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  • Author: Cristina Alvarez-Escola x
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Nicté Figueroa-Vega Service of Endocrinology, Department of Immunology, Department of Medical Sciences, Service of Endocrinology and Nutrition, Service of Pathology, Service of Endocrinology, Service of Immunology, Service of Digestive Surgery, Service of Digestive Diseases and CIBEREHD, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria Princesa, C/Diego de León 62, Madrid 28006, Spain
Service of Endocrinology, Department of Immunology, Department of Medical Sciences, Service of Endocrinology and Nutrition, Service of Pathology, Service of Endocrinology, Service of Immunology, Service of Digestive Surgery, Service of Digestive Diseases and CIBEREHD, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria Princesa, C/Diego de León 62, Madrid 28006, Spain
Service of Endocrinology, Department of Immunology, Department of Medical Sciences, Service of Endocrinology and Nutrition, Service of Pathology, Service of Endocrinology, Service of Immunology, Service of Digestive Surgery, Service of Digestive Diseases and CIBEREHD, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria Princesa, C/Diego de León 62, Madrid 28006, Spain

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Ángel Díaz Service of Endocrinology, Department of Immunology, Department of Medical Sciences, Service of Endocrinology and Nutrition, Service of Pathology, Service of Endocrinology, Service of Immunology, Service of Digestive Surgery, Service of Digestive Diseases and CIBEREHD, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria Princesa, C/Diego de León 62, Madrid 28006, Spain

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Magdalena Adrados Service of Endocrinology, Department of Immunology, Department of Medical Sciences, Service of Endocrinology and Nutrition, Service of Pathology, Service of Endocrinology, Service of Immunology, Service of Digestive Surgery, Service of Digestive Diseases and CIBEREHD, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria Princesa, C/Diego de León 62, Madrid 28006, Spain

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Cristina Álvarez-Escolá Service of Endocrinology, Department of Immunology, Department of Medical Sciences, Service of Endocrinology and Nutrition, Service of Pathology, Service of Endocrinology, Service of Immunology, Service of Digestive Surgery, Service of Digestive Diseases and CIBEREHD, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria Princesa, C/Diego de León 62, Madrid 28006, Spain

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Amalia Paniagua Service of Endocrinology, Department of Immunology, Department of Medical Sciences, Service of Endocrinology and Nutrition, Service of Pathology, Service of Endocrinology, Service of Immunology, Service of Digestive Surgery, Service of Digestive Diseases and CIBEREHD, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria Princesa, C/Diego de León 62, Madrid 28006, Spain

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Julián Aragonés Service of Endocrinology, Department of Immunology, Department of Medical Sciences, Service of Endocrinology and Nutrition, Service of Pathology, Service of Endocrinology, Service of Immunology, Service of Digestive Surgery, Service of Digestive Diseases and CIBEREHD, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria Princesa, C/Diego de León 62, Madrid 28006, Spain

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Elena Martín-Pérez Service of Endocrinology, Department of Immunology, Department of Medical Sciences, Service of Endocrinology and Nutrition, Service of Pathology, Service of Endocrinology, Service of Immunology, Service of Digestive Surgery, Service of Digestive Diseases and CIBEREHD, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria Princesa, C/Diego de León 62, Madrid 28006, Spain

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Susanna Leskela Service of Endocrinology, Department of Immunology, Department of Medical Sciences, Service of Endocrinology and Nutrition, Service of Pathology, Service of Endocrinology, Service of Immunology, Service of Digestive Surgery, Service of Digestive Diseases and CIBEREHD, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria Princesa, C/Diego de León 62, Madrid 28006, Spain

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Ricardo Moreno-Otero Service of Endocrinology, Department of Immunology, Department of Medical Sciences, Service of Endocrinology and Nutrition, Service of Pathology, Service of Endocrinology, Service of Immunology, Service of Digestive Surgery, Service of Digestive Diseases and CIBEREHD, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria Princesa, C/Diego de León 62, Madrid 28006, Spain

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Roberto González-Amaro Service of Endocrinology, Department of Immunology, Department of Medical Sciences, Service of Endocrinology and Nutrition, Service of Pathology, Service of Endocrinology, Service of Immunology, Service of Digestive Surgery, Service of Digestive Diseases and CIBEREHD, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria Princesa, C/Diego de León 62, Madrid 28006, Spain

