Skip to main content
SpringerLink
Log in

Benign and Malignant Diseases of the Adrenal Cortex

  • Chapter
  • First Online:
Molecular Pathology of Endocrine Diseases

Part of the book series: Molecular Pathology Library ((MPLB,volume 3))

  • 910 Accesses

Abstract

Adrenal cortical diseases are relatively rare but are important to recognize and understand because of their significant morbidity and mortality. Developments in both molecular biology and molecular genetics have significantly increased our understanding of the process of steroidogenesis and steroid action. This in turn has allowed us to broaden our understanding of the various inherited diseases that affect this pathway. The main diseases and their pathogenesis will be presented in this chapter.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Keegan CE, Hammer GD. Recent insights into organogenesis of the adrenal cortex. Trends Endocrinol Metab. 2002;13:200–208.

    Article  PubMed  CAS  Google Scholar 

  2. Beuschlein F, Keegan CE, Bavers DL, et al. SF-1, DAX-1, and acd: molecular determinants of adrenocortical growth and steroidogenesis. Endocr Res. 2002;28:597–607.

    Article  PubMed  CAS  Google Scholar 

  3. Nguyen AD, Conley AJ. Adrenal androgens in humans and nonhuman primates: production, zonation and regulation. Endocr Dev. 2008;13:33–54.

    Article  PubMed  CAS  Google Scholar 

  4. Miller WL. Steroidogenic acute regulatory protein (StAR), a novel mitochondrial cholesterol transporter. Biochim Biophys Acta. 2007;1771:663–676.

    PubMed  CAS  Google Scholar 

  5. Willenberg HS, Schinner S, Ansurudeen I. New mechanisms to control aldosterone synthesis. Horm Metab Res. 2008;40(7):435–441.

    Article  PubMed  CAS  Google Scholar 

  6. Soon PS, McDonald KL, Robinson BG, Sidhu SB. Molecular markers and the pathogenesis of adrenocortical cancer. Oncologist. 2008;13:548–561.

    Article  PubMed  CAS  Google Scholar 

  7. l’Allemand D, Penhoat A, Blum W, Saez JM. Is there a local IGF-system in human adrenocortical cells? Mol Cell Endocrinol. 1998;140:169–173.

    Article  PubMed  Google Scholar 

  8. Albertin G, Forneris M, Aragona F, Nussdorfer GG. Expression of adrenomedullin and its receptors in the human adrenal cortex and aldosteronomas. Int J Mol Med. 2001;8:423–426.

    PubMed  CAS  Google Scholar 

  9. Vanttinen T, Liu J, Kuulasmaa T, Kivinen P, Voutilainen R. Expression of activin/inhibin signaling components in the human adrenal gland and the effects of activins and inhibins on adrenocortical steroidogenesis and apoptosis. J Endocrinol. 2003;178:479–489.

    Article  PubMed  CAS  Google Scholar 

  10. Haidan A, Bornstein SR, Glasow A, Uhlmann K, Lubke C, Ehrhart-Bornstein M. Basal steroidogenic activity of adrenocortical cells is increased 10-fold by coculture with chromaffin cells. Endocrinology. 1998;139:772–780.

    Article  PubMed  CAS  Google Scholar 

  11. Haidan A, Bornstein SR, Liu Z, Walsh LP, Stocco DM, Ehrhart-Bornstein M. Expression of adrenocortical steroidogenic acute regulatory (StAR) protein is influenced by chromaffin cells. Mol Cell Endocrinol. 2000;165:25–32.

    Article  PubMed  CAS  Google Scholar 

  12. Young WF. Primary aldosteronism: renaissance of a syndrome. Clin Endocrinol (Oxf). 2007;66:607–618.

    Article  CAS  Google Scholar 

  13. Bourdeau I, Lampron A, Costa MH, Tadjine M, Lacroix A. Adrenocorticotropic hormone-independent Cushing’s syndrome. Curr Opin Endocrinol Diabetes Obes. 2007;14:219–225.

    Article  PubMed  CAS  Google Scholar 

  14. Christopoulos S, Bourdeau I, Lacroix A. Aberrant expression of hormone receptors in adrenal Cushing’s syndrome. Pituitary. 2004;7:225–235.

    Article  PubMed  CAS  Google Scholar 

  15. Chabre O, Liakos P, Vivier J, et al. Cushing’s syndrome due to a gastric inhibitory polypeptide-dependent adrenal adenoma: insights into hormonal control of adrenocortical tumorigenesis. J Clin Endocrinol Metab. 1998;83:3134–3143.

    Article  PubMed  CAS  Google Scholar 

  16. Carlson HE. Human adrenal cortex hyperfunction due to LH/hCG. Mol Cell Endocrinol. 2007;269:46–50.

    Article  PubMed  CAS  Google Scholar 

  17. Lacroix A, N’Diaye N, Mircescu H, Tremblay J, Hamet P. The diversity of abnormal hormone receptors in adrenal Cushing’s syndrome allows novel pharmacological therapies. Braz J Med Biol Res. 2000;33:1201–1209.

    Article  PubMed  CAS  Google Scholar 

  18. Nimkarn S, New MI. Steroid 11beta- hydroxylase deficiency congenital adrenal hyperplasia. Trends Endocrinol Metab. 2008;19:96–99.

