{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T08:36:21Z","timestamp":1775982981269,"version":"3.50.1"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T00:00:00Z","timestamp":1725580800000},"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":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Alpha-cell hyperplasia (ACH) is a rare pancreatic endocrine condition. Three types of ACH have been described: functional or nonglucagonoma hyperglucagonemic glucagonoma syndrome, reactive or secondary to defective glucagon signaling, and non-functional. Few cases of ACH with concomitant pancreatic neuroendocrine tumors (pNETs) have been reported and its etiology remains poorly understood. A case report of non-functional ACH with glucagon-producing NET is herein presented.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case report<\/jats:title><jats:p>A 72-year-old male was referred to our institution for a 2 cm single pNET incidentally found during imaging for acute cholecystitis. The patient\u2019s past medical history included type 2 diabetes (T2D) diagnosed 12 years earlier, for which he was prescribed metformin, dapagliflozin, and semaglutide. The pNET was clinically and biochemically non-functioning, apart from mildly elevated glucagon 217 pg\/ml (&amp;lt;209), and <jats:sup>68<\/jats:sup>Ga-SSTR PET\/CT positive uptake was only found at the pancreatic tail (SUVmax 11.45). The patient underwent a caudal pancreatectomy and the post-operative <jats:sup>68<\/jats:sup>Ga-SSTR PET\/CT was negative. A multifocal well-differentiated NET G1, pT1N0M0R0 (mf) strongly staining for glucagon on a background neuroendocrine alpha-cell hyperplasia with some degree of acinar fibrosis was identified on pathology analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion and conclusion<\/jats:title><jats:p>This case reports the incidental finding of a clinically non-functioning pNET in a patient with T2D and elevated glucagon levels, unexpectedly diagnosed as glucagon-producing NET and ACH. A high level of suspicion was required to conduct the glucagon immunostaining, which is not part of the pathology routine for a clinically non-functioning pNET, and was key for the diagnosis that otherwise would have been missed. This case highlights the need to consider the diagnosis of glucagon-producing pNET on an ACH background even in the absence of glucagonoma syndrome.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2024.1405835","type":"journal-article","created":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T04:36:23Z","timestamp":1725597383000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Non-functional alpha-cell hyperplasia with glucagon-producing NET: a case report"],"prefix":"10.3389","volume":"15","author":[{"given":"Catarina","family":"Cidade-Rodrigues","sequence":"first","affiliation":[]},{"given":"Ana Paula","family":"Santos","sequence":"additional","affiliation":[]},{"given":"Raquel","family":"Calheiros","sequence":"additional","affiliation":[]},{"given":"Sara","family":"Santos","sequence":"additional","affiliation":[]},{"given":"Catarina","family":"Matos","sequence":"additional","affiliation":[]},{"given":"Ana 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