{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:02:29Z","timestamp":1792512149179,"version":"4.5.0"},"reference-count":10,"publisher":"Bioscientifica","issue":"2","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":93,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>A 29-year-old male presented with central scotoma and was suspected of having acromegaly based on enlargement of facial features and extremities. Serum growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels were elevated to 10.14 ng\/mL and 571 ng\/mL (74.8 nmol\/L, +5.73 SDS), respectively. Magnetic resonance imaging revealed a giant pituitary neuroendocrine tumor (PitNET) measuring 48 \u00d7 48 \u00d7 58 mm with bilateral cavernous sinus invasion and high T2-weighted signal intensity. Because of poor GH suppression during an acute octreotide test (100 \u03bcg subcutaneously; nadir GH 6.25 ng\/mL, 19% reduction from baseline) and the invasive tumor phenotype, preoperative pasireotide (PAS) 40 mg every 4 weeks was initiated. After 2 months, partial tumor removal was performed via transsphenoidal surgery. Histological analysis revealed an immature PIT1-lineage PitNET with strong membranous expression of somatostatin receptor subtypes 2 and 5. Persistently elevated IGF-1 after surgery led to re-initiation of PAS (40 mg every 4 weeks, escalated to 60 mg), followed by the addition of pegvisomant (PEG) 10 mg\/day because biochemical control could not be achieved. Combination therapy with PAS and PEG normalized IGF-1 and maintained radiological tumor stability during long-term follow-up. This case highlights that biochemical response to somatostatin receptor ligands does not necessarily correlate with receptor expression in invasive PitNETs. Pathological classification using transcription factors may help guide individualized treatment strategies. Combination therapy with PAS and PEG may represent an effective option for aggressive acromegaly caused by immature PIT1-lineage PitNETs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Learning points<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1530\/edm-25-0171","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T11:52:11Z","timestamp":1781783531000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-2","source":"Crossref","is-referenced-by-count":2,"title":["Combination therapy of pasireotide and pegvisomant for aggressive acromegaly with an immature PIT1-lineage PitNET"],"prefix":"10.1530","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2523-7120","authenticated-orcid":true,"given":"Keiko","family":"Tomiyama","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Metabolism and Nephrology, Graduate School of Medicine, Nippon Medical School, Bunkyo, Tokyo, Japan 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0772-3837","authenticated-orcid":true,"given":"Izumi","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Metabolism and Nephrology, Graduate School of Medicine, Nippon Medical School, Bunkyo, Tokyo, Japan 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeyuki","family":"Tahara","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Nippon Medical School Musashikosugi Hospital, Kawasaki, Kanagawa, Japan 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chie","family":"Inomoto","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tokai University Hachioji Hospital, Hachioji, Tokyo, Japan 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert Yoshiyuki","family":"Osamura","sequence":"additional","affiliation":[{"name":"Department of Pathology, Nippon Kokan Hospital, Kawasaki, Kanagawa, Japan 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Iwabu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Metabolism and Nephrology, Graduate School of Medicine, Nippon Medical School, Bunkyo, Tokyo, Japan 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"2026081809164147000_bib1","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/j.1365-2265.2008.03514.x","article-title":"Silent subtype 3 pituitary adenoma: a clinicopathologic analysis of the Mayo clinic experience","volume":"71","author":"Erickson","year":"2009","journal-title":"Clin 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