    PubMed  CAS  Google Scholar 

  19. Bachelot A, Chakthoura Z, Rouxel A, Dulon J, Touraine P. Classical forms of congenital adrenal hyperplasia due to 21-hydroxylase deficiency in adults. Horm Res. 2008;69:203–211.

    Article  PubMed  CAS  Google Scholar 

  20. Torresani T, Biason-Lauber A. Congenital adrenal hyperplasia: diagnostic advances. J Inherit Metab Dis. 2007;30:563–575.

    Article  PubMed  CAS  Google Scholar 

  21. Goncalves J, Friaes A, Moura L. Congenital adrenal hyperplasia: focus on the molecular basis of 21-hydroxylase deficiency. Expert Rev Mol Med. 2007;9:1–23.

    Article  PubMed  Google Scholar 

  22. Bhangoo A, Anhalt H, Ten S, King SR. Phenotypic variations in lipoid congenital adrenal hyperplasia. Pediatr Endocrinol Rev. 2006;3:258–271.

    PubMed  Google Scholar 

  23. Merke DP, Bornstein SR. Congenital adrenal hyperplasia. Lancet. 2005;365:2125–2136.

    Article  PubMed  Google Scholar 

  24. Saeger W, Reinhard K, Reinhard C. Hyperplastic and tumorous lesions of the adrenals in an unselected autopsy series. Endocr Pathol. 1998;9:235–239.

    Article  PubMed  Google Scholar 

  25. Reinhard C, Saeger W, Schubert B. Adrenocortical nodules in post-mortem series. Development, functional significance, and differentiation from adenomas. Gen Diagn Pathol. 1996;141:203–208.

    PubMed  CAS  Google Scholar 

  26. 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.

    PubMed  CAS  Google Scholar 

  27. Kloos RT, Gross MD, Francis IR, Korobkin M, Shapiro B. Incidentally discovered adrenal masses. Endocr Rev. 1995;16:460–483.

    PubMed  CAS  Google Scholar 

  28. Watanabe N, Tsunoda K, Sasano H, et al. Bilateral aldosterone-producing adenomas in two patients diagnosed by immunohistochemical analysis of steroidogenic enzymes. Tohoku J Exp Med. 1996;179:123–129.

    Article  PubMed  CAS  Google Scholar 

  29. Grumbach MM, Biller BM, Braunstein GD, et al. Management of the clinically inapparent adrenal mass (“incidentaloma”). Ann Intern Med. 2003;138:424–429.

    PubMed  Google Scholar 

  30. Hutter AMJ, Kayhoe DE. Adrenal cortical carcinoma. Am J Med. 1966;41:572–580.

    Article  PubMed  Google Scholar 

  31. Ibanez ML. The pathology of adrenal cortical carcinomas. Study of 22 cases. In: Endocrine and Nonendocrine Hormone-Producing Tumors. Chicago: Year Book Medical Publishers; 1971:231–239.

    Google Scholar 

  32. MacFarlane DA. Cancer of the adrenal cortex. The natural history, prognosis and treatment in a study of fifty-five cases. Ann Royal Coll Surg Engl. 1958;23:155–186.

    CAS  Google Scholar 

  33. Abiven G, Coste J, Groussin L, et al. Clinical and biological features in the prognosis of adrenocortical cancer: poor outcome of cortisol-secreting tumors in a series of 202 consecutive patients. J Clin Endocrinol Metab. 2006;91:2650–2655.

    Article  PubMed  CAS  Google Scholar 

  34. Wooten MD, King DK. Adrenal cortical carcinoma. Epidemiology and treatment with mitotane and a review of the literature. Cancer. 1993;72:3145–3155.

    Article  PubMed  CAS  Google Scholar 

  35. Lack EE. Tumors of the Adrenal Gland and Extra-Adrenal Paraganglia. Third Series ed. Washington, DC: Armed Forces Institute of Pathology; 1997.

    Google Scholar 

  36. Meikle I, Hayes JD, Walker SW. Expression of an abundant alpha-class glutathione S-transferase in bovine and human adrenal cortex tissues. J Endocrinol. 1992;132:83–92.

    Article  PubMed  CAS  Google Scholar 

  37. Sarkar D, Imai T, Kambe F, et al. Overexpression of glutathione-S-transferase A1 in benign adrenocortical adenomas from patients with Cushing’s syndrome. J Clin Endocrinol Metab. 2001;86:1653–1659.

    Article  PubMed  CAS  Google Scholar 

  38. Ginn PE. Immunohistochemical detection of P-glycoprotein in formalin-fixed and paraffin-embedded normal and neoplastic canine tissues. Vet Pathol. 1996;33:533–541.

    Article  PubMed  CAS  Google Scholar 

  39. Haak HR, van Seters AP, Moolenaar AJ, Fleuren GJ. Expression of P-glycoprotein in relation to clinical manifestation, treatment and prognosis of adrenocortical cancer. Eur J Cancer. 1993;7:1036–1038.

    Article  Google Scholar 

  40. Hough AJ, Hollifield JW, Page DL, Hartmann WH. Prognostic factors in adrenal cortical tumours. Am J Clin Pathol. 1979;72:390–399.

    PubMed  CAS  Google Scholar 

  41. Van Slooten H, Schaberg A, Smeenk D, Moolenaar AJ. Morphologic characteristics of benign and malignant adrenocortical tumors. Cancer. 1985;55:766–773.

