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Marta Araujo-Castro Neuroendocrinology Unit, Department of Endocrinology and Nutrition
Department of Health Science, Universidad de Alcalá, Madrid, Spain

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Rogelio Garcia Centeno Department of Endocrinology & Nutrition, Hospital Universitario Gregorio Marañón, Madrid, Spain

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María-Carmen López-García Department of Endocrinology & Nutrition, Hospital Universitario de Albacete, Albacete, Spain

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Cristina Lamas Department of Endocrinology & Nutrition, Hospital Universitario de Albacete, Albacete, Spain

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Cristina Álvarez-Escolá Department of Endocrinology & Nutrition, Hospital Universitario La Paz, Madrid, Spain

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María Calatayud Gutiérrez Department of Endocrinology & Nutrition, Hospital Universitario Doce de Octubre, Madrid, Spain

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Concepción Blanco-Carrera Department of Endocrinology & Nutrition, Hospital Universitario Príncipe de Asturias, Madrid, Spain

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Paz de Miguel Novoa Department of Endocrinology & Nutrition, Hospital Universitario Clínico San Carlos, Madrid, Spain

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Nuria Valdés Department of Endocrinology & Nutrition, Hospital Universitario de Cabueñes, Asturias, Spain

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Paola Gracia Gimeno Department of Endocrinology & Nutrition, Hospital Royo Villanova, Zaragoza, Spain

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Mariana Tomé Fernández-Ladreda Department of Endocrinology & Nutrition, Hospital Universitario de Puerto Real, Cádiz, Spain

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César Mínguez Ojeda Department of Urology, IRYCIS, Hospital Universitario Ramón y Cajal, Madrid, Spain

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Juan Carlos Percovich Hualpa Department of Endocrinology & Nutrition, Hospital Universitario Gregorio Marañón, Madrid, Spain

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Mireia Mora Department of Endocrinology & Nutrition, Hospital Clinic, Barcelona, Spain
Group of Endocrine Disorders, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain

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Óscar Vidal Department of General Surgery, Hospital Clinic, Barcelona, Spain

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Ana Serrano Romero Department of Anesthesia, IRYCIS, Hospital Universitario Ramón y Cajal, Madrid, Spain

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Felicia Alexandra Hanzu Department of Endocrinology & Nutrition, Hospital Clinic, Barcelona, Spain
Group of Endocrine Disorders, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain

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Victoria Gómez Dos Santos Department of Urology, IRYCIS, Hospital Universitario Ramón y Cajal, Madrid, Spain

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We aimed to identify presurgical and surgical risk factors for intraoperative complications in patients with pheochromocytomas. A retrospective study of patients with pheochromocytomas who underwent surgery in ten Spanish hospitals between 2011 and 2021 was performed. One hundred and sixty-two surgeries performed in 159 patients were included. The mean age was 51.6 ± 16.4 years old and 52.8% were women. Median tumour size was 40 mm (range 10–110). Laparoscopic adrenalectomy was performed in 148 patients and open adrenalectomy in 14 patients. Presurgical alpha- and beta-blockade was performed in 95.1% and 51.9% of the surgeries, respectively. 33.3% of the patients (n = 54) had one or more intraoperative complications. The most common complication was the hypertensive crisis in 21.0%, followed by prolonged hypotension in 20.0%, and hemodynamic instability in 10.5%. Patients pre-treated with doxazosin required intraoperative hypotensive treatment more commonly than patients pre-treated with other antihypertensive drugs (51.1% vs 26.5%, P = 0.002). Intraoperative complications were more common in patients with higher levels of urine metanephrine (OR = 1.01 for each 100 μg/24 h, P = 0.026) and normetanephrine (OR = 1.00 for each 100 μg/24 h, P = 0.025), larger tumours (OR = 1.4 for each 10 mm, P < 0.001), presurgical blood pressure > 130/80 mmHg (OR = 2.25, P = 0.027), pre-treated with doxazosin (OR = 2.20, P = 0.023) and who had not received perioperative hydrocortisone (OR = 3.95, P = 0.008). In conclusion, intraoperative complications in pheochromocytoma surgery are common and can be potentially life-threatening. Higher metanephrine and normetanephrine levels, larger tumour size, insufficient blood pressure control before surgery, pre-treatment with doxazosin, and the lack of treatment with perioperative hydrocortisone are associated with higher risk of intraoperative complications.

