Download PDF
Horm Metab Res 2020; 52(08): 553-561
DOI: 10.1055/a-1143-5930
Review

Clinical and Molecular Update on Genetic Causes of Pituitary Adenomas

Vladimir Vasilev
1   Department of Endocrinology, CHU de Liège, Liège Université, Liège, Belgium
2   Department of Endocrinology, Medical University, Sofia, Bulgaria
,
Adrian F. Daly 
1   Department of Endocrinology, CHU de Liège, Liège Université, Liège, Belgium
,
Sabina Zacharieva
2   Department of Endocrinology, Medical University, Sofia, Bulgaria
,
Albert Beckers
1   Department of Endocrinology, CHU de Liège, Liège Université, Liège, Belgium
› Author Affiliations Funding: This work was supported by grants from the JABBS Foundation, UK and the Fonds d’Investissement Pour la Recherche Scientifique (FIRS), CHU de Liège, Belgium
› Further Information
Also available at
   Permissions and Reprints

Abstract

Pituitary adenomas are benign tumors with variable functional characteristics that can have a significant impact on patients. The majority arise sporadically, but an inherited genetic susceptibility is increasingly being recognized. Recent advances in genetics have widened the scope of our understanding of pituitary tumorigenesis. The clinical and genetic characteristics of pituitary adenomas that develop in the setting of germline-mosaic and somatic GNAS mutations (McCune–Albright syndrome and sporadic acromegaly), germline MEN1 mutations (multiple endocrine neoplasia type 1), and germline PRKAR1A mutations (Carney complex) have been well described. Non-syndromic familial cases of isolated pituitary tumors can occur as familial isolated pituitary adenomas (FIPA); mutations/deletions of the AIP gene have been found in a minority of these. Genetic alterations in GPR101 have been identified recently as causing X-linked acro-gigantism (X-LAG) leading to very early-onset pediatric gigantism. Associations of pituitary adenomas with other tumors have been described in syndromes like multiple endocrine neoplasia type 4, pheochromocytoma-paraganglioma with pituitary adenoma association (3PAs) syndrome and some of their genetic causes have been elucidated. The genetic etiologies of a significant proportions of sporadic corticotropinomas have recently been identified with the discovery of USP8 and USP48 mutations. The elucidation of genetic and molecular pathophysiology in pituitary adenomas is a key factor for better patient management and effective follow-up.

Key words

pituitary adenoma - GNAS - AIP - USP8 - MEN1 - GPR101 - Carney complex - X-LAG - FIPA


Publication History

Received: 14 August 2019

Accepted: 11 March 2020

Article published online:
16 April 2020

© Georg Thieme Verlag KG
Stuttgart · New York

 