    Article  PubMed  Google Scholar 

  42. Weiss LM. Comparable histologic study of 43 metastasizing and non metastasizing adrenocortical tumors. Am J Surg Pathol. 1984;8:163–169.

    Article  PubMed  CAS  Google Scholar 

  43. Weiss LM, Medeiros LJ, Vickery AL Jr. Pathologic features of prognostic significance in adrenocortical carcinoma. Am J Surg Pathol. 1989;13:202–206.

    Article  PubMed  CAS  Google Scholar 

  44. Aubert S, Wacrenier A, Leroy X, et al. Weiss system revisited: a clinicopathologic and immunohistochemical study of 49 adrenocortical tumors. Am J Surg Pathol. 2002;26:1612–1619.

    Article  PubMed  Google Scholar 

  45. van’t Sant HP, Bouvy ND, Kazemier G, et al. The prognostic value of two different histopathological scoring systems for adrenocortical carcinomas. Histopathology. 2007;51:239–245.

    Article  PubMed  Google Scholar 

  46. Pohlink C, Tannapfe A, Eichfeld U, et al. Does tumor heterogeneity limit the use of the Weiss criteria in the evaluation of adrenocortical tumors? J Endocrinol Invest. 2004;27:565–569.

    PubMed  CAS  Google Scholar 

  47. Sullivan M, Boileau M, Hodges CV. Adrenal cortical carcinoma. J Urol. 1978;120:660–665.

    PubMed  CAS  Google Scholar 

  48. Sidhu S, Gicquel C, Bambach CP, et al. Clinical and molecular aspects of adrenocortical tumourigenesis. ANZ J Surg. 2003;73:727–738.

    Article  PubMed  Google Scholar 

  49. Chu P, Wu E, Weiss LM. Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of 435 cases. Mod Pathol. 2000;13:962–972.

    Article  PubMed  CAS  Google Scholar 

  50. Henzen-Logmans SC, Stel HV, van Muijen GN, Mullink H, Meijer CJ. Expression of intermediate filament proteins in adrenal cortex and related tumours. Histopathology. 1988;12:359–372.

    Article  PubMed  CAS  Google Scholar 

  51. Wick MR, Cherwitz DL, McGlennen RC, Dehner LP. Adrenocortical carcinoma. An immunohistochemical comparison with renal cell carcinoma. Am J Pathol. 1986;122:343–352.

    PubMed  CAS  Google Scholar 

  52. Gaffey MJ, Traweek ST, Mills SE, et al. Cytokeratin expression in adrenocortical neoplasia: an immunohistochemical and biochemical study with implications for the differential diagnosis of adrenocortical, hepatocellular, and renal cell carcinoma. Hum Pathol. 1992;23:144–153.

    Article  PubMed  CAS  Google Scholar 

  53. Schroder S, Niendorf A, Achilles E, et al. Immunocytochemical differential diagnosis of adrenocortical neoplasms using the monoclonal antibody D11. Virchows Arch A Pathol Anat Histopathol. 1990;417:89–96.

    Article  PubMed  CAS  Google Scholar 

  54. Arola J, Liu J, Heikkila P, Voutilainen R, Kahri A. Expression of inhibin alpha in the human adrenal gland and adrenocortical tumors. Endocr Res. 1998;24:865–867.

    Article  PubMed  CAS  Google Scholar 

  55. Munro LM, Kennedy A, McNicol AM. The expression of inhibin/activin subunits in the human adrenal cortex and its tumours. J Endocrinol. 1999;161:341–347.

    Article  PubMed  CAS  Google Scholar 

  56. Ghorab Z, Jorda M, Ganjei P, Nadji M. Melan A (A103) is expressed in adrenocortical neoplasms but not in renal cell and hepatocellular carcinomas. Appl Immunohistochem Mol Morphol. 2003;11:330–333.

    PubMed  CAS  Google Scholar 

  57. Jorda M, De MB, Nadji M. Calretinin and inhibin are useful in separating adrenocortical neoplasms from pheochromocytomas. Appl Immunohistochem Mol Morphol. 2002;10:67–70.

    Article  PubMed  Google Scholar 

  58. Zhang H, Bu H, Chen H, et al. Comparison of immunohistochemical markers in the differential diagnosis of adrenocortical tumors: immunohistochemical analysis of adrenocortical tumors. Appl Immunohistochem Mol Morphol. 2008;16:32–39.

    PubMed  CAS  Google Scholar 

  59. Coulter CL, Smith RE, Stowasser M, Sasano H, Krozowski ZS, Gordon RD. Expression of 11betaHSD-2 in human adrenal cortical carcinoma and adenoma. Endocr Res. 1998;24:875–876.

    Article  PubMed  CAS  Google Scholar 

  60. Sasano H, Mason JI, Sasano N, Nagura H. Immunolocalization of 3 beta-hydroxysteroid dehydrogenase in human adrenal cortex and in its disorders. Endocr Pathol. 1990;1:94–101.

    Article  Google Scholar 

  61. Sasano H, Shizawa S, Suzuki T, et al. Ad4BP in the human adrenal cortex and its disorders. J Clin Endocrinol Metab. 1995;80:2378–2380.

    Article  PubMed  CAS  Google Scholar 

  62. Stratakis CA, Carney JA, Kirschner LS, et al. Synaptophysin immunoreactivity in primary pigmented nodular adrenocortical disease: neuroendocrine properties of tumors associated with Carney complex. J Clin Endocrinol Metab. 1999;84:1122–1128.

