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Pituitary

, Volume 7, Issue 4, pp 225–235 | Cite as

Aberrant Expression of Hormone Receptors in Adrenal Cushing's Syndrome

  • Stavroula Christopoulos
  • Isabelle Bourdeau
  • André Lacroix
Article

Abstract

In recent years, a novel understanding of the pathophysiology of adrenal Cushing's syndrome has emerged. The ectopic or aberrant expression of G-protein-coupled hormone receptors in the adrenal cortex was found to play a central role in the regulation of cortisol secretion in ACTH-independent macronodular adrenal hyperplasia (AIMAH) and in some unilateral adrenal adenomas. Various aberrant receptors, functionally coupled to steroidogenesis, have been reported: GIP, vasopressin, β-adrenergic, LH/hCG, and serotonin receptors have been best characterized, but angiotensin, leptin, glucagon, IL-1 and TSH receptors have also been described. The molecular mechanisms responsible for the aberrant expression of these receptors are currently unknown. One or many of these aberrant receptors are present in most cases of AIMAH and in some cases of adrenal adenomas with overt or sub-clinical secretion of cortisol. Clinical protocols to screen for such aberrant receptors have been developed and should be performed in all patients with AIMAH. The identification of such aberrant regulation of steroidogenesis in AIMAH provides the novel opportunity to treat some of these patients with pharmacological agents that either suppress the endogenous ligand or block the aberrant receptor, thus avoiding bilateral adrenalectomy.

Key Words

adrenocortical hyperplasias ACTH-independent macronodular adrenal hyperplasia (AIMAH) Adrenal adenoma Cushing's syndrome aberrant receptor ectopic receptor 

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References

  1. 1.
    Latronico AC, Chrousos GP. Extensive personal experience: Adrenocortical tumors. J Clin Endocrinol Metab 1997;82:1317–1324.CrossRefPubMedGoogle Scholar
  2. 2.
    Newell-Price J, Trainer P, Besser M, Grossman A. The diagnosis and differential diagnosis of Cushing's syndrome and pseudo-Cushing's states. Endocr Rev 1998;19:647–672.CrossRefPubMedGoogle Scholar
  3. 3.
    Nieman LK. Cushing's syndrome. In: De Groot LJ, Jameson JLe, Burger HG, et al., eds. Endocrinology, 4th ed. Philadephia: W. B. Saunders Co, 2000:1691–1720.Google Scholar
  4. 4.
    Bourdeau I, Stratakis CA. Cyclic AMP-dependent signaling aberrations in macronodular adrenal disease. Ann N Y Acad Sci 2002;968:240–255.PubMedGoogle Scholar
  5. 5.
    Shenker A, Laue L, Kosugi S, Merendino JJJ, Minegishi T, Cutler GBJ. A constitutively activating mutation of the luteinizing hormone receptor in familial male precocious puberty. Nature 1993;365:652–654.CrossRefPubMedGoogle Scholar
  6. 6.
    Mauras N, Blizzard RM. The McCune-Albright syndrome. Acta Endocrinol Suppl (Copenh) 1986;279:207–217.Google Scholar
  7. 7.
    Benjamin DR, McRoberts JW. Polyostotic fibrous dysplasia associated with Cushing syndrome. Arch Pathol 1973;96:175–178.PubMedGoogle Scholar
  8. 8.
    Kirk JM, Brain CE, Carson DJ, Hyde JC, Grant DB. Cushing's syndrome caused by nodular adrenal hyperplasia in children with McCune-Albright syndrome. J Pediatr 1999;134:789–792.PubMedGoogle Scholar
  9. 9.
    Aarskog D, Tveteraas E. McCune-Albright's syndrome following adrenalectomy for Cushing's syndrome in infancy. J Pediatr 1968;73:89–96.PubMedGoogle Scholar
  10. 10.
    MacMahon HE. Albright's syndrome—thirty years later. (Polyostotic fibrous dysplasia). Pathol Annu 1971;6:81–146.PubMedGoogle Scholar
  11. 11.
    Danon M, Robboy SJ, Kim S, Scully R, Crawford JD. Cushing syndrome, sexual precocity, and polyostotic fibrous dysplasia (Albright syndrome) in infancy. J Pediatr 1975;87:917–921.PubMedGoogle Scholar
  12. 12.
