The clinical and therapeutic profiles of prolactinomas associated with germline pathogenic variants in the aryl hydrocarbon receptor interacting protein (AIP) gene

Frontiers in Endocrinology

Endocrinology

Marie-Lise Jaffrain-Rea¹  Thomas Cuny²  Thierry Brue³  Laurent Vroonen⁴  Patrick Pétrossians⁴  Adrian F. Daly⁴  Albert Beckers⁴  Muriel Cogne⁵  Amandine Ferriere⁶  Atanaska Elenkova⁷  Luciana Naves⁸  Pablo Beckers⁹  Auli Karhu^1,10  Severine Camby^1,11  Anne Barlier^1,12  Pauline Romanet^1,12 

[1] Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy;Department of Neuroendocrinology, Neuromed IRCCS, Pozzilli, Italy;Department of Endocrinology, Aix Marseille University, Assistance publique Hôpitaux de Marseille (APHM), INSERM, Marseille Medical Genetics (MMG), Hopital La Conception, Institut MarMaRa, Marseille, France;Department of Endocrinology, Aix Marseille University, Assistance publique Hôpitaux de Marseille (APHM), INSERM, Marseille Medical Genetics (MMG), Hopital La Conception, Institut MarMaRa, Marseille, France;Laboratory of Molecular Biology, Aix Marseille University, Assistance publique Hôpitaux de Marseille (APHM), INSERM, Marseille Medical Genetics (MMG), Hospital La Conception, Institut MarMaRa, Marseille, France;Department of Endocrinology, Centre Hospitalier Universitaire de Liège, University of Liège, Liège, Belgium;Department of Endocrinology, Diabetes and Nutrition, Centre Hospitalo-Universitaire de la Réunion, Saint-Pierre, France;Department of Endocrinology, Hopital Haut-Leveque, Centre Hospitalier Universitaire (CHU) de Bordeaux, Pessac, France;Department of Endocrinology, Medical University of Sofia, Sofia, Bulgaria;Department of Endocrinology, University of Brasilia, Brasilia, Brazil;Department of Human Genetics, Centre Hospitalier Universitaire de Liège, University of Liège, Liège, Belgium;Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland;Applied Tumor Genomics Research Program, Research Programs Unit, University of Helsinki, Helsinki, Finland;Department of Otorhinolaryngology, Centre Hospitalier Universitaire de Liège, University of Liège, Liège, Belgium;Laboratory of Molecular Biology, Aix Marseille University, Assistance publique Hôpitaux de Marseille (APHM), INSERM, Marseille Medical Genetics (MMG), Hospital La Conception, Institut MarMaRa, Marseille, France;

关键词: prolactinoma;    genetic;    resistance;    dopamine agonist;    cabergoline;    AIP;    MEN1;   

DOI  :  10.3389/fendo.2023.1242588

 received in 2023-06-19, accepted in 2023-07-17,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionProlactinomas are the most frequent type of pituitary adenoma encountered in clinical practice. Dopamine agonists (DA) like cabergoline typically provide sign/ symptom control, normalize prolactin levels and decrease tumor size in most patients. DA-resistant prolactinomas are infrequent and can occur in association with some genetic causes like MEN1 and pathogenic germline variants in the AIP gene (AIPvar).MethodsWe compared the clinical, radiological, and therapeutic characteristics of AIPvar-related prolactinomas (n=13) with unselected hospital-treated prolactinomas (“unselected”, n=41) and genetically-negative, DA-resistant prolactinomas (DA-resistant, n=39).ResultsAIPvar-related prolactinomas occurred at a significantly younger age than the unselected or DA-resistant prolactinomas (p<0.01). Males were more common in the AIPvar (75.0%) and DA- resistant (49.7%) versus unselected prolactinomas (9.8%; p<0.001). AIPvar prolactinomas exhibited significantly more frequent invasion than the other groups (p<0.001) and exhibited a trend to larger tumor diameter. The DA-resistant group had significantly higher prolactin levels at diagnosis than the AIPvar group (p<0.001). Maximum DA doses were significantly higher in the AIPvar and DA-resistant groups versus unselected. DA-induced macroadenoma shrinkage (>50%) occurred in 58.3% in the AIPvar group versus 4.2% in the DA-resistant group (p<0.01). Surgery was more frequent in the AIPvar and DA- resistant groups (43.8% and 61.5%, respectively) versus unselected (19.5%: p<0.01). Radiotherapy was used only in AIPvar (18.8%) and DA-resistant (25.6%) groups.DiscussionAIPvar confer an aggressive phenotype in prolactinomas, with invasive tumors occurring at a younger age. These characteristics can help differentiate rare AIPvar related prolactinomas from DA-resistant, genetically-negative tumors.

【 授权许可】

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Copyright © 2023 Vroonen, Beckers, Camby, Cuny, Beckers, Jaffrain-Rea, Cogne, Naves, Ferriere, Romanet, Elenkova, Karhu, Brue, Barlier, Pétrossians and Daly