    Article  PubMed  CAS  Google Scholar 

  63. Komminoth P, Roth J, Schroder S, Saremaslani P, Heitz PU. Overlapping expression of immunohistochemical markers and synaptophysin mRNA in pheochromocytomas and adrenocortical carcinomas. Implications for the differential diagnosis of adrenal gland tumors. Lab Invest. 1995;72:424–431.

    PubMed  CAS  Google Scholar 

  64. Haak HR, Fleuren GJ. Neuroendocrine differentiation of adrenocortical tumors. Cancer. 1995;75:860–864.

    Article  PubMed  CAS  Google Scholar 

  65. Li FP, Fraumeni JF. Soft tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome? Ann Int Med. 1969;71:747–752.

    PubMed  CAS  Google Scholar 

  66. Rodier F, Campisi J, Bhaumik D. Two faces of p53: aging and tumor suppression. Nucleic Acids Res. 2007;35:7475–7484.

    Article  PubMed  CAS  Google Scholar 

  67. Varley JM, McGown G, Thorncroft M, et al. Are there low-penetrance TP53 Alleles? evidence from childhood adrenocortical tumors. Am J Hum Genet. 1999;65:995–1006.

    Article  PubMed  CAS  Google Scholar 

  68. Bell DW, Varley JM, Szydlo TE, et al. Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome. Science. 1999;286:2528–2531.

    Article  PubMed  CAS  Google Scholar 

  69. Bachinski LL, Olufemi SE, Zhou X, et al. Genetic mapping of a third Li-Fraumeni syndrome predisposition locus to human chromosome 1q23. Cancer Res. 2005;65:427–431.

    PubMed  CAS  Google Scholar 

  70. Cohen MM Jr. Beckwith-Wiedemann syndrome: historical, clinicopathological, and etiopathogenetic perspectives. Pediatr Dev Pathol. 2005;8(3):287–304.

    Article  PubMed  Google Scholar 

  71. Weksberg R, Squire JA. Molecular biology of Beckwith-Wiedemann syndrome. Med Pediatr Oncol. 1996;27:462–469.

    Article  PubMed  CAS  Google Scholar 

  72. Carney JA. The Carney complex (myxomas, spotty pigmentation, endocrine overactivity, and schwannomas). Dermatol Clin. 1995;13:19–26.

    PubMed  CAS  Google Scholar 

  73. Stratakis CA. Genetics of adrenocortical tumors: Carney complex. Ann Endocrinol (Paris). 2001;62:180–184.

    CAS  Google Scholar 

  74. Bertherat J. Carney complex (CNC). Orphanet J Rare Dis. 2006;1:21.

    Article  PubMed  Google Scholar 

  75. 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.

    Article  PubMed  CAS  Google Scholar 

  76. Courseaux A, Grosgeorge J, Gaudray P, et al. Definition of the minimal MEN1 candidate area based on a 5-Mb integrated map of proximal 11q13. The European Consortium on Men1, (GENEM 1; Groupe d’Etude des Neoplasies Endocriniennes Multiples de type 1). Genomics. 1996;37:354–365.

    Article  PubMed  CAS  Google Scholar 

  77. Agarwal SK, Kester MB, Debelenko LV, et al. Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type 1 and related states. Hum Mol Genet. 1997;6:1169–1175.

    Article  PubMed  CAS  Google Scholar 

  78. Skogseid B, Rastad J, Gobl A, et al. Adrenal lesion in multiple endocrine neoplasia type 1. Surgery. 1995;118:1077–1082.

    Article  PubMed  CAS  Google Scholar 

  79. Barzon L, Pasquali C, Grigoletto C, Pedrazzoli S, Boscaro M, Fallo F. Multiple endocrine neoplasia type 1 and adrenal lesions. J Urol. 2001;166:24–27.

    Article  PubMed  CAS  Google Scholar 

  80. Burgess JR, Harle RA, Tucker P, et al. Adrenal lesions in a large kindred with multiple endocrine neoplasia type 1. Arch Surg. 1996;131:699–702.

    PubMed  CAS  Google Scholar 

  81. 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;158:699–704.

    Article  PubMed  CAS  Google Scholar 

  82. DeLellis RA, Tischler AS. Clonality of endocrine proliferative lesions: a critical reappraisal. Endocr Pathol. 1998;9:281–285.

    Article  PubMed  Google Scholar 

  83. Beuschlein F, Reincke M, Karl M, et al. Clonal composition of human adrenocortical neoplasms. Cancer Res. 1994;54:4927–4932.

    PubMed  CAS  Google Scholar 

  84. Gicquel C, Leblond-Francillard M, Bertagna X, et al. Clonal analysis of human adrenocortical carcinomas and secreting adenomas. Clin Endocrinol (Oxf). 1994;40:465–477.

    Article  CAS  Google Scholar 

  85. Blanes A, Diaz-Cano SJ. DNA and kinetic heterogeneity during the clonal evolution of adrenocortical proliferative lesions. Hum Pathol. 2006;37:1295–1303.

    Article  PubMed  CAS  Google Scholar 

  86. Jaresch S, Kornely E, Kley HK, Schlaghecke R. Adrenal incidentaloma and patients with homozygous or heterozygous congenital adrenal hyperplasia. J Clin Endocrinol Metab. 1992;74:685–689.