    Fragoso MC, Domenice S, Latronico AC, Martin RM, Pereira MA, Zerbini MC, et al. Cushing's syndrome secondary to adrenocorticotropin-independent macronodular adrenocortical hyperplasia due to activating mutations of GNAS1 gene. J Clin Endocrinol Metab 2003;88:2147–2151.CrossRefPubMedGoogle Scholar
  13. 13.
    Skogseid B, Larsson C, Lindgren PG, Kvanta E, Rastad J, Theodorsson Wide L, 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
  14. 14.
    Marchesa P, Fazio VW, Church JM, McGannon E. Adrenal masses in patients with familial adenomatous polyposis. Dis Colon Rectum 1997;40:1023–1028.PubMedGoogle Scholar
  15. 15.
    Yamakita N, Murai T, Ito Y, Miura K, Ikeda T, Miyamoto K, et al. Adrenocorticotropin-independent macronodular adrenocortical hyperplasia associated with multiple colon adenomas/carcinomas which showed a point mutation in the APC gene. Intern Med 1997;36:536–542.PubMedGoogle Scholar
  16. 16.
    Bourdeau I, Lacroix A. G-protein mutations (Gsα and G12α) are infrequent in the adrenal atissues with Cushing's syndrome secondary to ACTH-independent bilateral macronodular adrenal hyperplasia. The Endocrine Society 84th Meeting 2002;P1-385:244.Google Scholar
  17. 17.
    Swords FM, Noon LA, King PJ, Clark AJ. Constitutive activation of the human ACTH receptor resulting from a synergistic interaction between two naturally occurring missence mutations in the MC2R gene. Mol Cell Endocrinol 2004;213:149–154.CrossRefPubMedGoogle Scholar
  18. 18.
    Latronico AC, Reincke M, Mendonca BB, Arai K, Mora P, Allolio B, et al. No evidence for oncogenic mutations in the adrenocorticotropin receptor gene in human adrenocortical neoplasms. J Clin Endocrinol Metab 1995;80:875–877.PubMedGoogle Scholar
  19. 19.
    Light K, Jenkins PJ, Weber A, Perrett C, Grossman A, Pistorello M, et al. Are activating mutations of the adrenocorticotropin receptor involved in adrenal cortical neoplasia? Life Sci 1995;56:1523–1527.CrossRefPubMedGoogle Scholar
  20. 20.
    Schorr I, Ney RL. Abnormal hormone responses of an adrenocortical cancer adenyl cyclase. J Clin Invest 1971;50:1295–1300.PubMedGoogle Scholar
  21. 21.
    Lacroix A, N'Diaye N, Tremblay J, Hamet P. Ectopic and Abnormal Hormone Receptors in Adrenal Cushing's Syndrome. Endocr Rev 2001;22:75–110.CrossRefPubMedGoogle Scholar
  22. 22.
    Lacroix A, Baldacchino V, Bourdeau I, Hamet P, Tremblay J. Cushing's syndrome variants secondary to aberrant hormone receptors. Trends Endocrinol Metab 2004;15:375–382.PubMedGoogle Scholar
  23. 23.
    Hamet P, Larochelle P, Franks DJ, Cartier P, Bolte E. Cushing syndrome with food-dependent periodic hormonogenesis. Clin Invest Med 1987;10:530–533.PubMedGoogle Scholar
  24. 24.
    Lacroix A, Bolte E, Tremblay J, Dupre J, Poitras P, Fournier H, et al. Gastric inhibitory polypeptide-dependent cortisol hypersecretion—a new cause of Cushing's syndrome. N Engl J Med 1992;327:974–980.PubMedGoogle Scholar
  25. 25.
    Reznik Y, Allali-Zerah V, Chayvialle JA, Leroyer R, Leymarie P, Travert G, et al. Food-dependent Cushing's syndrome mediated by aberrant adrenal sensitivity to gastric inhibitory polypeptide. N Engl J Med 1992;327:981–986.PubMedGoogle Scholar
  26. 26.
    N'Diaye N, Hamet P, Tremblay J, Boutin JM, Gaboury L, Lacroix A. Asynchronous development of bilateral nodular adrenal hyperplasia in gastric inhibitory polypeptide-dependent Cushing's syndrome. J Clin Endocrinol Metab 1999;84:2616–2622.CrossRefPubMedGoogle Scholar
  27. 27.
