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Genetics of Pituitary Gigantism: Syndromic and Nonsyndromic Causes

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Book cover Polyendocrine Disorders and Endocrine Neoplastic Syndromes

Part of the book series: Endocrinology ((ENDOCR))

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Abstract

The last decades have seen an expansion of knowledge regarding GH-secreting pituitary adenomas in general and gigantism in particular. New conditions, such as familial isolated pituitary adenomas (FIPA) and X-linked acrogigantism (X-LAG), have been identified, as have some important underlying genetic and molecular factors that contribute to somatotropinoma tumorigenesis and behavior. These discoveries have prompted the study of large series of patients, which have revealed specific disease characteristics. Thorough assessment of each patient in order to correctly classify the disease is essential for optimal treatment and follow-up.

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References

  • Agarwal SK, Lee Burns A, Sukhodolets KE, Kennedy PA, Obungu VH, Hickman AB, et al. Molecular pathology of the MEN1 gene. Ann N Y Acad Sci. 2004;1014:189–98.

    Article  CAS  PubMed  Google Scholar 

  • Agustsson TT, Baldvinsdottir T, Jonasson JG, Olafsdottir E, Steinthorsdottir V, Sigurdsson G, et al. The epidemiology of pituitary adenomas in Iceland, 1955-2012: a nationwide population-based study. Eur J Endocrinol. 2015;173:655–64.

    Article  CAS  PubMed  Google Scholar 

  • Akintoye SO, Kelly MH, Brillante B, Cherman N, Turner S, Butman JA, et al. Pegvisomant for the treatment of gsp-mediated growth hormone excess in patients with McCune-Albright syndrome. J Clin Endocrinol Metab. 2006;91:2960–6.

    Article  CAS  PubMed  Google Scholar 

  • Beckers A, Betea D, Valdes Socin H, Stevenaert A. The treatment of sporadic versus MEN1-related pituitary adenomas. J Intern Med. 2003;253:599–605.

    Article  CAS  PubMed  Google Scholar 

  • 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;34:239–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beckers A, Lodish MB, Trivellin G, Rostomyan L, Lee M, Faucz FR, et al. X-linked acrogigantism syndrome: clinical profile and therapeutic responses. Endocr Relat Cancer. 2015;22:353–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beckers A, Rostomyan L, Daly AF. Chapter 4 – functioning pituitary adenomas A2 – Weiss, Roy E. In: Refetoff S, editor. Genetic diagnosis of endocrine disorders. 2nd ed. San Diego: Academic Press; 2016.

    Google Scholar 

  • Beckers A, Fernandes D, Fina F, Novak M, Abati A, Rostomyan L, et al. Paleogenetic study of ancient DNA suggestive of X-linked acrogigantism. Endocr Relat Cancer. 2017;24:L17–20.

    Article  PubMed  Google Scholar 

  • Beckers A, Petrossians P, Hanson J, Daly AF. The causes and consequences of pituitary gigantism. Nat Rev Endocrinol. 2018;14(12):705–20.

    Article  CAS  PubMed  Google Scholar 

  • Benito M, Asa SL, Livolsi VA, West VA, Snyder PJ. Gonadotroph tumor associated with multiple endocrine neoplasia type 1. J Clin Endocrinol Metab. 2005;90:570–4.

    Article  CAS  PubMed  Google Scholar 

  • Bertherat J, Horvath A, Groussin L, Grabar S, Boikos S, Cazabat 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;94:2085–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boikos SA, Stratakis CA. Pituitary pathology in patients with Carney complex: growth-hormone producing hyperplasia or tumors and their association with other abnormalities. Pituitary. 2006;9:203–9.

    Article  CAS  PubMed  Google Scholar 

  • Borson-Chazot F, Garby L, Raverot G, Claustrat F, Raverot V, Sassolas G, G. T. E. group. Acromegaly induced by ectopic secretion of GHRH: a review 30 years after GHRH discovery. Ann Endocrinol (Paris). 2012;73:497–502.

    Article  CAS  Google Scholar 

  • Burgess JR, Shepherd JJ, Parameswaran V, Hoffman L, Greenaway TM. Spectrum of pituitary disease in multiple endocrine neoplasia type 1 (MEN 1): clinical, biochemical, and radiological features of pituitary disease in a large MEN 1 kindred. J Clin Endocrinol Metab. 1996;81:2642–6.

