Characteristics of familial isolated pituitary adenomas (FIPA) - Review

adenoma; aryl hydrocarbon receptor interacting protein; Carney's complex; familial; familial isolated pituitary adenomas; multiple endocrine neoplasia type 1; pituitary

Abstract :

[en] The familial occurrence of pituitary adenomas has been recognized for many years and currently accounts for approximately 5% of all cases. Molecular, genetic and clinical features of familial pituitary adenomas have been well characterized in multiple endocrine neoplasia type 1 (MEN-1) and Carney's complex (CNC), which account for the majority of familial pituitary tumor cases. These conditions are caused by MEN1 and PRKAR1A gene mutations, respectively, and the clinical and pathological features of pituitary pathology in these diseases differ from those of sporadic pituitary tumors. Familial acromegaly has been recognized for many years and, more recently, the clinical features of this clinical phenotype, referred to as isolated familial somatotropinoma, have been clarified. Over the past decade, the concept of non-MEN-1/CNC familial pituitary tumors has been expanded significantly to include all phenotypes, a condition known as familial isolated pituitary adenomas (FIPA). In FIPA, tumors can present homogeneously (same phenotype) or heterogeneously (different tumor phenotypes) within the same family. Compared with sporadic pituitary adenomas, patients with FIPA have a younger age at diagnosis and have larger tumors. The clinical features of FIPA differ from those of MEN-1 in terms of a higher frequency of somatotropinomas and a lower frequency of prolactinomas. The recent discovery of the involvement of mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene in association with pituitary tumors has provided new information regarding potential mechanisms of tumorigenesis in FIPA patients. While very infrequent in sporadic pituitary tumors, approximately 15% of FIPA patients have AIP mutations, rising to half of patients with familial acromegaly. In this review, we detail the clinical features of FIPA and discuss tumor pathology and genetic findings in this increasingly recognized clinical condition.

Disciplines :

Endocrinology, metabolism & nutrition

Author, co-author :

Daly, Adrian ; Université de Liège - ULiège > Département des sciences cliniques > Endocrinologie

Vanbellinghen, Jean-François ; Université de Liège - ULiège > Centre de diagnostic moleculaire

Beckers, Albert ; Université de Liège - ULiège > Département des sciences cliniques > Endocrinologie

Language :

English

Title :

Characteristics of familial isolated pituitary adenomas (FIPA) - Review

Publication date :

2007

Journal title :

Expert Review of Endocrinology and Metabolism

ISSN :

1744-6651

eISSN :

1744-8417

Publisher :

Future Medicine Ltd

Volume :

Issue :

Pages :

725-733

Peer reviewed :

Peer Reviewed verified by ORBi

Commentary :

Invited Review Article

Available on ORBi :