    Article  PubMed  CAS  Google Scholar 

  87. Russell AJ, Sibbald J, Haak H, Keith WN, McNicol AM. Increasing genome instability in adrenocortical carcinoma progression with involvement of chromosomes 3, 9 and X at the adenoma stage. Br J Cancer. 1999;81:684–689.

    Article  PubMed  CAS  Google Scholar 

  88. Shono T, Sakai H, Takehara K, Honda S, Kanetake H. Analysis of numerical chromosomal aberrations in adrenal cortical neoplasms by fluorescence in situ hybridization. J Urol. 2002;168:1370–1373.

    Article  PubMed  CAS  Google Scholar 

  89. 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.

    PubMed  CAS  Google Scholar 

  90. Dohna M, Reincke M, Mincheva A, Allolio B, Solinas-Toldo S, Lichter P. Adrenocortical carcinoma is characterized by a high frequency of chromosomal gains and high-level amplifications. Genes Chromosomes Cancer. 2000;28:145–152.

    Article  PubMed  CAS  Google Scholar 

  91. Sidhu S, Marsh DJ, Theodosopoulos G, et al. Comparative genomic hybridization analysis of adrenocortical tumors. J Clin Endocrinol Metab. 2002;87:3467–3474.

    Article  PubMed  CAS  Google Scholar 

  92. 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 Res. 2001;61:6762–6767.

    PubMed  CAS  Google Scholar 

  93. Soon PS, Libe R, Benn DE, et al. Loss of heterozygosity of 17p13, with possible involvement of ACADVL and ALOX15B, in the pathogenesis of adrenocortical tumors. Ann Surg. 2008;247:157–164.

    Article  PubMed  Google Scholar 

  94. Yano T, Linehan M, Anglard P, et al. Genetic changes in human adrenocortical carcinomas. J Natl Cancer Inst. 1989;81:518–523.

    Article  PubMed  CAS  Google Scholar 

  95. Heppner C, Reincke M, Agarwal SK, et al. MEN1 gene analysis in sporadic adrenocortical neoplasms. J Clin Endocrinol Metab. 1999;84:216–219.

    Article  PubMed  CAS  Google Scholar 

  96. 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.

    Article  PubMed  CAS  Google Scholar 

  97. Schulte KM, Mengel M, Heinze M, et al. Complete sequencing and messenger ribonucleic acid expression analysis of the MEN I gene in adrenal cancer. J Clin Endocrinol Metab. 2000;85:441–448.

    Article  PubMed  CAS  Google Scholar 

  98. Gicquel C, Raffin-Sanson ML, Gaston V, et al. Structural and functional abnormalities at 11p15 are associated with the malignant phenotype in sporadic adrenocortical tumors: study on a series of 82 tumors. J Clin Endocrinol Metab. 1997;82:2559–2565.

    Article  PubMed  CAS  Google Scholar 

  99. Bertherat J, Groussin L, Sandrini F, et al. Molecular and functional analysis of PRKAR1A and its locus (17q22-24) in sporadic adrenocortical tumors: 17q losses, somatic mutations, and protein kinase A expression and activity. Cancer Res. 2003;63:5308–5319.

    PubMed  CAS  Google Scholar 

  100. Reincke M, Mora P, Beuschlein F, Arlt W, Chrousos GP, Allolio B. Deletion of the adrenocorticotropin receptor gene in human adrenocortical tumors: implications for tumorigenesis. J Clin Endocrinol Metab. 1997;82:3054–3058.

    Article  PubMed  CAS  Google Scholar 

  101. Boulle N, Logie A, Gicquel C, Perin L, Le Bouc Y. Increased levels of insulin-like growth factor II (IGF-II) and IGF- binding protein-2 are associated with malignancy in sporadic adrenocortical tumors. J Clin Endocrinol Metab. 1998;83:1713–1720.

    Article  PubMed  CAS  Google Scholar 

  102. Ilvesmaki V, Kahri AI, Miettinen PJ, Voutilainen R. Insulin-like growth factors (IGFs) and their receptors in adrenal tumors: high IGF-II expression in functional adrenocortical carcinomas. J Clin Endocrinol Metab. 1993;77:852–858.

    Article  PubMed  CAS  Google Scholar 

  103. Gao ZH, Suppola S, Liu J, Heikkila P, Janne J, Voutilainen R. Association of H19 promoter methylation with the expression of H19 and IGF-II genes in adrenocortical tumors. J Clin Endocrinol Metab. 2002;87:1170–1176.

    Article  PubMed  CAS  Google Scholar 

  104. Liu J, Kahri AI, Heikkila P, Ilvesmaki V, Voutilainen R. H19 and insulin-like growth factor-II gene expression in adrenal tumors and cultured adrenal cells. J Clin Endocrinol Metab. 1995;80:492–496.

    Article  PubMed  CAS  Google Scholar 

  105. Spada A, Vallar L. G-protein oncogenes in acromegaly. Horm Res. 1992;38:90–93.

    Article  PubMed  CAS  Google Scholar 

  106. Lania A, Mantovani G, Spada A. G protein mutations in endocrine diseases. Eur J Endocrinol. 2001;145:543–559.

    Article  PubMed  CAS  Google Scholar 

  107. Weinstein LS, Shenker A, Gejman PV, Merino MJ, Friedman E, Spiegel AM. Activating mutations of the stimulatory G protein in the McCune-Albright syndrome. N Engl J Med. 1991;325:1688–1695.

