[en] Genetic testing of patients with pituitary adenomas enables delivery of genotype-based precision care. Germline testing might identify variants predisposing to formation of pituitary adenomas and, potentially, other neoplasms. These include loss-of-function variants in AIP, MEN1, CDKN1B, PRKAR1A, SDHA, SDHB, SDHC, SDHD and MAX; GPR101-containing Xq26.3 microduplications; and postzygotic gain-of-function GNAS variants. Somatic testing might help identify and manage aggressive pituitary adenoma types and very rarely encountered pituitary carcinomas. This Pituitary Society Consensus Statement provides evidence-based guidance on the clinical application of these genetic tests, focusing on germline genetic testing, with recommendations regarding genes for inclusion in panel testing, test indications, pre-test counselling, test methodologies, and the interpretation and follow-up of results. As somatic genetic testing is gradually becoming available in clinical practice, recommendations are provided regarding clinical scenarios in which somatic testing might be considered and which genes to test. The consensus group concluded that genetic testing is an increasingly valuable adjunct in the assessment and management of people with pituitary adenomas. When indicated, genetic testing should ideally be undertaken within a multidisciplinary team comprising endocrine, genetic and laboratory expertise to ensure high-quality testing and safe and effective result interpretation and follow-up.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
De Sousa, Sunita M C ; School of Medicine, Adelaide University, Adelaide, South Australia, Australia. Sunita.DeSousa@sa.gov.au
Andoniadou, Cynthia L ; Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, London, UK
Daly, Adrian ; Université de Liège - ULiège > Département des sciences cliniques
Gadelha, Mônica; Neuroendocrinology Research Center/Endocrinology Division, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
Gatto, Federico; Department of Internal Medicine and Medical Specialties, Endocrinology Unit, University of Genoa, Genoa, Italy
Kamenický, Peter; Physiologie et Physiopathologie Endocriniennes, Inserm, Université Paris-Saclay, Le Kremlin-Bicêtre, France
Marques, Pedro ; Endocrinology Department, Pituitary Tumor Unit, Hospital CUF Descobertas, Lisbon, Portugal
Reincke, Martin ; Department of Medicine IV, LMU Hospital, Ludwig Maximilians University, Munich, Germany
Ruf-Zamojski, Frederique ; Pituitary Center, Department of Medicine, Cedars-Sinai Health Sciences University, Los Angeles, CA, USA
Salvatori, Roberto ; Division of Endocrinology, Diabetes, and Metabolism, Johns Hopkins University, Baltimore, MD, USA
Takahashi, Yutaka ; Department of Diabetes and Endocrinology, Nara Medical University, Kashihara, Japan
Tatsi, Christina; Department of Pediatrics, NIH Clinical Center, National Institutes of Health, Bethesda, MD, USA
Araki, Takako; Department of Medicine, Division of Diabetes, Endocrinology & Metabolism, University of Minnesota, Minneapolis, MN, USA
Chiloiro, Sabrina ; Division of Endocrinology, Metabolic Disease and Internal Medicine, Agostino Gemelli University Hospital IRCCS, Rome, Italy
Dichtel, Laura; Department of Medicine, Neuroendocrine Unit, Massachusetts General Hospital, Boston, MA, USA
Ioachimescu, Adriana G; Department of Medicine, Division of Endocrinology and Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
Mallea-Gil, Susana; Endocrinology Division, Hospital Militar Central, Buenos Aires, Argentina
Niculescu, Dan A; Department of Endocrinology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
Pereira, Alberto M ; Department of Endocrinology and Metabolism, Amsterdam University Medical Center, Amsterdam, Netherlands
Shimon, Ilan; Gray Faculty of Medicine and Health Sciences, Institute of Endocrinology, Tel Aviv University, Tel Aviv, Israel
Wass, John; Department of Endocrinology, Churchill Hospital, Oxford, UK
Zada, Gabriel; Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Fleseriu, Maria ; Pituitary Center, Departments of Medicine and Neurological Surgery, Oregon Health & Science University, Portland, OR, USA
Melmed, Shlomo ; Pituitary Center, Department of Medicine, Cedars-Sinai Health Sciences University, Los Angeles, CA, USA
Melmed S et al. Clinical biology of the pituitary adenoma Endocr. Rev. 2022 43 1003 1037 35395078 9695123 10.1210/endrev/bnac010
Herman V Fagin J Gonsky R Kovacs K Melmed S Clonal origin of pituitary adenomas J. Clin. Endocrinol. Metab. 1990 71 1427 1433 1:STN:280:DyaK3M%2FjsFymuw%3D%3D 1977759 10.1210/jcem-71-6-1427
