Hormonal staining patterns and clinical outcomes in acromegaly: a 15-year single-center study

Abstract Purpose Acromegaly is most commonly caused by pituitary somatotroph adenomas, a substantial proportion of which exhibit prolactin (PRL) expression on immunohistochemistry. However, the clinical relevance and prognostic implications of this pathological phenotype remain controversial. We aimed to compare pathological features and treatment outcomes of growth hormone/prolactin (GH/PRL)–positive adenomas with GH-only adenomas. Methods We retrospectively analyzed 90 patients with acromegaly who underwent transsphenoidal surgery between 2010 and 2025. Adenomas were classified according to immunohistochemical staining as GH-only, GH/PRL, or other subtypes. Clinical, biochemical, radiological, and treatment outcomes were compared across groups. Results Of 90 adenomas, 47 (52.2%) were GH-only, 39 (43.3%) GH/PRL, and 4 (4.4%) other PIT-1 lineage adenomas. Postoperative remission was achieved in 32 patients (35.6%), with no significant difference between GH-only and GH/PRL adenomas. In multivariable analysis, optic chiasm compression was independently associated with lower odds of remission (OR 0.212, 95% CI 0.049–0.910; p = 0.037). Among 45 patients receiving SSA therapy, 25 (55.6%) achieved biochemical response. Perinuclear CK8/18 staining (OR 4.839, 95% CI 1.198–19.540; p = 0.027) and T2-weighted MRI hypointensity (OR 5.464, 95% CI 1.284–23.250; p = 0.022) were independently associated with SSA response. Although Ki-67 was higher in GH/PRL adenomas, it was not associated with treatment outcomes. Conclusion Despite higher proliferative activity, GH/PRL adenomas did not demonstrate inferior surgical or medical outcomes compared with GH-only adenomas. Prognosis appears to be driven primarily by anatomical features and cytokeratin patterns, supporting individualized treatment strategies.