Fernando Guerrero-Pérez1, Carmen Fajardo2, Elena Torres Vela3, Olga Giménez-Palop4, Arturo Lisbona Gil5, Tomas Martín6, Natividad González7, Juan José Díez8, Pedro Iglesias9, Mercedes Robledo10, Carles Villabona11. 1. Department of Endocrinology, Hospital Universitari de Bellvitge, Carrer de la Feixa Llarga, s/n, 08907, L'Hospitalet de Llobregat, Barcelona, Spain. Electronic address: fguerrerop@bellvitgehospital.cat. 2. Department of Endocrinology, Hospital Universitario de la Ribera, Ctra. Corbera, km 1, 46600 Alcira, Valencia, Spain. Electronic address: cfajardo@hospital-ribera.com. 3. Department of Endocrinology, Hospital Universitario San Cecilio, Av. del Conocimiento, s/n, 18016 Granada, Spain. 4. Department of Endocrinology, Hospital Universitari Parc Taulí, Parc Taulí, 1, 08208 Sabadell, Barcelona, Spain. Electronic address: ogimenez@tauli.cat. 5. Department of Endocrinology, Hospital Universitario Central de la Defensa, Glorieta Ejército, 1, 28047 Madrid, Spain. Electronic address: arlisbo@centromedicomapfre.com. 6. Department of Endocrinology, Hospital Universitario Virgen Macarena, Calle Dr. Fedriani, 3, 41009 Sevilla, Spain. Electronic address: tmartin@cica.es. 7. Department of Endocrinology, Hospital Universitario Virgen Macarena, Calle Dr. Fedriani, 3, 41009 Sevilla, Spain. 8. Department of Endocrinology, Hospital Universitario Ramón y Cajal, Ctra. Colmenar Viejo, km. 9, 100, 28034 Madrid, Spain. Electronic address: juanjose.diez@salud.madrid.org. 9. Department of Endocrinology, Hospital Universitario Ramón y Cajal, Ctra. Colmenar Viejo, km. 9, 100, 28034 Madrid, Spain. 10. Spanish National Cancer Research Centre (CNIO) & Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Calle de Melchor Fernández Almagro, 3, 28029 Madrid, Spain. Electronic address: mrobledo@cnio.es. 11. Department of Endocrinology, Hospital Universitari de Bellvitge, Carrer de la Feixa Llarga, s/n, 08907, L'Hospitalet de Llobregat, Barcelona, Spain. Electronic address: cvillabona@bellvitgehospital.cat.
Abstract
BACKGROUND: Pituitary adenomas (PA) associated with pheochromocytomas/paragangliomas (Pheo/PGL), also known as "the three P association" or "3PAs" could be the results of coincidence, but new evidence supports a common pathogenic mechanism in some patients. Our aim is to report the clinical data, surgical outcome, genetic findings of a large case series and review the current knowledge on this topic. METHODS AND RESULTS: In a retrospective multicentre study, we compiled 10 patients with PAs (6 new unreported cases). Six patients were female with mean age of 51.6 ± 18.0 years. PA were: 6 acromegaly, 3 prolactinoma and 1 non-functioning PA (NFPA). Among the Pheo/PGL, 7 patients had a single tumour (4 Pheo and 3 PGL) and 3 patients had multiple or bilateral disease (2 PGL and 1 Pheo). Patients with GH-secreting PA and NFPA underwent surgery, while patients with prolactinoma received medical treatment (one patient required surgery). Unilateral adrenalectomy was carried out in all single Pheo and a bilateral procedure was performed in the patient with bilateral tumour. A single tumour was resected in two patients with multiple PGL. We found 3 germline pathogenic mutations: 2 in SDHB (c.166-170delCCTCA and a gross deletion involving exon 1) and 1 SDHD (p.P81L exon 3). Two variants of uncertain significance: 1 in MEN1 (c.1618C > T; p.Pro540Ser) and 1 in RET (c.2556C > G, p.Ile852Met), and finally a RETM918T somatic mutation in a Pheo tissue. CONCLUSION: We actively suggest considering the possibility of hereditary disease in all cases with 3PA and performing a complete genetic study.
BACKGROUND:Pituitary adenomas (PA) associated with pheochromocytomas/paragangliomas (Pheo/PGL), also known as "the three P association" or "3PAs" could be the results of coincidence, but new evidence supports a common pathogenic mechanism in some patients. Our aim is to report the clinical data, surgical outcome, genetic findings of a large case series and review the current knowledge on this topic. METHODS AND RESULTS: In a retrospective multicentre study, we compiled 10 patients with PAs (6 new unreported cases). Six patients were female with mean age of 51.6 ± 18.0 years. PA were: 6 acromegaly, 3 prolactinoma and 1 non-functioning PA (NFPA). Among the Pheo/PGL, 7 patients had a single tumour (4 Pheo and 3 PGL) and 3 patients had multiple or bilateral disease (2 PGL and 1 Pheo). Patients with GH-secreting PA and NFPA underwent surgery, while patients with prolactinoma received medical treatment (one patient required surgery). Unilateral adrenalectomy was carried out in all single Pheo and a bilateral procedure was performed in the patient with bilateral tumour. A single tumour was resected in two patients with multiple PGL. We found 3 germline pathogenic mutations: 2 in SDHB (c.166-170delCCTCA and a gross deletion involving exon 1) and 1 SDHD (p.P81L exon 3). Two variants of uncertain significance: 1 in MEN1 (c.1618C > T; p.Pro540Ser) and 1 in RET (c.2556C > G, p.Ile852Met), and finally a RETM918T somatic mutation in a Pheo tissue. CONCLUSION: We actively suggest considering the possibility of hereditary disease in all cases with 3PA and performing a complete genetic study.
Authors: Aisha A Tepede; James Welch; Maya Lee; Adel Mandl; Sunita K Agarwal; Naris Nilubol; Dhaval Patel; Craig Cochran; William F Simonds; Lee S Weinstein; Abhishek Jha; Corina Millo; Karel Pacak; Jenny E Blau Journal: Endocrinol Diabetes Metab Case Rep Date: 2020-03-03
Authors: Paul Benjamin Loughrey; Federico Roncaroli; Estelle Healy; Philip Weir; Madhu Basetti; Ruth T Casey; Steven J Hunter; Márta Korbonits Journal: Endocr Relat Cancer Date: 2022-09-02 Impact factor: 5.900