Ho KKY et al. Pituitary adenoma or neuroendocrine tumour: the need for an integrated prognostic classification Nat. Rev. Endocrinol. 2023 19 671 678 10.1038/s41574-023-00883-8 37592077 12519436
Trouillas J et al. How to classify the pituitary neuroendocrine tumors (PitNET)s in 2020 Cancers 2020 12 514 1:CAS:528:DC%2BB3cXht1Kls77E 32098443 7072139 10.3390/cancers12020514
De Sousa SMC From bench to bedside in the sella: translational developments in pituitary tumour genetics Endocr. Relat. Cancer 2025 32 40197437 10.1530/ERC-24-0272 e240272
Guaraldi F et al. Epigenomic and somatic mutations of pituitary tumors with clinical and pathological correlations in 111 patients Clin. Endocrinol. 2022 97 763 772 10.1111/cen.14827
De Sousa SMC et al. Germline variants in familial pituitary tumour syndrome genes are common in young patients and families with additional endocrine tumours Eur. J. Endocrinol. 2017 176 635 644 28220018 10.1530/EJE-16-0944
Marques P et al. Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors J. Clin. Endocrinol. Metab. 2020 105 e2247 e2260 31996917 7137887 10.1210/clinem/dgaa040
Beckers A Petrossians P Hanson J Daly AF The causes and consequences of pituitary gigantism Nat. Rev. Endocrinol. 2018 14 705 720 1:CAS:528:DC%2BC1cXitVSltrnK 10.1038/s41574-018-0114-1 30361628
Daly AF et al. Clinical characteristics and therapeutic responses in patients with germ-line AIP mutations and pituitary adenomas: an international collaborative study J. Clin. Endocrinol. Metab. 2010 95 E373 E383 20685857 10.1210/jc.2009-2556
Hernandez-Ramirez LC et al. Landscape of familial isolated and young-onset pituitary adenomas: prospective diagnosis in AIP mutation carriers J. Clin. Endocrinol. Metab. 2015 100 E1242 E1254 26186299 4570169 10.1210/jc.2015-1869
Daly AF et al. AIP and MEN1 mutations and AIP immunohistochemistry in pituitary adenomas in a tertiary referral center Endocr. Connect. 2019 8 338 348 1:CAS:528:DC%2BC1MXhvVOjurfE 30822274 6432872 10.1530/EC-19-0027
Beckers A Aaltonen LA Daly AF Karhu A Familial isolated pituitary adenomas (FIPA) and the pituitary adenoma predisposition due to mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene Endocr. Rev. 2013 34 239 277 1:CAS:528:DC%2BC3sXmvVSru78%3D 23371967 3610678 10.1210/er.2012-1013
Brandi ML et al. Multiple endocrine neoplasia type 1 (MEN1): recommendations and guidelines for best practice Lancet Diabetes Endocrinol. 2025 13 699 721 1:CAS:528:DC%2BB2MXhsVChsbjI 40523372 10.1016/S2213-8587(25)00119-6
Pellegata NS et al. Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans Proc. Natl Acad. Sci. USA 2006 103 15558 15563 1:CAS:528:DC%2BD28XhtFCjtLbJ 17030811 1622862 10.1073/pnas.0603877103
Bertherat J et al. Mutations in regulatory subunit type 1A of cyclic adenosine 5’-monophosphate-dependent protein kinase (PRKAR1A): phenotype analysis in 353 patients and 80 different genotypes J. Clin. Endocrinol. Metab. 2009 94 2085 2091 1:CAS:528:DC%2BD1MXntFGmt7g%3D 19293268 2690418 10.1210/jc.2008-2333
Kirschner LS et al. Mutations of the gene encoding the protein kinase A type I-α regulatory subunit in patients with the Carney complex Nat. Genet. 2000 26 89 92 1:CAS:528:DC%2BD3cXmsVKrsr4%3D 10.1038/79238 10973256
Daly AF et al. Pheochromocytomas and pituitary adenomas in three patients with MAX exon deletions Endocr. Relat. Cancer 2018 25 L37 L42 1:CAS:528:DC%2BC1cXisVCksbbO 29535143 10.1530/ERC-18-0065
Loughrey PB et al. Succinate dehydrogenase and MYC-associated factor X mutations in pituitary neuroendocrine tumours Endocr. Relat. Cancer 2022 29 R157 R172 1:CAS:528:DC%2BB38XivVCmtrrK 35938916 9513646 10.1530/ERC-22-0157
Xekouki P Brennand A Whitelaw B Pacak K Stratakis CA The 3PAs: an update on the association of pheochromocytomas, paragangliomas, and pituitary tumors Horm. Metab. Res. 2019 51 419 436 1:CAS:528:DC%2BC1cXhvVegt7jO 30273935 10.1055/a-0661-0341
Trivellin G et al. Gigantism and acromegaly due to Xq26 microduplications and GPR101 mutation N. Engl. J. Med. 2014 371 2363 2374 1:CAS:528:DC%2BC2MXhvVKitLo%3D 25470569 4291174 10.1056/NEJMoa1408028
Landis CA et al. GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenylyl cyclase in human pituitary tumours Nature 1989 340 692 696 1:CAS:528:DyaL1MXlsFWgsL8%3D 10.1038/340692a0 2549426
Reincke M et al. Mutations in the deubiquitinase gene USP8 cause Cushing’s disease Nat. Genet. 2015 47 31 38 1:CAS:528:DC%2BC2cXitVCks7rJ 10.1038/ng.3166 25485838
Ma ZY et al. Recurrent gain-of-function USP8 mutations in Cushing’s disease Cell Res. 2015 25 306 317 1:CAS:528:DC%2BC2MXivFWmu7s%3D 10.1038/cr.2015.20 25675982 4349249