    Lebrethon MC, Avallet O, Reznik Y, Archambeaud F, Combes J, Usdin TB, et al. Food-dependent Cushing's syndrome: Characterization and functional role of gastric inhibitory polypeptide receptor in the adrenals of three patients. J Clin Endocrinol Metab 1998;83:4514–4519.CrossRefPubMedGoogle Scholar
  28. 28.
    Pralong FP, Gomez F, Guillou L, Mosimann F, Franscella S, Gaillard RC. Food-dependent Cushing's syndrome: Possible involvement of leptin in cortisol hypersecretion. J Clin Endocrinol Metab 1999;84:3817–3822.PubMedGoogle Scholar
  29. 29.
    Croughs RJ, Zelissen PM, Van Vroonhoven ThJ, Hofland LJ, N'Diaye N, Lacroix A, et al. GIP-dependent adrenal Cushing's syndrome with incomplete suppression of ACTH. Clin Endocrinol (Oxf) 2000;52:235–240.CrossRefGoogle Scholar
  30. 30.
    Gerl H, Rohde W, Biering H, Schulz N, Lochs H. [Food-dependent Cushing syndrome of long standing with mild clinical features]. Dtsch Med Wochenschr 2000;125:1565–1568.CrossRefPubMedGoogle Scholar
  31. 31.
    Groussin L, Perlemoine K, Contesse V, Lefebvre H, Tabarin A, Thieblot P, et al. The ectopic expression of the gastric inhibitory polypeptide receptor is frequent in adrenocorticotropin-independent bilateral macronodular adrenal hyperplasia, but rare in unilateral tumors. J Clin Endocrinol Metab 2002;87:1980–1985.PubMedGoogle Scholar
  32. 32.
    de Herder WW, Hofland LJ, Usdin TB, de Jong FH, Uitterlinden P, van Koetsveld P, et al. Food-dependent Cushing's syndrome resulting from abundant expression of gastric inhibitory polypeptide receptors in adrenal adenoma cells. J Clin Endocrinol Metab 1996;81:3168–3172.PubMedGoogle Scholar
  33. 33.
    Chabre O, Liakos P, Vivier J, Chaffanjon P, Labat-Moleur F, Martinie M, 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.CrossRefPubMedGoogle Scholar
  34. 34.
    Luton JP, Bertagna X. [Membrane receptors and endocrine tumors: Expression of vasopressin receptor V1 modulates the pharmacologic phenotype of adrenocortical tumors]. Bull Acad Natl Med 1998;182:299–309.PubMedGoogle Scholar
  35. 35.
    Tsagarakis S, Tsigos C, Vassiliou V, Tsiotra P, Pratsinis H, Kletsas D, et al. Food-dependent androgen and cortisol secretion by a gastric inhibitory polypeptide-receptor expressive adrenocortical adenoma leading to hirsutism and subclinical Cushing's syndrome: In vivo and in vitro studies. J Clin Endocrinol Metab 2001;86:583–589.CrossRefPubMedGoogle Scholar
  36. 36.
    N'Diaye N, Tremblay J, Hamet P, de Herder WW, Lacroix A. Adrenocortical overexpression of gastric inhibitory polypeptide receptor underlies food-dependent Cushing's syndrome. J Clin Endocrinol Metab 1998;83:2781–2785.CrossRefPubMedGoogle Scholar
  37. 37.
    Longo-Mazzuco T, Chabre O, Feige JJ, Thomas M. Démonstration du potentiel transformant du gène du récepteur du GIP dans les cellules du cortex surrénalien: un pas vers l'étiologie du syndrome de Cushing lié à l'alimentation. Ann Endocrinol (Paris) 2004;65, C024:267.Google Scholar
  38. 38.
    Lacroix A, Tremblay J, Touyz RM, Deng LY, Lariviere R, Cusson JR, et al. Abnormal adrenal and vascular responses to vasopressin mediated by a V1- vasopressin receptor in a patient with adrenocorticotropin-independent macronodular adrenal hyperplasia, Cushing's syndrome, and orthostatic hypotension. J Clin Endocrinol Metab 1997;82:2414–2422.CrossRefPubMedGoogle Scholar
  39. 39.
    Horiba N, Suda T, Aiba M, Naruse M, Nomura K, Imamura M, et al. Lysine vasopressin stimulation of cortisol secretion in patients with adrenocorticotropin-independent macronodular adrenal hyperplasia. J Clin Endocrinol Metab 1995;80:2336–2341.CrossRefPubMedGoogle Scholar
  40. 40.
