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Journal of Endocrinological Investigation

, Volume 30, Issue 9, pp 787–790 | Cite as

Familial pituitary adenomas with a heterogeneous functional pattern: Clinical and genetic features

  • G. Raverot
  • W. Arnous
  • A. Calender
  • J. Trouillas
  • G. Sassolas
  • C. Bournaud
  • M. Pugeat
  • F. Borson-Chazot
Case Report

Abstract

Familial pituitary adenoma is a rare syndrome which may present either as isolated lesions, or in association with other endocrine tumors, for example in the frame of multiple endocrine neoplasia (MEN-1) or Carney complex (CNC). The most frequently described forms of familial isolated pituitary adenoma (FIPA) are familial somatotropinomas or prolactinomas. Recently, some cases of familial isolated somatotropinoma have been associated with germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene. The present report shows heterogeneous FIPA with 3 subtypes of tumor in 3 individuals of the same family: somatotropinoma in the proband, giant prolactinoma in a brother, and gonadotroph cell macroadenoma in the father. A prospective survey also suggested the occurrence of a silent microadenoma in the proband’s sister. Clinical screening was performed in the 3 affected members, the 4th suspected case, and 9 additional, asymptomatic relatives. They had no clinical evidence of associated endocrine lesion suggesting MEN-1 or CNC. Genetic screening for germline mutation of the MEN-1, the gene encoding the protein kinase A (PKA) type 1 α regulatory subunit (R1 α) (PRKAR1α) and AIP gene was negative in 2 affected members. In conclusion, these data suggest that familial pituitary adenomas can occur with a heterogeneous functional pattern that is distinguished from MEN-1 or CNC. The absence of mutation of the recently described AIP gene suggests the implication of other predisposing gene(s). Collaborative, multicentric studies are needed to further define the location of gene(s) involved in heterogeneous FIPA.

Key-words

Familial pituitary adenomas MEN-1 gene menin Carney Complex PRKAR1α gene AIP gene 

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References

  1. 1.
    Daly AF, Jaffrain-Rea ML, Ciccarelli A, et al. Clinical characterization of familial isolated pituitary adenomas. J Clin Endocrinol Metab 2006, 91: 3316–23.PubMedCrossRefGoogle Scholar
  2. 2.
    Daly AF, Jaffrain-Rea ML, Beckers A. Clinical and genetic features of familial pituitary adenomas. Horm Metab Res 2005, 37: 347–54.PubMedCrossRefGoogle Scholar
  3. 3.
    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: 457–65.PubMedCrossRefGoogle Scholar
  4. 4.
    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.PubMedCrossRefGoogle Scholar
  5. 5.
    Stergiopoulos SG, Abu-Asab MS, Tsokos M, Stratakis CA. Pituitary pathology in Carney complex patients. Pituitary 2004, 7: 73–82.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Kirschner LS, Carney JA, Pack SD, et al. Mutations of the gene encoding the protein kinase Atype I-alpha regulatory subunit in patients with the Carney complex. Nat Genet 2000, 26: 89–92.PubMedCrossRefGoogle Scholar
  7. 7.
    Kirschner LS, Sandrini F, Monbo J, Lin JP, Carney JA, Stratakis CA. Genetic heterogeneity and spectrum of mutations of the PRKAR1A gene in patients with the carney complex. Hum Mol Genet 2000, 9: 3037–46.PubMedCrossRefGoogle Scholar
  8. 8.
    Bossis I, Stratakis CA. Minireview: PRKAR1A: normal and abnormal functions. Endocrinology 2004, 145: 5452–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Frohman LA, Eguchi K. Familial acromegaly. Growth Horm IGF Res 2004, 14 (Suppl A): S90–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Vierimaa O, Georgitsi M, Lehtonen R, et al. Pituitary adenoma predisposition caused by germline mutations in the AIP gene. Science 2006, 312: 1228–30.PubMedCrossRefGoogle Scholar
  11. 11.
    Giraud S, Zhang CX, Serova-Sinilnikova O, et al. Germ-line mutation analysis in patients with multiple endocrine neoplasia type 1 and related disorders. Am J Hum Genet 1998, 63: 455–67.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Casey M, Vaughan CJ, He J, et al. Mutations in the protein kinase A R1 alpha regulatory subunit cause familial cardiac myxomas and Carney complex. J Clin Invest 2000, 106: R31–8.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    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 2006, 91: 4769–75.PubMedCrossRefGoogle Scholar
  14. 14.
    Hall WA, Luciano MG, Doppman JL, Patronas NJ, Oldfield EH. Pituitary magnetic resonance imaging in normal human volunteers: occult adenomas in the general population. Ann Intern Med 1994, 120: 817–20.PubMedCrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2007

Authors and Affiliations

  • G. Raverot
    • 1
    • 2
    • 3
  • W. Arnous
    • 1
  • A. Calender
    • 2
    • 4
  • J. Trouillas
    • 2
    • 3
    • 5
  • G. Sassolas
    • 1
  • C. Bournaud
    • 1
  • M. Pugeat
    • 1
    • 2
  • F. Borson-Chazot
    • 1
    • 2
  1. 1.Fédération d’Endocrinologie du Pôle Est, Hospices Civils de LyonHôpital Edouard Herriot, Hospices Civils de LyonLyonFrance
  2. 2.Université de LyonHôpital Edouard Herriot, Hospices Civils de LyonLyonFrance
  3. 3.Inserm U842, Faculté de Médecine RTH LaennecHôpital Edouard Herriot, Hospices Civils de LyonLyonFrance
  4. 4.Laboratoire de génétique moléculaireHôpital Edouard Herriot, Hospices Civils de LyonLyonFrance
  5. 5.Laboratoire d’Histologie et Embryologie moléculairesFaculté de Médecine Lyon-RTH LaennecLyonFrance

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