SuperMEN1 pp 97-103 | Cite as

Adrenal Tumors in MEN1 Syndrome and the Role of Menin in Adrenal Tumorigenesis

  • Attila Patocs
  • Katalin Balogh
  • Karoly Racz
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 668)


Most of the adrenal tumors are benign adrenocortical adenoma (AA)and pheochromocytomas (Pheo) originatingfrom the adrenal medulla, but rarely malignant adrenocortical carcinomas (ACC) can be also found. Adrenal tumors causinghormonal overproduction such as aldosterone-producing and cortisol-producingtumors are also rare, whereas nonhyperfunctioning adenomas occur more frequently.1 During the last decades an extensive use of advanced imaging techniques (computer tomography, magnetic resonance imaging, endoscopic ultrasound) has led to an increased incidence of accidentally discovered adrenal masses, Le., incidentalomas.2, 3, 4 The prevalence of incidentalomas is up to 9% of all autopsy cases. The majority of these tumors are hormonally inactive and are of adrenocortical origin, but pheochromocytomas and hormonally active adrenocortical tumors associated with the development of Cushing’s syndrome or primary aldosteronism can also be found in some patient.1,4


Multiple Endocrine Neoplasia Type Primary Aldosteronism Adrenal Tumor Adrenocortical Carcinoma Adrenal Adenoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Beuschlein F, Reincke M. Adrenocortical tumorigenesis. Ann N Y Acad Sci 2006; 1088:319–334.CrossRefPubMedGoogle Scholar
  2. 2.
    Bovio S, Cataldi A, Reimondo G et al. Prevalence of adrenal incidentaloma in a contemporary computerized tomography series. J Endocrinol Invest 2006; 29:298–302.PubMedGoogle Scholar
  3. 3.
    Soon PS, McDonald KL, Robinson BG et al. Molecular markers and the pathogenesis of adrenocortical cancer. Oncologist 2008; 13(5):548–61.CrossRefPubMedGoogle Scholar
  4. 4.
    Igaz P, Wiener Z, Szabo P et al. Functional genomics approaches for the study of sporadic adrenal tumor pathogenesis: clinical implications. J Steroid Biochem Mol Bioi 2006; 101(2–3):87–96.CrossRefGoogle Scholar
  5. 5.
    Koch CA, Pacak K, Chrousos G-P. The molecular pathogenesis of hereditary and sporadic adrenocortical and adrenomedullary tumors. J Clin Endocrinol Metab 2002; 87(12):5367–5384.CrossRefPubMedGoogle Scholar
  6. 6.
    Neumann H-P-H, Bausch B, McWhinney S-R et al. C. Eng and Freiburg-Warsaw-Columbus pheochromocytoma study group, Germ-line mutations in nonsyndromic pheochromocytoma. New Engl J Med 2002; 346(19):1459–1466.CrossRefPubMedGoogle Scholar
  7. 7.
    Hisada M, Garber JE, Fung CY et al. Multiple primary cancers in families with Li-Fraumeni syndrome. J Natl Cancer lost 1998; 90:606–611.CrossRefGoogle Scholar
  8. 8.
    Frebourg T, Barbier N, Yan YX et al. Germ-line p53 mutations in 15 families with Li-Fraumeni syndrome. Am J Hum Genet 1995; 56:608–615.PubMedGoogle Scholar
  9. 9.
    Carney JA, Hruska LS, Beauchamp GD et al Dominant inheritance of the complex of myxomas, spotty pigmentation and endocrine overactivity. Mayo Clin Proc 1986; 61:165–172.PubMedGoogle Scholar
  10. 10.
    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
  11. 11.
    Horvath A, Boikos S, Giatzakis C et al. A genome-wide scan identifies mutations in the gene encoding phosphodiesterase 11A4 (PDE11A) in individuals with adrenocortical hyperplasia. Nat Genet 2006; 38(7):794–800.CrossRefPubMedGoogle Scholar
  12. 12.
    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
  13. 13.
    Lifton RP, Dluhy RG, Powers M et al. A chimaeric 11 β-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension. Nature 1992; 355:262–265.CrossRefPubMedGoogle Scholar
  14. 14.
    Speiser PW, White PC. Congenital adrenal hyperplasia. N Engl J Med 2003; 349:776–788.CrossRefPubMedGoogle Scholar
  15. 15.
