{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T23:55:41Z","timestamp":1788306941580,"version":"build-2803163510"},"reference-count":91,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"\n Introduction<\/jats:title>\n \n Acromegaly is a rare, insidious disease associated with significant morbidity and mortality usually caused by a growth hormone (GH)-secreting pituitary tumor. Somatic mutations in\n GNAS<\/jats:italic>\n are common in these tumors, yet their diagnostic, prognostic, and therapeutic implications are less clear.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We conducted a structured review of the literature and meta-analysis to investigate the association of\n GNAS<\/jats:italic>\n mutation status with clinical characteristics and treatment outcomes in adult patients with acromegaly. This was complemented by an analysis comparing patients with acromegaly and identified tumor somatic\n GNAS<\/jats:italic>\n mutations versus those without at our affiliated institution, NYU Langone Health.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n We identified 55 publications that met our inclusion criteria, all observational in nature and most retrospective in design. Twenty-two patients with acromegaly at our institution underwent pituitary tumor resection followed by tumor somatic mutation analysis from 2022 to 2024. The aggregate prevalence of somatic\n GNAS<\/jats:italic>\n mutations in acromegaly was 38% in the systematic review, which was similar to the prevalence of 41% at our institution. While some studies in our review found patients with\n GNAS<\/jats:italic>\n mutated tumors were older and more frequently male, most did not find this association. Whether these tumors demonstrate greater GH secretory capacity is unclear. There was greater consistency in findings that\n GNAS<\/jats:italic>\n + tumors are smaller and possibly less invasive. While greater GH suppression to acute octreotide treatment was frequently reported in patients with\n GNAS<\/jats:italic>\n + tumors, most studies that investigated the response to long-term somatostatin receptor ligand (SRL) therapy did not find an association between\n GNAS<\/jats:italic>\n mutation presence and biochemical control. At our institution, patients with\n GNAS<\/jats:italic>\n + tumors were older at the time of surgery and most classified as mammosomatotroph adenomas on pathology.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Despite their high prevalence,\n GNAS<\/jats:italic>\n mutations cannot reliably inform prognosis and treatment in acromegaly based on findings to date. Larger and prospective studies are needed exploring the frequency and intensity of preoperative symptoms and comorbidities, postoperative outcomes, and occurrence of prolactin co-secretion in\n GNAS<\/jats:italic>\n + tumors.\n <\/jats:p>\n <\/jats:sec>\n \n Systematic Review Registration<\/jats:title>\n \n https:\/\/www.crd.york.ac.uk\/prospero\/<\/jats:ext-link>\n , identifier CRD420251107763.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fendo.2026.1736208","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T05:37:35Z","timestamp":1768973855000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Clinical characteristics associated with somatic GNAS mutations in acromegaly: a systematic review and institutional experience"],"prefix":"10.3389","volume":"17","author":[{"given":"Brendan R.","family":"Dillon","sequence":"first","affiliation":[{"name":"Holman Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, New York University Langone Health","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Ruddy","sequence":"additional","affiliation":[{"name":"Holman Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, New York University Langone Health","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily C.","family":"McQuade","sequence":"additional","affiliation":[{"name":"Department of Medicine, New York University Langone Health","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shruti N.","family":"Shah","sequence":"additional","affiliation":[{"name":"New York University Grossman School of Medicine","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberta","family":"Twi-Yeboah","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, Department of Population Health, New York University Langone Health","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin A.","family":"Levinson","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, Department of Population Health, New York University Langone Health","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nidhi","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Holman Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, New York University Langone Health","place":["New York, NY, United 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