    Iida K, Kaji H, Matsumoto H, Okimura Y, Abe H, Fujisawa M, et al. Adrenocorticotrophin-independent macronodular adrenal hyperplasia in a patient with lysine vasopressin responsiveness but insensitivity to gastric inhibitory polypeptide. Clin Endocrinol (Oxf) 1997;47:739–745.CrossRefGoogle Scholar
  41. 41.
    Demura R, Demura H, Nunokawa T, Baba H, Miura K. Responses of plasma ACTH, GH, LH and 11-hydroxycorticosteroids to various stimuli in patients with Cushing's syndrome. J Clin Endocrinol Metab 1972;34:852–859.PubMedGoogle Scholar
  42. 42.
    Perraudin V, Delarue C, de Keyzer Y, Bertagna X, Kuhn JM, Contesse V, et al. Vasopressin-responsive adrenocortical tumor in a mild Cushing's syndrome: In vivo and in vitro studies. J Clin Endocrinol Metab 1995;80:2661–2667.CrossRefPubMedGoogle Scholar
  43. 43.
    Makino S, Hashimoto K, Sugiyama M, Hirasawa R, Takao T, Ota Z, et al. Cushing's syndrome due to huge nodular adrenocortical hyperplasia with fluctuation of urinary 17-OHCS excretion. Endocrinol Jpn 1989;36:655–663.PubMedGoogle Scholar
  44. 44.
    Itagaki E, Nozaki M, Abe Y, Takizawa M, Furukawa H, Murakawa S. Direct effect of lysine-vasopressin on cortisol production in isolated adrenal cells from nodular adrenocortical hyperplasia. In: Mantero F, ed., Serono Symposia, New York: Raven Press, 1989;57:403–408.Google Scholar
  45. 45.
    Daidoh H, Morita H, Hanafusa J, Mune T, Murase H, Sato M, et al. In vivo and in vitro effects of AVP and V1a receptor antagonist on Cushing's syndrome due to ACTH-independent bilateral macronodular adrenocortical hyperplasia. Clin Endocrinol (Oxf) 1998;49:403–409.CrossRefGoogle Scholar
  46. 46.
    Arnaldi G, Gasc JM, de Keyzer Y, Raffin-Sanson ML, Perraudin V, Kuhn JM, et al. Variable expression of the V1 vasopressin receptor modulates the phenotypic response of steroid-secreting adrenocortical tumors. J Clin Endocrinol Metab 1998;83:2029–2035.CrossRefPubMedGoogle Scholar
  47. 47.
    Mune T, Murase H, Yamakita N, Fukuda T, Murayama M, Miura A, et al. Eutopic overexpression of vasopressin V1a receptor in adrenocorticotropin-independent macronodular adrenal hyperplasia. J Clin Endocrinol Metab 2002;87:5706–5713.CrossRefPubMedGoogle Scholar
  48. 48.
    Campbell KK, Baysdorfer C, Antonini S, Lacroix A. V1 vasopressin receptor sequence and expression in adrenal Cushing's syndrome with abberant response to vasopressin. The Endocrine Society's 86th Meeting, New Orleans, LO 2004;P3-416, 566.Google Scholar
  49. 49.
    Lee S, Jun S, Hong SW, Kim DJ, Rhee Y, Lim SK. Familial adrenocorticotropin-independent macronodular adrenal hyperplasia: Ectopic expression of vasopressin V1b, V2 receptors in the adrenal gland. The Endocrine Society's 86th Meeting, New Orleans, LO 2004;P3-417, 566.Google Scholar
  50. 50.
    Louiset E, Contesse V, Cartier D, Bertherat J, Duparc C, Barrande G, et al. Pharmacological profile and coupling mechanisms of illegitimate receptors in ACTH-independent macronodular bilateral adrenal hyperplasia causing Cushing's syndrome. The Endocrine Society's 86th Meeting, New Orleans LO 2004;P3-410, 564.Google Scholar
  51. 51.
    Matsukura S, Kakita T, Sueoka S, Yoshimi H, Hirata Y, Yokota M, et al. Multiple hormone receptors in the adenylate cyclase of human adrenocortical tumors. Cancer Res 1980;40:3768–3771.PubMedGoogle Scholar
  52. 52.