Simon J et al. Prevalence and clinical correlations of SF3B1 variants in lactotroph tumours Eur. J. Endocrinol. 2023 189 372 378 1:CAS:528:DC%2BB2MXhtVemsLnO 37721395 10.1093/ejendo/lvad114
Korbonits M et al. Consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence: part 1, general recommendations Nat. Rev. Endocrinol. 2024 20 278 289 10.1038/s41574-023-00948-8 38336897
Korbonits M et al. Consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence: part 2, specific diseases Nat. Rev. Endocrinol. 2024 20 290 309 10.1038/s41574-023-00949-7 38336898
Raverot G et al. Revised European Society of Endocrinology Clinical Practice Guideline for the management of aggressive pituitary tumours and pituitary carcinomas Eur. J. Endocrinol. 2025 192 R45 R78 40506054 10.1093/ejendo/lvaf100
Petersenn S et al. Diagnosis and management of prolactin-secreting pituitary adenomas: a Pituitary Society International Consensus Statement Nat. Rev. Endocrinol. 2023 19 722 740 10.1038/s41574-023-00886-5 37670148
Fleseriu M et al. Consensus on diagnosis and management of Cushing’s disease: a guideline update Lancet Diabetes Endocrinol. 2021 9 847 875 34687601 8743006 10.1016/S2213-8587(21)00235-7
Guyatt GH et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations BMJ 2008 336 924 926 18436948 2335261 10.1136/bmj.39489.470347.AD
Fleseriu M et al. Pituitary incidentaloma: a Pituitary Society International Consensus guideline statement Nat. Rev. Endocrinol. 2025 21 638 655 10.1038/s41574-025-01134-8 40555795
Vandeva S Daly AF Petrossians P Zacharieva S Beckers A Somatic and germline mutations in the pathogenesis of pituitary adenomas Eur. J. Endocrinol. 2019 181 R235 R254 1:CAS:528:DC%2BB3cXhvVCrtLc%3D 31658440 10.1530/EJE-19-0602
Piazzola C et al. From misclassified AIP variant to Carney complex: a case report and retrospective evaluation of PRKAR1A in pituitary tumor predisposition Pituitary 2025 29 15 10.1007/s11102-025-01616-y 41364279
Daly AF et al. Clinical characterization of familial isolated pituitary adenomas J. Clin. Endocrinol. Metab. 2006 91 3316 3323 1:CAS:528:DC%2BD28Xpslajtro%3D 16787992 10.1210/jc.2005-2671
Vierimaa O et al. Pituitary adenoma predisposition caused by germline mutations in the AIP gene Science 2006 312 1228 1230 1:CAS:528:DC%2BD28XkvVOhs70%3D 16728643 10.1126/science.1126100
Balogh K Racz K Patocs A Hunyady L Menin and its interacting proteins: elucidation of menin function Trends Endocrinol. Metab. 2006 17 357 364 1:CAS:528:DC%2BD28XhtFWjurzF 16997566 10.1016/j.tem.2006.09.004
Chevalier B et al. Beyond MEN1, when to think about MEN4? Retrospective study on 5600 patients in the French population and literature review J. Clin. Endocrinol. Metab. 2024 109 e1482 e1493 1:CAS:528:DC%2BB2MXhs1Snsr%2FE 38288531 10.1210/clinem/dgae055
Singeisen H et al. Multiple endocrine neoplasia type 4: a new member of the MEN family Endocr. Connect. 2023 12 1:CAS:528:DC%2BB3sXjslGrt7c%3D 36520683 9874964 10.1530/EC-22-0411 e220411
Espiard S et al. Frequency and incidence of Carney complex manifestations: a prospective multicenter study with a three-year follow-up J. Clin. Endocrinol. Metab. 2020 105 dgaa002 31912137 10.1210/clinem/dgaa002
Tatsi C Pitsava G Faucz FR Keil M Stratakis CA The spectrum of GH excess in Carney complex and genotype-phenotype correlations J. Clin. Endocrinol. Metab. 2025 110 e694 e702 1:CAS:528:DC%2BB2MXhtVyltrjP 38626285 11834726 10.1210/clinem/dgae253
Cascon A Robledo M Clinical and molecular markers guide the genetics of pheochromocytoma and paraganglioma Biochim. Biophys. Acta Rev. Cancer 2024 1879 189141 1:CAS:528:DC%2BB2cXhsVamtbjK 38908536 10.1016/j.bbcan.2024.189141
Mougel G et al. Germinal defects of SDHx genes in patients with isolated pituitary adenoma Eur. J. Endocrinol. 2020 183 369 379 1:CAS:528:DC%2BB3cXhvFGjtL3K 32621582 10.1530/EJE-20-0054
Fernandez-Pombo A et al. New insights into the clinical characterization of SDHAF2-related familial paraganglioma syndrome J. Clin. Endocrinol. Metab. 2025 110 e3635 e3647 1:CAS:528:DC%2BB2MXis1eqtb7O 40079348 12527445 10.1210/clinem/dgaf149
Seabrook AJ et al. Multiple endocrine tumors associated with germline MAX mutations: multiple endocrine neoplasia type 5? J. Clin. Endocrinol. Metab. 2021 106 1163 1182 33367756 10.1210/clinem/dgaa957
Daly AF et al. Chromatin conformation capture in the clinic: 4C-seq/HiC distinguishes pathogenic from neutral duplications at the GPR101 locus Genome Med. 2024 16 1:CAS:528:DC%2BB2cXhvF2nu7zL 10.1186/s13073-024-01378-5 39272130 11396275 112
Hilditch C Curtis S Cotton S LeBlanc S De Sousa S Non-penetrant Xq26.3 duplication involving the invariant TAD border: clinical evidence for the VGLL1 region as the GPR101 pituitary enhancer of X-linked acrogigantism Pituitary 2025 28 85 1:CAS:528:DC%2BB2MXisV2gtbnO 10.1007/s11102-025-01559-4 40684399 12277222
