{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T02:08:59Z","timestamp":1784167739701,"version":"3.55.0"},"reference-count":47,"publisher":"The Endocrine Society","issue":"5","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Proyectos de Investigacion en Salud","award":["PI22\/01404"],"award-info":[{"award-number":["PI22\/01404"]}]},{"name":"Proyectos de Investigacion en Salud","award":["PMP22\/00021"],"award-info":[{"award-number":["PMP22\/00021"]}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031478","name":"NextGenerationEU","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100031478","id-type":"DOI","asserted-by":"publisher"}]},{"name":"iTIRONET","award":["P2022\/BMD7379"],"award-info":[{"award-number":["P2022\/BMD7379"]}]},{"DOI":"10.13039\/100012818","name":"Comunidad de Madrid","doi-asserted-by":"publisher","award":["IPI\/2022\/N5"],"award-info":[{"award-number":["IPI\/2022\/N5"]}],"id":[{"id":"10.13039\/100012818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016389","name":"Sociedad de Endocrinolog\u00eda, Nutrici\u00f3n y Diabetes de la Comunidad de Madrid","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100016389","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sociedad Espa\u00f1ola de Endocrinolog\u00eda y Nutrici\u00f3n"},{"DOI":"10.13039\/501100008530","name":"FEDER","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Predoctorales de Formaci\u00f3n en Investigaci\u00f3n en Salud","award":["FI20\/00035"],"award-info":[{"award-number":["FI20\/00035"]}]},{"name":"Predoctorales de Formaci\u00f3n en Investigaci\u00f3n en Salud","award":["FI23\/00052"],"award-info":[{"award-number":["FI23\/00052"]}]},{"name":"Predoctorales de Formaci\u00f3n en Investigaci\u00f3n en Salud","award":["IFEQ21\/00085"],"award-info":[{"award-number":["IFEQ21\/00085"]}]},{"name":"Predoctorales de Formaci\u00f3n en Investigaci\u00f3n en Salud","award":["IFCS22\/00014"],"award-info":[{"award-number":["IFCS22\/00014"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Acromegaly is a rare disease usually caused by a pituitary neuroendocrine tumor (PitNET) that produces GH PitNET. PitNETs secreting GH and prolactin (GH&amp;PRL PitNETs) contribute up to 30% to the spectrum of acromegaly and have been attributed a more aggressive behavior. GH&amp;PRL PitNETs can be classified into 2 predominant phenotypes: mammosomatotroph arising from a single-cell population of Pit-1 lineage and mixed somatotroph\u2013lactotroph PitNETs (mixed SL PitNETs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To evaluate the clinical and molecular differences between GH PitNETs, mammosomatotroph, and mixed SL PitNETs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We quantified GH and PRL expression by double immunofluorescence in 51 PitNETs (23 GH PitNETs, 20 mammosomatotrophs, and 8 mixed SL PitNETs) from patients with acromegaly. These findings were correlated with clinical data and histologic markers such as somatostatin receptor (SSTR)2, SSTR3, SSTR5, E-cadherin, and CAM 5.2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results did not reveal significant differences in GH or IGF-1 levels between GH PitNETs and mixed SL PitNETs, but PRL levels were significantly higher in mammosomatotrophs. Tumor size and invasiveness were comparable between the 2 groups. Interestingly, 41% of prolactin (PRL)-positive tumors did not show hyperprolactinemia, representing silent PRL-positive GH PitNETs. Mixed SL PitNETs exhibited reduced SSTR2 expression, while GH PitNETs exhibited higher SSTR5 levels. Moreover, all tumors lacking cytokeratin expression were nonresponders to medical therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings highlight the heterogeneity within GH&amp;PRL PitNETs, including silent PRL-positive GH PitNETs. Our data suggest mixed SL tumors may be less responsive to SSTR ligands, emphasizing the need for tailored strategies based on tumor subtype and receptor profile.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgaf634","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T12:49:58Z","timestamp":1764074998000},"page":"1258-1271","source":"Crossref","is-referenced-by-count":3,"title":["Clinical and Pathological Spectrum of Acromegaly: Distinguishing GH PitNETs, Mammosomatotrophs, and Mixed Tumors"],"prefix":"10.1210","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2479-1882","authenticated-orcid":false,"given":"Rebeca","family":"Mart\u00ednez-Hern\u00e1ndez","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Nutrition and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER GCV14\/ER\/12), Hospital Universitario de la Princesa, Instituto de Investigaci\u00f3n Sanitaria Princesa, Universidad Aut\u00f3noma de Madrid , 28006 Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando F","family":"M\u00e9ndez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER GCV14\/ER\/12), Hospital Universitario de la Princesa, Instituto de Investigaci\u00f3n Sanitaria Princesa, Universidad Aut\u00f3noma de Madrid , 28006 Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Serrano-Somavilla","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER GCV14\/ER\/12), Hospital Universitario de la Princesa, Instituto de Investigaci\u00f3n Sanitaria Princesa, Universidad Aut\u00f3noma de Madrid , 28006 Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Sacrist\u00e1n-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER GCV14\/ER\/12), Hospital Universitario de la Princesa, Instituto de Investigaci\u00f3n Sanitaria Princesa, Universidad Aut\u00f3noma de Madrid , 28006 Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"S\u00e1nchez de la Blanca","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER GCV14\/ER\/12), Hospital Universitario de la Princesa, Instituto de Investigaci\u00f3n Sanitaria Princesa, Universidad Aut\u00f3noma de Madrid , 28006 Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Sampedro-N\u00fa\u00f1ez","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER GCV14\/ER\/12), Hospital Universitario de la Princesa, Instituto de Investigaci\u00f3n Sanitaria Princesa, Universidad Aut\u00f3noma de Madrid , 28006 Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00edctor","family":"Navas-Moreno","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER GCV14\/ER\/12), Hospital Universitario de la Princesa, Instituto de Investigaci\u00f3n Sanitaria Princesa, Universidad Aut\u00f3noma de Madrid , 28006 Madrid 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Nutrition Department, Vall d\u2019Hebron University Hospital and Vall d\u2019Hebron Research Institute, Department of Medicine, Autonomous University of Barcelona, Reference Networks (ERN) , 08035 Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Ruz-Caracuel","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hospital Universitario Ram\u00f3n y Cajal, IRYCIS, CIBERONC , 28034 Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0519-0072","authenticated-orcid":false,"given":"Marta","family":"Araujo-Castro","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Hospital Universitario Ram\u00f3n y Cajal, IRYCIS, CIBERONC , 28034 Madrid 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