  • References

  • 1 Ostrom QT, Gittleman H, Truitt G. et al. CBTRUS Statistical Report: Primary brain and other central nervous system tumors diagnosed in the United States in 2011–2015. Neuro Oncol 2018; 20: iv1-iv86
    CrossrefPubMedGoogle Scholar
  • 2 Ezzat S, Asa SL, Couldwell WT. et al. The prevalence of pituitary adenomas: a systematic review. Cancer 2004; 101: 613-619
    CrossrefPubMedGoogle Scholar
  • 3 Daly AF, Rixhon M, Adam C. et al. High prevalence of pituitary adenomas: A cross-sectional study in the province of Liege, Belgium. J Clin Endocrinol Metab 2006; 91: 4769-4775
    CrossrefPubMedGoogle Scholar
  • 4 Fontana E, Gaillard R. Epidemiology of pituitary adenoma: Results of the first Swiss study. Rev Med Suisse 2009; 5: 2172-2174
    PubMedGoogle Scholar
  • 5 Fernandez A, Karavitaki N, Wass JA. Prevalence of pituitary adenomas: A community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clin Endocrinol (Oxf) 2010; 72: 377-382
    CrossrefPubMedGoogle Scholar
  • 6 Gruppetta M, Mercieca C, Vassallo J. Prevalence and incidence of pituitary adenomas: A population based study in Malta. Pituitary 2013; 16: 545-553
    CrossrefPubMedGoogle Scholar
  • 7 Herman V, Fagin J, Gonsky R. et al. Clonal origin of pituitary adenomas. J Clin Endocrinol Metab 1990; 71: 1427-1433
    CrossrefPubMedGoogle Scholar
  • 8 Daly AF, Tichomirowa MA, Beckers A. The epidemiology and genetics of pituitary adenomas. Best Pract Res Clin Endocrinol Metab 2009; 23: 543-554
    CrossrefPubMedGoogle Scholar
  • 9 Landis CA, Masters SB, Spada A. et al. GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenylyl cyclase in human pituitary tumours. Nature 1989; 340: 692-696
    CrossrefPubMedGoogle Scholar
  • 10 Xekouki P, Azevedo M, Stratakis CA. Anterior pituitary adenomas: Inherited syndromes, novel genes and molecular pathways. Expert Rev Endocrinol Metab 2010; 5: 697-709
    CrossrefPubMedGoogle Scholar
  • 11 Taboada GF, Tabet AL, Naves LA. et al. Prevalence of gsp oncogene in somatotropinomas and clinically non-functioning pituitary adenomas: Our experience. Pituitary 2009; 12: 165-169
    CrossrefPubMedGoogle Scholar
  • 12 Riminucci M, Collins MT, Lala R. et al. An R201H activating mutation of the GNAS1 (Gsalpha) gene in a corticotroph pituitary adenoma. Mol Pathol 2002; 55: 58-60
    CrossrefPubMedGoogle Scholar
  • 13 Spada A, Arosio M, Bochicchio D. et al. Clinical, biochemical, and morphological correlates in patients bearing growth hormone-secreting pituitary tumors with or without constitutively active adenylyl cyclase. J Clin Endocrinol Metab 1990; 71: 1421-1426
    CrossrefPubMedGoogle Scholar
  • 14 Picard C, Silvy M, Gerard C. et al. Gs alpha overexpression and loss of Gs alpha imprinting in human somatotroph adenomas: Association with tumor size and response to pharmacologic treatment. Int J Cancer 2007; 121: 1245-1252
    CrossrefPubMedGoogle Scholar
  • 15 McCune DJ. Osteita fibrosa cystica : the case of nine-year-old girl who also exhibits precocious puberty, multiple pigmentation of the skin and hyperthyroidism. Am J Dis. Children 1936; 52: 743-744
    PubMedGoogle Scholar
  • 16 Vasilev V, Daly AF, Thiry A. et al. McCune-Albright syndrome: A detailed pathological and genetic analysis of disease effects in an adult patient. J Clin Endocrinol Metab 2014; 99: E2029-E2038
    CrossrefPubMedGoogle Scholar
  • 17 Collins MT, Singer FR, Eugster E. McCune-Albright syndrome and the extraskeletal manifestations of fibrous dysplasia. Orphanet J Rare Dis. 2012 7. (Suppl 1): S4
    PubMedGoogle Scholar
  • 18 Mantovani G, Bondioni S, Lania AG. et al. Parental origin of Gsalpha mutations in the McCune-Albright syndrome and in isolated endocrine tumors. J Clin Endocrinol Metab 2004; 89: 3007-3009