    Jaresch S, Komely E, Kley HK et al. Adrenal incidentaloma and patients with homozygous or heterozygous congenital adrenal hyperplasia. J Clin Endocrinol Metab 1992; 74:685–689.CrossRefPubMedGoogle Scholar
  16. 16.
    Bianco P, Riminucci M, Majolagbe A et al. Mutations of the GNAS1 gene, stromal cell dysfunction and osteomalacic changes in nonMcCune-Albright fibrous dysplasia of bone. J Bone Miner Res 2000; 15:120–128.CrossRefPubMedGoogle Scholar
  17. 17.
    Sidhu S, Marsh DJ, Theodosopoulos G et al. Comparative genomic hybridization analysis of adrenocortical tumors. Journal of Clinical Endocrinology and Metabolism 2002; 87:3467–3474.CrossRefPubMedGoogle Scholar
  18. 18.
    Kjellman M, Roshani L, Teh BT et al. Genotyping of adrenocortical tumors: Very frequent deletions of the MEN1 locus in 11q13 and of a 1-centimorgan region in 2p16. J Clin Endocrinol Metab 1999; 84:730–735.CrossRefPubMedGoogle Scholar
  19. 19.
    Kjellman M, Kallioniemi OP, Karhu R et al. Genetic aberrations in adrenocortical tumors detected using comparative genomic hybridization correlate with tumor size and malignancy. Cancer Res 1996; 56:4219–4223.PubMedGoogle Scholar
  20. 20.
    Heppner C, Reincke M, Agarwal SK et al. MEN1 gene analysis in sporadic adrenocortical neoplasms. Journal of Clinical Endocrinology and Metabolism 1999; 84:216–219.CrossRefPubMedGoogle Scholar
  21. 21.
    Schulte KM, Mengel M, Heinze M et al. Complete sequencing and messenger ribonucleic acid expression analysis of the MEN1 gene in adrenal cancer. Journal of Clinical Endocrinology and Metabolism 2000; 85:441–448.CrossRefPubMedGoogle Scholar
  22. 22.
    Yano T, Linehan M, Anglard P et al. Genetic changes in human adrenocortical carcinomas. Journal of the National Cancer Institute 1989; 81:518–523.CrossRefPubMedGoogle Scholar
  23. 23.
    Gicquel C, Bertagna X, Gaston V et al. Molecular markers and long-term recurrences in a large cohort of patients with sporadic adrenocortical tumors. Cancer Research 2001; 61:6762–6767.PubMedGoogle Scholar
  24. 24.
    Gicquel C, Bertagna X, Schneid H et al. Rearrangements at the 11p15 locus and overexpression of insulin-like growth factor-II gene in sporadic adrenocortical tumors. J Clin Endocrinol Metab 1994; 78:1444–1453.CrossRefPubMedGoogle Scholar
  25. 25.
    Skogseid B, Larsson C, Lindgren PG et al. Clinical and genetic features of adrenocortical lesions in multiple endocrine neoplasia type 1. J Clin Endocrinol Metab 1992; 75:76–81.CrossRefPubMedGoogle Scholar
  26. 26.
    Marx SJ, Agarwal SK, Kester MB et al. Germline and somatic mutation of the gene for multiple endocrine neoplasia type 1 (MEN-1). J Intern Med 1998; 243:447–453.CrossRefPubMedGoogle Scholar
  27. 27.
    Dong Q, Debelenko LV, Chandrasekharappa SC et al. Loss of heterozygosity at 11q13: analysis of pituitary tumors, lung carcinoids, lipomas and other uncommon tumors with familial multiple endocrine neoplasia type 1. J Clin Endocrinol Metab 1997; 82:1416–1420.CrossRefPubMedGoogle Scholar
  28. 28.
    Paul Wermer. Genetic aspects of adenomatosis of endocrine glands. The American Journal of Medicine 1954; 16(3):363–371.CrossRefPubMedGoogle Scholar
  29. 29.
    Paul Wermer. Endocrine adenomatosis and peptic ulcer in a large kindred: Inherited multiple tumors and mosaic pleiotropism in man. The American Journal of Medicine 1963; 35(2):205–212.CrossRefPubMedGoogle Scholar
  30. 30.
    Vierimaa O, Ebeling TM, Kytola S et al. Multiple endocrine neoplasia type 1 in Northern Finland; clinical features and genotype phenotype correlation. Eur J Endocrinol 2007; 157(3):285–94.CrossRefPubMedGoogle Scholar
  31. 31.
    Ellard S, Hattersley AT, Brewer CM et al. Detection of an MEN1 gene mutation depends on clinical features and supports current referral criteria for diagnostic molecular genetic testing. Clin Endocrinol (Oxf) 2005; 62(2):169–75.CrossRefGoogle Scholar
  32. 32.