    Hirata Y, Uchihashi M, Sueoka S, Matsukura S, Fujita T. Presence of ectopic beta-adrenergic receptors on human adrenocortical cortisol-producing adenomas. J Clin Endocrinol Metab 1981;53:953–957.PubMedGoogle Scholar
  53. 53.
    Katz MS, Kelly TM, Dax EM, Pineyro MA, Partilla JS, Gregerman RI. Ectopic beta-adrenergic receptors coupled to adenylate cyclase in human adrenocortical carcinomas. J Clin Endocrinol Metab 1985;60:900–909.PubMedGoogle Scholar
  54. 54.
    Lacroix A, Tremblay J, Rousseau G, Bouvier M, Hamet P. Propranolol therapy for ectopic beta-adrenergic receptors in adrenal Cushing's syndrome. N Engl J Med 1997;337:1429–1434.CrossRefPubMedGoogle Scholar
  55. 55.
    Mircescu H, Jilwan J, N'Diaye N, Bourdeau I, Tremblay J, Hamet P, et al. Are ectopic or abnormal membrane hormone receptors frequently present in adrenal Cushing's syndrome? J Clin Endocrinol Metab 2000;85:3531–3536.CrossRefPubMedGoogle Scholar
  56. 56.
    Miyamura N, Tsutsumi A, Senokuchi H, Nakamaru K, Kawashima J, Sakai K, et al. A case of ACTH-independent macronodular adrenal hyperplasia: Simultaneous expression of several aberrant hormone receptors in the adrenal gland. Endocr J 2003;50:333–340.CrossRefPubMedGoogle Scholar
  57. 57.
    Pignatelli D, Rodrigues E, Barbosa AM, Medina JL. Cushing syndrome due to the ectopic expression of adrenergic receptors in the adrenal cortex. A case of ACTH independent macronodular adrenal hyperplasia (AIMAH). The Endocrine Society's 86th Meeting, New Orleans, LO 2004;P3-592, 611.Google Scholar
  58. 58.
    Imohl M, Koditz R, Stachon A, Muller KM, Nicolas V, Pfeilschifter J, et al. [Catecholamine-dependent hereditary Cushing's syndrome—Follow-up after unilateral adrenalectomy]. Med Klin (Munich) 2002;97:747–753.Google Scholar
  59. 59.
    Mazzuco TL, Martinie M, Favre S, Bachelot I, Chabre O. ACTH-independent Cushing's Syndrome treated solely with propranolol therapy. The Endocrine Society 84th Meeting 2002;P25-2.Google Scholar
  60. 60.
    Sesmilo G, et al. Spanish Endocrine Society, Alicante, Spain. 2002.Google Scholar
  61. 61.
    Rao CV. The Beginning of a New Era in Reproductive Biology and Medicine: Expression of low levels of functional luteinizing hormone/human chorionic gonadotropin receptors in nongondal tissues. J Physiol Pharmacol 1996;47:41–53.Google Scholar
  62. 62.
    Pabon JE, Li X, Lei ZM, Sanfilippo JS, Yussman MA, Rao CV. Novel presence of luteinizing hormone/chorionic gonadotropin receptors in human adrenal glands. J Clin Endocrinol Metab 1996;81:2397–2400.PubMedGoogle Scholar
  63. 63.
    Seron-Ferre M, Lawrence CC, Jaffe RB. Role of hCG in regulation of the fetal zone of the human fetal adrenal gland. J Clin Endocrinol Metab 1978;46:834–837.PubMedGoogle Scholar
  64. 64.
    Lacroix A, Hamet P, Boutin JM. Leuprolide acetate therapy in luteinizing hormone–dependent Cushing's syndrome. N Engl J Med 1999;341:1577–1581.CrossRefPubMedGoogle Scholar
  65. 65.
    N'Diaye N, Cartier D, Bourdeau I, Tremblay J, Hamet P, Lefebvre H, et al. Characterization of aberrant LH/hCG and serotonin 5-HT4 receptors in adrenal Cushing's syndrome. The 83rd Annual Meeting of the Endocrine Society, Denver, CO Abstract P1-407, 2001:235.Google Scholar
  66. 66.
    Feelders RA, Lamberts SW, Hofland LJ, van Koetsveld PM, Verhoef-Post M, Themmen AP, et al. Luteinizing hormone (LH)-responsive Cushing's syndrome: The demonstration of LH receptor messenger ribonucleic acid in hyperplastic adrenal cells, which respond to chorionic gonadotropin and serotonin agonists in vitro. J Clin Endocrinol Metab 2003;88:230–237.CrossRefPubMedGoogle Scholar
  67. 67.