    Article  PubMed  CAS  Google Scholar 

  108. Latronico AC. Role of ACTH receptor in adrenocortical tumor formation. Braz J Med Biol Res. 2000;33:1249–1252.

    Article  PubMed  CAS  Google Scholar 

  109. Light K, Jenkins PJ, Weber A, et al. Are activating mutations of the adrenocorticotropin receptor involved in adrenal cortical neoplasia? Life Sci. 1995;56:1523–1527.

    Article  PubMed  CAS  Google Scholar 

  110. Demeure MJ, Doffek KM, Komorowski RA, Gorski J. Gip-2 codon 179 oncogene mutations: absent in adrenal cortical tumors. World J Surg. 1996;20:928-931. discussion 931–932.

    Article  PubMed  CAS  Google Scholar 

  111. Gicquel C, Dib A, Bertagna X, Amselem S, Le Bouc Y. Oncogenic mutations of alpha-Gi2 protein are not determinant for human adrenocortical tumourigenesis. Eur J Endocrinol. 1995;133:166–172.

    Article  PubMed  CAS  Google Scholar 

  112. Lyons J, Landis CA, Harsh G, et al. Two G protein oncogenes in human endocrine tumors. Science. 1990;249:655–659.

    Article  PubMed  CAS  Google Scholar 

  113. Reincke M, Karl M, Travis W, Chrousos GP. No evidence for oncogenic mutations in guanine nucleotide-binding proteins of human adrenocortical neoplasms. J Clin Endocrinol Metab. 1993;77:1419–1422.

    Article  PubMed  CAS  Google Scholar 

  114. Vincent-Dejean C, Cazabat L, Groussin L, et al. Identification of a clinically homogenous subgroup of benign cortisol-secreting adrenocortical tumors characterized by alterations of the protein kinase A (PKA) subunits and high PKA activity. Eur J Endocrinol. 2008;158:829–839.

    Article  PubMed  CAS  Google Scholar 

  115. 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;38:794–800.

    Article  PubMed  CAS  Google Scholar 

  116. Stratakis CA. Cushing syndrome caused by adrenocortical tumors and hyperplasias (corticotropin-independent Cushing syndrome). Endocr Dev. 2008;13:117–132.

    Article  PubMed  CAS  Google Scholar 

  117. Kestler HA, Kuhl M. From individual Wnt pathways towards a Wnt signalling network. Philos Trans R Soc Lond B Biol Sci. 2008;363:1333–1347.

    Article  PubMed  CAS  Google Scholar 

  118. Chen X, Yang J, Evans PM, Liu C. Wnt signaling: the good and the bad. Acta Biochim Biophys Sin (Shanghai). 2008;40:577–594.

    Article  CAS  Google Scholar 

  119. Tissier F, Cavard C, Groussin L, et al. Mutations of beta-catenin in adrenocortical tumors: activation of the Wnt signaling pathway is a frequent event in both benign and malignant adrenocortical tumors. Cancer Res. 2005;65:7622–7627.

    PubMed  CAS  Google Scholar 

  120. Tadjine M, Lampron A, Ouadi L, Bourdeau I. Frequent mutations of beta-catenin gene in sporadic secreting adrenocortical adenomas. Clin Endocrinol (Oxf). 2008;68:264–270.

    CAS  Google Scholar 

  121. Tadjine M, Lampron A, Ouadi L, Horvath A, Stratakis CA, Bourdeau I. Detection of somatic beta-catenin mutations in primary pigmented nodular adrenocortical disease. Clin Endocrinol (Oxf). 2008;69(3):367–373.

    Article  CAS  Google Scholar 

  122. Bourdon JC. p53 and its isoforms in cancer. Br J Cancer. 2007;97:277–282.

    Article  PubMed  CAS  Google Scholar 

  123. Ohgaki H, Kleihues P, Heitz PU. p53 mutations in sporadic adrenocortical tumors. Int J Cancer. 1993;54:408–410.

    Article  PubMed  CAS  Google Scholar 

  124. Reincke M, Karl M, Travis WH, et al. p53 mutations in human adrenocortical neoplasms: immunohistochemical and molecular studies. J Clin Endocrinol Metab. 1994;78:790–794.

    Article  PubMed  CAS  Google Scholar 

  125. Sidhu S, Martin E, Gicquel C, et al. Mutation and methylation analysis of TP53 in adrenal carcinogenesis. Eur J Surg Oncol. 2005;31:549–554.

    Article  PubMed  CAS  Google Scholar 

  126. McNicol AM, Nolan CE, Struthers AJ, Farquharson MA, Hermans J, Haak HR. Expression of p53 in adrenocortical tumours: clinicopathological correlations. J Pathol. 1997;181:146–152.

    Article  PubMed  CAS  Google Scholar 

  127. Lin SR, Lee YJ, Tsai JH. Mutations of the p53 gene in human functional adrenal neoplasms. J Clin Endocrinol Metab. 1994;78:483–491.

    Article  PubMed  CAS  Google Scholar 

  128. Reincke M, Wachenfeld C, Mora P, et al. p53 mutations in adrenal tumors: Caucasian patients do not show the exon 4 “hot spot” found in Taiwan. J Clin Endocrinol Metab. 1996;81:3636–3638.