    CAS  PubMed  Google Scholar 

  • Caputo M, Ucciero A, Mele C, De Marchi L, Magnani C, Cena T, et al. Use of administrative health databases to estimate incidence and prevalence of acromegaly in Piedmont region, Italy. J Endocrinol Investig. 2018;42(4):397–402.

    Article  CAS  Google Scholar 

  • Carney JA, Hruska LS, Beauchamp GD, Gordon H. Dominant inheritance of the complex of myxomas, spotty pigmentation, and endocrine overactivity. Mayo Clin Proc. 1986;61:165–72.

    Article  CAS  PubMed  Google Scholar 

  • Castinetti F, Daly AF, Stratakis CA, Caberg JH, Castermans E, Trivellin G, et al. GPR101 mutations are not a frequent cause of congenital isolated growth hormone deficiency. Horm Metab Res. 2016;48:389–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chahal HS, Stals K, Unterlander M, Balding DJ, Thomas MG, Kumar AV, et al. AIP mutation in pituitary adenomas in the 18th century and today. N Engl J Med. 2011;364:43–50.

    Article  CAS  PubMed  Google Scholar 

  • Chahal HS, Trivellin G, Leontiou CA, Alband N, Fowkes RC, Tahir A, et al. Somatostatin analogs modulate AIP in somatotroph adenomas: the role of the ZAC1 pathway. J Clin Endocrinol Metab. 2012;97:E1411–20.

    Article  CAS  PubMed  Google Scholar 

  • Chandrasekharappa SC, Guru SC, Manickam P, Olufemi SE, Collins FS, Emmert-Buck MR, et al. Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science. 1997;276:404–7.

    Article  CAS  PubMed  Google Scholar 

  • Concolino P, Costella A, Capoluongo E. Multiple endocrine neoplasia type 1 (MEN1): an update of 208 new germline variants reported in the last nine years. Cancer Genet. 2016;209:36–41.

    Article  PubMed  Google Scholar 

  • Correa R, Salpea P, Stratakis CA. Carney complex: an update. Eur J Endocrinol. 2015;173:M85–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cuny T, Pertuit M, Sahnoun-Fathallah M, Daly A, Occhi G, Odou MF, et al. Genetic analysis in young patients with sporadic pituitary macroadenomas: besides AIP don't forget MEN1 genetic analysis. Eur J Endocrinol. 2013;168:533–41.

    Article  CAS  PubMed  Google Scholar 

  • Daly AF, Beckers A. Familial isolated pituitary adenomas (FIPA) and mutations in the aryl hydrocarbon receptor interacting protein (<em>AIP</em>) gene. Endocrinol Metab Clin. 2015;44:19–25.

    Article  Google Scholar 

  • Daly AF, Beckers A. The role of AIP mutations in pituitary adenomas: 10 years on. Endocrine. 2017;55:333–5.

    Article  CAS  PubMed  Google Scholar 

  • Daly AF, Jaffrain-Rea ML, Ciccarelli A, Valdes-Socin H, Rohmer V, Tamburrano G, et al. Clinical characterization of familial isolated pituitary adenomas. J Clin Endocrinol Metab. 2006a;91:3316–23.

    Article  CAS  PubMed  Google Scholar 

  • 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. 2006b;91:4769–75.

    Article  CAS  PubMed  Google Scholar 

  • Daly AF, Vanbellinghen JF, Khoo SK, Jaffrain-Rea ML, Naves LA, Guitelman MA, et al. Aryl hydrocarbon receptor-interacting protein gene mutations in familial isolated pituitary adenomas: analysis in 73 families. J Clin Endocrinol Metab. 2007;92:1891–6.

    Article  CAS  PubMed  Google Scholar 

  • Daly AF, Tichomirowa MA, Petrossians P, Heliovaara E, Jaffrain-Rea ML, Barlier A, 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:E373–83.

    Article  PubMed  Google Scholar 

  • Daly AF, Lysy PA, Desfilles C, Rostomyan L, Mohamed A, Caberg JH, et al. GHRH excess and blockade in X-LAG syndrome. Endocr Relat Cancer. 2016a;23:161–70.