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Marta Araujo-Castro Endocrinology & Nutrition Department, Hospital Universitario Ramón y Cajal, Madrid, Spain
Instituto de Investigación Biomédica Ramón y Cajal (IRYCIS), Madrid, Spain
University of Alcalá, Madrid, Spain

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César Mínguez Ojeda Urology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain

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Rogelio García Centeno Endocrinology & Nutrition Department, Hospital Universitario Gregorio Marañón, Madrid, Spain

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María-Carmen López-García Endocrinology & Nutrition Department, Hospital Universitario de Albacete, Albacete, Spain

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Cristina Lamas Endocrinology & Nutrition Department, Hospital Universitario de Albacete, Albacete, Spain

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Felicia Alexandra Hanzu Endocrinology & Nutrition Department, Hospital Clinic, Barcelona, Spain

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Mireia Mora Endocrinology & Nutrition Department, Hospital Clinic, Barcelona, Spain

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María del Castillo Tous Endocrinology & Nutrition Department, Hospital Universitario Virgen de la Macarena, Sevilla, Spain

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Pablo Rodríguez de Vera Gómez Endocrinology & Nutrition Department, Hospital Universitario Virgen de la Macarena, Sevilla, Spain

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Paola Parra Ramírez Endocrinology & Nutrition Department, Hospital Universitario La Paz Madrid, Madrid, Spain

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Cristina Alvarez-Escola Endocrinology & Nutrition Department, Hospital Universitario La Paz Madrid, Madrid, Spain

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Concepción Blanco Carrera Endocrinology & Nutrition Department, Hospital Universitario Príncipe de Asturias, Madrid, Spain

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Rebeca Barahona San Millán Endocrinology & Nutrition Department, Institut Català de la Salut Girona, Girona, Spain

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Mónica Recasens Endocrinology & Nutrition Department, Institut Català de la Salut Girona, Girona, Spain

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Nuria Valdés Endocrinology & Nutrition Department, Hospital Universitario de Cabueñes, Asturias, Spain

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Paola Gracia Gimeno Endocrinology & Nutrition Department, Hospital Royo Villanova, Zaragoza, Spain

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Paz de Miguel Novoa Endocrinology & Nutrition Department, Hospital Clínico San Carlos, Madrid, Spain

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Almudena Vicente Endocrinology & Nutrition Department, Hospital Universitario de Toledo, Toledo, Spain

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Laura Manjón Endocrinology & Nutrition Department, Hospital Universitario Central de Asturias, Oviedo, Spain
Instituto de Investigación Sanitaria del Principado de Asturias (ISPA)

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Iñigo García Sanz General & Digestive Surgery Department, Hospital Universitario de La Princesa, Madrid, Spain

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Theodora Michalopoulou Department of Endocrinology and Nutrition, Joan XXIII University Hospital, Tarragona, Spain

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María Calatayud Endocrinology & Nutrition Department, Hospital Universitario Doce de Octubre, Madrid, Spain

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The objective of our study was to determine the prevalence of glycemic disorders (diabetes mellitus and prediabetes) in patients with pheochromocytomas and sympathetic paragangliomas (PPGLs) and identify risk factors for their development and the likelihood of their resolution after surgery. A multicentric retrospective study of patients with PPGLs submitted to surgery between 2000 and 2021 in 17 Spanish hospitals was performed. Diabetes-specific data were collected at diagnosis, in the immediate- and long-term postsurgical follow-up. A total of 229 patients with PPGLs were included (218 with pheochromocytomas and 11 with sympathetic paragangliomas). Before surgery, glycemic disorders were diagnosed in 35.4% of the patients (n = 81): 54 with diabetes and 27 with prediabetes. The variables independently associated with a higher risk of glycemic disorders were sporadic PPGL (odds ratio (OR) = 3.26 (1.14–9.36)) and hypertension (OR = 3.14 (1.09–9.01)). A significant decrease in fasting plasma glucose and HbA1c levels was observed after surgery, in the short-term and long-term follow-up (P < 0.001). After a median follow-up of 48.5 months (range 3.3–168.9), after surgery, 52% of diabetic and 68% of prediabetic patients experienced a complete resolution. Lower body mass index (BMI) (P = 0.001), lower glucose levels (P = 0.047) and shorter duration of diabetes prior to surgery (P = 0.021) were associated with a higher probability of diabetes resolution. In conclusion, glycemic disorders in patients with PPGLs are present in more than a third of them at diagnosis. Sporadic PPGLs and hypertension are risk factors for their development. More than 50% of cases experience a complete resolution of the glycemic disorder after resection of the PPGLs.