    Article  PubMed  CAS  Google Scholar 

  129. Wagner J, Portwine C, Rabin K, Leclerc JM, Narod SA, Malkin D. High frequency of germline p53 mutations in childhood adrenocortical cancer. J Natl Cancer Inst. 1994;86:1707–1710.

    Article  PubMed  CAS  Google Scholar 

  130. Ribeiro RC, Sandrini F, Figueiredo B, et al. An inherited p53 mutation that contributes in a tissue-specific manner to pediatric adrenal cortical carcinoma. Proc Natl Acad Sci USA. 2001;98:9330–9335.

    Article  PubMed  CAS  Google Scholar 

  131. Latronico AC, Pinto EM, Domenice S, et al. An inherited mutation outside the highly conserved DNA-binding domain of the p53 tumor suppressor protein in children and adults with sporadic adrenocortical tumors. J Clin Endocrinol Metab. 2001;86:4970–4973.

    Article  PubMed  CAS  Google Scholar 

  132. Figueiredo BC, Sandrini R, Zambetti GP, et al. Penetrance of adrenocortical tumours associated with the germline TP53 R337H mutation. J Med Genet. 2006;43:91–96.

    Article  PubMed  CAS  Google Scholar 

  133. Zwermann O, Beuschlein F, Mora P, Weber G, Allolio B, Reincke M. Multiple endocrine neoplasia type 1 gene expression is normal in sporadic adrenocortical tumors. Eur J Endocrinol. 2000;142:689–695.

    Article  PubMed  CAS  Google Scholar 

  134. De Fraipont F, Le Moigne G, Defaye G, et al. Transcription profiling of benign and malignant adrenal tumors by cDNA macro-array analysis. Endocr Res. 2002;28:785–786.

    Article  PubMed  Google Scholar 

  135. Giordano TJ, Thomas DG, Kuick R, et al. Distinct transcriptional profiles of adrenocortical tumors uncovered by DNA microarray analysis. Am J Pathol. 2003;162:521–531.

    PubMed  CAS  Google Scholar 

  136. de Fraipont F, El Atifi M, Cherradi N, et al. Gene expression profiling of human adrenocortical tumors using complementary deoxyribonucleic Acid microarrays identifies several candidate genes as markers of malignancy. J Clin Endocrinol Metab. 2005;90:1819–1829.

    Article  PubMed  CAS  Google Scholar 

  137. Slater EP, Diehl SM, Langer P, et al. Analysis by cDNA microarrays of gene expression patterns of human adrenocortical tumors. Eur J Endocrinol. 2006;154:587–598.

    Article  PubMed  CAS  Google Scholar 

  138. Giordano TJ. Molecular pathology of adrenal cortical tumors: separating adenomas from carcinomas. Endocr Pathol. 2006;17:355–363.

    Article  PubMed  CAS  Google Scholar 

  139. Allolio B, Fassnacht M. Clinical review: adrenocortical carcinoma: clinical update. J Clin Endocrinol Metab. 2006;91:2027–2037.

    Article  PubMed  CAS  Google Scholar 

  140. McNicol AM, Struthers AJ, Nolan CE, Hermans J, Haak HR. Proliferation in adrenocortical tumors: correlation with clinical outcome and p53 status. Endocr Pathol. 1997;8:29–36.

    Article  PubMed  Google Scholar 

  141. Riepe FG, Sippell WG. Recent advances in diagnosis, treatment, and outcome of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Rev Endocr Metab Disord. 2007;8:349–363.

    Article  PubMed  CAS  Google Scholar 

  142. New MI. An update of congenital adrenal hyperplasia. Ann N Y Acad Sci. 2004;1038:14–43.

    Article  PubMed  CAS  Google Scholar 

  143. Pang S, Murphey W, Levine LS, et al. A pilot newborn screening for congenital adrenal hyperplasia in Alaska. J Clin Endocrinol Metab. 1982;55:413–420.

    Article  PubMed  CAS  Google Scholar 

  144. Pang SY, Wallace MA, Hofman L, et al. Worldwide experience in newborn screening for classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Pediatrics. 1988;81:866–874.

    PubMed  CAS  Google Scholar 

  145. Speiser PW, Dupont B, Rubinstein P, et al. High frequency of non-classical steroid 21-hydroxylase deficiency. Am J Hum Genet. 1985;37:650–657.

    PubMed  CAS  Google Scholar 

  146. Fitness J, Dixit N, Webster D, et al. Genotyping of CYP21, linked chromosome 6p markers, and a sex-specific gene in neonatal screening for congenital adrenal hyperplasia. J Clin Endocrinol Metab. 1999;84:960–966.

    Article  PubMed  CAS  Google Scholar 

  147. Levine LS, Sachmann M, New MI, et al. Genetic mapping of the 21-hydroxylase deficiency gene within the HLA linkage group. N Engl J Med. 1978;299:911–915.

    Article  PubMed  CAS  Google Scholar 

  148. White PC, New MI, Dupont B. Structure of the human steroid 21-hydroxylase genes. Proc Natl Acad Sci USA. 1986;83:5111–5115.

    Article  PubMed  CAS  Google Scholar 

  149. Simard J, Ricketts ML, Gingras S, Soucy P, Feltus FA, Melner MH. Molecular biology of the 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase gene family. Endocr Rev. 2005;26:525–582.

    Article  PubMed  CAS  Google Scholar 

  150. Bauman A, Bauman CG. Virilizing adrenocortical carcinoma. Development in a patient with salt- losing congenital adrenal hyperplasia. JAMA. 1982;248:3140–3141.

