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Patients with hypothalamic and pituitary damage have a higher risk for medical and psychiatric comorbidities despite standard-of-care hormone replacement, and a clinically relevant OXT-deficient state has been identified in patients with arginine vasopressin deficiency (formerly known as central diabetes insipidus) in the last decade. Therefore, OXT deficiency in patients with hypothalamic and pituitary damage is an emerging field. While intranasal oxytocin is readily available to patients, it is not Food and Drug Administration approved in the United States and the quality of compounded formulations is unclear. In addition, more research is needed to establish the safety and efficacy of OXT-based therapeutics in patients with hypothalamic and pituitary damage before recommending treatment. This review summarizes the current knowledge of the OXT system, OXT deficiency in other clinical conditions, and relevance to patients with hypothalamic and pituitary damage. We highlight emerging data supporting OXT deficiency in hypothalamic-pituitary disease, diagnostic challenges, development of therapeutic strategies, and future research directions to advance the field.<\/jats:p>","DOI":"10.1210\/endrev\/bnaf008","type":"journal-article","created":{"date-parts":[[2025,2,22]],"date-time":"2025-02-22T09:22:06Z","timestamp":1740216126000},"page":"518-548","source":"Crossref","is-referenced-by-count":29,"title":["The Oxytocin System and Implications for Oxytocin Deficiency in Hypothalamic-Pituitary Disease"],"prefix":"10.1210","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1205-7114","authenticated-orcid":false,"given":"Anna","family":"Aulinas","sequence":"first","affiliation":[{"name":"Endocrinology Department, Hospital de la Santa Creu i Sant Pau, IR-Sant Pau, CIBERER U747 (ISCIII), EndoERN , 08041, Barcelona ,","place":["Spain"]},{"name":"Faculty of Medicine, University of Vic-University Central of Catalonia (UVic-UCC) , 08500, Vic\/Manresa, Catalonia ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8619-3349","authenticated-orcid":false,"given":"Elizabeth A","family":"Lawson","sequence":"additional","affiliation":[{"name":"Neuroendocrine Unit, Division of Endocrinology, Department of Medicine, Massachusetts General Hospital , 02114, Boston ,","place":["USA"]},{"name":"Department of Medicine, Harvard Medical School , 02115, Boston ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2025,2,24]]},"reference":[{"issue":"2","key":"2025071419563770000_bnaf008-B1","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/s41574-020-00437-2","article-title":"Insights into non-classic and emerging causes of hypopituitarism","volume":"17","author":"Prodam","year":"2021","journal-title":"Nat Rev Endocrinol"},{"issue":"11","key":"2025071419563770000_bnaf008-B2","doi-asserted-by":"crossref","first-page":"3888","DOI":"10.1210\/jc.2016-2118","article-title":"Hormonal replacement in hypopituitarism in adults: an Endocrine Society Clinical practice guideline","volume":"101","author":"Fleseriu","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"issue":"9254","key":"2025071419563770000_bnaf008-B3","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/S0140-6736(00)04006-X","article-title":"Association between premature mortality and hypopituitarism. 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