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Pedro Iglesias Department of Endocrinology, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Madrid, Spain
Instituto de Investigación Sanitaria Puerta de Hierro Segovia de Arana (IDIPHISA), Majadahonda, Madrid, Spain

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Inmaculada Peiró Clinical Nutrition Unit, Catalan Institute of Oncology, L’Hospitalet de Llobregat, Barcelona, Spain
Unit of Nutrition and Cancer-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain

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Betina Biagetti Department of Endocrinology, Universitari Vall d’Hebron, Barcelona, Spain

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Miguel Paja-Fano Department of Endocrinology, Hospital Universitario de Basurto, Bilbao, Spain

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Diana Ariadel Cobo Department of Endocrinology, Complejo Asistencial Universitario de León, León, Spain

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Carlos García Gómez Department of Endocrinology, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Madrid, Spain

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Manuel Mateu-Salat Department of Endocrinology, Hospital Sant Pau, Hospital Sant Pau, Barcelona, Spain
Department of Medicine/Endocrinology, IIB-Sant Pau, Research Center for Pituitary Diseases, Barcelona, Spain

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Idoia Genua Department of Endocrinology, Hospital Sant Pau, Hospital Sant Pau, Barcelona, Spain
Department of Medicine/Endocrinology, IIB-Sant Pau, Research Center for Pituitary Diseases, Barcelona, Spain

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Margarita Majem Department of Oncology, Hospital Sant Pau, Barcelona, Spain

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Mariona Riudavets Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France

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Javier Gavira Department of Oncology, Hospital Sant Pau, Barcelona, Spain

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Cristina Lamas Department of Endocrinology, Hospital General Universitario de Albacete, Albacete, Spain

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Antía Fernández Pombo Department of Endocrinology, Hospital Clínico Universitario de Santiago, Santiago de Compostela, A Coruña, Spain

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Fernando Guerrero-Pérez Department of Endocrinology, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain

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Carles Villabona Department of Endocrinology, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain

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José Manuel Cabezas Agrícola Department of Endocrinology, Hospital Clínico Universitario de Santiago, Santiago de Compostela, A Coruña, Spain

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Susan M Webb Department of Endocrinology, Hospital Sant Pau, Hospital Sant Pau, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, Unidad 747), ISCIII, Universitat Autònoma de Barcelona, Barcelona, Spain

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Juan J Díez Department of Endocrinology, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Madrid, Spain
Instituto de Investigación Sanitaria Puerta de Hierro Segovia de Arana (IDIPHISA), Majadahonda, Madrid, Spain
Department of Medicine, Universidad Autónoma de Madrid, Madrid, Spain

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Central adrenal insufficiency (AI) due to isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) has been recently associated with immune checkpoint inhibitor (ICI) therapy. Our aim was to analyze the prevalence, clinical characteristics, and therapeutic outcomes in cancer patients with IAD induced by ICI therapy. A retrospective and multicenter study was performed. From a total of 4447 cancer patients treated with ICI antibodies, 37 (0.8%) (23 men (62.2%), mean age 64.7 ± 8.3 years (range 46–79 years)) were diagnosed with IAD. The tumor most frequently related to IAD was lung cancer (n = 20, 54.1%), followed by melanoma (n = 8, 21.6%). The most common ICI antibody inhibitors reported were nivolumab (n = 18, 48.6%), pembrolizumab (n = 16, 43.2%), and ipilimumab (n = 8, 21.6%). About half of the patients (n = 19, 51.4%) had other immune-related adverse events, mainly endocrine adverse effects (n = 10, 27.0%). IAD was diagnosed at a median time of 7.0 months (IQR, 5–12) after starting immunotherapy. The main reported symptom at presentation was fatigue (97.3%), followed by anorexia (81.8%) and general malaise (81.1%). Mean follow-up time since IAD diagnosis was 15.2 ± 12.5 months (range 0.3–55 months). At last visit, all patients continued with hormonal deficiency of ACTH. Median overall survival since IAD diagnosis was 6.0 months. In conclusion, IAD is a rare but a well-established complication associated with ICI therapy in cancer patients. It develops around 7 months after starting the treatment, mainly anti-PD1 antibodies. Recovery of the corticotropic axis function should not be expected.

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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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