Trivellin G et al. Distinguishing benign from pathogenic duplications involving GPR101 and VGLL1-adjacent enhancers in the clinical setting with the bioinformatic tool POSTRE NPJ Genom. Med. 2026 11 12 10.1038/s41525-025-00548-7 41540017 12890961
Daly AF Beckers A The genetic pathophysiology and clinical management of the TADopathy, X-linked acrogigantism Endocr. Rev. 2024 45 737 754 1:CAS:528:DC%2BB2MXhslyjtbnM 38696651 10.1210/endrev/bnae014
Vasilev V et al. Hereditary endocrine tumours: current state-of-the-art and research opportunities: the roles of AIP and GPR101 in familial isolated pituitary adenomas (FIPA) Endocr. Relat. Cancer 2020 27 T77 T86 1:CAS:528:DC%2BB3cXitVWgsLnL 32083999 10.1530/ERC-20-0015
Dumitrescu CE Collins MT McCune-Albright syndrome Orphanet J. Rare Dis. 2008 3 10.1186/1750-1172-3-12 18489744 2459161 12
Akintoye SO et al. Characterization of gsp-mediated growth hormone excess in the context of McCune-Albright syndrome J. Clin. Endocrinol. Metab. 2002 87 5104 5112 1:CAS:528:DC%2BD38Xos1yntrY%3D 12414879 10.1210/jc.2001-012022
Weinstein LS et al. Activating mutations of the stimulatory G protein in the McCune-Albright syndrome N. Engl. J. Med. 1991 325 1688 1695 1:STN:280:DyaK38%2FkvFKhsg%3D%3D 1944469 10.1056/NEJM199112123252403
Lumbroso S Paris F Sultan C European Collaborative Study Activating Gsα mutations: analysis of 113 patients with signs of McCune-Albright syndrome — a European Collaborative Study J. Clin. Endocrinol. Metab. 2004 89 2107 2113 1:CAS:528:DC%2BD2cXjvFyrsbY%3D 15126527 10.1210/jc.2003-031225
Uraki S et al. Atypical pituitary adenoma with MEN1 somatic mutation associated with abnormalities of DNA mismatch repair genes; MLH1 germline mutation and MSH6 somatic mutation Endocr. J. 2017 64 895 906 28701629 10.1507/endocrj.EJ17-0036
Loughrey PB et al. Invasive ACTH-producing pituitary gland neoplasm secondary to MSH2 mutation Cancer Genet. 2021 256-257 36 39 1:CAS:528:DC%2BB3MXhs1OhsbzN 33866195 10.1016/j.cancergen.2021.03.008
Teuber J et al. Aggressive pituitary adenoma in the context of Lynch syndrome: a case report and literature review on this rare coincidence Br. J. Neurosurg. 2024 38 775 780 34431732 10.1080/02688697.2021.1967881
Bengtsson D et al. Corticotroph pituitary carcinoma in a patient with Lynch syndrome (LS) and pituitary tumors in a nationwide LS cohort J. Clin. Endocrinol. Metab. 2017 102 3928 3932 28938458 10.1210/jc.2017-01401
Bares V Netuka D Recurrent pituitary adenoma causing cushing’s disease in a patient with lynch syndrome Cureus 2026 18 41608252 12842832 e102414
De Sousa SMC et al. Increased prevalence of germline pathogenic CHEK2 variants in individuals with pituitary adenomas J. Clin. Endocrinol. Metab. 2024 109 2720 2728 38651569 11479685
Gaspar LM et al. Germline genetic variants in young-onset sporadic pituitary macroadenomas: a multigene panel analysis J. Clin. Transl. Endocrinol. 2025 40 1:CAS:528:DC%2BB2MXosVGmsr4%3D 40248171 12005325 100389
Orsmond A De Sousa SMC McCormack A The landscape of germline variants in breast and colorectal cancer susceptibility genes in patients with pituitary tumours J. Neurooncol. 2025 175 379 388 1:CAS:528:DC%2BB2MXisV2gu7bE 10.1007/s11060-025-05140-8 40563065 12367850
Alzahrani AS et al. Germline variants in sporadic pituitary adenomas J. Endocr. Soc. 2024 8 1:CAS:528:DC%2BB2cXhtlKlu7jE 38745824 11091836 10.1210/jendso/bvae085 bvae085
Forlino A et al. PRKACB and Carney complex N. Engl. J. Med. 2014 370 1065 1067 1:CAS:528:DC%2BC2cXkvVyqtb8%3D 24571725 10.1056/NEJMc1309730
Mignone E Sorvina A Torpy DJ Scott HS De Sousa SMC The germline landscape of pituitary adenomas: established and emerging predisposition genes J. Clin. Endocrinol. Metab. 2026 111 e1926 e1936 1:CAS:528:DC%2BB28XhslyisLvN 42141904 13368367 10.1210/clinem/dgag195
Martinez de Lapiscina I et al. Prevalence of germline variants in USP8, USP48, CABLES1 and PAM in patients with pituitary adenomas Eur. J. Endocrinol. 2026 194 603 614 1:CAS:528:DC%2BB28XhtFyms7rI 42045809 10.1093/ejendo/lvag074
Hannah-Shmouni F et al. Neurofibromatosis type 1 has a wide spectrum of growth hormone excess J. Clin. Med. 2022 11 2168 1:CAS:528:DC%2BB38XhtFWksrrN 35456261 9029762 10.3390/jcm11082168
De Sousa SMC Lenders NF Lamb LS Inder WJ McCormack A Pituitary tumours: molecular and genetic aspects J. Endocrinol. 2023 257 36951812 10.1530/JOE-22-0291 e220291
Statement of the American Society of Clinical Oncology: genetic testing for cancer susceptibility, adopted on February 20, 1996. J. Clin. Oncol.14, 1730–1736 (1996).
