Clinical, Laboratory, and Imaging Features Associated with Arginine Vasopressin Deficiency (Central Diabetes Insipidus) in Erdheim-Chester Disease (ECD).

Purpose: 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.

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' -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 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.

Conclusions: 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.