Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Abstract

Context: Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) geneare responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadicpituitary neuroendocrine tumors (PitNETs).Objective: To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patientswith clinically presenting patients and to compare the clinical characteristics of AIPmut andAIPneg PitNET patients.Design: 12-year prospective, observational study.Participants & Setting: We studied probands and family members of FIPA kindreds and sporadicpatients with disease onset =18 years or macroadenomas with onset =30 years (n = 1477). Thiswas a collaborative study conducted at referral centers for pituitary diseases.Interventions & Outcome: AIP testing and clinical screening for pituitary disease. Comparison ofcharacteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients(n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310).Results: Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellarextension or cavernous sinus invasion and required fewer treatments with fewer operationsand no radiotherapy compared with clinically presenting cases; there were fewer cases withactive disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases,AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy,suprasellar extension, and more patients required multimodal therapy, including radiotherapy.AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions: Prospectively diagnosed AIPmut patients show better outcomes than clinicallypresenting cases, demonstrating the benefits of genetic and clinical screening. AIP-relatedpituitary disease has a wide spectrum ranging from aggressively growing lesions to stable orindolent disease course.