    Article  CAS  PubMed  Google Scholar 

  • Daly AF, Yuan B, Fina F, Caberg JH, Trivellin G, Rostomyan L, et al. Somatic mosaicism underlies X-linked acrogigantism syndrome in sporadic male subjects. Endocr Relat Cancer. 2016b;23:221–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Daly AF, Castermans E, Oudijk L, Guitelman MA, Beckers P, Potorac I, et al. Pheochromocytomas and pituitary adenomas in three patients with MAX exon deletions. Endocr Relat Cancer. 2018;25:L37–42.

    Article  CAS  PubMed  Google Scholar 

  • Daly A, Rostomyan L, Betea D, Bonneville JF, Villa C, Pellegata NS, Waser B, Reubi JC, Waeber Stephan C, Christ E, Beckers A. AIP-mutated acromegaly resistant to first-generation somatostatin analogs: long-term control with pasireotide LAR in two patients. Endocr Connect. 2019a. pii: EC-19-0004.R1. https://doi.org/10.1530/EC-19-0004.

    Article  PubMed Central  PubMed  Google Scholar 

  • Daly A, Cano DA, Venegas E, Petrossians P, Dios E, Castermans E, Flores-Martínez A, Bours V, Beckers A, Soto A. AIP and MEN1 mutations and AIP immunohistochemistry in pituitary adenomas in a tertiary referral center. Endocr Connect. 2019b. pii: EC-19-0027.R3. https://doi.org/10.1530/EC-19-0027.

    Article  PubMed Central  PubMed  Google Scholar 

  • De Menis E, Prezant TR. Isolated familial somatotropinomas: clinical features and analysis of the MEN1 gene. Pituitary. 2002;5:11–5.

    Article  PubMed  Google Scholar 

  • Denes J, Swords F, Rattenberry E, Stals K, Owens M, Cranston T, et al. Heterogeneous genetic background of the association of pheochromocytoma/paraganglioma and pituitary adenoma: results from a large patient cohort. J Clin Endocrinol Metab. 2015;100:E531–41.

    Article  CAS  PubMed  Google Scholar 

  • Dumitrescu CE, Collins MT. McCune-Albright syndrome. Orphanet J Rare Dis. 2008;3:12.

    Article  PubMed  PubMed Central  Google Scholar 

  • Dwight T, Mann K, Benn DE, Robinson BG, McKelvie P, Gill AJ, et al. Familial SDHA mutation associated with pituitary adenoma and pheochromocytoma/paraganglioma. J Clin Endocrinol Metab. 2013;98:E1103–8.

    Article  CAS  PubMed  Google Scholar 

  • Fernandez A, Karavitaki N, Wass JAH. Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clin Endocrinol. 2010;72:377–82.

    Article  Google Scholar 

  • Forlino A, Vetro A, Garavelli L, Ciccone R, London E, Stratakis CA, Zuffardi O. PRKACB and Carney complex. N Engl J Med. 2014;370:1065–7.

    Article  CAS  PubMed  Google Scholar 

  • Formosa R, Vassallo J. Aryl hydrocarbon receptor-interacting protein (AIP) N-terminus gene mutations identified in pituitary adenoma patients alter protein stability and function. Horm Cancer. 2017;8:174–84.

    Article  CAS  PubMed  Google Scholar 

  • Formosa R, Xuereb-Anastasi A, Vassallo J. Aip regulates cAMP signalling and GH secretion in GH3 cells. Endocr Relat Cancer. 2013;20:495–505.

    Article  CAS  PubMed  Google Scholar 

  • Gadelha MR, Une KN, Rohde K, Vaisman M, Kineman RD, Frohman LA. Isolated familial somatotropinomas: establishment of linkage to chromosome 11q13.1-11q13.3 and evidence for a potential second locus at chromosome 2p16-12. J Clin Endocrinol Metab. 2000;85:707–14.

    CAS  PubMed  Google Scholar 

  • Galland F, Kamenicky P, Affres H, Reznik Y, Pontvert D, Le Bouc Y, et al. McCune-Albright syndrome and acromegaly: effects of hypothalamopituitary radiotherapy and/or pegvisomant in somatostatin analog-resistant patients. J Clin Endocrinol Metab. 2006;91:4957–61.