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Mónica Marazuela Service of Endocrinology, Department of Immunology, Department of Medical Sciences, Service of Endocrinology and Nutrition, Service of Pathology, Service of Endocrinology, Service of Immunology, Service of Digestive Surgery, Service of Digestive Diseases and CIBEREHD, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria Princesa, C/Diego de León 62, Madrid 28006, Spain

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The aim of this study was to explore the possible involvement of the angiopoietin (Ang)-1, -2/Tie-2 system in the development, growth, and metastases evolution of gastroenteropancreatic-neuroendocrine tumors (GEP-NETs). We prospectively examined the serum levels of Tie-2, Ang-1, and Ang-2 by ELISA in 42 patients with proven GEP-NETs and 27 controls. We also determined the expression of the Ang/Tie-2 system in freshly isolated peripheral blood monocytes and in tumor cells from malignant primary tumors and/or liver metastases samples from GEP-NET patients by flow cytometry and/or RT-PCR. Furthermore, the function of the Ang/Tie-2 system in monocytes from controls and patients was assessed by a chemotaxis assay. GEP-NET patients showed enhanced serum levels of soluble form of Tie-2 (sTie-2), Ang-1, and Ang-2 (P<0.05 in all cases), compared to controls. sTie-2 and Ang-2 levels were significantly higher in GEP-NETs with metastases compared to those with no metastases. In addition, a significant correlation was detected between Ang-2 levels and chromogranin A or sTie-2 concentrations or 5-hydroxy-indole acetic acid excretion (r=0.71, r=0.60, and r=0.81 respectively, P<0.01 in all cases). Furthermore, we observed an enhanced expression of Ang-1, Ang-2, and Tie-2 in freshly isolated tumor cells from GEP-NET both by immunohistochemistry and by RT-PCR. Interestingly, an enhanced expression and function of Tie-2 was detected in monocytes from GEP-NET patients. Our data suggest that the Ang/Tie-2 system is involved in the growth and development of metastases of GEP-NETs, and that favors the recruitment of Tie-2+ monocytes to the tumor site, where they can promote inflammation and angiogenesis.