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Iulia Potorac CHU de Liège-University of Liège, Liège, Belgium

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Patrick Petrossians CHU de Liège-University of Liège, Liège, Belgium

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Adrian F Daly CHU de Liège-University of Liège, Liège, Belgium

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Orsalia Alexopoulou Université Catholique de Louvain, Brussels, Belgium

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Sophie Borot CHU Jean Minjoz, Besancon, France

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Mona Sahnoun-Fathallah CHU Marseille, Marseille, France

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Frederic Castinetti CHU Marseille, Marseille, France

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France Devuyst Université Libre de Bruxelles, Bruxelles, Belgium

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Marie-Lise Jaffrain-Rea Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila and Neuroendocrinology, Neuromed IRCCS, Pozzilli, Italy

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Claire Briet CHU Angers, Angers, France

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Florina Luca CHU Strasbourg, Strasbourg, France

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Marion Lapoirie CHU Lyon, Lyon, France

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Flavius Zoicas Universitätsklinikum Erlangen, Erlangen, Germany

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Isabelle Simoneau CHU Bocage, Dijon, France

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Alpha M Diallo CHU Reims, Reims, France

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Ammar Muhammad Erasmus University Medical Center Rotterdam, Rotterdam, Netherlands

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Fahrettin Kelestimur Faculty of Medicine, Erciyes University, Kayseri, Turkey

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Elena Nazzari University of Genova, Genova, Italy

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Rogelio Garcia Centeno Hospital Universitario Gregorio Marañon, Madrid, Spain

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Susan M Webb Hospital Sant Pau, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, Unidad 747), IIB-Sant Pau, ISCIII and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain

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Marie-Laure Nunes CHU Bordeaux, Bordeaux, France

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Vaclav Hana Charles University, Prague, Czech Republic

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Véronique Pascal-Vigneron CHU Nancy, Nancy, France

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Irena Ilovayskaya Moscow Regional Research and Clinical Institute, Russia

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Farida Nasybullina Kazan State Medical Academy, Kazan, Russia

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Samia Achir Centre Pierre et Marie Curie, Algiers, Algeria

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Diego Ferone University of Genova, Genova, Italy

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Sebastian J C M M Neggers Erasmus University Medical Center Rotterdam, Rotterdam, Netherlands

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Brigitte Delemer CHU Reims, Reims, France

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Jean-Michel Petit CHU Bocage, Dijon, France

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Christof Schöfl Center of Endocrinology & Metabolism, Bamberg, Germany

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Gerald Raverot CHU Lyon, Lyon, France

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Bernard Goichot CHU Strasbourg, Strasbourg, France

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Patrice Rodien CHU Angers, Angers, France

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Bernard Corvilain Université Libre de Bruxelles, Bruxelles, Belgium

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Thierry Brue CHU Marseille, Marseille, France

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Franck Schillo CHU Jean Minjoz, Besancon, France

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Luaba Tshibanda CHU de Liège-University of Liège, Liège, Belgium

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Dominique Maiter Université Catholique de Louvain, Brussels, Belgium

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Jean-François Bonneville CHU de Liège-University of Liège, Liège, Belgium

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Albert Beckers CHU de Liège-University of Liège, Liège, Belgium

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GH-secreting pituitary adenomas can be hypo-, iso- or hyper-intense on T2-weighted MRI sequences. We conducted the current multicenter study in a large population of patients with acromegaly to analyze the relationship between T2-weighted signal intensity on diagnostic MRI and hormonal and tumoral responses to somatostatin analogs (SSA) as primary monotherapy. Acromegaly patients receiving primary SSA for at least 3 months were included in the study. Hormonal, clinical and general MRI assessments were performed and assessed centrally. We included 120 patients with acromegaly. At diagnosis, 84, 17 and 19 tumors were T2-hypo-, iso- and hyper-intense, respectively. SSA treatment duration, cumulative and mean monthly doses were similar in the three groups. Patients with T2-hypo-intense adenomas had median SSA-induced decreases in GH and IGF-1 of 88% and 59% respectively, which were significantly greater than the decreases observed in the T2-iso- and hyper-intense groups (P < 0.001). Tumor shrinkage on SSA was also significantly greater in the T2-hypo-intense group (38%) compared with the T2-iso- and hyper-intense groups (8% and 3%, respectively; P < 0.0001). The response to SSA correlated with the calculated T2 intensity: the lower the T2-weighted intensity, the greater the decrease in random GH (P < 0.0001, r = 0.22), IGF-1 (P < 0.0001, r = 0.14) and adenoma volume (P < 0.0001, r = 0.33). The T2-weighted signal intensity of GH-secreting adenomas at diagnosis correlates with hormone reduction and tumor shrinkage in response to primary SSA treatment in acromegaly. This study supports its use as a generally available predictive tool at diagnosis that could help to guide subsequent treatment choices in acromegaly.