    CrossrefPubMedGoogle Scholar
  • 19 Ruggieri P, Sim FH, Bond JR. et al. Malignancies in fibrous dysplasia. Cancer 1994; 73: 1411-1424
    CrossrefPubMedGoogle Scholar
  • 20 Volkl TM, Dorr HG. McCune-Albright syndrome: Clinical picture and natural history in children and adolescents. J Pediatr Endocrinol Metab 2006; 19 (Suppl 2) 551-559
    CrossrefPubMedGoogle Scholar
  • 21 Akintoye SO, Kelly MH, Brillante B. et al. Pegvisomant for the treatment of gsp-mediated growth hormone excess in patients with McCune-Albright syndrome. J Clin Endocrinol Metab 2006; 91: 2960-2966
    CrossrefPubMedGoogle Scholar
  • 22 Reincke M, Sbiera S, Hayakawa A. et al. Mutations in the deubiquitinase gene USP8 cause Cushing's disease. Nat Genet 2015; 47: 31-38
    CrossrefPubMedGoogle Scholar
  • 23 Reyes-Turcu FE, Ventii KH, Wilkinson KD. Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes. Annu Rev Biochem 2009; 78: 363-397
    CrossrefPubMedGoogle Scholar
  • 24 Meijer IM, Kerperien J, Sotoca AM. et al. The Usp8 deubiquitination enzyme is post-translationally modified by tyrosine and serine phosphorylation. Cell Signal 2013; 25: 919-930
    CrossrefPubMedGoogle Scholar
  • 25 Faucz FR, Tirosh A, Tatsi C. et al. Somatic USP8 gene mutations are a common cause of pediatric cushing disease. J Clin Endocrinol Metab 2017; 102: 2836-2843
    CrossrefPubMedGoogle Scholar
  • 26 Albani A, Theodoropoulou M, Reincke M. Genetics of Cushingʼs disease. Clin Endocrinol (Oxf) 2018; 88: 3-12
    CrossrefPubMedGoogle Scholar
  • 27 Hayashi K, Inoshita N, Kawaguchi K. et al. The USP8 mutational status may predict drug susceptibility in corticotroph adenomas of Cushingʼs disease. Eur J Endocrinol 2016; 174: 213-226
    CrossrefPubMedGoogle Scholar
  • 28 Cohen M, Persky R, Stegemann R. et al. Germline USP8 mutation associated with pediatric Cushing disease and other clinical features: A new syndrome. J Clin Endocrinol Metab 2019; 104: 4676-4682
    CrossrefPubMedGoogle Scholar
  • 29 Hernandez-Ramirez LC, Gam R, Valdes N. et al. Loss-of-function mutations in the CABLES1 gene are a novel cause of Cushingʼs disease. Endocr Relat Cancer 2017; 24: 379-392
    CrossrefPubMedGoogle Scholar
  • 30 Roussel-Gervais A, Couture C, Langlais D. et al. The Cables1 gene in glucocorticoid regulation of pituitary corticotrope growth and cushing disease. J Clin Endocrinol Metab 2016; 101: 513-522
    CrossrefPubMedGoogle Scholar
  • 31 Thakker RV. Multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4). Mol Cell Endocrinol 2014; 386: 2-15
    CrossrefPubMedGoogle Scholar
  • 32 Larsson C, Skogseid B, Oberg K. et al. Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma. Nature 1988; 332: 85-87
    CrossrefPubMedGoogle Scholar
  • 33 Chandrasekharappa SC, Guru SC, Manickam P. et al. Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science 1997; 276: 404-407
    CrossrefPubMedGoogle Scholar
  • 34 Lemos MC, Thakker RV. Multiple endocrine neoplasia type 1 (MEN1): Analysis of 1336 mutations reported in the first decade following identification of the gene. Hum Mutat 2008; 29: 22-32
    CrossrefPubMedGoogle Scholar
  • 35 Falchetti A. Genetics of multiple endocrine neoplasia type 1 syndrome: Whatʼs new and what's old. [version 1; peer review: 3 approved]. F1000 Research 2017, 6 (F1000 Faculty Rev): 73
    PubMedGoogle Scholar
  • 36 Falchetti A, Marini F, Luzi E. et al. Multiple endocrine neoplasms. Best Pract Res Clin Rheumatol 2008; 22: 149-163
    CrossrefPubMedGoogle Scholar
  • 37 Marini F, Falchetti A, Del Monte F. et al. Multiple endocrine neoplasia type 1. Orphanet J Rare Dis 2006; 1: 38
    CrossrefPubMedGoogle Scholar
  • 38 Syro LV, Scheithauer BW, Kovacs K. et al. Pituitary tumors in patients with MEN1 syndrome. Clinics (Sao Paulo) 2012; 67 (Suppl. 01) 43-48
