Significant Benefits of <i>AIP</i> Testing and Clinical Screening in Familial Isolated and Young-onset Pituitary Tumors
Pedro Marques, Francisca Caimari, Laura C. Hernández‐Ramírez, David Collier, Donato Iacovazzo, Amy Ronaldson, Kesson Magid, Chung Thong Lim, Karen Stals, Sian Ellard, Ashley Grossman, Márta Korbonits, Prakash Abraham, Elena Daniela Aflorei, Amar Agha, James Ahlquist, Scott Akker, Krystallenia Alexandraki, Sándor Alföldi, João Anselmo, Wiebke Arlt, Brew Atkinson, Anna Aulinas-Masó, Simon Aylwin, Atik Baborie, Philippe Backeljauw, Corin Badiu, Stephanie E Baldeweg, Steve Ball, Gul Bano, Ariel Barkan, John Barton, Julian Barwell, P. C. Bates, Carmen Bernal-González, Michael Besser, John S. Bevan, Alex Bickerton, Joanne Blair, Marek Bolanowski, Pierre Bouloux, Lisa Bradley, Karin Bradley, Caroline Brain, Antonia Brooke, Roger Brown, Michael Buchfelder, Christine Burren, Mehtap Çakır, Natalie Canham, Joël Capraro, Paul Carroll, Philippa Carter, David Carty, Dominic Cavlan, Harvinder Chahal, Tim Cheetham, F. Chentli, Catherine S. Choong, Mirjam Christ‐Crain, Teng‐Teng Chung, Peter Clayton, Richard N. Clayton, Mark L. Cohen, Hamish Courtney, David J. Cove, Elizabeth Crowne, Daniel J. Cuthbertson, Jacob Dal, Nadezhda Dalantaeva, Svetozar Damjanović, Christina Daousi, Ken Darzy, Mehul Dattani, Michaela Davies, Justin Davies, J.R. Davis, Margaret de Castro, Laura De Marinis, Cheri Deal, Judit Dénes, Paul Dimitri, Neil Dorward, Graham Dow, William Drake, Maralyn Druce, Juliana Drummond, Pinaki Dutta, Larisa Dzeranova, Britt Edén Engström, Rosalind A. Eeles, Maria Elfving, Kate Ellis, Marianne S. Elston, Louise Emmerson, Shereen Ezzat, Naomi Fersht, Simona Fica, Stefan Fischli, Maria Fleseriu
Abstract
CONTEXT: Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). OBJECTIVE: To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. DESIGN: 12-year prospective, observational study. PARTICIPANTS & SETTING: We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. INTERVENTIONS & OUTCOME: AIP testing and clinical screening for pituitary disease. Comparison of characteristics 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 suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active 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 clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course.