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Marta Araujo-Castro Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Madrid, Spain & Instituto de Investigación Biomédica Ramón y Cajal (IRYCIS), Madrid, Spain

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Betina Biagetti Department of Endocrinology and Nutrition, Hospital Universitario Vall de Hebrón, CIBERER U747 (ISCIII), ENDO-ERN, Barcelona, Spain

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Edelmiro Menéndez Torre Department of Endocrinology and Nutrition, Hospital Universitario Central de Asturias & Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Asturias, Spain

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Iría Novoa-Testa Department of Endocrinology and Nutrition, Hospital Universitario de A Coruña, A Coruña, Spain

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Fernando Cordido Department of Endocrinology and Nutrition, Hospital Universitario de A Coruña, A Coruña, Spain

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Eider Pascual-Corrales Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Madrid, Spain & Instituto de Investigación Biomédica Ramón y Cajal (IRYCIS), Madrid, Spain

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Víctor Rodríguez Berrocal Department of Neurosurgery, Hospital Universitario Ramón y Cajal, Madrid, Spain

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Fernando Guerrero-Pérez Department of Endocrinology and Nutrition, Hospital Universitario de Bellvitge, Cataluña L’Hospitalet de Llobregat, Spain

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Almudena Vicente Department of Endocrinology and Nutrition, Hospital Universitario de Toledo, Toledo, Spain

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Juan Carlos Percovich Hualpa Department of Endocrinology and Nutrition, Hospital Universitario Gregorio Marañón, Madrid, Spain

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Rogelio García-Centeno Department of Endocrinology and Nutrition, Hospital Universitario Gregorio Marañón, Madrid, Spain

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Laura González-Fernández Department of Endocrinology and Nutrition, Hospital Universitario Gregorio Marañón, Madrid, Spain

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María Dolores Ollero García Department of Endocrinology and Nutrition, Hospital Universitario Navarra, Pamplona, Spain

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Ana Irigaray Echarri Department of Endocrinology and Nutrition, Hospital Universitario Navarra, Pamplona, Spain

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María Dolores Moure Rodríguez Department Endocrinology and Nutrition, Hospital Universitario de Cruces, Bilbao, Spain

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Cristina Novo-Rodríguez Department of Endocrinology and Nutrition, Hospital Universitario Virgen de las Nieves, Granada, Spain

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María Calatayud Department of Endocrinology and Nutrition, Hospital Universitario Doce de Octubre, Madrid, Spain

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Rocío Villar-Taibo Department of Endocrinology and Nutrition, Hospital Universitario de Santiago de Compostela, Madrid, Spain

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Ignacio Bernabéu Department of Endocrinology and Nutrition, Hospital Universitario de Santiago de Compostela, Madrid, Spain

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Cristina Alvarez-Escola Department of Endocrinology and Nutrition, Hospital Universitario La Paz, Madrid, Spain

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Pamela Benítez Valderrama Department of Endocrinology and Nutrition, Hospital Universitario La Paz, Madrid, Spain

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Carmen Tenorio-Jiménez Department of Endocrinology and Nutrition, Hospital Universitario Virgen de las Nieves, Granada, Spain

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Pablo Abellán Galiana Department of Endocrinology and Nutrition, Hospital General Universitario de Castellón, Castellón, Spain
Department of Medicine and Surgery, Universidad Cardenal Herrera-CEU, CEU Universities, Castellón, Spain

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Eva Venegas Department of Endocrinology and Nutrition, Hospital Universitario Virgen del Rocío, Sevilla, Spain

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Inmaculada González-Molero Endocrinology and Nutrition Department, Hospital Regional Universitario de Málaga, IBIMA Plataforma Bionand, Málaga, Spain

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Pedro Iglesias Department of Endocrinology and Nutrition, Hospital Universitario Puerta de Hierro, Madrid, Spain

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Concepción Blanco-Carrera Department of Endocrinology and Nutrition, Hospital Universitario Príncipe de Asturias, Madrid, Spain

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Fernando Vidal-Ostos De Lara Department of Endocrinology and Nutrition, Hospital Universitario Príncipe de Asturias, Madrid, Spain

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Paz de Miguel Novoa Department of Endocrinology and Nutrition, Hospital Clínico San Carlos, Madrid, Spain

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Elena López Mezquita Department of Endocrinology and Nutrition, Hospital Universitario Clínico San Cecilio, Granada, Spain

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Felicia Alexandra Hanzu Department of Endocrinology and Nutrition, Hospital Clinic de Barcelona, Barcelona, Spain

