SAT603 A Heterogeneous Genetic Background Underlies Familial And Young-onset Pituitary Tumors
Authors: Zuarth-Vazquez Julia M , Rebollar-Vega Rosa G , Ramírez-Rentería Claudia , Hernández-Núñez Wellbert E , Torres-Morán Mariana , Franco-Álvarez Alexa L , Eseiza-Acevedo Jocelyn , Aguilar-Soto Mercedes , Cuevas-Ramos Daniel , Sosa-Eroza Ernesto , Mercado Moises , Gamboa-Dominguez Armando , Hernández-Ramírez Laura C 
Published: October 2023

Disclosure: J.M. Zuarth-Vazquez: None. R.G. Rebollar-Vega: None. C. Ramírez-Rentería: None. W.E. Hernández-Núñez: None. M. Torres-Morán: None. A.L. Franco-Álvarez: None. J. Eseiza-Acevedo: None. M. Aguilar-Soto: None. D. Cuevas-Ramos: None. E. Sosa-Eroza: None. M. Mercado: None. A. Gamboa-Dominguez: None. L.C. Hernández-Ramírez: None.

Introduction: Inherited pituitary neuroendocrine tumors (PitNETs) are considered rare and may present either as isolated lesions or in association with other endocrine tumors. Despite significant progress in the understanding of their molecular basis, the precise pathophysiological mechanisms in many patients with familial and sporadic pituitary tumors are unknown. Although the clinical presentation may point towards a specific genetic cause, a combination of careful clinical assessment and state-of-the-art genetic testing is required. Objective: To describe 4 cases of PitNETs with heterogeneous clinical presentations and genetic causes from a cohort of Mexican patients with neuroendocrine tumors. Methodology: Patients were recruited under informed consent from two different reference hospitals in Mexico City. Germline genetic testing was performed using either a custom-made or a commercial next-generation sequencing (NGS) panel. When available, relevant variants were confirmed in tissue samples. Genetic results were correlated with clinical, biochemical, and imaging characteristics. Results: Case 1 is an 18-year-old male with gigantism due to a 3-cm GH/prolactin-secreting PitNET, that was not cured after transsphenoidal surgery (TSS). Genetic testing showed a CDKN1B (NM_004064.5) c.356T&gt;C, p.I119T variant of uncertain significance. No relevant family history was informed. Currently, the patient is treated with monthly octreotide LAR. Case 2 is a patient with young-onset acromegaly (15y) due to a GH-secreting PitNET. She was initially treated with bromocriptine and then underwent TSS without achieving remission. Radiotherapy was therefore indicated, resulting in panhypopituitarism. The likely pathogenic variant of AIP (NM_003977.4) c.872_877del, p.V291_L292del, was identified. Case 3 was diagnosed at the age of 15 with gigantism, treated with TSS and radiotherapy, subsequently demonstrating biochemical cure. Whole-exome sequencing showed the AIP pathogenic variant c.910C.T, p.R304*, indicative of familial isolated pituitary adenoma, confirmed by the history of two paternal first cousins with gigantism. Finally, a 54-year-old man (case 4), with a personal and family history of neurofibromatosis type 1, was incidentally diagnosed with a 16 mm, apparently non-functional PitNET, for which he is awaiting surgery. The pathogenic NF1 (NM_001042492.3) variant c.147C&gt;A, p.Y49* was identified. Conclusions: Our data confirm that inherited PitNETs encompass a variety of clinical phenotypes. Modern NGS-based genetic testing is an effective method for identifying such cases. Precise molecular testing has an impact on the timely diagnosis of these lesions, as well as on their prognosis and the need for genetic counseling.

Presentation: Saturday, June 17, 2023