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The ASD measured the daily severity of 7 core and 2 exploratory acromegaly symptoms, each rated on a scale from 0 to 10 based on 24-hour recall. Breakthrough acromegaly symptom exacerbations were defined as \u2265\u20092-point increases for any individual symptom score, comparing a 2-day average with the prior 2-day average.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Despite no significant changes in IGF-I levels or overall core symptom severity scores, mean (SE) symptom exacerbation frequencies declined progressively after switching to paltusotine, from 30.2% (5.6%) of days during screening (SRL treatment) to 6.2% (1.6%) of days (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200922,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). The reduction in individual symptom exacerbation frequencies with paltusotine treatment was consistent across all acromegaly symptoms assessed. IGF-I levels did not correlate significantly with symptom severity scores or symptom variability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In patients with acromegaly biochemically controlled with injected SRLs, switching to once-daily oral paltusotine was associated with stable biochemical control, stable symptom severity, and a significantly reduced frequency of symptom exacerbations. A simple daily symptom assessment tool provided important information pertaining to acromegaly disease control that was not apparent from IGF-I measurements.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11102-026-01733-2","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T16:24:17Z","timestamp":1784823857000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reduced breakthrough symptom exacerbations in patients with biochemically controlled acromegaly switched from injected depot somatostatin receptor ligands to once-daily oral paltusotine in the PATHFNDR-1 clinical trial"],"prefix":"10.1007","volume":"29","author":[{"given":"David R.","family":"Clemmons","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany P.","family":"Quock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Casagrande","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Krasner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"issue":"19","key":"1733_CR1","doi-asserted-by":"publisher","first-page":"1926","DOI":"10.1056\/NEJMra2409076","volume":"393","author":"A Giustina","year":"2025","unstructured":"Giustina A, Colao A (2025) Acromegaly. 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