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Iban Aldecoa Biomedical Diagnostic Center, Department of Pathology, Hospital Clinic - University of Barcelona, Barcelona, Spain
Neurological Tissue Bank of the Biobank, FCRB-IDIBAPS-Hospital Clinic Barcelona, Barcelona, Spain

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Silvia Aznar Department of Endocrinology and Nutrition, Hospital Universitario De Albacete, Albacete, Spain

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Cristina Lamas Department of Endocrinology and Nutrition, Hospital Universitario De Albacete, Albacete, Spain

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Anna Aulinas Department of Endocrinology and Nutrition, Hospital de la Santa Creu i Sant Pau, IR-SANT PAU, CIBERER U747 (ISCIII), Barcelona, Spain
Department of Medicine, Universitat de Vic-Universitat Central de Catalunya, Vic, Spain

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Queralt Asla Department of Endocrinology and Nutrition, Hospital de la Santa Creu i Sant Pau, IR-SANT PAU, CIBERER U747 (ISCIII), Barcelona, Spain
Department of Medicine, Universitat de Vic-Universitat Central de Catalunya, Vic, Spain

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Paola Gracia Gimeno Department of Endocrinology and Nutrition, Hospital Royo Villanova, Zaragoza, Spain

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José María Recio-Córdova Department of Endocrinology and Nutrition, Hospital Royo Villanova, Zaragoza, Spain

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María Dolores Avilés-Pérez Department of Endocrinology and Nutrition, Hospital Universitario Clínico San Cecilio, Granada, Spain

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Diego Asensio-Wandosell Department of Endocrinology and Nutrition, Hospital Universitario Germans Trias i Pujol, Cataluña, Spain

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Miguel Sampedro-Núñez Department of Endocrinology and Nutrition, Hospital Universitario La Princesa Madrid, Spain

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Rosa Cámara Department of Endocrinology and Nutrition, Hospital Universitario y Politécnico La Fe, Valencia, Spain

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Miguel Paja Fano Department of Endocrinology and Nutrition, OSI Bilbao-Basurto, Hospital Universitario de Basurto & University of the Basque Country UPV/EHU, Bilbao, Spain

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Ignacio Ruz-Caracuel Department of Pathology, Hospital Universitario Ramón y Cajal, IRYCIS & CIBER Cáncer (CIBERONC), Madrid, Spain

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Carmen Fajardo Department of Endocrinology and Nutrition, Hospital Universitario La Ribera, Valencia, Spain

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Mónica Marazuela Department of Endocrinology and Nutrition, Hospital Universitario La Princesa Madrid, Spain

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Manel Puig-Domingo Department of Endocrinology and Nutrition, Hospital Universitario Germans Trias i Pujol, Cataluña, Spain

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The objective of the study was to evaluate the efficacy of second-line therapies in patients with acromegaly caused by a growth hormone (GH) and prolactin (PRL) co-secreting pituitary neuroendocrine tumor (GH&PRL-Pit-NET) compared to their efficacy in patients with acromegaly caused by a GH-secreting pituitary neuroendocrine tumor (GH-Pit-NET). This is a multicenter retrospective study of patients with acromegaly on treatment with pasireotide and/or pegvisomant. Patients were classified in two groups: GH&PRL-Pit-NETs when evidence of hyperprolactinemia and immunohistochemistry (IHC) for GH and PRL was positive or if PRL were >200 ng/dL regardless of the PRL-IHC and GH-Pit-NETs when the previously mentioned criteria were not met. A total of 28 cases with GH&PRL-Pit-NETs and 122 with GH-Pit-NETs met the inclusion criteria. GH&PRL-Pit-NETs presented at a younger age, caused hypopituitarism, and were invasive more frequently than GH-Pit-NETs. There were 124 patients treated with pegvisomant and 49 with pasireotide at any time. The efficacy of pegvisomant for IGF-1 normalization was of 81.5% and of pasireotide of 71.4%. No differences in IGF-1 control with pasireotide and with pegvisomant were observed between GH&PRL-Pit-NETs and GH-Pit-NETs. All GH&PRL-Pit-NET cases treated with pasireotide (n = 6) and 82.6% (n = 19/23) of the cases treated with pegvisomant normalized PRL levels. No differences in the rate of IGF-1 control between pegvisomant and pasireotide were detected in patients with GH&PRL-Pit-NETs (84.9% vs 66.7%, P = 0.178). We conclude that despite the more aggressive behavior of GH&PRL-Pit-NETs than GH-Pit-NETs, no differences in the rate of IGF-1 control with pegvisomant and pasireotide were observed between both groups, and both drugs have shown to be effective treatments to control IGF-1 and PRL hypersecretion in these tumors.

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