    CrossrefPubMedGoogle Scholar
  • 39 Scheithauer BW, Laws ER, Kovacs K. et al. Pituitary adenomas of the multiple endocrine neoplasia type I syndrome. Semin Diagn Pathol 1987; 4: 205-211
    PubMedGoogle Scholar
  • 40 Verges B, Boureille F, Goudet P. 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
    CrossrefPubMedGoogle Scholar
  • 41 Kamilaris CDC, Faucz FR, Voutetakis A. et al. Carney Complex. Exp Clin Endocrinol Diabetes 2019; 127: 156-164
    Article in Thieme ConnectPubMedGoogle Scholar
  • 42 Kirschner LS, Carney JA, Pack SD. et al. Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex. Nat Genet 2000; 26: 89-92
    CrossrefPubMedGoogle Scholar
  • 43 Robinson-White A, Meoli E, Stergiopoulos S. et al. PRKAR1A Mutations and protein kinase A interactions with other signaling pathways in the adrenal cortex. J Clin Endocrinol Metab 2006; 91: 2380-2388
    CrossrefPubMedGoogle Scholar
  • 44 Stratakis CA, Carney JA, Lin JP. et al. Carney complex, a familial multiple neoplasia and lentiginosis syndrome. Analysis of 11 kindreds and linkage to the short arm of chromosome 2. J Clin Invest 1996; 97: 699-705
    CrossrefPubMedGoogle Scholar
  • 45 Forlino A, Vetro A, Garavelli L. et al. PRKACB and Carney complex. N Engl J Med 2014; 370: 1065-1067
    CrossrefPubMedGoogle Scholar
  • 46 Boikos SA, Stratakis CA. Carney complex: The first 20 years. Curr Opin Oncol 2007; 19: 24-29
    CrossrefPubMedGoogle Scholar
  • 47 Kirschner LS. PRKAR1A and the evolution of pituitary tumors. Mol Cell Endocrinol 2010; 326: 3-7
    CrossrefPubMedGoogle Scholar
  • 48 Pepe S, Korbonits M, Iacovazzo D. Germline and mosaic mutations causing pituitary tumours: Genetic and molecular aspects. J Endocrinol 2019; 240: R21-R45
    CrossrefPubMedGoogle Scholar
  • 49 Bertherat J, Horvath A, Groussin L. 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
    CrossrefPubMedGoogle Scholar
  • 50 Pellegata NS, Quintanilla-Martinez L, Siggelkow H. 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
    CrossrefPubMedGoogle Scholar
  • 51 Alrezk R, Hannah-Shmouni F, Stratakis CA. MEN4 and CDKN1B mutations: The latest of the MEN syndromes. Endocr Relat Cancer 2017; 24: T195-T208
    CrossrefPubMedGoogle Scholar
  • 52 Frederiksen A, Rossing M, Hermann P. et al. Clinical Features of Multiple Endocrine Neoplasia Type 4 - Novel pathogenic variant and review of published cases. J Clin Endocrinol Metab 2019; 104: 3637-3646
    CrossrefPubMedGoogle Scholar
  • 53 Lee M, Pellegata NS. Multiple endocrine neoplasia type 4. Front Horm Res 2013; 41: 63-78
    CrossrefPubMedGoogle Scholar
  • 54 Agarwal SK, Mateo CM, Marx SJ. Rare germline mutations in cyclin-dependent kinase inhibitor genes in multiple endocrine neoplasia type 1 and related states. J Clin Endocrinol Metab 2009; 94: 1826-1834
    CrossrefPubMedGoogle Scholar
  • 55 Daly AF, Jaffrain-Rea ML, Ciccarelli A. et al. Clinical characterization of familial isolated pituitary adenomas. J Clin Endocrinol Metab 2006; 91: 3316-3323
    CrossrefPubMedGoogle Scholar
  • 56 Beckers A, Daly AF. The clinical, pathological, and genetic features of familial isolated pituitary adenomas. Eur J Endocrinol 2007; 157: 371-382
    CrossrefPubMedGoogle Scholar
  • 57 Beckers A, Aaltonen LA, Daly AF. et al. 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
    CrossrefPubMedGoogle Scholar
  • 58 Marques NV, Kasuki L, Coelho MC. et al. Frequency of familial pituitary adenoma syndromes among patients with functioning pituitary adenomas in a reference outpatient clinic. J Endocrinol Invest 2017; 40: 1381-1387
    CrossrefPubMedGoogle Scholar
