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Etiologies of Cushing’s Syndrome

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Cushing's Syndrome

Part of the book series: Contemporary Endocrinology ((COE))

Summary

Harvey Cushing described the first case of Cushing’s syndrome with a severe phenotype in 1912. Since then investigation and management of Cushing’s syndrome has remained a significant clinical challenge (1, 2), and patients suspected of this diagnosis warrant referral to major centers. Knowledge of the varying etiologies of Cushing’s syndrome is important so that the likelihood of a precise cause may be considered during initial consultation and diagnostic workup.

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References

  1. Newell-Price J, Bertagna X, Grossman AB, Nieman LK. Cushing’s syndrome. Lancet 2006;367(9522):1605–1617.

    Article  PubMed  CAS  Google Scholar 

  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(5):647–672.

    Article  PubMed  CAS  Google Scholar 

  3. Nieman LK, Biller BM, Findling JW, et al. The diagnosis of Cushing’s syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2008;93(5):1526–1540.

    Article  PubMed  CAS  Google Scholar 

  4. Schteingart DE, Lloyd RV, Akil H, et al. Cushing’s syndrome secondary to ectopic corticotropin-releasing hormone-adrenocorticotropin secretion. J Clin Endocrinol Metab 1986;63(3):770–775.

    Article  PubMed  CAS  Google Scholar 

  5. Muller OA, von Werder K. Ectopic production of ACTH and corticotropin-releasing hormone (CRH). J Steroid Biochem Mol Biol 1992;43(5):403–408.

    Article  PubMed  CAS  Google Scholar 

  6. Bayraktar F, Kebapcilar L, Kocdor MA, et al. Cushing’s syndrome due to ectopic CRH secretion by adrenal pheochromocytoma accompanied by renal infarction. Exp Clin Endocrinol Diabetes 2006;114(8):444–447.

    Article  PubMed  CAS  Google Scholar 

  7. Rod A, Voicu M, Chiche L, et al. Cushing’s syndrome associated with a nested stromal epithelial tumor of the liver: hormonal, immunohistochemical, and molecular studies. Eur J Endocrinol 2009;161(5):805–810.

    Article  PubMed  CAS  Google Scholar 

  8. Woo YS, Isidori AM, Wat WZ, et al. Clinical and biochemical characteristics of adrenocorticotropin-secreting macroadenomas. J Clin Endocrinol Metab 2005;90(8):4963–4969.

    Article  PubMed  CAS  Google Scholar 

  9. Newell-Price J, Morris DG, Drake WM, et al. Optimal response criteria for the human CRH test in the differential diagnosis of ACTH-dependent Cushing’s syndrome. J Clin Endocrinol Metab 2002;87(4):1640–1645.

    Article  PubMed  CAS  Google Scholar 

  10. Nieman LK, Oldfield EH, Wesley R, Chrousos GP, Loriaux DL, Cutler GB, Jr. A simplified morning ovine corticotropin-releasing hormone stimulation test for the differential diagnosis of adrenocorticotropin-dependent Cushing’s syndrome. J Clin Endocrinol Metab 1993;77(5):1308–1312.

    Article  PubMed  CAS  Google Scholar 

  11. de Keyzer Y, Auzan C, Lenne F, et al. Cloning and characterization of the human V3 pituitary vasopressin receptor. FEBS Lett 1994;356(2–3):215–220.

    Article  PubMed  CAS  Google Scholar 

  12. Dahia PL, Ahmed-Shuaib A, Jacobs RA, et al. Vasopressin receptor expression and mutation analysis in corticotropin-secreting tumors. J Clin Endocrinol Metab 1996;81(5):1768–1771.

    Article  PubMed  CAS  Google Scholar 

  13. de Keyzer Y, Lenne F, Auzan C, et al. The pituitary V3 vasopressin receptor and the corticotroph phenotype in ectopic ACTH syndrome. J Clin Invest 1996;97(5):1311–1318.