    Bourdeau I, D'Amour P, Hamet P, Boutin JM, Lacroix A. Aberrant membrane hormone receptors in incidentally discovered bilateral macronodular adrenal hyperplasia with subclinical Cushing's syndrome. J Clin Endocrinol Metab 2001;86:5534–5540.CrossRefPubMedGoogle Scholar
  68. 68.
    Bertherat J, Barrande G, Lefebvre H, Raffin-Sanson ML, Bertagna X. Systematic screening confirms that illicit membrane receptors are frequent and often multiple in bilateral ACTH-independent macronodular adrenal hyperplasia (AIMAH). Program & Abstracts The Endocrine Society's 83rd Annual Meeting, Denver, CO 2001;Abstract P1-397, 233.Google Scholar
  69. 69.
    Goodarzi MO, Dawson DW, Li X, Lei Z, Shintaku P, Rao CV, et al. Virilization in bilateral macronodular adrenal hyperplasia controlled by luteinizing hormone. J Clin Endocrinol Metab 2003;88:73–77.CrossRefPubMedGoogle Scholar
  70. 70.
    Lefebvre H, Contesse V, Delarue C, Vaudry H, Kuhn JM. Serotonergic regulation of adrenocortical function. Horm Metab Res 1998;30:398–403.PubMedGoogle Scholar
  71. 71.
    Cartier D, Lihrmann I, Parmentier F, Bastard C, Bertherat J, Caron P, et al. Overexpression of serotonin4 receptors in cisapride-responsive adrenocorticotropin-independent bilateral macronodular adrenal hyperplasia causing Cushing's syndrome. J Clin Endocrinol Metab 2003;88:248–254.CrossRefPubMedGoogle Scholar
  72. 72.
    Mannelli M, Ferruzzi P, Luciani P, Crescioli C, Buci L, Corona G, et al. Cushing's syndrome in a patient with bilateral macronodular adrenal hyperplasia responding to cisapride: An in vivo and in vitro study. J Clin Endocrinol Metab 2003;88:4616–4622.CrossRefPubMedGoogle Scholar
  73. 73.
    Yared Z, Antonini S, Lacroix A. Macronodular adrenal hyperplasia with long-term primary hyperaldosteronism and recent cyclical Cushing's syndrome with aberrant response of cortisol to serotonin agonist 5-HT4 R. The Endocrine Society 85th Meeting Philadelphia, PA 2003;P2-568, 445.Google Scholar
  74. 74.
    Contesse V, Reznik Y, Louiset E, Duparc C, Cartier D, Sicard F, et al. Abnormal sensitivity of cortisol-producing adrenocortical adenomas to serotonin: In vivo and in vitro studies. J Clin Endocrinol Metab 2005.Google Scholar
  75. 75.
    Louiset E, Cartier D, Contesse V, Duparc C, Lihrmann I, Young J, et al. Paradoxical inhibitory effect of serotonin on cortisol production from adrenocortical lesions causing Cushing's syndrome. Endocr Res 2004;30:951–954.CrossRefPubMedGoogle Scholar
  76. 76.
    Nakamura Y, Son Y, Kohno Y, Shimono D, Kuwamura N, Koshiyama H, et al. Case of adrenocorticotropic hormone-independent macronodular adrenal hyperplasia with possible adrenal hypersensitivity to angiotensin II. Endocrine 2001;15:57–61.CrossRefPubMedGoogle Scholar
  77. 77.
    Bertherat J, Contesse V, Louiset E, Barrande G, Duparc C, Groussin L, et al. Abnormal sensitivity of the adrenocortical tissue to multiple stimuli in ACTH-independent macronodular adrenal hyperplasia (AIMAH) causing Cushing's syndrome: in vivo and in vitro studies. The Endocrine Society's 86th Meeting, New Orleans, LO 2004;P3-403, 562.Google Scholar
  78. 78.
    Willenberg HS, Stratakis CA, Marx C, Ehrhart-Bornstein M, Chrousos GP, Bornstein SR. Aberrant interleukin-1 receptors in a cortisol-secreting adrenal adenoma causing Cushing's syndrome. N Engl J Med 1998;339:27–31.CrossRefPubMedGoogle Scholar
  79. 79.