    Article  CAS  PubMed  Google Scholar 

  • Gatto F, Trifiro G, Lapi F, Cocchiara F, Campana C, Dell’Aquila C, et al. Epidemiology of acromegaly in Italy: analysis from a large longitudinal primary care database. Endocrine. 2018;61:533–41.

    Article  CAS  PubMed  Google Scholar 

  • Gordon RJ, Bell J, Chung WK, David R, Oberfield SE, Wardlaw SL. Childhood acromegaly due to X-linked acrogigantism: long term follow-up. Pituitary. 2016;19:560–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goudet P, Murat A, Binquet C, Cardot-Bauters C, Costa A, Ruszniewski P, et al. Risk factors and causes of death in MEN1 disease. A GTE (Groupe d'Etude des Tumeurs endocrines) cohort study among 758 patients. World J Surg. 2010;34:249–55.

    Article  PubMed  Google Scholar 

  • Gruppetta M, Mercieca C, Vassallo J. Prevalence and incidence of pituitary adenomas: a population based study in Malta. Pituitary. 2013;16:545–53.

    Article  PubMed  Google Scholar 

  • Hernandez-Ramirez LC, Gabrovska P, Denes J, Stals K, Trivellin G, Tilley D, et al. Landscape of familial isolated and young-onset pituitary adenomas: prospective diagnosis in AIP mutation carriers. J Clin Endocrinol Metab. 2015;100:E1242–54.

    Article  PubMed  PubMed Central  Google Scholar 

  • Iacovazzo D, Caswell R, Bunce B, Jose S, Yuan B, Hernandez-Ramirez LC, et al. Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study. Acta Neuropathol Commun. 2016;4:56.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Igreja S, Chahal HS, King P, Bolger GB, Srirangalingam U, Guasti L, et al. Characterization of aryl hydrocarbon receptor interacting protein (AIP) mutations in familial isolated pituitary adenoma families. Hum Mutat. 2010;31:950–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jaffrain-Rea ML, Angelini M, Gargano D, Tichomirowa MA, Daly AF, Vanbellinghen JF, et al. Expression of aryl hydrocarbon receptor (AHR) and AHR-interacting protein in pituitary adenomas: pathological and clinical implications. Endocr Relat Cancer. 2009;16:1029–43.

    Article  CAS  PubMed  Google Scholar 

  • Jennings JE, Georgitsi M, Holdaway I, Daly AF, Tichomirowa M, Beckers A, et al. Aggressive pituitary adenomas occurring in young patients in a large Polynesian kindred with a germline R271W mutation in the AIP gene. Eur J Endocrinol. 2009;161:799–804.

    Article  CAS  PubMed  Google Scholar 

  • Joshi K, Daly AF, Beckers A, Zacharin M. Resistant paediatric somatotropinomas due to AIP mutations: role of pegvisomant. Horm Res Paediatr. 2018;90:196–202.

    Article  CAS  PubMed  Google Scholar 

  • Kaltsas G, Kanakis G, Chrousos G. Carney complex. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, editors. Endotext. South Dartmouth: MDText.com, Inc.; 2000.

    Google Scholar 

  • Kasuki L, Vieira Neto L, Wildemberg LE, Colli LM, de Castro M, Takiya CM, Gadelha MR. AIP expression in sporadic somatotropinomas is a predictor of the response to octreotide LAR therapy independent of SSTR2 expression. Endocr Relat Cancer. 2012;19:L25–9.

    Article  CAS  PubMed  Google Scholar 

  • Kirschner LS, Carney JA, Pack SD, Taymans SE, Giatzakis C, Cho YS, 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.

    Article  CAS  PubMed  Google Scholar 

  • Kobza AO, Dizon S, Arnaout A. CASE REPORT OF BILATERAL PHEOCHROMOCYTOMAS DUE TO A NOVEL MAX MUTATION IN A PATIENT KNOWN TO HAVE A PITUITARY PROLACTINOMA. AACE Clin Case Rep. 2018;4(6):e453–6.

