Objective: Erdheim-Chester disease (ECD) is a rare, non-Langerhans histiocytosis of unknown origin with characteristic radiologic and histologic features. Methods: This report describes a patient with multiple endocrine manifestations in the context of this uncommon disease. Results: A 78-year-old man presented with polyuria, polydypsia, fever, and a constitutional syndrome. Investigations revealed central diabetes insipidus, hypogonadism with inappropriate gonadotropin levels, and mild hyperprolactinemia. Pituitary magnetic resonance imaging showed stalk thickening and absence of the normal bright signal from the posterior pituitary lobe. Orchiectomy biopsy support the diagnosis of ECD, and therapy with peginterferon alfa-2a was initiated. Conclusion: ECD is a multisystemic and heterogeneous clinicopathologic condition. This disease should be considered in patients with diabetes insipidus, hyperprolactinemia, and hypogonadism in the setting of a multi-organ disease. (AACE Clinical Case Rep. 2017;3:e111-e115) Abbreviations: CT = computed tomography; DI = diabetes insipidus; ECD = Erdheim-Chester disease; IGF-1 = insulin-like growth factor 1; 18 FDG-PET/CT = fluorodeoxyglucose-positron emission tomography/computed tomography e112 Multisystemic Involvement in ECD, AACE Clinical Case Rep. 2017;3(No. 2)