    Machens A, Schaaf L, Karges W et al. Age-related penetrance of endocrine tumours in multiple endocrine neoplasia type 1 (MEN1): a multicentre study of 258 gene carriers. Clin Endocrinol (Oxf) 2007; 67(4):613–22.Google Scholar
  33. 33.
    Waldmann J, Bartsch DK, Kann PH et al. Adrenal involvement in multiple endocrine neoplasia type 1: results of 7 years prospective screening. Langenbecks Arch Surg 2007; 392(4):437–43.CrossRefPubMedGoogle Scholar
  34. 34.
    Langer P, Cupisti K, Bartsch DK et al. Adrenal involvement in multiple endocrine neoplasia type 1. World J Surg 2002; 26(8):891–6.CrossRefPubMedGoogle Scholar
  35. 35.
    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(2):455–67.CrossRefPubMedGoogle Scholar
  36. 36.
    Balogh K, Hunyady L, Patocs A et al. MEN1 gene mutations in Hungarian patients with multiple endocrine neoplasia type 1. Clin Endocrinol (Oxf) 2007; 67(5):727–34.CrossRefGoogle Scholar
  37. 37.
    Schaefer S, Shipotko M, Meyer S et al. Natural course of small adrenal lesions in multiple endocrine neoplasia type 1: an endoscopic ultrasound imaging study. Eur J Endocrinol 2008; 158(5):699–704.CrossRefPubMedGoogle Scholar
  38. 38.
    Beckers A, Abs R, Willems P et al. Aldosterone-secreting adrenal adenoma as part of multiple endocrine neoplasia type 1 (MEN1): loss of heterozygosity for polymorphic chromosome 11 deoxyribonucleic acid markers, including the MEN1locus. J Clin Endocrinol Metab 1992; 75:564–570.CrossRefPubMedGoogle Scholar
  39. 39.
    Iida A, Blake K, Tunny T et al. Allelic losseson chromosome band l1q13 in aldosterone-producing adrenal tumors. Gene Chromosome Cancer 1995; 12:73–75.CrossRefGoogle Scholar
  40. 40.
    Dohna M, Reincke M, Mincheva A et al. Adrenocortical carcinoma is characterized by a high frequency of chromosomal gains and high-level amplifications. Genes Chromosomes Cancer 2000; 28:145–152.CrossRefPubMedGoogle Scholar
  41. 41.
    Furuta N, Kiyota H, Yoshigoe F et al. Diagnosis of pheochromocytoma using 123I-compared with 131I-metaiodobenzylguanidine scintigraphy. Int J Urol 1999; 6:119–124.CrossRefPubMedGoogle Scholar
  42. 42.
    d’Herbomez M, Gouze V, Huglo D et al. Chromogranin A assayand 131I-MIBG scintigraphy for diagnosis and follow-up of pheochromocytoma. J Nucl Med 2001; 42:993–997.PubMedGoogle Scholar
  43. 43.
    Lenders JWM, Pacak K, Walther MM et al. Biochemical diagnosis of pheochromocytoma: which is the best test? JAMA 2002; 287:1427–1434.CrossRefPubMedGoogle Scholar
  44. 44.
    NCCN Clinical Practice Guidelines in Oncology, V. I. 2007, www.nccn.orgGoogle Scholar
  45. 45.
    Brandi ML, Gagel RF, Angeli A et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 2001; 86:5658–5671.CrossRefPubMedGoogle Scholar
  46. 46.
    Asgharian B, Turner ML, Gibril F et al. Cutaneous tumors in patients with multiple endocrine neoplasm type 1 (MEN1) and gastrinomas: prospective study of frequency and development of criteria with high sensitivity and specificity for MEN1. J Clin Endocrinol Metab 2004; 89(11):5328–36.CrossRefPubMedGoogle Scholar
  47. 47.
    Bhuiyan MM, Sato M, Murao K et al. Differential expression of menin in various adrenal tumors. The role of menin in adrenal tumors. Cancer 2001; 92(6): 1393–401.CrossRefPubMedGoogle Scholar
  48. 48.
    Zwermann O, Beuschlein F, Mora P et al. Multiple endocrine neoplasia type 1 gene expression is normal in sporadic adrenocortical tumors. Eur J Endocrinol 2000; 142:689–695.CrossRefPubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2009

Authors and Affiliations

  • Attila Patocs
    • 1
  • Katalin Balogh
    • 2
  • Karoly Racz
    • 2
  1. 1.Hungarian Academy of Sciences Molecular Medicine Research Group and 2nd Department of Medicine, Faculty of MedicineSemmelweis University, Central Isotope Laboratory Semmelweis UniversityBudapestHungary
  2. 2.2nd Department of Medicine Faculty of MedicineSemmelweis UniversityBudapestHungary

Personalised recommendations