    Article  Google Scholar 

  • Lee M, Pellegata NS. Multiple endocrine neoplasia type 4. Front Horm Res. 2013;41:63–78.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Mangupli R, Rostomyan L, Castermans E, Caberg JH, Camperos P, Krivoy J, et al. Combined treatment with octreotide LAR and pegvisomant in patients with pituitary gigantism: clinical evaluation and genetic screening. Pituitary. 2016;19:507–14.

    Article  CAS  PubMed  Google Scholar 

  • Marx S, Spiegel AM, Skarulis MC, Doppman JL, Collins FS, Liotta LA. Multiple endocrine neoplasia type 1: clinical and genetic topics. Ann Intern Med. 1998;129:484–94.

    Article  CAS  PubMed  Google Scholar 

  • Naves LA, Daly AF, Vanbellinghen JF, Casulari LA, Spilioti C, Magalhaes AV, et al. Variable pathological and clinical features of a large Brazilian family harboring a mutation in the aryl hydrocarbon receptor-interacting protein gene. Eur J Endocrinol. 2007;157:383–91.

    Article  CAS  PubMed  Google Scholar 

  • Naves LA, Daly AF, Dias LA, Yuan B, Zakir JC, Barra GB, et al. Aggressive tumor growth and clinical evolution in a patient with X-linked acro-gigantism syndrome. Endocrine. 2016;51:236–44.

    Article  CAS  PubMed  Google Scholar 

  • O’Brien T, O’Riordan DS, Gharib H, Scheithauer BW, Ebersold MJ, van Heerden JA. Results of treatment of pituitary disease in multiple endocrine neoplasia, type I. Neurosurgery. 1996;39:273–8; discussion 78-9

    Article  PubMed  Google Scholar 

  • Occhi G, Jaffrain-Rea ML, Trivellin G, Albiger N, Ceccato F, De Menis E, et al. The R304X mutation of the aryl hydrocarbon receptor interacting protein gene in familial isolated pituitary adenomas: mutational hot-spot or founder effect? J Endocrinol Investig. 2010;33:800–5.

    Article  CAS  Google Scholar 

  • Pellegata NS, Quintanilla-Martinez L, Siggelkow H, Samson E, Bink K, Hofler H, et al. Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans. Proc Natl Acad Sci U S A. 2006;103:15558–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Radian S, Diekmann Y, Gabrovska P, Holland B, Bradley L, Wallace H, et al. Increased population risk of AIP-related acromegaly and gigantism in Ireland. Hum Mutat. 2017;38:78–85.

    Article  CAS  PubMed  Google Scholar 

  • Ramirez-Renteria C, Hernandez-Ramirez LC, Portocarrero-Ortiz L, Vargas G, Melgar V, Espinosa E, et al. AIP mutations in young patients with acromegaly and the Tampico Giant: the Mexican experience. Endocrine. 2016;53:402–11.

    Article  CAS  PubMed  Google Scholar 

  • Rodd C, Millette M, Iacovazzo D, Stiles CE, Barry S, Evanson J, et al. Somatic GPR101 duplication causing X-linked acrogigantism (XLAG)-diagnosis and management. J Clin Endocrinol Metab. 2016;101:1927–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Romanet P, Mohamed A, Giraud S, Odou MF, North MO, Pertuit M, et al. UMD-MEN1 database: an overview of the 370 MEN1 variants present in 1,676 patients from the French population. J Clin Endocrinol Metab. 2018;104(3):753–64.

    Article  Google Scholar 

  • Rostomyan L, Beckers A. Screening for genetic causes of growth hormone hypersecretion. Growth Hormon IGF Res. 2016;30–31:52–7.

    Article  CAS  Google Scholar 

  • Rostomyan L, Daly AF, Beckers A. Pituitary gigantism: causes and clinical characteristics. Ann Endocrinol (Paris). 2015a;76:643–9.

    Article  Google Scholar 

  • Rostomyan L, Daly AF, Petrossians P, Nachev E, Lila AR, Lecoq AL, et al. Clinical and genetic characterization of pituitary gigantism: an international collaborative study in 208 patients. Endocr Relat Cancer. 2015b;22:745–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roszko KL, Blouch E, Blake M, Powers JF, Tischler AS, Hodin R, et al. Case report of a prolactinoma in a patient with a novel MAX mutation and bilateral pheochromocytomas. J Endocr Soc. 2017;1:1401–7.