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Cristina Rodríguez-Antona Hereditary Endocrine Cancer Group, ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Pathology Department, Histopathology Core Unit, Endocrinology Division, Endocrinology Service, Human Cancer Genetics Programme, Spanish National Cancer Center (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain
Hereditary Endocrine Cancer Group, ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Pathology Department, Histopathology Core Unit, Endocrinology Division, Endocrinology Service, Human Cancer Genetics Programme, Spanish National Cancer Center (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Iván Muñoz-Repeto Hereditary Endocrine Cancer Group, ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Pathology Department, Histopathology Core Unit, Endocrinology Division, Endocrinology Service, Human Cancer Genetics Programme, Spanish National Cancer Center (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Lucia Inglada-Pérez Hereditary Endocrine Cancer Group, ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Pathology Department, Histopathology Core Unit, Endocrinology Division, Endocrinology Service, Human Cancer Genetics Programme, Spanish National Cancer Center (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain
Hereditary Endocrine Cancer Group, ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Pathology Department, Histopathology Core Unit, Endocrinology Division, Endocrinology Service, Human Cancer Genetics Programme, Spanish National Cancer Center (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Aguirre A de Cubas Hereditary Endocrine Cancer Group, ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Pathology Department, Histopathology Core Unit, Endocrinology Division, Endocrinology Service, Human Cancer Genetics Programme, Spanish National Cancer Center (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Veronika Mancikova Hereditary Endocrine Cancer Group, ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Pathology Department, Histopathology Core Unit, Endocrinology Division, Endocrinology Service, Human Cancer Genetics Programme, Spanish National Cancer Center (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Marta Cañamero Hereditary Endocrine Cancer Group, ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Pathology Department, Histopathology Core Unit, Endocrinology Division, Endocrinology Service, Human Cancer Genetics Programme, Spanish National Cancer Center (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Agnieszka Maliszewska Hereditary Endocrine Cancer Group, ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Pathology Department, Histopathology Core Unit, Endocrinology Division, Endocrinology Service, Human Cancer Genetics Programme, Spanish National Cancer Center (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Álvaro Gómez Hereditary Endocrine Cancer Group, ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Pathology Department, Histopathology Core Unit, Endocrinology Division, Endocrinology Service, Human Cancer Genetics Programme, Spanish National Cancer Center (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Rocío Letón Hereditary Endocrine Cancer Group, ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Pathology Department, Histopathology Core Unit, Endocrinology Division, Endocrinology Service, Human Cancer Genetics Programme, Spanish National Cancer Center (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Luis J Leandro-García Hereditary Endocrine Cancer Group, ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Pathology Department, Histopathology Core Unit, Endocrinology Division, Endocrinology Service, Human Cancer Genetics Programme, Spanish National Cancer Center (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Iñaki Comino-Méndez Hereditary Endocrine Cancer Group, ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Pathology Department, Histopathology Core Unit, Endocrinology Division, Endocrinology Service, Human Cancer Genetics Programme, Spanish National Cancer Center (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Lara Sanchez Hereditary Endocrine Cancer Group, ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Pathology Department, Histopathology Core Unit, Endocrinology Division, Endocrinology Service, Human Cancer Genetics Programme, Spanish National Cancer Center (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Cristina Álvarez-Escolá Hereditary Endocrine Cancer Group, ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Pathology Department, Histopathology Core Unit, Endocrinology Division, Endocrinology Service, Human Cancer Genetics Programme, Spanish National Cancer Center (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Javier Aller Hereditary Endocrine Cancer Group, ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Pathology Department, Histopathology Core Unit, Endocrinology Division, Endocrinology Service, Human Cancer Genetics Programme, Spanish National Cancer Center (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Alberto Cascón Hereditary Endocrine Cancer Group, ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Pathology Department, Histopathology Core Unit, Endocrinology Division, Endocrinology Service, Human Cancer Genetics Programme, Spanish National Cancer Center (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain
Hereditary Endocrine Cancer Group, ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Pathology Department, Histopathology Core Unit, Endocrinology Division, Endocrinology Service, Human Cancer Genetics Programme, Spanish National Cancer Center (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Mercedes Robledo Hereditary Endocrine Cancer Group, ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Pathology Department, Histopathology Core Unit, Endocrinology Division, Endocrinology Service, Human Cancer Genetics Programme, Spanish National Cancer Center (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain
Hereditary Endocrine Cancer Group, ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Pathology Department, Histopathology Core Unit, Endocrinology Division, Endocrinology Service, Human Cancer Genetics Programme, Spanish National Cancer Center (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain

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The therapeutic options for patients with metastatic medullary thyroid carcinoma (MTC) have recently increased due to the development of tyrosine kinase inhibitors (TKIs), some of which have achieved remarkable clinical responses in MTC patients. However, the molecular basis for the large variability in TKI responses is unknown. In this exploratory study, we investigated the expression of eight key TKI target proteins (EGFR, KIT, MET, PDGFRB, VEGF (VEGFA), VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4)) by immunohistochemistry in 103 molecularly characterized MTC samples and identified the associated clinical and molecular features. A number of MTC samples exhibited a high expression of VEGFR2 and VEGFR3, which were overexpressed in 57 and 43% of the MTC samples respectively. VEGFR1, PDGFRB, VEGF, KIT, and MET were present in 34–20% of the cases, while EGFR was highly expressed in only 10% of the MTC samples. Some proteins exhibited large differences in expression between sporadic and familial cases, suggesting that different RET mutations may be associated with the immunohistochemical profiles. MTC samples with the C634 RET mutation exhibited a higher expression of VEGFR3 and KIT than the M918T RET-mutated and non-mutated RET tumor samples (P=0.005 and P=0.007 respectively) and a lower expression of VEGFR1 (P=0.04). Non-mutated RET MTC cases exhibited a lower expression of PDGFRB (P=0.04). Overall, this is the first study, to our knowledge, to show that multiple TKI targets are highly expressed in a subset of MTCs, suggesting that molecular stratification of patients may have the potential to improve TKI therapies for MTC.