Caimari F et al. Risk category system to identify pituitary adenoma patients with AIP mutations J. Med. Genet. 2018 55 254 260 1:CAS:528:DC%2BC1MXkvFSmsr0%3D 29440248 5869708 10.1136/jmedgenet-2017-104957
Tichomirowa MA et al. High prevalence of AIP gene mutations following focused screening in young patients with sporadic pituitary macroadenomas Eur. J. Endocrinol. 2011 165 509 515 1:CAS:528:DC%2BC3MXhsVSju7rI 21753072 10.1530/EJE-11-0304
Worthy CC et al. Genotype-phenotype correlation in multiple endocrine neoplasia type 1 JCI Insight 2025 10 39946193 11949022 10.1172/jci.insight.176993 e176993
Verges B et al. Pituitary disease in MEN type 1 (MEN1): data from the France-Belgium MEN1 multicenter study J. Clin. Endocrinol. Metab. 2002 87 457 465 1:CAS:528:DC%2BD38XhsVSjtLg%3D 11836268 10.1210/jcem.87.2.8145
Goudet P et al. MEN1 disease occurring before 21 years old: a 160-patient cohort study from the Groupe d’etude des Tumeurs Endocrines J. Clin. Endocrinol. Metab. 2015 100 1568 1577 1:CAS:528:DC%2BC2MXmsFaisbY%3D 25594862 10.1210/jc.2014-3659
Brandi ML et al. Multiple endocrine neoplasia type 1: latest insights Endocr. Rev. 2021 42 133 170 33249439 7958143 10.1210/endrev/bnaa031
Salenave S et al. Macroprolactinomas in children and adolescents: factors associated with the response to treatment in 77 patients J. Clin. Endocrinol. Metab. 2015 100 1177 1186 1:CAS:528:DC%2BC2MXlvVGitbo%3D 25532043 10.1210/jc.2014-3670
English KA et al. Treatments for MEN1-associated endocrine tumours: three systematic reviews and a meta-analysis Lancet Diabetes Endocrinol. 2025 13 685 698 1:CAS:528:DC%2BB2MXhsVChsbjJ 40523371 10.1016/S2213-8587(25)00118-4
Chasseloup F et al. Germline CDKN1B loss-of-function variants cause pediatric Cushing’s disease with or without an MEN4 phenotype J. Clin. Endocrinol. Metab. 2020 105 1983 2005 32232325 7190031 10.1210/clinem/dgaa160
Stelmachowska-Banas M Zgliczynski W Tutka P Carney JA Korbonits M Fatal carney complex in siblings due to de novo large gene deletion J. Clin. Endocrinol. Metab. 2017 102 3924 3927 28973408 5673275 10.1210/jc.2017-01045
Romanet P et al. Using digital droplet polymerase chain reaction to detect the mosaic GNAS mutations in whole blood DNA or circulating cell-free DNA in fibrous dysplasia and McCune-Albright syndrome J. Pediatr. 2019 205 281 285.e4 1:CAS:528:DC%2BC1cXitFyhtbrE 30442414 10.1016/j.jpeds.2018.09.070
Salenave S Boyce AM Collins MT Chanson P Acromegaly and McCune-Albright syndrome J. Clin. Endocrinol. Metab. 2014 99 1955 1969 1:CAS:528:DC%2BC2cXps12rtrg%3D 24517150 4037730 10.1210/jc.2013-3826
Stratakis CA Carney complex: a familial lentiginosis predisposing to a variety of tumors Rev. Endocr. Metab. Disord. 2016 17 367 371 1:CAS:528:DC%2BC28XitV2mtrfM 10.1007/s11154-016-9400-1 27943004 5192557
Butz H Blair J Patocs A Molecular genetic testing strategies used in diagnostic flow for hereditary endocrine tumour syndromes Endocrine 2021 71 641 652 1:CAS:528:DC%2BB3MXjvVOlsb4%3D 10.1007/s12020-021-02636-x 33570725 8016766
Katsanis SH Katsanis N Molecular genetic testing and the future of clinical genomics Nat. Rev. Genet. 2013 14 415 426 1:CAS:528:DC%2BC3sXnslagsbk%3D 10.1038/nrg3493 23681062 4461364
Burke W Genetic tests: clinical validity and clinical utility Curr. Protoc. Hum. Genet. 2014 81 9.15.11 19.15.18
Coopmans EC Korbonits M Molecular genetic testing in the management of pituitary disease Clin. Endocrinol. 2022 97 424 435 1:CAS:528:DC%2BB38XhsVansrnN 10.1111/cen.14706
Newey PJ Clinical genetic testing in endocrinology: current concepts and contemporary challenges Clin. Endocrinol. 2019 91 587 607 10.1111/cen.14053
Korbonits, M. & Hernandez-Ramirez, L. C. in GeneReviews (eds Adam, M. P. et al.) https://www.ncbi.nlm.nih.gov/books/NBK97965/ (2025).
Cancer Genetics Risk Assessment and Counseling (PDQ): Health Professional Version. National Cancer Institute PDQ Cancer Information Summaries https://www.ncbi.nlm.nih.gov/books/NBK65817/ (2025).