    Article  PubMed  PubMed Central  Google Scholar 

  • Salenave S, Boyce AM, Collins MT, Chanson P. Acromegaly and McCune-Albright syndrome. J Clin Endocrinol Metab. 2014;99:1955–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sambugaro S, Di Ruvo M, Ambrosio MR, Pellegata NS, Bellio M, Guerra A, et al. Early onset acromegaly associated with a novel deletion in CDKN1B 5'UTR region. Endocrine. 2015;49:58–64.

    Article  CAS  PubMed  Google Scholar 

  • Scacheri PC, Davis S, Odom DT, Crawford GE, Perkins S, Halawi MJ, et al. Genome-wide analysis of menin binding provides insights into MEN1 tumorigenesis. PLoS Genet. 2006;2:e51.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Scheithauer BW, Kovacs K, Nose V, Lombardero M, Osamura YR, Lloyd RV, et al. Multiple endocrine neoplasia type 1-associated thyrotropin-producing pituitary carcinoma: report of a probable de novo example. Hum Pathol. 2009;40:270–8.

    Article  CAS  PubMed  Google Scholar 

  • Stratakis CA, Carney JA, Lin JP, Papanicolaou DA, Karl M, Kastner DL, 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stratakis CA, Schussheim DH, Freedman SM, Keil MF, Pack SD, Agarwal SK, et al. Pituitary macroadenoma in a 5-year-old: an early expression of multiple endocrine neoplasia type 1. J Clin Endocrinol Metab. 2000;85:4776–80.

    CAS  PubMed  Google Scholar 

  • 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;86:4041–6.

    Article  CAS  PubMed  Google Scholar 

  • Stratakis CA, Tichomirowa MA, Boikos S, Azevedo MF, Lodish M, Martari M, et al. The role of germline AIP, MEN1, PRKAR1A, CDKN1B and CDKN2C mutations in causing pituitary adenomas in a large cohort of children, adolescents, and patients with genetic syndromes. Clin Genet. 2010;78:457–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thakker RV. Multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4). Mol Cell Endocrinol. 2014;386:2–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thakker RV, Newey PJ, Walls GV, Bilezikian J, Dralle H, Ebeling PR, et al. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012;97:2990–3011.

    Article  CAS  PubMed  Google Scholar 

  • Thevenon J, Bourredjem A, Faivre L, Cardot-Bauters C, Calender A, Murat A, et al. Higher risk of death among MEN1 patients with mutations in the JunD interacting domain: a Groupe d'etude des Tumeurs endocrines (GTE) cohort study. Hum Mol Genet. 2013;22:1940–8.

    Article  CAS  PubMed  Google Scholar 

  • Tichomirowa MA, Barlier A, Daly AF, Jaffrain-Rea ML, Ronchi C, Yaneva M, et al. High prevalence of AIP gene mutations following focused screening in young patients with sporadic pituitary macroadenomas. Eur J Endocrinol. 2011;165:509–15.

    Article  CAS  PubMed  Google Scholar 

  • Tichomirowa MA, Lee M, Barlier A, Daly AF, Marinoni I, Jaffrain-Rea ML, et al. Cyclin-dependent kinase inhibitor 1B (CDKN1B) gene variants in AIP mutation-negative familial isolated pituitary adenoma kindreds. Endocr Relat Cancer. 2012;19:233–41.

    Article  CAS  PubMed  Google Scholar 

  • Trivellin G, Daly AF, Faucz FR, Yuan B, Rostomyan L, Larco DO, et al. Gigantism and acromegaly due to Xq26 microduplications and GPR101 mutation. N Engl J Med. 2014;371:2363–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trivellin G, Bjelobaba I, Daly AF, Larco DO, Palmeira L, Faucz FR, et al. Characterization of GPR101 transcript structure and expression patterns. J Mol Endocrinol. 2016;57:97–111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tuominen I, Heliovaara E, Raitila A, Rautiainen MR, Mehine M, Katainen R, et al. AIP inactivation leads to pituitary tumorigenesis through defective Galphai-cAMP signaling. Oncogene. 2015;34:1174–84.

