{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T17:45:30Z","timestamp":1774979130828,"version":"3.50.1"},"reference-count":21,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background: Paraneoplastic limbic encephalitis (PLE) with anti-Ma2 antibodies is a rare immune-mediated disorder associated with testicular cancer, particularly in young males. While neurological manifestations are well documented, hypothalamic\u2013pituitary dysfunctions remain underreported. We present a case of anti-Ma2 PLE associated with testicular cancer together with a systematic review of PLE associated with testicular cancer, selectively restricted to anti-Ma2 positive cases and focusing on hypothalamic\u2013endocrine involvement. Case presentation: We describe a 21-year-old male diagnosed with anti-Ma2 PLE and intratubular germ cell neoplasia of the right testis. He underwent orchifunicolectomy and immunosuppressive therapy with neurological improvement. Four years later, he developed new-onset temporal seizures, decreased libido, and a polyuria\u2013polydipsia syndrome. Dynamic endocrine testing, including a water deprivation test and copeptin measurement, supported a diagnosis of partial central diabetes insipidus (CDI). Methods: A systematic literature review was performed in accordance with PRISMA guidelines. PubMed was searched using predefined keywords without time restriction. Studies reporting PLE associated with testicular tumors in humans with confirmed anti-Ma2 antibody positivity were included. Results: Eleven studies were included, reporting a total of 38 patients with anti-Ma2-associated PLE and testicular cancer. Hypothalamic or diencephalic involvement was described in 16 patients (42.0%), while endocrine manifestations were explicitly reported in four cases. Only two previous reports mentioned CDI, without detailed diagnostic evaluation. Conclusions: This study highlights the importance of recognizing hypothalamic-endocrine manifestations in PLE. In patients presenting with polydipsia and polyuria, CDI should be carefully differentiated from primary polydipsia using dynamic testing. Hypothalamic involvement may emerge years after tumor treatment, warranting long-term endocrine surveillance.<\/jats:p>","DOI":"10.3390\/medsci14020175","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T16:34:08Z","timestamp":1774974848000},"page":"175","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anti-Ma2 Paraneoplastic Encephalitis and Testicular Cancer: When the Hypothalamus Whispers\u2014A Case Report and Systematic Review with Emphasis on Hypothalamic-Endocrine Dysfunction"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2422-9673","authenticated-orcid":false,"given":"Virginia","family":"Zamponi","sequence":"first","affiliation":[{"name":"Endocrinology Unit, Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piero","family":"Paravani","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rossella","family":"Mazzilli","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4703-4358","authenticated-orcid":false,"given":"Flaminia","family":"Russo","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina Paola","family":"Gardiman","sequence":"additional","affiliation":[{"name":"Surgical Pathology and Cytopathology Unit, Department of Medicine, University of Padua, 35122 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2311-9752","authenticated-orcid":false,"given":"Bruno","family":"Giometto","sequence":"additional","affiliation":[{"name":"Neurology Unit, Hospital of Trento, Azienda Provinciale per i Servizi Sanitari-APSS, 38122 Trento, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raffaele","family":"Iorio","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Universit\u00e0 Cattolica del Sacro Cuore, 38122 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6417-434X","authenticated-orcid":false,"given":"Alessandro","family":"Peri","sequence":"additional","affiliation":[{"name":"Pituitary Diseases and Sodium Alterations Unit, Endocrinology, Careggi University Hospital, University of Florence, 50121 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0182-6555","authenticated-orcid":false,"given":"Marco","family":"Zoccarato","sequence":"additional","affiliation":[{"name":"Neurology Unit, Ospedale Sant\u2019Antonio, Azienda Ospedale Universit\u00e0 di Padova, 35128 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9324-3946","authenticated-orcid":false,"given":"Antongiulio","family":"Faggiano","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/1750-1172-2-22","article-title":"Paraneoplastic Neurological Syndromes","volume":"2","author":"Honnorat","year":"2007","journal-title":"Orphanet J. 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