  • 59 Vierimaa O, Georgitsi M, Lehtonen R. et al. Pituitary adenoma predisposition caused by germline mutations in the AIP gene. Science 2006; 312: 1228-1230
    CrossrefPubMedGoogle Scholar
  • 60 Daly AF, Tichomirowa MA, Petrossians P. 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
    CrossrefPubMedGoogle Scholar
  • 61 Hernandez-Ramirez LC, Gabrovska P, Denes J. 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
    CrossrefPubMedGoogle Scholar
  • 62 Lecoq AL, Kamenicky P, Guiochon-Mantel A. et al. Genetic mutations in sporadic pituitary adenomas–what to screen for?. Nat Rev Endocrinol 2015; 11: 43-54
    CrossrefPubMedGoogle Scholar
  • 63 Beckers A, Petrossians P, Hanson J, Daly AF. The causes and consequences of pituitary gigantism. Nat Rev Endocrinol 2018; 14: 705-720
    CrossrefPubMedGoogle Scholar
  • 64 Ozfirat Z, Korbonits M. AIP gene and familial isolated pituitary adenomas. Mol Cell Endocrinol 2010; 326: 71-79
    CrossrefPubMedGoogle Scholar
  • 65 Formosa R, Borg J, Vassallo J. Aryl hydrocarbon receptor (AHR) is a potential tumour suppressor in pituitary adenomas. Endocr Relat Cancer 2017; 24: 445-457
    CrossrefPubMedGoogle Scholar
  • 66 Kazlauskas A, Poellinger L, Pongratz I. The immunophilin-like protein XAP2 regulates ubiquitination and subcellular localization of the dioxin receptor. J Biol Chem 2000; 275: 41317-41324
    CrossrefPubMedGoogle Scholar
  • 67 Tuominen I, Heliovaara E, Raitila A. et al. AIP inactivation leads to pituitary tumorigenesis through defective Galphai-cAMP signaling. Oncogene 2015; 34: 1174-1184
    CrossrefPubMedGoogle Scholar
  • 68 Hernandez-Ramirez LC, Trivellin G, Stratakis CA. Role of Phosphodiesterases on the Function of Aryl Hydrocarbon Receptor-Interacting Protein (AIP) in the Pituitary Gland and on the Evaluation of AIP Gene Variants. Horm Metab Res 2017; 49: 286-295
    Article in Thieme ConnectPubMedGoogle Scholar
  • 69 Schernthaner-Reiter MH, Trivellin G, Stratakis CA. Interaction of AIP with protein kinase A (cAMP-dependent protein kinase). Hum Mol Genet 2018; 27: 2604-2613
    CrossrefPubMedGoogle Scholar
  • 70 Hernandez-Ramirez LC, Morgan RML, Barry S. et al. Multi-chaperone function modulation and association with cytoskeletal proteins are key features of the function of AIP in the pituitary gland. Oncotarget 2018; 9: 9177-9198
    CrossrefPubMedGoogle Scholar
  • 71 Rostomyan L, Potorac I, Beckers P. et al. AIP mutations and gigantism. Ann Endocrinol (Paris) 2017; 78: 123-130
    CrossrefPubMedGoogle Scholar
  • 72 Trivellin G, Daly AF, Faucz FR. et al. Gigantism and acromegaly due to Xq26 microduplications and GPR101 mutation. N Engl J Med 2014; 371: 2363-2374
    CrossrefPubMedGoogle Scholar
  • 78 Beckers A, Lodish MB, Trivellin G. et al. X-linked acrogigantism syndrome: Clinical profile and therapeutic responses. Endocr Relat Cancer 2015; 22: 353-367
    CrossrefPubMedGoogle Scholar
  • 73 Iacovazzo D, Caswell R, Bunce B. et al. Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study. Acta Neuropathol Commun 2016; 4: 56
    CrossrefPubMedGoogle Scholar
  • 74 Trivellin G, Bjelobaba I, Daly AF. et al. Characterization of GPR101 transcript structure and expression patterns. J Mol Endocrinol 2016; 57: 97-111
    CrossrefPubMedGoogle Scholar
  • 75 Daly AF, Lysy PA, Desfilles C. et al. GHRH excess and blockade in X-LAG syndrome. Endocr Relat Cancer 2016; 23: 161-170
    CrossrefPubMedGoogle Scholar
  • 76 Beckers A, Rostomyan L, Potorac I. et al. X-LAG: How did they grow so tall?. Ann Endocrinol (Paris) 2017; 78: 131-136
    CrossrefPubMedGoogle Scholar
  • 77 Daly AF, Yuan B, Fina F. et al. Somatic mosaicism underlies X-linked acrogigantism syndrome in sporadic male subjects. Endocr Relat Cancer 2016; 23: 221-233
    CrossrefPubMedGoogle Scholar
