共有22例（36%；19例男性和3例女性）患有AVP-D；18例患有AVP-D的患者正在接受去氨加压素的积极治疗。患有AVP-D与未患AVP-D的患者相比更年轻[平均（±标准差）：50.00（±10.45）岁对56.72（±10.45）岁]，V600E致病变异的患病率更高[68%对43%]，胰岛素样生长因子-1更低[平均（±标准差）：137.05（±67.97）对175.92（±61.89）ng/mL]，尿渗透压更低[416.00（250.00 - 690.00）对644.50（538.75 - 757.75）]mOsm/kg，中枢性性腺功能减退的负担更高[81.82%对36.00%]，中枢性甲状腺功能减退[23%对2.5%]，全垂体功能减退[41%对0%]，垂体前叶内分泌缺陷，垂体后叶亮点缺失[63.64%对20.51%]，以及垂体影像学异常。在调整模型中，[比值比（95%置信区间）]V600E突变[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）]、垂体后叶亮点缺失[12.84（3.275 - 65.04）]和垂体影像学异常[10.60（2.844 - 48.29）]与患AVP-D的较高几率相关。
AVP-D在ECD中很常见，并且伴有更高的垂体内分泌疾病负担、V600E致病变异、垂体影像学异常和垂体后叶亮点缺失。
