The clinical and therapeutic profiles of prolactinomas associated with germline pathogenic variants in the aryl hydrocarbon receptor interacting protein gene
[en] Introduction: Prolactinomas 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).
Methods: We 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).
Results: AIPvar-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.
Discussion: AIPvar 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.
Vroonen, Laurent ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'endocrinologie clinique
Beckers, Albert ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'endocrinologie clinique
CAMBY, Séverine ; Centre Hospitalier Universitaire de Liège - CHU > > Service de chirurgie plastique et maxillo-faciale
Cuny, Thomas; APHM, Department of Endocrinology, Institut MarMaRa, INSERM, Hospital La Conception, Aix-Marseille Université, France
Beckers, Pablo ; Centre Hospitalier Universitaire de Liège - CHU > > Service de génétique
Jaffrain-Rea, Marie-Lise; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Italy ; Neuromed IRCCS, Pozzilli, Italy
Cogne, Muriel; Department of Endocrinology, Diabetes and Nutrition, GHSR, Centre Hospitalo-Universitaire de la Réunion, Saint-Pierre, La Réunion, France
Naves, Luciana; Department of Endocrinology, University of Brasilia, Brazil
Ferriere, Amandine; Department of Endocrinology, Hopital Haut-Leveque, CHU de Bordeaux, Pessac, France
Romanet, Pauline; Laboratory of Molecular Biology, INSERM, MMG, Hospital La Conception ; Department of Endocrinology, Institut MarMaRa, Marseille, France. 10
Elenkova, Atanaska; Department of Endocrinology, Medical University Sofia, Bulgaria
Karhu, Auli; Research Programs Unit, Department of Medical and Clinical Genetics, Applied Tumor Genomics Research Program, University of Helsinki, Finland
Brue, Thierry; APHM, Department of Endocrinology, Institut MarMaRa, INSERM, Hospital La Conception, Aix-Marseille Université, France
Barlier, Anne; Department of Endocrinology, University Hospital Center Bordeaux, Hopital Haut Leveque, France ; Laboratory of Molecular Biology, Institut MarMaRa, INSERM, Hospital La Conception ; Aix-Marseille Université, France
Pétrossians, Patrick ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'endocrinologie clinique
Daly, Adrian ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'endocrinologie clinique ; Université de Liège - ULiège > Département des sciences cliniques
The clinical and therapeutic profiles of prolactinomas associated with germline pathogenic variants in the aryl hydrocarbon receptor interacting protein gene
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