{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T11:52:20Z","timestamp":1791805940039,"version":"4.3.4"},"reference-count":21,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T00:00:00Z","timestamp":1740614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Human Genome Research Institute (NHGRI)"},{"name":"National Institute of Environmental Health Sciences (NIEHS)"},{"name":"National Institutes of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Purpose: Erdheim\u2013Chester disease (ECD) is an L Group Langerhans histiocytosis associated with pathogenic variants within the MAPK pathways, most commonly the BRAF 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\u2019 t-tests, nonparametric tests, Fisher\u2019s 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 (\u00b1SD): 50.00 (\u00b110.45) vs. 56.72 (\u00b110.45) years], had higher prevalence of BRAF V600E pathogenic variants [68% vs. 43%], lower IGF-1 [mean (\u00b1SD): 137.05 (\u00b167.97) vs. 175.92 (\u00b161.89) ng\/mL], lower urine osmolality [416.00 (250.00\u2013690.00) vs. 644.50 (538.75\u2013757.75)) 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)] BRAF V600E mutation [7.38 (1.84\u201339.01)], central hypogonadism [6.193 (1.44\u201334.80)], primary hypothyroidism [13.89 (1.401\u2013406.5)], absent posterior pituitary bright spot [12.84 (3.275\u201365.04)], and abnormal pituitary imaging [10.60 (2.844\u201348.29)] 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, BRAF V600E pathogenic variants, abnormal pituitary imaging, and absent posterior pituitary bright spots.<\/jats:p>","DOI":"10.3390\/cancers17050824","type":"journal-article","created":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T08:05:54Z","timestamp":1740729954000},"page":"824","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Clinical, Laboratory, and Imaging Features Associated with Arginine Vasopressin Deficiency (Central Diabetes Insipidus) in Erdheim\u2013Chester Disease (ECD)"],"prefix":"10.3390","volume":"17","author":[{"given":"Sonal","family":"Vaid","sequence":"first","affiliation":[{"name":"Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health (NIH), Research Triangle Park, NC 27709, USA"},{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juvianee","family":"Estrada-Veras","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Gahl","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Patronas","sequence":"additional","affiliation":[{"name":"Clinical Center, National Institutes of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul H.","family":"Dave","sequence":"additional","affiliation":[{"name":"Inova Multiple Sclerosis and Neuro-Immunology Center, Fairfax, VA 22031, USA"},{"name":"National Institute of Neurological Disorders and Stroke, National Institutes of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6829-6205","authenticated-orcid":false,"given":"Fady","family":"Hannah-Shmouni","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD 20892, USA"},{"name":"Department of Medicine, Division of Endocrinology, University of British Columbia, Vancouver, BC V5Z 1M9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3056-8516","authenticated-orcid":false,"given":"Kevin","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9287-6664","authenticated-orcid":false,"given":"Skand","family":"Shekhar","sequence":"additional","affiliation":[{"name":"Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health (NIH), Research Triangle Park, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2672","DOI":"10.1182\/blood-2016-01-690636","article-title":"Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages","volume":"127","author":"Emile","year":"2016","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1182\/blood.2019003507","article-title":"Erdheim-Chester disease: Consensus recommendations for evaluation, diagnosis, and treatment in the molecular era","volume":"135","author":"Goyal","year":"2020","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1182\/blood-2012-07-446286","article-title":"Dramatic efficacy of vemurafenib in both multisystemic and refractory Erdheim-Chester disease and Langerhans cell histiocytosis harboring the BRAF V600E mutation","volume":"121","author":"Haroche","year":"2013","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.1182\/blood-2010-10-313510","article-title":"Systemic perturbation of cytokine and chemokine networks in Erdheim-Chester disease: A single-center series of 37 patients","volume":"117","author":"Arnaud","year":"2011","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/s11926-014-0412-0","article-title":"Erdheim-Chester disease","volume":"16","author":"Haroche","year":"2014","journal-title":"Curr. 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