Ilie MD Vasiljevic A Bertolino P Raverot G Biological and therapeutic implications of the tumor microenvironment in pituitary adenomas Endocr. Rev. 2023 44 297 311 36269838 10.1210/endrev/bnac024
Souza ABA et al. Germline genetic testing in breast cancer: utilization and disparities in a middle-income country JCO Glob. Oncol. 2025 11 40053901 10.1200/GO-24-00337 e2400337
Clayton EW Evans BJ Hazel JW Rothstein MA The law of genetic privacy: applications, implications, and limitations J. Law Biosci. 2019 6 1 36 31666963 6813935 10.1093/jlb/lsz007
Committee on Bioethics et al. Ethical and policy issues in genetic testing and screening of children Pediatrics 2013 131 620 622 10.1542/peds.2012-3680
Evans JP Powell BC Berg JS Finding the rare pathogenic variants in a human genome JAMA 2017 317 1904 1905 28492888 10.1001/jama.2017.0432
Wiesner GL et al. Returning results in the genomic era: initial experiences of the eMERGE network J. Pers. Med. 2020 10 30 32349224 7354592 10.3390/jpm10020030
Wauters A Van Hoyweghen I Global trends on fears and concerns of genetic discrimination: a systematic literature review J. Hum. Genet. 2016 61 275 282 1:CAS:528:DC%2BC28XmvFCgsrg%3D 10.1038/jhg.2015.151 26740237
Berwouts S Morris MA Dequeker E Approaches to quality management and accreditation in a genetic testing laboratory Eur. J. Hum. Genet. 2010 18 S1 S19 10.1038/ejhg.2010.104 20720559 3327516
Richards S et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology Genet. Med. 2015 17 405 424 10.1038/gim.2015.30 25741868 4544753
Izatt L Owens MM Pierce H Wilcox S Park SM A practical guide to genetic testing in endocrinology Clin. Endocrinol. 2022 97 388 399 10.1111/cen.14596
Patocs A et al. Cost-effectiveness of genetic testing of endocrine tumor patients using a comprehensive hereditary cancer gene panel J. Clin. Endocrinol. Metab. 2024 109 3220 3233 1:CAS:528:DC%2BB2MXhs1SgtbnM 38701358 11570362 10.1210/clinem/dgae300
Brock P et al. Hereditary endocrine tumours: current state-of-the-art and research opportunities: challenges and opportunities in genetic counseling for hereditary endocrine neoplasia syndromes Endocr. Relat. Cancer 2020 27 T65 T75 1:CAS:528:DC%2BB3cXitVWgsLbJ 32106089 10.1530/ERC-19-0454
Romanet P et al. Proposition of adjustments to the ACMG-AMP framework for the interpretation of MEN1 missense variants Hum. Mutat. 2019 40 661 674 1:CAS:528:DC%2BC1MXpvFKlt7Y%3D 30869828 10.1002/humu.23746
Landrum MJ et al. ClinVar: public archive of interpretations of clinically relevant variants Nucleic Acids Res. 2016 44 D862 D868 1:CAS:528:DC%2BC2sXhtV2nsrzI 26582918 10.1093/nar/gkv1222
Rehm HL et al. ClinGen-the clinical genome resource N. Engl. J. Med. 2015 372 2235 2242 1:CAS:528:DC%2BC2MXhtFyrsbfI 26014595 4474187 10.1056/NEJMsr1406261
Katsonis P Wilhelm K Williams A Lichtarge O Genome interpretation using in silico predictors of variant impact Hum. Genet. 2022 141 1549 1577 10.1007/s00439-022-02457-6 35488922 9055222
Basel-Salmon L Phenotypic compatibility and specificity in genomic variant classification Eur. J. Hum. Genet. 2024 32 471 473 10.1038/s41431-024-01554-6 38351291 11061282
Biesecker LG et al. ClinGen guidance for use of the PP1/BS4 co-segregation and PP4 phenotype specificity criteria for sequence variant pathogenicity classification Am. J. Hum. Genet. 2024 111 24 38 1:CAS:528:DC%2BB3sXis1amsbjP 38103548 10.1016/j.ajhg.2023.11.009
Ramirez-Renteria C Hernandez-Ramirez LC Genetic diagnosis in acromegaly and gigantism: from research to clinical practice Best Pract. Res. Clin. Endocrinol. Metab. 2024 38 101892 1:CAS:528:DC%2BB2cXpvFGgtLs%3D 38521632 10.1016/j.beem.2024.101892
Singh AK et al. Detecting copy number variation in next generation sequencing data from diagnostic gene panels BMC Med. Genomics 2021 14 1:CAS:528:DC%2BB3MXit1elu77N 10.1186/s12920-021-01059-x 34465341 8406611 214
Akkus G Korbonits M Genetic testing in hereditary pituitary tumors Arch. Med. Res. 2023 54 102920 1:CAS:528:DC%2BB3sXisVeqtbrO 38007383 10.1016/j.arcmed.2023.102920
Rattenberry E et al. A comprehensive next generation sequencing-based genetic testing strategy to improve diagnosis of inherited pheochromocytoma and paraganglioma J. Clin. Endocrinol. Metab. 2013 98 E1248 E1256 1:CAS:528:DC%2BC3sXhtFChsrrK 23666964 10.1210/jc.2013-1319
Tham E et al. Clinical testing for mutations in the MEN1 gene in Sweden: a report on 200 unrelated cases J. Clin. Endocrinol. Metab. 2007 92 3389 3395 1:CAS:528:DC%2BD2sXhtVGqsrvO 17623761 10.1210/jc.2007-0476
De Sousa SMC Daly AF Genetics of familial acromegaly and pituitary gigantism J. Clin. Endocrinol. Metab. 2026 111 S13 S26 41965096 13235292 10.1210/clinem/dgag151
Lagarde A et al. Systematic detection of mosaicism by using digital NGS reveals three new MEN1 mosaicisms Endocr. Connect. 2022 11 1:CAS:528:DC%2BB38XjtV2jtrnJ 36112497 9578105 10.1530/EC-22-0093 e220093
Roszko KL et al. Identification of GNAS variants in circulating cell-free DNA from patients with fibrous dysplasia/McCune Albright syndrome J. Bone Min. Res. 2023 38 443 450 1:CAS:528:DC%2BB3sXhvFGjtLY%3D 10.1002/jbmr.4766
Narumi S Matsuo K Ishii T Tanahashi Y Hasegawa T Quantitative and sensitive detection of GNAS mutations causing mccune-albright syndrome with next generation sequencing PLoS One 2013 8 1:CAS:528:DC%2BC3sXlsVOksro%3D 23536913 3607597 10.1371/journal.pone.0060525 e60525
Szymczuk, V. et al. in GeneReviews (eds Adam, M. P. et al.) https://www.ncbi.nlm.nih.gov/books/NBK274564/ (2024).
