SAT614 Clinical, Laboratory And Imaging Features Associated With Central Diabetes Insipidus (Arginine Vasopressin Deficiency) In Erdheim-Chester Disease (ECD)

Abstract

Abstract Disclosure: S. Vaid: None. J. Estrada-Veras: None. W. Gahl: None. P. Nicholas: None. R. Dave: None. B. Gochuico: None. K. O'Brien: None. F. Hannah-Shmouni: None. S. Shekhar: None. Background: Erdheim-Chester disease (ECD) is a rare, non-Langerhans, histiocytic multisystemic disorder commonly associated with somatic pathogenic variants in the BRAF or MAPK pathways. In ECD, diabetes insipidus (DI) is among the most common endocrinopathies and is often the presenting feature. We analyzed the prevalence and the genetic, biochemical, and imaging features associated with DI in subjects with ECD. Methods: A cross-sectional descriptive study of subjects with biopsy-confirmed ECD was conducted from January 2011 to December 2018 at the National Institutes of Health Clinical Center. Subjects underwent molecular genetics, baseline biochemical and pituitary endocrine function studies, and dedicated pituitary MRI. DI was diagnosed based on clinical and biochemical features. Other endocrinopathies were diagnosed based on standardized criteria. Continuous data were analyzed using t-tests or nonparametric tests between subjects with and without DI. Categorical data were analyzed via Fisher's exact tests. Results: Sixty-one subjects with ECD [23 females (37.7%) and 38 males (62.3%)] were evaluated. Twenty-three subjects (38%) had DI, with a higher percentage of males (87%) vs females (13%). DI subjects compared to those without DI were younger [mean (SD):50.1(10.4) vs 57.5 (14.5) years; p=0.01] and had a higher prevalence of BRAF V600E pathogenic variants [76.19% vs 39.47%; p<0.01], lower IGF-1 [mean (SEM):136.5 (13.87) vs 161.67(10.22) ng/mL; p=0.02], and lower urine osmolality [466.6 (±260.18) vs 641.05 (±179.7) mOsm/kg; p<0.01]. DI subjects also had a higher prevalence of central hypogonadism [78% vs 34%; p<0.01], a higher prevalence of panhypopituitarism [39% vs 0%; p <0.01] and a higher number of anterior pituitary deficits [mean (SEM):1.23 (1.15) vs 0.56 (0.67); p =0.01] than non-DI subjects. Subjects with DI had a higher frequency of absent posterior pituitary bright spots [61% vs 21%; p<0.01] compared to those without DI. There were no differences in BMI, serum prolactin, vasopressin, serum osmolality, serum sodium, total cholesterol or hsCRP. The frequencies of central adrenal insufficiency, central hypothyroidism and abnormal pituitary imaging were similar between the two groups. Conclusion: DI is among the most common endocrinopathies in Erdheim-Chester disease. In DI subjects, a higher burden of anterior pituitary endocrinopathies, BRAF V600E pathogenic variants and absence of the posterior pituitary bright spot was noted, which may allow for early stratification and targeted clinical management. Presentation: Saturday, June 17, 2023