  • 79 Xekouki P, Pacak K, Almeida M. et al. Succinate dehydrogenase (SDH) D subunit (SDHD) inactivation in a growth-hormone-producing pituitary tumor: A new association for SDH?. J Clin Endocrinol Metab 2012; 97: E357-E366
    CrossrefPubMedGoogle Scholar
  • 80 Xekouki P, Szarek E, Bullova P. et al. Pituitary adenoma with paraganglioma/pheochromocytoma (3PAs) and succinate dehydrogenase defects in humans and mice. J Clin Endocrinol Metab 2015; 100: E710-E719
    CrossrefPubMedGoogle Scholar
  • 81 Hernandez-Ramirez LC, Stratakis CA. Genetics of Cushingʼs Syndrome. Endocrinol Metab Clin North Am 2018; 47: 275-297
    CrossrefPubMedGoogle Scholar
  • 82 O'Toole SM, Denes J, Robledo M. et al. 15 Years of Paraganglioma: The association of pituitary adenomas and phaeochromocytomas or paragangliomas. Endocr Relat Cancer 2015; 22: T105-T122
    CrossrefPubMedGoogle Scholar
  • 83 Selak MA, Armour SM, MacKenzie ED. et al. Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer Cell 2005; 7: 77-85
    CrossrefPubMedGoogle Scholar
  • 84 Letouze E, Martinelli C, Loriot C. et al. SDH mutations establish a hypermethylator phenotype in paraganglioma. Cancer Cell 2013; 23: 739-752
    CrossrefPubMedGoogle Scholar
  • 85 Mannelli M, Canu L, Ercolino T. et al. Diagnosis of Endocrine Disease: SDHx mutations: beyond pheochromocytomas and paragangliomas. Eur J Endocrinol 2018; 178: R11-R17
    CrossrefPubMedGoogle Scholar
  • 86 Tufton N, Roncaroli F, Hadjidemetriou I. et al. Pituitary carcinoma in a patient with an SDHB mutation. Endocr Pathol 2017; 28: 320-325
    CrossrefPubMedGoogle Scholar
  • 87 Denes J, Swords F, Rattenberry E. et al. Heterogeneous genetic background of the association of pheochromocytoma/paraganglioma and pituitary adenoma: Rresults from a large patient cohort. J Clin Endocrinol Metab 2015; 100: E531-E541
    CrossrefPubMedGoogle Scholar
  • 88 Daly AF, Castermans E, Oudijk L. et al. Pheochromocytomas and pituitary adenomas in three patients with MAX exon deletions. Endocr Relat Cancer 2018; 25: L37-L42
    CrossrefPubMedGoogle Scholar
  • 89 Williams VC, Lucas J, Babcock MA. et al. Neurofibromatosis type 1 revisited. Pediatrics 2009; 123: 124-133
    CrossrefPubMedGoogle Scholar
  • 90 Hannah-Shmouni F, Trivellin G, Stratakis CA. Genetics of gigantism and acromegaly. Growth Horm IGF Res 2016; 30–31: 37-41
    CrossrefPubMedGoogle Scholar
  • 91 Schultz KAP, Williams GM, Kamihara J. et al. DICER1 and associated conditions: Identification of at-risk individuals and recommended surveillance strategies. Clin Cancer Res 2018; 24: 2251-2261
    CrossrefPubMedGoogle Scholar
  • 92 de Kock L, Sabbaghian N, Plourde F. et al. Pituitary blastoma: A pathognomonic feature of germ-line DICER1 mutations. Acta Neuropathol 2014; 128: 111-122
    CrossrefPubMedGoogle Scholar
  • 93 Solarski M, Rotondo F, Foulkes WD. et al. DICER1 gene mutations in endocrine tumors. Endocr Relat Cancer 2018; 25: R197-R208
    CrossrefPubMedGoogle Scholar
  • 94 Scheithauer BW, Kovacs K, Horvath E. et al. Pituitary blastoma. Acta Neuropathol 2008; 116: 657-666
    CrossrefPubMedGoogle Scholar
  • 95 Lam HC, Nijmeh J, Henske EP. New developments in the genetics and pathogenesis of tumours in tuberous sclerosis complex. J Pathol 2017; 241: 219-225
    CrossrefPubMedGoogle Scholar
  • 96 Tigas S, Carroll PV, Jones R. et al. Simultaneous Cushingʼs disease and tuberous sclerosis; a potential role for TSC in pituitary ontogeny. Clin Endocrinol (Oxf) 2005; 63: 694-695
    CrossrefPubMedGoogle Scholar
  • 97 Nandagopal R, Vortmeyer A, Oldfield EH. et al. Cushing's syndrome due to a pituitary corticotropinoma in a child with tuberous sclerosis: An association or a coincidence?. Clin Endocrinol (Oxf) 2007; 67: 639-641
    PubMedGoogle Scholar