{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:13:29Z","timestamp":1787318009417,"version":"build-2736575974"},"reference-count":187,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T00:00:00Z","timestamp":1745280000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health\u2014Ricerca Corrente Annual Program 2026"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Gestational trophoblastic disease (GTD) is a group of disorders including complete, partial, and invasive\/metastatic hydatidiform moles, as well as gestational trophoblastic neoplasia (GTN) (choriocarcinoma; placental site trophoblastic tumor, PSTT; epithelioid trophoblastic tumor, ETT; or mixed forms). These entities are characterized by increased trophoblast proliferation, rarely complicated by hyperthyroidism. Methods: Our systematic literature review (PRISMA guidelines; PubMed, Web of Science, and Scopus databases) searched for histologically confirmed cases of GTN associated with clinical or subclinical hyperthyroidism. We described the clinical\u2013pathologic features and the pathways of hyperthyroidism in GTD. Results: We identified just 32 choriocarcinomas and one PSTT; other non-histologically confirmed cases could have been identified, as some patients received a clinical diagnosis based on serum human chorionic gonadotropin (hCG) levels and imagining data and were treated accordingly. As regards choriocarcinomas, patients\u2019 age range was 15\u201345 (mean 27) years. Metastases involved the lungs (53%), brain (25%), and liver (19%) (less frequently, the kidneys, spleen, ovaries, vagina, pelvis\/abdomen, or thyroid). The time to recurrence range was 1\u201336 (mean 12) months. On follow-up, 10 patients (32%) were alive with disease and 6 (19%) showed no evidence of disease, while most of the women (15 cases, 48%) died of disease. The hCG level range was 10,000\u20133,058,000,000 (mean 128,957,613) IU\/L. At least some symptoms and\/or signs of hyperthyroidism were evident with variable intensity in most cases and significantly improved within 2\u20133 weeks after treatment. Conclusions: Increased trophoblast proliferation could stimulate thyroid function via increasing the half-life of thyroxine-binding globulin. Secondly, increased hCG demonstrates cross-reactivity with the thyroid-stimulating hormone due to similar \u03b1-subunits. Moreover, basic isoforms of hCG may facilitate thyrotropic activity.<\/jats:p>","DOI":"10.3390\/cancers17091398","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T20:11:48Z","timestamp":1745352708000},"page":"1398","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Hyperthyroidism Associated with Gestational Trophoblastic Neoplasia: Systematic Literature Review and Pathways Analysis"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5223-9767","authenticated-orcid":false,"given":"Alina","family":"Badlaeva","sequence":"first","affiliation":[{"name":"1st Pathology Department, National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I. Kulakov of the Ministry of Health of Russia, Bldg. 4, Oparina Street, Moscow 117513, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Tregubova","sequence":"additional","affiliation":[{"name":"1st Pathology Department, National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I. Kulakov of the Ministry of Health of Russia, Bldg. 4, Oparina Street, Moscow 117513, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8739-5209","authenticated-orcid":false,"given":"Aleksandra","family":"Asaturova","sequence":"additional","affiliation":[{"name":"1st Pathology Department, National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I. Kulakov of the Ministry of Health of Russia, Bldg. 4, Oparina Street, Moscow 117513, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1366-2081","authenticated-orcid":false,"given":"Beatrice","family":"Melli","sequence":"additional","affiliation":[{"name":"Molecular Pathology, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"},{"name":"Unit of Obstetrics and Gynecology, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4958-0419","authenticated-orcid":false,"given":"Vincenza Ylenia","family":"Cusenza","sequence":"additional","affiliation":[{"name":"Molecular Pathology, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2299-5160","authenticated-orcid":false,"given":"Andrea","family":"Palicelli","sequence":"additional","affiliation":[{"name":"Pathology Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"},{"name":"Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, 41121 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,22]]},"reference":[{"key":"ref_1","unstructured":"WHO Classification of Tumours Editorial Board (2020). 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