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Aguirre A de Cubas Hereditary Endocrine Cancer Group, Familial Cancer Clinic, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Confocal Microscopy Unit, Proteomics Unit, Endocrinology and Nutrition Service, Endocrinology and Nutrition Service, Department of Medical and Surgical Sciences, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029 Madrid, Spain

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L Javier Leandro-García Hereditary Endocrine Cancer Group, Familial Cancer Clinic, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Confocal Microscopy Unit, Proteomics Unit, Endocrinology and Nutrition Service, Endocrinology and Nutrition Service, Department of Medical and Surgical Sciences, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Francesca Schiavi Hereditary Endocrine Cancer Group, Familial Cancer Clinic, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Confocal Microscopy Unit, Proteomics Unit, Endocrinology and Nutrition Service, Endocrinology and Nutrition Service, Department of Medical and Surgical Sciences, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Veronika Mancikova Hereditary Endocrine Cancer Group, Familial Cancer Clinic, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Confocal Microscopy Unit, Proteomics Unit, Endocrinology and Nutrition Service, Endocrinology and Nutrition Service, Department of Medical and Surgical Sciences, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Iñaki Comino-Méndez Hereditary Endocrine Cancer Group, Familial Cancer Clinic, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Confocal Microscopy Unit, Proteomics Unit, Endocrinology and Nutrition Service, Endocrinology and Nutrition Service, Department of Medical and Surgical Sciences, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029 Madrid, Spain
Hereditary Endocrine Cancer Group, Familial Cancer Clinic, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Confocal Microscopy Unit, Proteomics Unit, Endocrinology and Nutrition Service, Endocrinology and Nutrition Service, Department of Medical and Surgical Sciences, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Lucía Inglada-Pérez Hereditary Endocrine Cancer Group, Familial Cancer Clinic, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Confocal Microscopy Unit, Proteomics Unit, Endocrinology and Nutrition Service, Endocrinology and Nutrition Service, Department of Medical and Surgical Sciences, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029 Madrid, Spain
Hereditary Endocrine Cancer Group, Familial Cancer Clinic, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Confocal Microscopy Unit, Proteomics Unit, Endocrinology and Nutrition Service, Endocrinology and Nutrition Service, Department of Medical and Surgical Sciences, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Manuel Perez-Martinez Hereditary Endocrine Cancer Group, Familial Cancer Clinic, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Confocal Microscopy Unit, Proteomics Unit, Endocrinology and Nutrition Service, Endocrinology and Nutrition Service, Department of Medical and Surgical Sciences, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Nuria Ibarz Hereditary Endocrine Cancer Group, Familial Cancer Clinic, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Confocal Microscopy Unit, Proteomics Unit, Endocrinology and Nutrition Service, Endocrinology and Nutrition Service, Department of Medical and Surgical Sciences, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Pilar Ximénez-Embún Hereditary Endocrine Cancer Group, Familial Cancer Clinic, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Confocal Microscopy Unit, Proteomics Unit, Endocrinology and Nutrition Service, Endocrinology and Nutrition Service, Department of Medical and Surgical Sciences, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Elena López-Jiménez Hereditary Endocrine Cancer Group, Familial Cancer Clinic, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Confocal Microscopy Unit, Proteomics Unit, Endocrinology and Nutrition Service, Endocrinology and Nutrition Service, Department of Medical and Surgical Sciences, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Agnieszka Maliszewska Hereditary Endocrine Cancer Group, Familial Cancer Clinic, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Confocal Microscopy Unit, Proteomics Unit, Endocrinology and Nutrition Service, Endocrinology and Nutrition Service, Department of Medical and Surgical Sciences, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Rocío Letón Hereditary Endocrine Cancer Group, Familial Cancer Clinic, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Confocal Microscopy Unit, Proteomics Unit, Endocrinology and Nutrition Service, Endocrinology and Nutrition Service, Department of Medical and Surgical Sciences, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Álvaro Gómez Graña Hereditary Endocrine Cancer Group, Familial Cancer Clinic, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Confocal Microscopy Unit, Proteomics Unit, Endocrinology and Nutrition Service, Endocrinology and Nutrition Service, Department of Medical and Surgical Sciences, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Carmen Bernal Hereditary Endocrine Cancer Group, Familial Cancer Clinic, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Confocal Microscopy Unit, Proteomics Unit, Endocrinology and Nutrition Service, Endocrinology and Nutrition Service, Department of Medical and Surgical Sciences, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Cristina Álvarez-Escolá Hereditary Endocrine Cancer Group, Familial Cancer Clinic, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Confocal Microscopy Unit, Proteomics Unit, Endocrinology and Nutrition Service, Endocrinology and Nutrition Service, Department of Medical and Surgical Sciences, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Cristina Rodríguez-Antona Hereditary Endocrine Cancer Group, Familial Cancer Clinic, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Confocal Microscopy Unit, Proteomics Unit, Endocrinology and Nutrition Service, Endocrinology and Nutrition Service, Department of Medical and Surgical Sciences, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029 Madrid, Spain
Hereditary Endocrine Cancer Group, Familial Cancer Clinic, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Confocal Microscopy Unit, Proteomics Unit, Endocrinology and Nutrition Service, Endocrinology and Nutrition Service, Department of Medical and Surgical Sciences, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Giuseppe Opocher Hereditary Endocrine Cancer Group, Familial Cancer Clinic, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Confocal Microscopy Unit, Proteomics Unit, Endocrinology and Nutrition Service, Endocrinology and Nutrition Service, Department of Medical and Surgical Sciences, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029 Madrid, Spain
Hereditary Endocrine Cancer Group, Familial Cancer Clinic, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Confocal Microscopy Unit, Proteomics Unit, Endocrinology and Nutrition Service, Endocrinology and Nutrition Service, Department of Medical and Surgical Sciences, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Javier Muñoz Hereditary Endocrine Cancer Group, Familial Cancer Clinic, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Confocal Microscopy Unit, Proteomics Unit, Endocrinology and Nutrition Service, Endocrinology and Nutrition Service, Department of Medical and Surgical Sciences, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Diego Megias Hereditary Endocrine Cancer Group, Familial Cancer Clinic, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Confocal Microscopy Unit, Proteomics Unit, Endocrinology and Nutrition Service, Endocrinology and Nutrition Service, Department of Medical and Surgical Sciences, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Alberto Cascón Hereditary Endocrine Cancer Group, Familial Cancer Clinic, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Confocal Microscopy Unit, Proteomics Unit, Endocrinology and Nutrition Service, Endocrinology and Nutrition Service, Department of Medical and Surgical Sciences, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029 Madrid, Spain
Hereditary Endocrine Cancer Group, Familial Cancer Clinic, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Confocal Microscopy Unit, Proteomics Unit, Endocrinology and Nutrition Service, Endocrinology and Nutrition Service, Department of Medical and Surgical Sciences, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Mercedes Robledo Hereditary Endocrine Cancer Group, Familial Cancer Clinic, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Confocal Microscopy Unit, Proteomics Unit, Endocrinology and Nutrition Service, Endocrinology and Nutrition Service, Department of Medical and Surgical Sciences, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029 Madrid, Spain
Hereditary Endocrine Cancer Group, Familial Cancer Clinic, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Confocal Microscopy Unit, Proteomics Unit, Endocrinology and Nutrition Service, Endocrinology and Nutrition Service, Department of Medical and Surgical Sciences, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029 Madrid, Spain