    Article  PubMed  CAS  Google Scholar 

  14. de Keyzer Y, Rene P, Lenne F, Auzan C, Clauser E, Bertagna X. V3 vasopressin receptor and corticotropic phenotype in pituitary and nonpituitary tumors. Horm Res 1997;47(4–6):259–262.

    Article  PubMed  CAS  Google Scholar 

  15. Newell-Price J, Perry L, Medbak S, et al. A combined test using desmopressin and corticotropin-releasing hormone in the differential diagnosis of Cushing’s syndrome. J Clin Endocrinol Metab 1997;82(1):176–181.

    Article  PubMed  CAS  Google Scholar 

  16. Dahia PL, Grossman AB. The molecular pathogenesis of corticotroph tumors. Endocr Rev 1999;20(2):136–155.

    Article  PubMed  CAS  Google Scholar 

  17. Drouin J, Trifiro MA, Plante RK, Nemer M, Eriksson P, Wrange O. Glucocorticoid receptor binding to a specific DNA sequence is required for hormone-dependent repression of pro-opiomelanocortin gene transcription. Mol Cell Biol 1989;9(12):5305–5314.

    PubMed  CAS  Google Scholar 

  18. Philips A, Maira M, Mullick A, et al. Antagonism between Nur77 and glucocorticoid receptor for control of transcription. Mol Cell Biol 1997;17(10):5952–5959.

    PubMed  CAS  Google Scholar 

  19. Bilodeau S, Vallette-Kasic S, Gauthier Y, et al. Role of Brg1 and HDAC2 in GR trans-repression of the pituitary POMC gene and misexpression in Cushing disease. Genes Dev 2006;20(20):2871–2886.

    Article  PubMed  CAS  Google Scholar 

  20. Storr HL, Isidori AM, Monson JP, Besser GM, Grossman AB, Savage MO. Prepubertal Cushing’s disease is more common in males, but there is no increase in severity at diagnosis. J Clin Endocrinol Metab 2004;89(8):3818–3820.

    Article  PubMed  CAS  Google Scholar 

  21. Ilias I, Torpy DJ, Pacak K, Mullen N, Wesley RA, Nieman LK. Cushing’s syndrome due to ectopic corticotropin secretion: twenty years’ experience at the National Institutes of Health. J Clin Endocrinol Metab 2005;90(8):4955–4962.

    Article  PubMed  CAS  Google Scholar 

  22. Isidori AM, Kaltsas GA, Pozza C, et al. The ectopic adrenocorticotropin syndrome: clinical features, diagnosis, management, and long-term follow-up. J Clin Endocrinol Metab 2006;91(2):371–377.

    PubMed  CAS  Google Scholar 

  23. Salgado LR, Fragoso MC, Knoepfelmacher M, et al. Ectopic ACTH syndrome: our experience with 25 cases. Eur J Endocrinol 2006;155(5):725–733.

    Article  PubMed  CAS  Google Scholar 

  24. Picon A, Bertagna X, de Keyzer Y. Analysis of the human proopiomelanocortin gene promoter in a small cell lung carcinoma cell line reveals an unusual role for E2F transcription factors. Oncogene 1999;18(16):2627–2633.

    Article  PubMed  CAS  Google Scholar 

  25. Newell-Price J, King P, Clark AJ. The CpG island promoter of the human proopiomelanocortin gene is methylated in nonexpressing normal tissue and tumors and represses expression. Mol Endocrinol 2001;15(2):338–348.

    Article  PubMed  CAS  Google Scholar 

  26. Lacroix A, Ndiaye N, Tremblay J, Hamet P. Ectopic and abnormal hormone receptors in adrenal Cushing’s syndrome. Endocr Rev 2001;22(1):75–110.

    Article  PubMed  CAS  Google Scholar 

  27. Storr HL, Mitchell H, Swords FM, et al. Clinical features, diagnosis, treatment and molecular studies in paediatric Cushing’s syndrome due to primary nodular adrenocortical hyperplasia. Clin Endocrinol (Oxf) 2004;61(5):553–559.

