Araujo-Castro, MartaBiagetti, BetinaMenéndez, EdelmiroNovoa-Testa, IríaCordido, FernandoBerrocal, Víctor RodríguezPascual-Corrales, EiderGuerrero-Pérez, FernandoVicente, AlmudenaGarcía-Centeno, RogelioGonzález, LauraGarcía, María Dolores OlleroEcharri, Ana IrigarayRodríguez, María Dolores MoureNovo-Rodríguez, CristinaCalatayud, MaríaVillar-Taibo, RocíoBernabéu, IgnacioAlvarez-Escola, CristinaJimenéz, Carmen TenorioAbellán-Galiana, PabloVenegas, EvaGonzález-Molero, InmaculadaIglesias, PedroBlanco, ConcepciónLara, Fernando Vidal Ostos deNovoa, María Paz de MiguelTorres, Elena López MezquitaHanzu, FeliciaLamas, CristinaRodríguez, Silvia AznarAulinas, AnnaRecio, José MaríaAviles-Pérez, María DoloresNúñez, Miguel Antonio SampedroCamara, RosaFano, Miguel PajaFajardo, CarmenCardoso, LuísMarques, PedroMartínez-Sáez, ElenaRuz-Caracuel, IgnacioMarazuela, MónicaPuig-Domingo, Manel2025-08-132025-08-132025-07-1571b22915-e0fe-4c0c-b26f-9eec9916d6cchttp://hdl.handle.net/10400.14/54495Aim: To evaluate which factors are associated with a higher probability of failure to surgical and first-generation somatostatin receptor ligands (fgSRLs) treatment in patients with growth hormone and prolactin co-secreting pituitary adenomas (GH&PRL-PAs). Methods: Acromegaly patients with GH&PRL-PAs included in the ACRO-SPAIN study were enrolled. GH&PRL-PAs were defined as tumors with serum PRL levels above the upper limit of normal and positive immunostaining for GH and PRL, or with PRL levels ≥100 ng/mL when immunostaining data were not available. Results: A total of 126 acromegaly patients with GH&PRL-PAs who underwent transsphenoidal pituitary surgery were included, and 42.1% (n = 53) were biochemically cured at the immediate postoperative evaluation. Knosp grade >2 (odds ratio (OR) 3.48, 95% CI 1.28–9.38), higher serum GH (OR 1.01, 95% CI 1.01–1.08) and IGF-1 (OR 1.60, 95% CI 1.05–2.45) levels were associated with a lower probability of surgical cure. Sixty-eight patients received first-line medical therapy as follows: fgSRLs in monotherapy (n = 22), fgSRL plus cabergoline (n = 37), cabergoline in monotherapy (n = 7) and pegvisomant in monotherapy (n = 2). Among the cases treated with fgSRL in monotherapy, 18.2% (n = 4/22) were resistant. We identified as predictors of fgSRL resistance (in monotherapy and combined with cabergoline) a Knosp grade >2 (OR 8.75, P = 0.003), high GH levels at acromegaly diagnosis (OR 1.02, P = 0.031) and higher postoperative GH levels (OR 1.05, P = 0.006), but no predictors of response to fgSRL in monotherapy were identified. Conclusion: The clinical predictors of surgical failure and of fgSRL resistance in patients with GH&PRL-PAs are similar to those described in acromegaly without PRL, co-secretion.engAcromegalyGrowth hormoneProlactin co-secreting pituitary adenomaSomatostatin receptor ligandsSurgical remissionresearch article10.1530/EC-25-0103105012021956PMC1226898740590355