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) 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.

Metadata

Item Type:	Article
Authors/Creators:	Marques, P Caimari, F Hernández-Ramírez, LC Collier, D Iacovazzo, D Ronaldson, A Magid, K Lim, CT Stals, K Ellard, S Grossman, AB Korbonits, M Abraham, P Aflorei, E Agha, A Ahlquist, J Akker, SA Alexandraki, K Alföldi, S Anselmo, J Arlt, W Atkinson, B Aulinas-Masó, A Aylwin, SJ Baborie, A Backeljauw, PF Badiu, C Baldeweg, S Ball, S Bano, G Barkan, A Barton, J Barwell, J Bates, P Bernal-González, C Besser, M Bevan, JS Bickerton, A Blair, J Bolanowski, M Bouloux, P Bradley, L Bradley, K Brain, C Brooke, A Brown, R Buchfelder, M Burren, C Cakir, M Canham, N Capraro, J Carroll, P Carter, P Carty, D Cavlan, D Chahal, HS Cheetham, T Chentli, F Choong, C Christ-Crain, M Chung, T-T Clayton, P Clayton, RN Cohen, M Courtney, H Cove, D Crowne, E Cuthbertson, D Dal, J Dalantaeva, N Damjanovic, S Daousi, C Darzy, K Dattani, M Davies, M Davies, J Davis, J de Castro, M de Marinis, L Deal, C Dénes, J Dimitri, P https://orcid.org/0000-0001-7625-6713 Dorward, N Dow, G Drake, W Druce, M Drummond, J Dutta, P Dzeranova, L Edén-Engström, B Eeles, R Elfving, M Ellis, K Elston, M Emmerson, L Ezzat, S Fersht, N Fica, S Fischli, S Fleseriu, M Forsythe, E Foulkes, W Freda, P Friedman, T Gadelha, M Gainsborough, M Gallacher, S Gallego, P Gan, H-W Georgescu, C Gevers, E Gilkes, C Glynn, N Goldman, JE Goldstone, AP Góth, M Green, A Greenhalgh, L Grieve, J Griz, L Guitelman, M Gürlek, A Gurnell, M Hamblin, PS Hana, V Harding, P Hay, E Hilton, DA Ho, W Hong, G Horváth, K Howell, S Howlett, TA Höybye, C Hunter, S Idampitiya, C Igaz, P Imran, A Inder, WJ Iwata, T Izatt, L Jagadeesh, S Johnston, C Jose, B Kaltsas, G Kaplan, F Karavitaki, N Kastelan, D Katz, M Kearney, T Kershaw, M Khoo, B Kiraly-Borri, C Knispelis, R Kovács, GL Kumar, A Kumar, AV Kun, IZ Kyriaku, A Lambrescu, I Lampe, AK Laws, ER Lebek-Szatanska, A Lechan, RM Leese, G Levy, A Levy, MJ Lewandowski, K Lin, E Lo, J Lyons, C Maartens, N Maghnie, M Makaya, T Marcus, H Niedziela, M Martin, N Matsuno, A McGowan, B McQuaid, SE Medic-Stojanoska, M Mendoza, N Mercado-Atri, M Mettananda, S Mezősi, E Miljic, D Miller, KK Modenesi, S Molitch, ME Monson, J Morris, DG Morrison, PJ Mosterman, B Munir, A Murray, RD Musat, M Musolino, N Nachtigall, L Nagi, D Nair, R Nelson, R Newell-Price, J Nikookam, K Ogilivie, A Orme, SM O´Weickert, M Pal, A Pascanu, I Patócs, A Patterson, C Pearce, SH Giraldi, FP Penney, L Perez-Rivas, LG Pfeifer, M Pirie, F Poplawski, N Popovic, V Powell, M Pullan, P Quinton, R Radian, S Randeva, H Reddy, N Rees, A Renals, V de Oliveira, AR Richardson, T Rodd, C Ross, RJM Roncaroli, F Ryan, F Salvatori, R Schöfl, C Shears, D Shotliff, K Skelly, R Snape, K Soares, BS Somasundaram, N Spada, A Sperber, J Spoudeas, H Stelmachowska-Banas, M Stewart, S Storr, HL Strasburger, C Street, ME Suter-Widmer, I Suthers, G Swords, F Syro, LV Swantje, B Sze, C Taylor, J Thakker, RV Tham, E Thompson, C Thorner, MO Tóth, M Trainer, PJ Tsagarakis, S Twine, G Tzanela, M Vadasz, J Vaidya, B Vaks, V Vance, ML Verkauskiene, R Von Esch, H Wass, JA Waterhouse, M Webb, S Weber, A Wernig, F Widell, H Yamada, S Yap, P Yarman, S Yeoh, P Yoshimoto, K Yuen, K Zammitt, NN
Copyright, Publisher and Additional Information:	© Endocrine Society 2020. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords:	pituitary neuroendocrine tumor; pituitary adenoma; familial isolated pituitary adenoma; somatotropinoma; gigantism; aryl hydrocarbon receptor-interacting protein
Dates:	Accepted: 28 January 2020 Published (online): 30 January 2020 Published: 1 June 2020
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Sheffield Teaching Hospitals
Depositing User:	Symplectic Sheffield
Date Deposited:	12 Jun 2020 06:55
Last Modified:	12 Jun 2020 08:00
Status:	Published
Publisher:	The Endocrine Society
Refereed:	Yes
Identification Number:	10.1210/clinem/dgaa040
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:161800

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

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