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Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine neoplasias of neural crest origin that can be part of several inherited syndromes. Although their mRNA profiles are known to depend on genetic background, a number of questions related to tumor biology and clinical behavior remain unanswered. As microRNAs (miRNAs) are key players in the modulation of gene expression, their comprehensive analysis could resolve some of these issues. Through characterization of miRNA profiles in 69 frozen tumors with germline mutations in the genes SDHD, SDHB, VHL, RET, NF1, TMEM127, and MAX, we identified miRNA signatures specific to, as well as common among, the genetic groups of PCCs/PGLs. miRNA expression profiles were validated in an independent series of 30 composed of VHL-, SDHB-, SDHD-, and RET-related formalin-fixed paraffin-embedded PCC/PGL samples using quantitative real-time PCR. Upregulation of miR-210 in VHL- and SDHB-related PCCs/PGLs was verified, while miR-137 and miR-382 were confirmed as generally upregulated in PCCs/PGLs (except in MAX-related tumors). Also, we confirmed overexpression of miR-133b as VHL-specific miRNAs, miR-488 and miR-885-5p as RET-specific miRNAs, and miR-183 and miR-96 as SDHB-specific miRNAs. To determine the potential roles miRNAs play in PCC/PGL pathogenesis, we performed bioinformatic integration and pathway analysis using matched mRNA profiling data that indicated a common enrichment of pathways associated with neuronal and neuroendocrine-like differentiation. We demonstrated that miR-183 and/or miR-96 impede NGF-induced differentiation in PC12 cells. Finally, global proteomic analysis in SDHB and MAX tumors allowed us to determine that miRNA regulation occurs primarily through mRNA degradation in PCCs/PGLs, which partially confirmed our miRNA–mRNA integration results.

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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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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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