    Hashimoto K, Kawada Y, Murakami K, Hattori T, Suemaru S, Kageyama J, et al. Cortisol responsiveness to insulin-induced hypoglycemia in Cushing's syndrome with huge nodular adrenocortical hyperplasia. Endocrinol Jpn 1986;33:479–487.PubMedGoogle Scholar
  80. 80.
    Yared Z, Bourdeau I, Lacroix A. Failure to control Cushing's syndrome with leuprolide acetate in a case of ACTH-independent bilateral macronodular adrenal hyperplasia with partial regulation of cortisol secretion by LH and hCG. The Endocrine Society 84th Meeting. San Francisco, CA 2002;649.Google Scholar
  81. 81.
    Lefebvre H, Duparc C, Chartrel N, Jegou S, Pellerin A, Laquerriere A, et al. Intraadrenal adrenocorticotropin production in a case of bilateral macronodular adrenal hyperplasia causing Cushing's syndrome. J Clin Endocrinol Metab 2003;88:3035–3042.CrossRefPubMedGoogle Scholar
  82. 82.
    Lacroix A, Mircescu H, Hamet P. Clinical evaluation of the presence of abnormal hormone receptors in adrenal Cushing's syndrome. The Endocrinologist 1999;9:9–15.Google Scholar
  83. 83.
    Reznik Y, Lefebvre H, Rohmer V, et al. Aberrant sensitivity to multiple ligands in unilateral adrenal incidentaloma: A prospective study. Clin Endocrinol (Oxf) 2004;61:311–319.CrossRefGoogle Scholar
  84. 84.
    Bertherat J, Barrande G, Lefebvre H, et al. Illegitimate membrane receptors are frequent and often multiple in bilateral ACTH-independent macronodular adrenal hyperplasia. The Endocrine Society 85th Meeting. Philadelphia, PA 2003;P3-410, 570.Google Scholar
  85. 85.
    Bertherat J, Contesse V, Louiset E, Barrande G, Duparc C, Groussin L, et al. In vivo and in vitro screening for illegitimate receptors in ACTH-independent macronodular adrenal hyperplasia (AIMAH) causing cushing's syndrome: Identification of two cases of gonadotropin/gastric inhibitory polypeptide-dependent hypercortisolism. J Clin Endocrinol Metab 2004.Google Scholar
  86. 86.
    Dall'Asta C, Ballare E, Mantovani G, Ambrosi B, Spada A, Barbetta L, et al. Assessing the presence of abnormal regulation of cortisol secretion by membrane hormone receptors: In vivo and in vitro studies in patients with functioning and non-functioning adrenal adenoma. Horm Metab Res 2004;36:578–583.CrossRefPubMedGoogle Scholar
  87. 87.
    Tatsuno I, Uchida D, Tanaka T, Koide H, Shigeta A, Ichikawa T, et al. Vasopressin responsiveness of subclinical Cushing's syndrome due to ACTH-independent macronodular adrenocortical hyperplasia. Clin Endocrinol (Oxf) 2004;60:192–200.CrossRefGoogle Scholar
  88. 88.
    Farfel Z, Bourne HR, Iiri T. The expanding spectrum of G protein diseases. N Engl J Med 1999;340:1012–1020.CrossRefPubMedGoogle Scholar
  89. 89.
    Bourdeau I, D'Amour P, Hamet P, Boutin J-M, Lacroix A. Abberant membrane hormone receptors in incidentally discovered bilateral macronodular adrenal hyperplasia with subclinical Cushing's syndrome. J Clin Endocrinol Metab 2001;86:5534–5540.CrossRefPubMedGoogle Scholar
  90. 90.
    Bourdeau I, Antonini S, Lacroix A, Kirschner LS, Lorang D, Libutti SK, et al. Gene array analysis of macronodular adrenal hyperplasis confirms clinical heterogenity and identifies several genes as molecular mediators. Oncogene 2004;26:1575–1585.Google Scholar
  91. 91.
    Gicquel C, Bertagna X, Le Bouc Y. Recent advances in the pathogenesis of adrenocortical tumours. Eur J Endocrinol 1995;133:133–144.PubMedGoogle Scholar
  92. 92.
    Diaz-Cano SJ, de Miguel M, Blanes A, Tashjian R, Galera H, Wolfe HJ. Clonality as expression of distinctive cell kinetics patterns in nodular hyperplasias and adenomas of the adrenal cortex. Am J Pathol 2000;156:311–319.PubMedGoogle Scholar
  93. 93.