since 08 July 2010

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Bibliography

Ezzat S, Asa SL, Couldwell WT et al. The prevalence of pituitary adenomas: a systematic review. Cancer 101 (3), 613-619 (2004).
Davis JR, Farrell WE, Clayton RN. Pituitary tumours. Reproduction 121(3), 363-371 (2001).
Daly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA, Beckers A. High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium. J. Clin. Endocrinol. Metab. 91, 4769-4775 (2006).
Asa SL, Ezzat S. Genetics and proteomics of pituitary tumors. Endocrine 28 (1), 43-47 (2005).
Daly AF, Jaffrain-Rea ML, Beckers A. Clinical and genetic features of familial pituitary adenomas. Horm. Metab. Res. 37(6), 347-354 (2005).
Scheithauer BW, Laws ER Jr, Kovacs K, Horvath E, Randall RV, Carney JA. Pituitary adenomas of the multiple endocrine neoplasia type I syndrome. Semin. Diagn. Pathol. 4(3), 205-211 (1987).
Daly AF, Jaffrain-Rea ML, Ciccarelli A et al. Clinical characterization of familial isolated pituitary adenomas. J. Clin. Endocrinol. Metab. 91(9), 3316-3323 (2006).
Vierimaa 0, Georgitsi M, Lehtonen R et al. Pituitary adenoma predisposition caused by germline mutations in the AIP gene. Science 312(5777), 1228-30 (2006).
Daly AF, Vanbellinghen JF, Khoo SK et al. Aryl hydrocarbon receptor-interacting protein gene mutations in familial isolated pituitary adenomas: analysis in 73 families. J. Clin. Endocrinol. Metab. 92(5), 1891-1896 (2007).
Agarwal SK, Lee Burns A, Sukhodolets KE et al. Molecular pathology of the MEN1 gene. Ann. NY Acad. Sci. 1014, 189-198 (2004).
Chandrasekharappa SC, Guru SC, Manickam P et al. A Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science 276 (5311), 404-407 (1997).
Hai N, Aoki N, Shimatsu A, Mori T, Kosugi S. Clinical features of multiple endocrine neoplasia type 1 (MEN1) phenocopy without germline MEN1 gene mutations: analysis of 20 Japanese sporadic cases with MEN1. Clin. Endocrinol. (Oxford) 52(4), 509-518 (2000).
Burgess JR, Nord B, David R et al. Phenotype and phenocopy: the relationship between genotype and clinical phenotype in a single large family with multiple endocrine neoplasia type 1 (MEN1). Clin. Endocrinol. (Oxford) 53(2), 205-211 (2000).
Scacheri PC, Davis S, Odom DT et al. Genome-wide analysis of menin binding provides insights into MEN1 tumorigenesis. PLoS Genet. 2(4), e51 (2006).
Agarwal SK, Impey S, McWeeney S et al. Distribution of menin-occupied regions in chromatin specifies a broad role of menin in transcriptional regulation. Neoplasia 9 (2), 101-107 (2007).
Crabtree JS, Scacheri PC, Ward JM et al. A mouse model of multiple endocrine neoplasia, type 1, develops multiple endocrine tumors. Proc. Natl Acad. Sci, USA 980, 1118-1123 (2001).
Bertolino P, Tong WM, Galendo D, Wang ZQ, Zhang CX. Heterozygous Men1 mutant mice develop a range of endocrine tumors mimicking multiple endocrine neoplasia type 1. Mol. Endocrinol. 17(9), 1880-1892 (2003).
Biondi CA, Gartside MG, Waring P et al. Conditional inactivation of the MEN1 gene leads to pancreatic and pituitary tumorigenesis but does not affect normal development of these tissues. Mol. Cell. Biol. 24(8), 3125-3131 (2004).
Zhuang Z, Vortmeyer AO, Pack S et al. Somatic mutations of the MEN1 tumor suppressor gene in sporadic gastrinomas and insulinomas. Cancer Res. 57(21), 4682-4686 (1997).
Vergès 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. 87(2), 457-465 (2002).
Beckers A, Betea D, Valdes Socin H, Stevenaert A. The treatment of sporadic versus MEN1-related pituitary adenomas. J. Intern. Med. 253(6), 599-605 (2003).
Carney JA, Hruska LS, Beauchamp GD, Gordon H. Dominant inheritance of the complex of myxomas, spotty pigmentation and endocrine overactivity. Mayo Clin. Proc. 61, 165-172 (1985).
Casey M, Mah C, Merliss AD et al. Identification of a novel genetic locus for familial cardiac myxomas and Carney complex. Circulation 98, 2560-2566 (1998).
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. 86(9), 4041-4046 (2001).
Griffin KJ, Kirschner LS, Matyakhina L et al. Down-regulation of regulatory subunit Type 1A of protein kinase A leads to endocrine and other tumors. Cancer Res. 64(24), 8811-5 (2004).
Griffin KJ, Kirschner LS, Matyakhina L et al. A transgenic mouse bearing an antisense construct of regulatory subunit type 1A of protein kinase A develops endocrine and other tumours. J Med. Genet. 41(12), 923-31 (2004).
Stergiopoulos SC, Stratakis CA. Human tumors associated with Carney complex and germline PPKAR1A mutations: a protein kinase A disease! FEBS Lett. 546, 59-64 (2003).