    Article  CAS  Google Scholar 

  28. 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(9):4041–4046.

    Article  PubMed  CAS  Google Scholar 

  29. 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(1):89–92.

    PubMed  CAS  Google Scholar 

  30. Casey M, Vaughan CJ, He J, et al. Mutations in the protein kinase A R1alpha regulatory subunit cause familial cardiac myxomas and Carney complex. J Clin Invest 2000;106(5):R31–38.

    Article  PubMed  CAS  Google Scholar 

  31. 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(24):1688–1695.

    Article  PubMed  CAS  Google Scholar 

  32. Etxabe J, Vazquez JA. Morbidity and mortality in Cushing’s disease: an epidemiological approach. Clin Endocrinol (Oxf) 1994;40(4):479–484.

    Article  CAS  Google Scholar 

  33. Young WF, Jr. Clinical practice. The incidentally discovered adrenal mass. N Engl J Med 2007;356(6):601–610.

    Article  PubMed  CAS  Google Scholar 

  34. Garrapa GG, Pantanetti P, Arnaldi G, Mantero F, Faloia E. Body composition and metabolic features in women with adrenal incidentaloma or Cushing’s syndrome. J Clin Endocrinol Metab 2001;86(11):5301–5306.

    Article  PubMed  CAS  Google Scholar 

  35. Rossi R, Tauchmanova L, Luciano A, et al. Subclinical Cushing’s syndrome in patients with adrenal incidentaloma: clinical and biochemical features. J Clin Endocrinol Metab 2000;85(4):1440–1448.

    Article  PubMed  CAS  Google Scholar 

  36. Tauchmanova L, Rossi R, Biondi B, et al. Patients with subclinical Cushing’s syndrome due to adrenal adenoma have increased cardiovascular risk. J Clin Endocrinol Metab 2002;87(11):4872–4878.

    Article  PubMed  CAS  Google Scholar 

  37. Terzolo M, Pia A, Ali A, et al. Adrenal incidentaloma: a new cause of the metabolic syndrome? J Clin Endocrinol Metab 2002;87(3):998–1003.

    Article  PubMed  CAS  Google Scholar 

  38. Kloos RT, Gross MD, Francis IR, Korobkin M, Shapiro B. Incidentally discovered adrenal masses. Endocr Rev 1995;16(4):460–484.

    PubMed  CAS  Google Scholar 

  39. Mansmann G, Lau J, Balk E, Rothberg M, Miyachi Y, Bornstein SR. The clinically inapparent adrenal mass: update in diagnosis and management. Endocr Rev 2004;25(2):309–340.

    Article  PubMed  Google Scholar 

  40. Terzolo M, Reimondo G, Bovio S, Angeli A. Subclinical Cushing’s syndrome. Pituitary 2004;7(4):217–223.

    Article  PubMed  Google Scholar 

  41. Tauchmanova L, Pivonello R, Di Somma C, et al. Bone demineralization and vertebral fractures in endogenous cortisol excess: role of disease etiology and gonadal status. J Clin Endocrinol Metab 2006;91(5):1779–1784.

    Article  PubMed  CAS  Google Scholar 

  42. Francucci CM, Pantanetti P, Garrapa GG, Massi F, Arnaldi G, Mantero F. Bone metabolism and mass in women with Cushing’s syndrome and adrenal incidentaloma. Clin Endocrinol (Oxf) 2002;57(5):587–593.

    Article  CAS  Google Scholar 

  43. Chiodini I, Tauchmanova L, Torlontano M, et al. Bone involvement in eugonadal male patients with adrenal incidentaloma and subclinical hypercortisolism. J Clin Endocrinol Metab 2002;87(12):5491–5494.

    Article  PubMed  CAS  Google Scholar 

  44. Osella G, Terzolo M, Borretta G, et al. Endocrine evaluation of incidentally discovered adrenal masses (incidentalomas). J Clin Endocrinol Metab 1994;79(6):1532–1539.

    Article  PubMed  CAS  Google Scholar 

  45. Terzolo M, Osella G, Ali A, et al. Subclinical Cushing’s syndrome in adrenal incidentaloma. Clin Endocrinol (Oxf) 1998;48(1):89–97.

    Article  CAS  Google Scholar 

  46. Hebert PR, Moser M, Mayer J, Glynn RJ, Hennekens CH. Recent evidence on drug therapy of mild to moderate hypertension and decreased risk of coronary heart disease. Arch Intern Med 1993;153(5):578–581.

    Article  PubMed  CAS  Google Scholar 

  47. Lawes CM, Bennett DA, Feigin VL, Rodgers A. Blood pressure and stroke: an overview of published reviews. Stroke 2004;35(4):1024.

    PubMed  Google Scholar 

  48. Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria. The DECODE study group. European Diabetes Epidemiology Group. Diabetes Epidemiology: Collaborative analysis of diagnostic criteria in Europe. Lancet 1999;354(9179):617–621.

    Google Scholar 

  49. Midorikawa S, Sanada H, Hashimoto S, Suzuki T, Watanabe T. The improvement of insulin resistance in patients with adrenal incidentaloma by surgical resection. Clin Endocrinol (Oxf) 2001;54(6):797–804.

    Article  CAS  Google Scholar 

  50. Terzolo M, Bovio S, Pia A, et al. Midnight serum cortisol as a marker of increased cardiovascular risk in patients with a clinically inapparent adrenal adenoma. Eur J Endocrinol 2005;153(2):307–315.

    Article  PubMed  CAS  Google Scholar 

  51. Barzon L, Scaroni C, Sonino N, Fallo F, Paoletta A, Boscaro M. Risk factors and long-term follow-up of adrenal incidentalomas. J Clin Endocrinol Metab 1999;84(2):520–526.

    Article  PubMed  CAS  Google Scholar 

  52. Mantero F, Terzolo M, Arnaldi G, et al. A survey on adrenal incidentaloma in Italy. Study Group on Adrenal Tumors of the Italian Society of Endocrinology. J Clin Endocrinol Metab 2000;85(2):637–644.

    Article  PubMed  CAS  Google Scholar 

  53. Pecori Giraldi F, Ambrogio AG, De Martin M, Fatti LM, Scacchi M, Cavagnini F. Specificity of first-line tests for the diagnosis of Cushing’s syndrome: assessment in a large series. J Clin Endocrinol Metab 2007;92(11):4123–4129.

    Article  PubMed  Google Scholar 

  54. Chiodini I, Mascia ML, Muscarella S, et al. Subclinical hypercortisolism among outpatients referred for osteoporosis. Ann Intern Med 2007;147(8):541–548.

    PubMed  Google Scholar 

  55. Arnaldi G, Angeli A, Atkinson AB, et al. Diagnosis and complications of Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab 2003;88(12):5593–5602.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Academic Unit of Diabetes and Endocrinology, Royal Hallamshire Hospital, University of Sheffield, Room 0U142, Floor O, Sheffield, UK

    John Newell-Price MA/PhD/FRCP (Reader and Consultant Endocrinologist)

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  1. John Newell-Price MA/PhD/FRCP
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Editors and Affiliations

  1. , Division of Endocrinology and Metabolism, Hospital das Clínicas, University of Sao, Sao Paulo, 05403-000, Brazil

    Marcello D. Bronstein

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Newell-Price, J. (2010). Etiologies of Cushing’s Syndrome. In: Bronstein, M. (eds) Cushing's Syndrome. Contemporary Endocrinology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-449-4_2

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  • DOI: https://doi.org/10.1007/978-1-60327-449-4_2

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60327-448-7

  • Online ISBN: 978-1-60327-449-4

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