Vado Y Manero-Azua A Pereda A Perez de Nanclares G Choosing the best tissue and technique to detect mosaicism in fibrous dysplasia/McCune-Albright syndrome (FD/MAS) Genes 2024 15 120 1:CAS:528:DC%2BB2cXis1entrs%3D 38255009 10815810 10.3390/genes15010120
Papalou O Korbonits M New directions in MEN1 management: navigating the new clinical practice guidelines Eur. J. Endocrinol. 2025 193 R71 R82 1:CAS:528:DC%2BB2MXjtVGnsbnE 41347880 10.1093/ejendo/lvaf247
Omotosho YB et al. Radiological surveillance for pituitary adenomas in multiple endocrine neoplasia type 1: a longitudinal cohort study J. Clin. Endocrinol. Metab. 2026 111 1575 1583 1:CAS:528:DC%2BB28Xht1KgtLfN 41498210 13183421 10.1210/clinem/dgaf704
Srinivasan S Won NY Dotson WD Wright ST Roberts MC Barriers and facilitators for cascade testing in genetic conditions: a systematic review Eur. J. Hum. Genet. 2020 28 1631 1644 10.1038/s41431-020-00725-5 32948847 7784694
Luger A et al. ESE clinical practice guideline on functioning and nonfunctioning pituitary adenomas in pregnancy Eur. J. Endocrinol. 2021 185 G1 G33 1:CAS:528:DC%2BB3MXitV2ltbjO 34425558 10.1530/EJE-21-0462
Hoekstra AS Devilee P Bayley JP Models of parent-of-origin tumorigenesis in hereditary paraganglioma Semin. Cell Dev. Biol. 2015 43 117 124 26067997 10.1016/j.semcdb.2015.05.011
Al-Salameh A Cadiot G Calender A Goudet P Chanson P Clinical aspects of multiple endocrine neoplasia type 1 Nat. Rev. Endocrinol. 2021 17 207 224 10.1038/s41574-021-00468-3 33564173
Lima AD et al. Preimplantation genetic diagnosis for a patient with multiple endocrine neoplasia type 1: case report JBRA Assist. Reprod. 2018 22 67 70 29266898 5844663
Hardy T The role of prenatal diagnosis following preimplantation genetic testing for single-gene conditions: a historical overview of evolving technologies and clinical practice Prenat. Diagn. 2020 40 647 651 32037566 10.1002/pd.5662
Loughrey PB et al. Reassessing the role of the p.(Arg304Gln) missense AIP variant in pituitary tumorigenesis Eur. J. Endocrinol. 2025 192 385 397 1:CAS:528:DC%2BB2MXhtVemtrzK 40070360 11962913 10.1093/ejendo/lvaf044
Wright MW et al. Generating clinical-grade gene-disease validity classifications through the clingen data platforms Annu. Rev. Biomed. Data Sci. 2024 7 31 50 38663031 12001867 10.1146/annurev-biodatasci-102423-112456
De Sousa SMC et al. Aberrant splicing of SDHC in families with unexplained succinate dehydrogenase-deficient paragangliomas J. Endocr. Soc. 2020 4 33195952 7646550 10.1210/jendso/bvaa071 bvaa071
PFMG Contributors. PFMG2025-integrating genomic medicine into the national healthcare system in France Lancet Reg. Health Eur. 2025 50 101183 10.1016/j.lanepe.2024.101183
McInerney-Leo AM Duncan EL Massively parallel sequencing for rare genetic disorders: potential and pitfalls Front. Endocrinol. 2020 11 628946 10.3389/fendo.2020.628946
Zhang Q et al. Risk of recurrence after successful surgery for Cushing’s disease and association with USP8 genotype and tumour size: an international, retrospective, longitudinal cohort study Lancet Diabetes Endocrinol. 2026 14 327 336 1:CAS:528:DC%2BB28XlvFyqs7w%3D 41785910 13179832 10.1016/S2213-8587(25)00396-1
Ronchi CL et al. Landscape of somatic mutations in sporadic GH-secreting pituitary adenomas Eur. J. Endocrinol. 2016 174 363 372 1:CAS:528:DC%2BC28XksVenu7w%3D 26701869 10.1530/EJE-15-1064
Yamamoto M Takahashi Y Genetic and epigenetic pathogenesis of acromegaly Cancers 2022 14 3861 1:CAS:528:DC%2BB38XitlSlsL7F 36010855 9405703 10.3390/cancers14163861
Neou M et al. Pangenomic classification of pituitary neuroendocrine tumors Cancer Cell 2020 37 123 134 1:CAS:528:DC%2BB3cXhvFGitA%3D%3D 31883967 10.1016/j.ccell.2019.11.002
Puig-Domingo M et al. Molecular profiling for acromegaly treatment: a validation study Endocr. Relat. Cancer 2020 27 375 389 1:CAS:528:DC%2BB3cXitVWgsL3L 32302973 10.1530/ERC-18-0565
Perez-Rivas LG von Selzam V Sharma P Reincke M Theodoropoulou M Prevalence and clinical associations of USP8 variants in corticotroph tumours: a systematic review and aggregate data meta-analysis of 2171 cases Eur. J. Endocrinol. 2025 192 S41 S52 1:CAS:528:DC%2BB2MXhsFOmu7%2FJ 40392165 10.1093/ejendo/lvaf097
Cristescu R et al. Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy Science 2018 362 30309915 6718162 10.1126/science.aar3593 eaar3593
Le DT et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade Science 2017 357 409 413 1:CAS:528:DC%2BC2sXht1aksLnN 28596308 5576142 10.1126/science.aan6733
Ronaghy A et al. Clinical outcomes of tumor-agnostic targeting of BRAF, tumor mutation burden-high, and RET ESMO Open 2025 10 1:STN:280:DC%2BA3cvpt1KqsQ%3D%3D 40460677 12167085 10.1016/j.esmoop.2025.105061 105061
Lin AL et al. Immune checkpoint inhibitor therapy for aggressive pituitary neuroendocrine tumors J. Clin. Endocrinol. Metab. 2025 110 3066 3073 1:CAS:528:DC%2BB2MXis1eqtb7F 40109237 12527438 10.1210/clinem/dgaf178
Chen J et al. Identification of recurrent USP48 and BRAF mutations in Cushing’s disease Nat. Commun. 2018 9 10.1038/s41467-018-05275-5 30093687 6085354 3171
Li C et al. Somatic SF3B1 hotspot mutation in prolactinomas Nat. Commun. 2020 11 1:CAS:528:DC%2BB3cXpvF2lt7k%3D 10.1038/s41467-020-16052-8 32427851 7237453 2506
Perez-Rivas LG et al. TP53 mutations in functional corticotroph tumors are linked to invasion and worse clinical outcome Acta Neuropathol. Commun. 2022 10 139 1:CAS:528:DC%2BB38XisVemt7fP 10.1186/s40478-022-01437-1 36123588 9484083
Pekul M et al. Relevance of mutations in protein deubiquitinases genes and TP53 in corticotroph pituitary tumors Front. Endocrinol. 2024 15 10.3389/fendo.2024.1302667 1302667
Miller DT et al. ACMG SF v3.1 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG) Genet. Med. 2022 24 1407 1414 1:CAS:528:DC%2BB3sXovVeitg%3D%3D 35802134 10.1016/j.gim.2022.04.006
Kuzbari Z et al. Germline-focused analysis of tumour-detected variants in 49,264 cancer patients: ESMO precision medicine working group recommendations Ann. Oncol. 2023 34 215 227 1:CAS:528:DC%2BB3sXhs1Shtbg%3D 36529447 10.1016/j.annonc.2022.12.003
Jaber D Zhang J Godley LA Detecting likely germline variants during tumor-based molecular profiling J. Clin. Invest. 2025 135 1:CAS:528:DC%2BB2MXitFGhsbnO 40759574 12321393 10.1172/JCI190264 e190264
Mosella MS et al. DNA methylation-based signatures classify sporadic pituitary tumors according to clinicopathological features Neuro-Oncology 2021 23 1292 1303 1:CAS:528:DC%2BB3MXisFSht7vM 33631002 8328022 10.1093/neuonc/noab044
Castano JP et al. EndoCompass Project: research roadmap for pituitary and neuroendocrine tumor endocrinology Horm. Res. Paediatr. 2025 98 105 120 1:CAS:528:DC%2BB2MXjtFygu7nP 41308051 12698125
Dutta P et al. Surgery, octreotide, temozolomide, bevacizumab, radiotherapy, and pegvisomant treatment of an AIP mutation-positive child J. Clin. Endocrinol. Metab. 2019 104 3539 3544 31125088 6619489 10.1210/jc.2019-00432
Casey RT et al. International consensus statement on the diagnosis and management of phaeochromocytoma and paraganglioma in children and adolescents Nat. Rev. Endocrinol. 2024 20 729 748 10.1038/s41574-024-01024-5 39147856
Stratakis CA Kirschner LS Carney JA Clinical and molecular features of the Carney complex: diagnostic criteria and recommendations for patient evaluation J. Clin. Endocrinol. Metab. 2001 86 4041 4046 1:CAS:528:DC%2BD3MXmvFCktrk%3D 11549623 10.1210/jcem.86.9.7903
Amar L et al. International consensus on initial screening and follow-up of asymptomatic SDHx mutation carriers Nat. Rev. Endocrinol. 2021 17 435 444 1:CAS:528:DC%2BB3MXhtlegsLfK 10.1038/s41574-021-00492-3 34021277 8205850
eviQ. MEN1 or CDKN1B – risk management. Cancer Institute NSWhttps://www.eviq.org.au/cancer-genetics/adult/risk-management/192-men1-or-cdkn1b-risk-management# (2022).
Stratakis, C. A. in GeneReviews (eds Adam M. P. et al.) https://www.ncbi.nlm.nih.gov/books/NBK1286/ (2023).