Pack SD, Kirschner LS, Pak E, Zhuang Z, Carney JA, Stratakis CA. Genetic and histological studies of somatomammotropic tumors in patients with the 'complex of spotty skin pigmentation, myxomas, endocrine everactivity and schwannomas' (Carney complex). J Clin. Endocripol. Metab. 85(10), 3860-3865 (2000).
Frohman LA, Eguchi K. Familial acromegaly. Growth Horm. IGF Res. 14(Suppl. A), S90-S96 (2004).
Yamada S, Yoshimoto K, Sano T et al. Inactivation of the tumor suppressor gene on 11q13 in brothers with familial acrogigantism without multiple endocrine neoplasia type 1. J. Clin. Endocrinol. Metab. 82(1), 239-242 (1997).
Lucio-Camelo DC, Une KN, Ferreira RES et al. A meiotic recombination in a new isolated familial somatotropinoma kindred. Eur. J. Endocrinol. 150, 643-648 (2004).
Valdes-Socin H, Poncin I Stevens V, Stevenaert A, Beckers A. Adenomes hypophysaires familiaux-isoles non lies ayec la mutation somatique NEM-1. Suivi de 27 patients. Ann. Endocrinol. (Paris) 61(4), 301 (2000).
Beckers A. Familial isolated pituitary adenomas. In: The Ninth International Workshop on Multiple Endocrine Neoplasia MEN2004). J. Intern. Med. 255(6), 696-730 (2004).
Marx SJ, Simonds WF. Hereditary hormone excess: genes, molecular pathways, and syndromes. Endocr. Rev. 26(5), 615-661 (2005).
Ciccarelli A, Daly AF, Beckers A. The epidemiology of prolactinomas. Pituitary 8(1), 3-6 (2005).
Iwata T, Yamada S, Mizusawa N, Golam HM, Sano T, Yoshimoto K. The aryl hydrocarbon receptor-interacting protein gene is rarely mutated in sporadic GH-secreting adenomas. Clin. Endocrinol. (Oxford) 66(4), 499-502 (2007).
Toledo RA, Lourenco DM Jr, Liberman B et al. Germline mutation in the aryl hydrocarbon receptor interacting protein gene in familial somatotropinoma. J. Clin. Endocrinol. Metab. 92(5), 1934-1937 (2007).
Yu R, Bonert V, Saporta I, Raffel LJ, Melmed S. AIP variants in sporadic pituitary adenomas. J. Clin. Endocrinol. Metab. 91(12), 5126-5129 (2006).
Barlier A, Vanbellinghen JF, Daly AF et al. Mutations in the aryl hydrocarbon receptor interacting protein gene are not highly prevalent among subjects with sporadic pituitary adenomas. J. Clin. Endocrinol. Metab. 92(5), 1952-1955 (2007).
Georgitsi M, Raitila A, Karhu A et al. Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations. Proc. Natl Acad. Sci. USA 104(10), 4101-4105 (2007).
Cazabat L, Libe R, Perlemoine K et al. Germline inactivating mutations of the aryl hydrocarbon receptor-interacting protein gene in a large cohort of sporadic acromegaly: mutations are found in a subset of young patients with macroadenomas. Eur. J. Endocrinol. 157(1), 1-8 (2007).
Georgitsi M, Karhu A, Winqvist R et al. Mutation analysis of aryl hydrocarbon receptor interacting protein (AIP) gene in colorectal, breast, and prostate cancers. Br. J. Cancer 96(2), 352-356 (2007).
Carver LA, LaPres JJ, Jain S, Dunham EE, Bradfield CA. Characterization of the Ah receptor-associated protein, ARA9. J. Biol. Chem. 273(50), 33580-33587 (1998).
Petruits JR, Perdew GH. The role of chaperone proteins in the aryl hydrocarbon receptor core complex. Chem. Biol. Interact. 141(1-2), 25-40 (2002).
Meyer BK, Petrulis JR, Perdew GH. Aryl hydrocarbon (Ah) receptor levels are selectively modulated by hsp90-associated immunophilin homolog XAP2. Cell Stress Chaperones 5(3), 243-254 (2000).
Bell DR, Poland A. Binding of aryl hydrocarbon receptor (AhR)) to AhR-interacting protein. The role of hsp90. J Biol. Chem. 275(46), 36407-36414 (2000).
Meyer BK, Perdew GH. Characterization of the AhR-hsp90-XAP2 core complex and the role of the immunophilin-related protein XAP2 in AhR stabilization. Biochemistry 38(28), 8907-8917 (1999).
Lees MJ, Peet DJ, Whitelaw ML. Defining the role for XAP2 in stabilization of the dioxin receptor. J Biol. Chem. 278(38), 35878-35888 (2003).
Lee K, Burgoon LD, Lamb L et al. Identification and characterization of genes susceptible to transcriptional cross-talk between the hypoxia and dioxin signaling cascades. Chem. Res. Toxicol. 19(10), 1284-1293 (2006).
Bolger GB, Peden AH, Steele MR et al. Attenuation of the activity of the cAMP-specific phosphodiesterase PDE4A5 by interaction with the immunophilin XAP2. J. Biol. Chem. 278(35), 33351-33363 (2003).
de Oliveira SK, Hoffmeister M, Gambaryan S, Muller-Esterl W, Guimaraes A Smolenski AP. Phosphodiesterase 2A forms a complex with the co-chaperone XAP2 and regulates nuclear translocation of the aryl hydrocarbon receptor. J. Biol. Chem. 4(18) 13656-13663 (2007).
Gueorguiev M, Quinton R, Chapple R et al. The role of AIP in familial acromegaly. The Endocrine Society 89th Annual Congress, Toronto, Canada, June 2-5, 2007 (OR15-2).