    Beuschlein F, Reincke M, Karl M, Travis WD, Jaursch-Hancke C, Abdelhamid S, et al. Clonal composition of human adrenocortical neoplasms. Cancer Res 1994;54:4927–4932.PubMedGoogle Scholar
  94. 94.
    Gicquel C, Leblond-Francillard M, Bertagna X, Louvel A, Chapuis Y, Luton JP, et al. Clonal analysis of human adrenocortical carcinomas and secreting adenomas. Clin Endocrinol (Oxf) 1994;40:465–477.Google Scholar
  95. 95.
    Antonini SR, N'Diaye N, Baldacchino V, Hamet P, Tremblay J, Lacroix A. Analysis of the putative regulatory region of the gastric inhibitory polypeptide receptor gene in food-dependent Cushing's syndrome. J Steroid Biochem Mol Biol 2004;91:171–177.CrossRefPubMedGoogle Scholar
  96. 96.
    Baldacchino V, Oble S, Hamet P, Tremblay J, Lacroix A. Partial characterisation of the 5′ flanking region of the human GIP receptor (GIPR) gene. Endocr Res 2002;28:577.CrossRefPubMedGoogle Scholar
  97. 97.
    Findlay JC, Sheeler LR, Engeland WC, Aron DC. Familial adrenocorticotropin-independent Cushing's syndrome with bilateral macronodular adrenal hyperplasia. J Clin Endocrinol Metab 1993;76:189–191.CrossRefPubMedGoogle Scholar
  98. 98.
    Minami S, Sugihara H, Sato J, Tatsukuchi A, Sugisaki Y, Sasano H, et al. ACTH independent Cushing's syndrome occurring in siblings. Clin Endocrinol (Oxf) 1996;44:483–488.CrossRefGoogle Scholar
  99. 99.
    Nies C, Bartsch DK, Ehlenz K, Wild A, Langer P, Fleischhacker S, et al. Familial ACTH-independent Cushing's syndrome with bilateral macronodular adrenal hyperplasia clinically affecting only female family members. Exp Clin Endocrinol Diabetes 2002;110:277–283.CrossRefPubMedGoogle Scholar
  100. 100.
    Kero J, Poutanen M, Zhang FP, Rahman N, McNicol AM, Nilson JH, et al. Elevated luteinizing hormone induces expression of its receptor and promotes steroidogenesis in the adrenal cortex. J Clin Invest 2000;105:633–641.PubMedGoogle Scholar
  101. 101.
    Swords FM, Aylwin S, Perry L, Arola J, Grossman AB, Monson JP, et al. The aberrant expression of the gastric inhibitory polypeptide (GIP) receptor in adrenal hyperplasia: Does chronic ACTH exposure stimulate up-regulation of GIP receptors in Cushing's disease? J Clin Endocrinol Metab 2005.Google Scholar
  102. 102.
    Sturrock ND, Morgan L, Jeffcoate WJ. Autonomous nodular hyperplasia of the adrenal cortex: Tertiary hypercortisolism? Clin Endocrinol (Oxf) 1995;43:753–758.Google Scholar
  103. 103.
    Hocher B, Bahr V, Dorfmuller S, Oelkers W. Hypercortisolism with non-pigmented micronodular adrenal hyperplasia: Transition from pituitary-dependent to adrenal-dependent Cushing's syndrome. Acta Endocrinol (Copenh) 1993;128:120–125.Google Scholar
  104. 104.
    Choi Y, Werk EE Jr, Sholiton LJ. Cushing's syndrome with dual pituitary-adrenal control. Arch Intern Med 1970;125:1045–1049.CrossRefPubMedGoogle Scholar
  105. 105.
    Aron DC, Findling JW, Fitzgerald PA, Brooks RM, Fisher FE, Forsham PH, et al. Pituitary ACTH dependency of nodular adrenal hyperplasia in Cushing's syndrome. Report of two cases and review of the literature. Am J Med 1981;71:302–306.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Stavroula Christopoulos
    • 1
  • Isabelle Bourdeau
    • 1
  • André Lacroix
    • 1
    • 2
  1. 1.Division of Endocrinology, Department of MedicineCentre hospitalier de l'Université de Montréal (CHUM)MontréalCanada
  2. 2.Division of Endocrinology, Department of MedicineHôtel-Dieu du CHUMMontréalCanada

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