    Article  CAS  PubMed  Google Scholar 

  • Valdes Socin H, Poncin J, Stevens V, Stevenaert A, Beckers A. Adénomes hypophysaires familiaux isolés non liés avec la mutation somatique NEM-1. Suivi de 27 patients. Ann Endocrinol (Paris). 2000;61:301.

    Google Scholar 

  • Vasilev V, Daly AF, Thiry A, Petrossians P, Fina F, Rostomyan L, et al. McCune-Albright syndrome: a detailed pathological and genetic analysis of disease effects in an adult patient. J Clin Endocrinol Metab. 2014;99:E2029–38.

    Article  CAS  PubMed  Google Scholar 

  • Verges B, Boureille F, Goudet P, Murat A, Beckers A, Sassolas G, et al. Pituitary disease in MEN type 1 (MEN1): data from the France-Belgium MEN1 multicenter study. J Clin Endocrinol Metab. 2002;87:457–65.

    Article  CAS  PubMed  Google Scholar 

  • Verloes A, Stevenaert A, Teh BT, Petrossians P, Beckers A. Familial acromegaly: case report and review of the literature. Pituitary. 1999;1:273–7.

    Article  CAS  PubMed  Google Scholar 

  • Vierimaa O, Georgitsi M, Lehtonen R, Vahteristo P, Kokko A, Raitila A, et al. Pituitary adenoma predisposition caused by germline mutations in the AIP gene. Science. 2006;312:1228–30.

    Article  CAS  PubMed  Google Scholar 

  • Vroonen L, Jaffrain-Rea ML, Petrossians P, Tamagno G, Chanson P, Vilar L, et al. Prolactinomas resistant to standard doses of cabergoline: a multicenter study of 92 patients. Eur J Endocrinol. 2012;167:651–62.

    Article  CAS  PubMed  Google Scholar 

  • Wick MJ. Clinical and molecular aspects of multiple endocrine neoplasia. Clin Lab Med. 1997;17:39–57.

    Article  CAS  PubMed  Google Scholar 

  • Xekouki P, Pacak K, Almeida M, Wassif CA, Rustin P, Nesterova 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:E357–66.

    Article  CAS  PubMed  Google Scholar 

  • Xekouki P, Szarek E, Bullova P, Giubellino A, Quezado M, Mastroyannis SA, et al. Pituitary adenoma with paraganglioma/pheochromocytoma (3PAs) and succinate dehydrogenase defects in humans and mice. J Clin Endocrinol Metab. 2015;100:E710–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Endocrinology, Centre Hospitalier Universitaire de Liège, University of Liège, Domaine Universitaire du Sart-Tilman, Liège, Belgium

    Liliya Rostomyan, Iulia Potorac, Adrian F. Daly & Albert Beckers

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  1. Liliya Rostomyan
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  2. Iulia Potorac
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  3. Adrian F. Daly
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  4. Albert Beckers
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Correspondence to Albert Beckers .

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Editors and Affiliations

  1. Neuroendocrine Unit, University of Naples Federico II Neuroendocrine Unit, Naples, Italy

    Annamaria Colao

  2. Dept. Experimental Medicine, University of L'Aquila Dept. Experimental Medicine, L'Aquila, Italy

    Marie-Lise Jaffrain-Rea

  3. Department of Endocrinology, Centre Hospitalier Universitaire de Lièg Department of Endocrinology, Liège, Belgium

    Albert Beckers

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Rostomyan, L., Potorac, I., Daly, A.F., Beckers, A. (2019). Genetics of Pituitary Gigantism: Syndromic and Nonsyndromic Causes. In: Colao, A., Jaffrain-Rea, ML., Beckers, A. (eds) Polyendocrine Disorders and Endocrine Neoplastic Syndromes. Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-319-73082-0_12-2

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  • DOI: https://doi.org/10.1007/978-3-319-73082-0_12-2

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-73082-0

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  1. Latest

    Genetics of Pituitary Gigantism: Syndromic and Nonsyndromic Causes
    Published:
    13 July 2019

    DOI: https://doi.org/10.1007/978-3-319-73082-0_12-2

  2. Original

    Genetics of Pituitary Gigantism: Syndromic and Nonsyndromic Causes
    Published:
    04 May 2019

    DOI: https://doi.org/10.1007/978-3-319-73082-0_12-1

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