    Article  PubMed  CAS  Google Scholar 

  151. Merke DP, Bornstein SR, Braddock D, Chrousos GP. Adrenal lymphocytic infiltration and adrenocortical tumors in a patient with 21-hydroxylase deficiency [letter]. N Engl J Med. 1999;340:1121–1122.

    Article  PubMed  CAS  Google Scholar 

  152. Fujieda K, Okuhara K, Abe S, Tajima T, Mukai T, Nakae J. Molecular pathogenesis of lipoid adrenal hyperplasia and adrenal hypoplasia congenita. J Steroid Biochem Mol Biol. 2003;85:483–489.

    Article  PubMed  CAS  Google Scholar 

  153. Sugawara T, Holt JA, Driscoll D, et al. Human steroidogenic acute regulatory protein: functional activity in COS-1 cells, tissue-specific expression, and mapping of the structural gene to 8p11.2 and a pseudogene to chromosome 13. Proc Natl Acad Sci USA. 1995;92:4778–4782.

    Article  PubMed  CAS  Google Scholar 

  154. Peter M, Viemann M, Partsch CJ, Sippell WG. Congenital adrenal hypoplasia: clinical spectrum, experience with hormonal diagnosis, and report on new point mutations of the DAX-1 gene. J Clin Endocrinol Metab. 1998;83:2666–2674.

    Article  PubMed  CAS  Google Scholar 

  155. Lin L, Hindmarsh PC, Metherell LA, et al. Severe loss-of-function mutations in the adrenocorticotropin receptor (ACTHR, MC2R) can be found in patients diagnosed with salt-losing adrenal hypoplasia. Clin Endocrinol (Oxf). 2007;66:205–210.

    Article  CAS  Google Scholar 

  156. Smith KD, Kemp S, Braiterman LT, et al. X-linked adrenoleukodystrophy: genes, mutations, and phenotypes. Neurochem Res. 1999;24:521–535.

    Article  PubMed  CAS  Google Scholar 

  157. Savary S, Troffer-Charlier N, Gyapay G, Mattei MG, Chimini G. Chromosomal localization of the adrenoleukodystrophy-related gene in man and mice. Eur J Hum Genet. 1997;5:99–101.

    PubMed  CAS  Google Scholar 

  158. Dodd A, Rowland SA, Hawkes SL, Kennedy MA, Love DR. Mutations in the adrenoleukodystrophy gene. Hum Mutat. 1997;9:500–511.

    Article  PubMed  CAS  Google Scholar 

  159. Krasemann EW, Meier V, Korenke GC, Hunneman DH, Hanefeld F. Identification of mutations in the ALD-gene of 20 families with adrenoleukodystrophy/adrenomyeloneuropathy. Hum Genet. 1996;97:194–197.

    Article  PubMed  CAS  Google Scholar 

  160. Laureti S, Casucci G, Santeusanio F, Angeletti G, Aubourg P, Brunetti P. X-linked adrenoleukodystrophy is a frequent cause of idiopathic Addison’s disease in young adult male patients. J Clin Endocrinol Metab. 1996;81:470–474.

    Article  PubMed  CAS  Google Scholar 

  161. Collares CV, Antunes-Rodrigues J, Moreira AC, et al. Heterogeneity in the molecular basis of ACTH resistance syndrome. Eur J Endocrinol. 2008;159:61–68.

    Article  PubMed  CAS  Google Scholar 

  162. Metherell LA, Chan LF, Clark AJ. The genetics of ACTH resistance syndromes. Best Pract Res Clin Endocrinol Metab. 2006;20:547–560.

    Article  PubMed  CAS  Google Scholar 

  163. Connell JM, Inglis GC, Fraser R, Jamieson A. Dexamethasone-suppressible hyperaldosteronism: clinical, biochemical and genetic relations. J Hum Hypertens. 1995;9:505–509.

    PubMed  CAS  Google Scholar 

  164. Miyahara K, Kawamoto T, Mitsuuchi Y, et al. The chimeric gene linked to glucocorticoid- suppressible hyperaldosteronism encodes a fused P-450 protein possessing aldosterone synthase activity. Biochem Biophys Res Commun. 1992;189:885–891.

    Article  PubMed  CAS  Google Scholar 

  165. So A, Duffy DL, Gordon RD, et al. Familial hyperaldosteronism type II is linked to the chromosome 7p22 region but also shows predicted heterogeneity. J Hypertens. 2005;23:1477–1484.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular and Cellular Pathology, UQ Centre for Clinical Research, The Royal Brisbane and Women’s Hospital, Brisbane, Australia

    Anne Marie McNicol BSc, MBChB, MD, MRCP(UK), FRCPGlas, FRCPath (Professor)

Authors
  1. Anne Marie McNicol BSc, MBChB, MD, MRCP(UK), FRCPGlas, FRCPath
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Pathology Service, WRN202, Massachusetts General Hospital, Fruit Street 55, Boston, 02114, USA

    Jennifer L. Hunt

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

McNicol, A.M. (2010). Benign and Malignant Diseases of the Adrenal Cortex. In: Hunt, J. (eds) Molecular Pathology of Endocrine Diseases. Molecular Pathology Library, vol 3. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-1707-2_21

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-1707-2_21

  • Published:

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4419-1706-5

  • Online ISBN: 978-1-4419-1707-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation