Skip to main content

Cushing Syndrome

Differential Diagnosis and Treatment

  • Chapter

Part of the book series: Contemporary Endocrinology ((COE,volume 3))

Abstract

Harvey Cushing first described the homonymous syndrome in 1912 (1). Cushing syndrome, which results from prolonged exposure of the organism to high levels of glucocorticoids, represents a subcategory of hypercortisolism (Table 1).

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

Buying options

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

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Cushing H. The Pituitary Body and Its Disorders. Lippincott, Philadelphia, PA, 1912, pp. 219.

    Google Scholar 

  2. Tsigos C, Kamilaris T, Chrousos GP. Adrenal diseases. In: Moore WT, Eastman R, eds. Diagnostic Endocrinology. B.C. Decker, Toronto, 1996, pp. 123–156.

    Google Scholar 

  3. Magiakou MA, Chrousos GP. Corticosteroid therapy, nonendocrine disease and corticosteroid withdrawal. In: Bardin CW, ed. Current Therapy in Endocrinology and Metabolism. 5th ed., Mosby, New York, 1994, pp. 120–124.

    Google Scholar 

  4. Magiakou MA, Chrousos GP. Diagnosis and treatment of Cushing disease In: Imura H, ed. The Pituitary Gland. 2nd ed., Raven, New York, 1994, pp. 391–508.

    Google Scholar 

  5. Doppman JL, Travis WD, Nieman L, Miller DL, Chrousos GP, Gomez GT, Cutler GB Jr, Loriaux DL, Norton JA. Cushing syndrome due to primary pigmented nodular adrenocortical disease: findings at CT and MR imaging. Radiology 189; 172:415–420.

    Google Scholar 

  6. Doppman JL, Nieman LK, Travis WD, Miller DL, Cutler GB Jr, Chrousos GP, Norton JA. CT and MR imaging of massive macronodular adrenocortical disease: a rare cause of autonomous primary adrenal hypercortisolism. J Comput Assist Tomogr 1991; 15:773–779.

    Article  PubMed  CAS  Google Scholar 

  7. Lacroix A, Bolte E, Tremblay J, Dupre J, Poitras P, Fournier H, Garon J, Garrel D, Bayard F, Taillefer R. Gastric inhibitory polypeptide-dependent Cortisol hypersecretion—a new cause of Cushing’s syndrome. N Engl J Med 1992; 327:974–980.

    Article  PubMed  CAS  Google Scholar 

  8. Danon M, Robboy SL, Kim S, Scully R, Crawford JD. Cushing syndrome, sexual precocity, and polyostotic fibrous dysplasia (Albright syndrome) in infancy. J Pediatr 1975; 87:917–921.

    Article  PubMed  CAS  Google Scholar 

  9. Carey RM, Varma SK, Drake CR Jr, Thorner MO, Kovacs K, Rivier J, Vale W Ectopic secretion of corticotropin-releasing factor as a cause of Cushing’s syndrome. N Engl J Med 1984; 311:13–20.

    Article  PubMed  CAS  Google Scholar 

  10. Auchus RJ, Mastorakos G, Friedman TC, Chrousos GP. Corticotropin-releasing hormone production by a small cell carcinoma in a patient with ACTH-dependent Cushing syndrome. J Endocrinol Invest 1994; 17:447–452.

    PubMed  CAS  Google Scholar 

  11. Malchoff CD, Rosa J, DeBold CR, Kozol RA, Ramsby GR, Page DL, Malchoff DM, Orth DN. Adrenocorticotropin-independent bilateral macronodular adrenal hyperplasia: an unusual cause of Cushing’s syndrome. J Clin Endocrinol Metab 1989; 68:855–860.

    Article  PubMed  CAS  Google Scholar 

  12. Buckley N, Bates AS, Broome JC, Strange RC, Perrett CW, Burke CW, Clayton RN. P53 protein accumulates in Cushing’s adenomas and invasive non-functional adenomas. J Clin Endocrinol Metab 1994; 79:1518–1521.

    Article  Google Scholar 

  13. Tsigos C, Chrousos GP. Clinical presentation, diagnosis and treatment of Cushing’s syndrome in Current opinion in Endocrinology and Diabetes, Current Science, Philadelphia, 1995; p. 1–11.

    Google Scholar 

  14. Magiakou MA, Mastorakos G, Oldfield EH, Gomez MT, Doppman JL, Cutler GB Jr, Nieman LK, Chrousos GP. Cushing syndrome in children and adolescents: Presentation, Diagnosis and Therapy. N Engl J Med 1994; 331:629–636.

    Article  PubMed  CAS  Google Scholar 

  15. Plotz CM, Knowlton AL, Ragan C. The natural history of Cushing’s syndrome. Am J Med 1952; 13:597–614.

    Article  PubMed  CAS  Google Scholar 

  16. Soffer LJ, Iannaccone A, Gabrilove JL. Cushing’s syndrome: a study of fifty patients. Am J Med 1961; 30:129–146.

    Article  Google Scholar 

  17. Murphy BEP. Clinical evaluation of urinary Cortisol determinations by competitive protein-binding radioassay. J Clin Endocrinol Metab 1968; 28:343–348.

    Article  PubMed  CAS  Google Scholar 

  18. Gomez MT, Malozowski S, Winterer J, and Chrousos GP. Urinary free Cortisol values in normal children and adolescents. J Pediatrics 1968; 118:256–258.

    Article  Google Scholar 

  19. Schoneschofer M, Weber B, Oelkers W, Nahoul K, Mantero F. Measurement of urinary free 20 alpha dihydrocortisol in biochemical diagnosis of chronic corticoidism. Clin Chem 1986; 32:808–810.

    Google Scholar 

  20. Connolly CK, Gore MBR, Stanley N, Wills MR. Single-dose dexamethasone suppression in normal subjects and hospital patients. Brit Med J 1968; 2:665–667.

    Article  PubMed  CAS  Google Scholar 

  21. Pavlatos FC, Smilo RP, Forsham PH. A rapid screening test for Cushing’s syndrome. J Amer Med Assoc 193:720–723.

    Google Scholar 

  22. Kao M, Voina S, Nichols A, Horton R. Parallel radioimmunoassay for plasma Cortisol and 11 -deoxyCortisol. Clin Chem 1965; 1975; 21:1644–1647.

    Google Scholar 

  23. Brown RD, Van Loon GR, Orth DN, Liddle GW Cushing’s disease with periodic hormonogenesis: one explanation for paradoxical response to dexamethasone. J Clin Endocrinol Metab 1973; 36:445–151.

    Article  PubMed  CAS  Google Scholar 

  24. Buescher MA, McClamrock HD, Adashi EY Cushing syndrome in pregnancy. Obstet Gynecol 1992; 79:130–137.

    PubMed  CAS  Google Scholar 

  25. Chrousos GP, Vingerhoeds A, Brandon D, Eil C, Pugeat M, DeVroede M, Loriaux DL, Lipsett MB. Primary Cortisol resistance in man: a glucocorticoid receptor-mediated disease. J Clin Invest 1982; 69:1261–1269.

    Article  PubMed  CAS  Google Scholar 

  26. Chrousos GP, Detera-Wadleigh SD, Karl M. Syndromes of glucocorticoid resistance. Ann Intern Med 1993; 119:1113–1124.

    PubMed  CAS  Google Scholar 

  27. Mastorakos G, Chrousos GP. Adrenal androgens In: Reproductive Endocrinology, Surgery, and Technology. Adashi EY, Rock JA, Rosenwaks Z, eds. Lippincott-Raven, New York 1996; 1539–1553.

    Google Scholar 

  28. Jubiz W, Meikle AW, Levinson RA, Mizutani S, West CD, Tyler FH. Effect of diphenylhydantoin on the metabolism of dexamethasone. N Engl J Med 1970; 283:11–14.

    Article  PubMed  CAS  Google Scholar 

  29. Caro JE, Meikle AW, Check JH, Cohen SN. “Normal suppression” to dexamethasone in Cushing’s disease: an expression of decreased metabolic clearance for dexamethasone. J Clin Endocrinol Metab 1978; 47:667–670.

    Article  PubMed  CAS  Google Scholar 

  30. Meikle AW, Lagerquist LG, Tyler FH. Apparently normal pituitary-adrenal suppressibility in Cushing’s syndrome: dexamethasone metabolism and plasma levels. J Lab Clin Med 1975; 86:472–478.

    PubMed  CAS  Google Scholar 

  31. Carey RM. Suppression of ACTH by Cortisol in dexamethasone-non-suppressible Cushing’s disease. N Engl J Med 1980; 302:275–279.

    Article  PubMed  CAS  Google Scholar 

  32. Sachar EJ. Twenty-four-hour Cortisol secretory patterns in depressed and manic patients. Prog Brain Res 1975;42:81–91.

    Article  PubMed  CAS  Google Scholar 

  33. Gold PW, Loriaux DL, Roy A, Kling MA, Calabrese JR, Kellner CH, Nieman LK, Post RM, Pickar D, Gallucci W Responses to corticotropin-releasing hormone in the hypercortisolism of depression and Cushing’s disease: pathophysiology and diagnostic implications. N Engl J Med 1986; 314:1329–1335.

    Article  PubMed  CAS  Google Scholar 

  34. Lamberts SWJ, Klijn JGM, deJong FH, Birkenhager JC. Hormone secretion in alcohol-induced pseudo-Cushing’s syndrome. Differential diagnosis with Cushing’s disease. J Am Med Assoc 1979; 242:1640–1643.

    Article  CAS  Google Scholar 

  35. Yanovski JA, Cutler GB Jr, Chrousos GP, Nieman LK. Corticotropin-Releasing Hormone stimulation following low-dose dexamethasone administration: a new test to distinguish Cushing’s syndrome from pseudo-Cushing’s states. JAMA 1993; 269:17:2232–2238.

    Article  PubMed  Google Scholar 

  36. Orth DN. Adrenocorticotropic hormone (ACTH). In Jaffe PM, Behram HR (eds) Methods of Hormone Radioimmunoassay. Academic, New York 1978; 245–284.

    Google Scholar 

  37. White A, Stewart MF, Farrell WE, Crosby SR, Lavender PM, Twentyman PR, Rees LH, Clark AJ. Proopiomelanocortin gene expression and peptide secretion in human small-cell lung cancer cell lines. J Mol Endocrinol 1989; 3:1:65–70.

    Article  PubMed  Google Scholar 

  38. Schteingart DE, Lloyd RV, Akil H, Chandler WF, Ibarra-Perez G, Rosen SG, Ogletree R. Cushing’s syndrome secondary to ectopic corticotropin-releasing hormone-adrenocorticotropin secretion. J Clin Endocrinol Metab 1986; 63:770–775.

    Article  PubMed  CAS  Google Scholar 

  39. Liddle GW Tests of pituitary-adrenal suppressibility in the diagnosis of Cushing’s syndrome. J Clin Endocrinol Metab 1960; 20:1539–61.

    Article  PubMed  CAS  Google Scholar 

  40. Flack MR, Oldfield EH, Cutler GB Jr, Zweig MH, Malley JD, Chrousos GP, Loriaux DL, Nieman LK. The use of urine free Cortisol in the high dose dexamethasone suppression test for the differential diagnosis of Cushing’s syndrome. Ann Int Med 1992; 116:211–217.

    PubMed  CAS  Google Scholar 

  41. Tyrrell JB, Findling JW, Aron DC, Fitzgerald PA, Forsham PH. An overnight high-dose dexamethasone suppression test for rapid differential diagnosis of Cushing’s syndrome. Ann Intern Med 1986; 104:180–186.

    PubMed  CAS  Google Scholar 

  42. Dichek HL, Nieman LK, Oldfield EH, Pass HI, Malley JD, Cutler GB Jr. A comparison of the standard high dose dexamethasone suppression test and the overnight 8-mg dexamethasone suppression test for the differential diagnosis of the adrenocorticotropin-dependent Cushing’s syndrome. J Clin Endocrinol Metab 1994; 78:418–22.

    Article  PubMed  CAS  Google Scholar 

  43. de Lange WE, Sluiter WJ, Pratt JJ, Doorenbos H. Plasma 11–deoxycortisol, androstenedione, testosterone and ACTH in comparison with the urinary excretion of tetrahydro-11–deoxycortisol as indices of the pituitary-adrenal response to oral metyrapone. Acta Endocrinol 1980; 93:488–94.

    PubMed  Google Scholar 

  44. Chrousos GP, Schulte HM, Oldfield EH, Gold PW, Cutler GB Jr, Loriaux DL. The corticotropin releasing factor stimulation test: an aid in the evaluation of patients with Cushing’s syndrome. N Engl J Med 1984; 310:622–626.

    Article  PubMed  CAS  Google Scholar 

  45. Nieman LK, Chrousos GP, Oldfield EH, Avgerinos PC, Cutler GB Jr, Loriaux DL. The ovine CRH test and the dexamethasone suppression test in the differential diagnosis of Cushing’s syndrome. Ann Intern Med 1986; 105:862–867.

    PubMed  CAS  Google Scholar 

  46. Nieman LK, Cutler GB Jr, Oldfield EH, Loriaux DL, and Chrousos GR The ovine corticotropin-releasing hormone stimulation test is superior to the human corticotropin-releasing hormone stimulation test for the diagnosis of Cushing’s disease. J Clin Endocrinol Metab 1989; 69:165–170.

    Article  PubMed  CAS  Google Scholar 

  47. Saris SC, Patranas NJ, Doppman JL, Loriaux DL, Cutler GB Jr, Nieman LK, Chrousos, GP, Oldfield EH. Pituitary CT scanning in Cushing’s syndrome. Radiology 1986; 162:775–777.

    Google Scholar 

  48. Dwyer AJ, Frank JA, Doppman JL, Oldfield EH, Hickey AM, Cutler GB Jr, Loriaux DL, Schiable TF. Gadolinium DTPA enhanced magnetic resonance imaging of pituitary adenomas in patients with Cushing’s disease: initial experience. Radiology 1987; 163:421–426.

    PubMed  CAS  Google Scholar 

  49. Doppman JL, Frank JA, Dwyer AJ, Oldfield EH, Miller DL, Nieman LK, Chrousos GP, Cutler GB Jr, Loriaux DL. Gadolinium DPTA enhanced MR imaging of ACTH-secreting microadenomas of the pituitary gland. J Comp Assist Tom 1988; 12:728–735.

    Article  CAS  Google Scholar 

  50. Aran DC, Findling JW, Fitzgerald PA, Brooks RM, Fisher FE, Forsham PH, Tyrrell JB. Pituitary ACTH dependency of nodular adrenal hyperplasia in Cushing’s syndrome-report of 2 cases and review of the literature. Am JMed 1981; 71:302–306.

    Google Scholar 

  51. Doppman Jl, Miller DL, Dwyer AJ, Loughlin T, Nieman LK, Cutler GB Jr, Chrousos GP, Oldfield EH, Loriaux DL. Macronodular adrenal hyperplasia in Cushing’s disease. Radiology 1988; 166:347–352.

    PubMed  CAS  Google Scholar 

  52. Flack MR, Chrousos GP. Neoplasms of the adrenal cortex in Holland JF, Frei III E, Bast Jr. RC, Kufe DW, Morton DL, Weichselbaum RR, eds. Cancer Medicine, third ed, Lea and Febiger, PA, p. 1147–1152.

    Google Scholar 

  53. Sarkar SD, Cohen EL, Beierwaltes WH, Ice RD, Cooper R, Gold EN. A new superior adrenal imaging agent, 131I-6ß-iodomethyl-19–norcholesterol (NP-59): evaluation in humans. J Clin Endocrinol Metab 1977; 45:353–362.

    Article  PubMed  CAS  Google Scholar 

  54. Herwig KR, Schteingart DE. Successful removal of adrenal remnant localized by I-19–iodocholesterol. J Urol 1984; 111:713–714.

    Google Scholar 

  55. Doppman JL, Nieman LK, Miller DL, Pass HI, Chung R, Cutler GB Jr, Schauf M, Chrousos GP, Norton JA, Zirrsman HA, Oldfield EH, Loriaux DL. Ectopic adrenocorticotropic hormone syndrome: localization studies in 28 patients. Radiology 1989; 172:115–124.

    PubMed  CAS  Google Scholar 

  56. Leinung MC, Young WF Jr, Whitaker MD, Scheithauer BW, Tvastek VF, Kvols LK. Diagnosis of corticotropin-producing bronchial carcinoid tumors causing Cushing’s syndrome. Mayo Clin Proc 1990; 65:131–1321.

    Google Scholar 

  57. Doppman JL, Pass HI, Nieman LK, Findling TW, Dwyer AJ, Fenerstein IM, Ling A, Travis WD, Cutler GB Jr, Chrousos GP, Loriaux DL. Detection of ACTH-producing bronchial carcinoid tumors: MR imaging versus CT. Am J Radiol 1991; 156:39–43.

    CAS  Google Scholar 

  58. Limper AH, Carpenter PC, Scheithauser B, Staats BA. The Cushing syndrome induced by bronchial carcinoid tumors. Ann Intern Med 1992; 117:209–214.

    PubMed  CAS  Google Scholar 

  59. Miller DL, Doppman JL. Petrosal sinus sampling; technique and rationale. Radiology 1991; 178:37–47.

    PubMed  CAS  Google Scholar 

  60. Oldfield EH, Chrousos GP, Schulte HM, Loriaux DL, Schaaf M, Doppman JL. Preoperative lateralization of ACTH secreting pituitary microadenomas by bilateral and simultaneous inferior petrosal sinus sampling. N Engl J Med 1985; 312:100–103.

    Article  PubMed  CAS  Google Scholar 

  61. Oldfield EH, Doppman J, Nieman LK, Chrousos GP, Miller DL, Katz DA, Cutler GB Jr, Loriaux DL. Petrosal sinus sampling with and without corticotropin releasing hormone in patients with Cushing’s syndrome. N Engl J Med 1991; 325:897–905.

    Article  PubMed  CAS  Google Scholar 

  62. Miller DL, Doppman JL, Peterman SB, Nieman LK, Oldfield EH, Chang R. Neurologic complications of petrosal sinus sampling. Radiology 1992; 185:143–147.

    PubMed  CAS  Google Scholar 

  63. Doppman JL, Pass HI, Nieman LK, Miller DL, Chang R, Cutler GB Jr, Chrousos GP, Jaffe GS, Norton JA. Corticotropin-secreting carcinoid tumors of the thymus: diagnostic unreliability of thymic venous sampling. Radiology 1992; 184:71–74.

    PubMed  CAS  Google Scholar 

  64. Loriaux DL, Cutler GB Jr. Diseases of the adrenal glands. In: Kohler PO, ed. Clinical Endocrinology. Wiley, New York, 1986, pp. 167–238.

    Google Scholar 

  65. Tyrrell JB, Brooks RM, Fitzgerald PA, Cofoid PB, Forsham PH, Wilson CB. Cushing’s disease. Selective transsphenoidal resection of pituitary microadenomas. N Engl J Med 1978; 298:753–758.

    Article  PubMed  CAS  Google Scholar 

  66. Salassa RM, Laws ER Jr, Carpenter PC, Northcutt RC. Transsphenoidal removal of pituitary microadenoma in Cushing’s disease. Mayo Clin Proc 1978; 53:24–28.

    PubMed  CAS  Google Scholar 

  67. Malpalam TJ, Tyrrell JB, Wilson CB. Transsphenoidal microsurgery for Cushing disease: a report of 216 cases. Ann Intern Med 1989; 109:487–493.

    Google Scholar 

  68. Friedman RB, Oldfield EH, Nieman LK, Chrousos GP, Doppman JL, Cutler GB Jr, Loriaux DL. Repeat transsphenoidal surgery in Cushing’s disease. J Neurosurg 1989; 71:520–527.

    Article  PubMed  CAS  Google Scholar 

  69. Avgerinos PC, Chrousos GP, Nieman LK, Oldfield EH, Loriaux DL, Cutler GB. The corticotropin releasing hormone test in the postoperative evaluation of patients with Cushing’s syndrome. J Clin Endocrinol Metab 1987;65:906–913.

    Article  PubMed  CAS  Google Scholar 

  70. Doherty GM, Nieman LK, Cutler GB Jr, Chrousos GP, Norton JA. Time to recovery of the hypothalamic-pituitary-adrenal axis after curative resection of adrenal tumors in patients with Cushing’s syndrome. Surgery 1990; 108:1085–1090.

    PubMed  CAS  Google Scholar 

  71. Gomez MT, Magiakou MA, Mastorakos G, Chrousos GP. The pituitary corticotroph is not the rate limiting step in the postoperative recovery of the hypothalamic-pituitary-adrenal axis in patients with Cushing syndrome. J Clin Endocrinol Metab 1992; 77:173–177.

    Article  Google Scholar 

  72. Schteingart DE, Tsao HS, Taylor CI, McKenzie A, Victoria R, Themen BA. Sustained remission of Cushing’s disease with mitotane and pituitary irradiation. Ann Intern Med 1980; 92:613–619.

    PubMed  CAS  Google Scholar 

  73. Jennings AS, Liddle GW, Orth DN. Results of treating childhood Cushing’s disease with pituitary irradiation. N Engl J Med 1977; 297:957–962.

    Article  PubMed  CAS  Google Scholar 

  74. Gomez MT, Chrousos GP. Cushing’s syndrome. In: Bardin W, ed. Current Therapy in Endocrinology and Metabolism, 4th ed. BC Decker, Toronto, pp. 134–137.

    Google Scholar 

  75. Tabarin A, Navarranne A, Guerin J, Corcuff JB, Parneix M, Roger P. Use of ketokonazole in the treatment of Cushing’s disease and ectopic ACTH syndrome. Clin Endocrinol (Oxf) 1991; 34:63–69.

    Article  CAS  Google Scholar 

  76. Moore TJ, Dluhy RG, Williams GH, Cain JP. Nelson’s syndrome: frequency, prognosis, and effect of prior pituitary irradiation. Ann Intern Med 1976; 85:731–734.

    PubMed  CAS  Google Scholar 

  77. Laue L, Kawai S, Udelsman R. Glucocorticoid antagonists: pharmacological attributes of the prototype antiglucocorticoid RU 486. In: Lichtenstein LM, Claman H, Oronsky A, Schleimer RP, eds. Antiinflammatory Steroid Action: Basic and Clinical Aspects. New York: Academic, New York, 1989, pp. 643–649.

    Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Humana Press Inc.

About this chapter

Cite this chapter

Magiakou, M.A., Mastorakos, G., Chrousos, G.P. (1997). Cushing Syndrome. In: Wierman, M.E. (eds) Diseases of the Pituitary. Contemporary Endocrinology, vol 3. Humana Press. https://doi.org/10.1007/978-1-4612-3954-3_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-4612-3954-3_9

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-4612-8438-3

  • Online ISBN: 978-1-4612-3954-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics