Skip to main content

Psychiatric Manifestations of Cushing’s Syndrome

  • Chapter

Abstract

The constellation of clinical signs and symptoms that we now call “Cushing’s syndrome” was first described by Cushing in 1932. Cushing’s syndrome results from chronic exposure to excessive concentrations of glucocorticoids. The physical features of Cushing’s syndrome include weight gain, central obesity (i.e., accumulation of adipose tissue in the facial, nuchal, truncal and girdle areas), facial plethora, hirsutism, cutaneous striae, muscle wasting, weakness, and osteoporosis. Other common manifestations of hypercortisolemia include hypertension, glucose intolerance or diabetes mellitus, impotence and testicular atrophy, amenorrhea, mild erythrocytosis, lymphopenia, eosinopenia and frequent fungal infections. Cushing’s syndrome can be divided into two major categories, each of which has two major causes. ACTH-dependent Cushing’s syndrome can be caused by excessive ACTH secretion by a pituitary microadenoma (referred to as “Cushing’s disease”) or by ACTH secretion by a non-pituitary tumor (“ectopic ACTH syndrome”), usually a small cell carcinoma of the lung or a bronchial, thymic or pancreatic carcinoid tumor, which together account for 75% of all cases. ACTH-independent Cushing’s syndrome is caused by adrenocortical tumors that secrete cortisol autonomously or by administration of pharmacologic doses of synthetic glucocorticoids.

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   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
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 basophil adenomas of the pituitary body and their clinical manifestation (pituitary basophilism). Bull Johns Hopkins Hosp 1932; 50: 137–195.

    Google Scholar 

  2. Orth DN, Kovacs WJ, deBold CR. The adrenal cortex. In: Wilson JD, Foster DW, editors. Williams Textbook of Endocrinology. Philadelphia: W.B. Saunders, 1992: 489–619.

    Google Scholar 

  3. Yanovski JA, Cutler GBJ. Glucocorticoid action and the clinical features of Cushing’s syndrome. Endocrinol Metab Clin North Am 1994; 23(3):487–509.

    PubMed  CAS  Google Scholar 

  4. Krieger DT. Physiopathology of Cushing’s disease. Endocr Rev 1983; 4:22–43.

    Article  PubMed  CAS  Google Scholar 

  5. Orth DN. Medical progress: Cushing’s syndrome. N Engl J Med 1995; 332:791–803.

    Article  PubMed  CAS  Google Scholar 

  6. Gold PW, Chrousos G, Kellner C et al. Psychiatric implications of basic and clinical studies with corticotropin-releasing factor. Am J Psychiatry 1984; 141:619–627.

    PubMed  CAS  Google Scholar 

  7. Nathan KI, Musselman DL, Nemeroff CB. Biology of mood disorders. In: Schatzberg AF, Nemeroff CB, editors. Textbook of Psychopharmacology. Washington: American Psychiatric Press, 1995.

    Google Scholar 

  8. Haskett RF. Diagnostic categorization of psychiatric disturbance in Cushing’s syndrome. Am J Psychiatry 1985; 142:911–916.

    PubMed  CAS  Google Scholar 

  9. Hudson JI, Hudson MS, Griffing GT, Melby JC, Pope HGJ. Phenomenology and family history of affective disorder in Cushing’s disease. Am J Psychiatry 1987; 144:951–953.

    PubMed  CAS  Google Scholar 

  10. Sonino N, Fava GA, Belluardo P, Girelli ME, Boscaro M. Course of depression in Cushing’s syndrome: response to treatment and comparison with Graves’ disease. Hormone Research 1993; 39(5–6):202–206.

    Article  PubMed  CAS  Google Scholar 

  11. Dom LD, Burgess ES, Dubbert B et al. Psychopathology in patients with endogenous Cushing’s syndrome: ‘Atypical’ or melancholic features. Clinical Endocrinology 1995; 43(4):433–442.

    Article  Google Scholar 

  12. Loosen PT, Chambliss B, deBold CR, Shelton R, Orth DN. Psychiatric phenomenology in Cushing’s disease. Pharmacopsychiat 1992; 25(4): 192–198.

    Article  CAS  Google Scholar 

  13. Dorn LD, Burgess ES, Friedman TC, Dubbert B, Gold PW, Chrousos GP. The longitudinal course of psychopathology in Cushing’s syndrome after correction of hypercortisolism. J Clin Endocrinol Metab 1997; 82(3):912–919.

    Article  PubMed  CAS  Google Scholar 

  14. Sonino N, Fava GA, Raffi AR, Boscaro M, Fallo F. Clinical correlates of major depression in Cushing’s disease. Psychopathology 1998; 31(6):302–306.

    Article  PubMed  CAS  Google Scholar 

  15. Kelly WF. Psychiatric aspects of Cushing’s syndrome. QJM 1996; 89(7):543–551.

    Article  PubMed  CAS  Google Scholar 

  16. American Psychiatric Association. Diagnostic and Statistical Manual for Mental Disorders (DSM-IV). Fourth ed. Washington: American Psychiatric Association, 1994.

    Google Scholar 

  17. Boyd JH, Weissman MM. Epidemiology. In: Paykel ES, editor. Handbook of Affective Disorders. New York: Guilford Press, 1982: 109–125.

    Google Scholar 

  18. Pearson Murphy BE. Steroids and depression. J Steroid Biochem Molec Biol 1991; 38:537–559.

    Article  Google Scholar 

  19. Arana GW, Baldessarini RJ, Ornsteen M. The dexamethasone suppression test for diagnosis and prognosis in psychiatry. Commentary and review. Arch Gen Psychiatry 1985; 42:1193–1204.

    Article  PubMed  CAS  Google Scholar 

  20. Miller KB, Nelson JC. Does the dexamethasone suppression test relate to subtypes, factors, symptoms, or severity? Arch Gen Psychiatry 1987; 44:769–774.

    Article  PubMed  CAS  Google Scholar 

  21. Thakore JH, Dinan TG. Cortisol synthesis inhibition: A new treatment strategy for the clinical and endocrine manifestations of depression. Biol Psychiatry 1995; 37:364–368.

    Article  PubMed  CAS  Google Scholar 

  22. Wolkowitz OM, Reus VI, Manfredi F, Ingbar J, Brizendine L, Weingartner H. Ketokonazole administration in hypercortisolemic depression. Am J Psychiatry 1993; 150:810–812.

    PubMed  CAS  Google Scholar 

  23. Pearson Murphy BE, Ghadirian AM, Filipini D, Dhar V. Endocrine responses to antiglucocorticoid strategies in refractory depression. Biol Psychiatry 1994; 35:618.

    Article  Google Scholar 

  24. Ghadirian AM, Engelsman F, Dhar V et al. Psychotropic effects of steroid synthesis inhibitors in refractory depression. Biol Psychiatry 1994; 35:618.

    Article  Google Scholar 

  25. Wolkowitz OM, Reus VI, Manfredi F et al. Antiglucocorticoid medication effects on specific depressive symptoms. Biol Psychiatry 1994; 35:678–679.

    Article  Google Scholar 

  26. Nemeroff CB. The role of corticotropin-releasing factor in the pathogenesis of major depression. Pharmacopsychiat 1994; 21:76–82.

    Article  Google Scholar 

  27. Nemeroff CB, Widerlov E, Bissette G et al. Elevated concentrations of CSF corticotropinreleasing factor-like immunoreactivity in depressed patients. Science 1984; 226:1342–1344.

    Article  PubMed  CAS  Google Scholar 

  28. Geracioti TD, Orth DN, Ekhator NN, Blumenkopf B, Loosen PT. Serial cerebrospinal fluid corticotropin-releasing hormone concentrations in healthy and depressed subjects. J Clin Endocrinol Metab 1992; 74: 1325–1330.

    Article  PubMed  CAS  Google Scholar 

  29. Kling MA, Roy A, Doran AR et al. Cerebrospinal fluid immunoreactive corticotropinreleasing hormone and adrenocorticotropin secretion in Cushing’s disease and major depression: potential clinical implications [see comments]. J Clin Endocrinol & Metab 1991; 72(2):260–271.

    Article  CAS  Google Scholar 

  30. Stewart MA, Drake F, Winokur G. Depression among medically ill patients. Dis Nerv Syst 1965; 26:479–485.

    PubMed  CAS  Google Scholar 

  31. Schwab JJ, Bialow M, Brown JM, Holzer CE. Diagnosing depression in medical inpatients. Ann Intern Med 1967; 67:695–707.

    PubMed  CAS  Google Scholar 

  32. Moffic HS, Paykel ES. Depression in medical in-patients. Brit J Psychiatry 1975; 126:346–353.

    Article  CAS  Google Scholar 

  33. Abdel-Nasser AM, Abd EI-Azim S, Taal E, El Badawy SA, Rasker JJ, Valkenburg HA. Depression and depressive symptoms in rheumatoid arthritis patients: an analysis of their occurrence and determinants. Br J Rheumatol 1998; 37(4):391–397.

    Article  PubMed  CAS  Google Scholar 

  34. Starkman MN, Schteingart DE. Neuropsychiatric manisfestations of patients with Cushing’s syndrome: Relationship to cortisol and adrenocorticotropin hormone levels. Arch Intern Med 1981; 141:215–219.

    Article  PubMed  CAS  Google Scholar 

  35. Grigoriadis DE, Pearsall D, deSouza EB. Effects of chronic antidepressant and benzodiazepine treatment on corticotropin-releasing factor receptors in rat brain and pituitary. Neuropsychopharm 1988; 2:53–60.

    Article  Google Scholar 

  36. Starkman MN, Schteingart DE, Schork MA. Depressed mood and other psychiatric manifestations of Cushing’s syndrome: Relationship to hormone levels. Psychosom Med 1981; 43:3–18.

    PubMed  CAS  Google Scholar 

  37. Cohen SI. Cushing’s syndrome: A psychiatric study of 29 patients. Brit J Psychiatry 1980; 136:120–124.

    Article  CAS  Google Scholar 

  38. Kelly WF, Checkley SA, Bender DA, Mashiter K. Cushing’s syndrome and depression—a prospective study of 26 patients. Brit J Psychiatry 1983; 142:16–19.

    Article  CAS  Google Scholar 

  39. Jeffcoate WJ, Silverstone J, Edwards C, Besser G. Psychiatric man ifestation of Cushing’s syndrome: response to lowering of plasma cortisol. Qtrly J Med 1979; 48:465–472.

    CAS  Google Scholar 

  40. Kelly WF, Checkley SA, Bender DA. Cushing’s syndrome, tryptophan and depression. Brit J Psychiatry 1980; 136:125–132.

    Article  CAS  Google Scholar 

  41. Sonino N, Fava GA. Psychosomatic aspects of Cushing’s disease. Psychother Psychosom 1998; 67(3):140–146.

    Article  PubMed  CAS  Google Scholar 

  42. Voigt KH, Bossert S, Bretschneider S, Bliestle A, Fehm HL. Disturbed cortisol secretion in man: contrasting Cushing’s disease and endogenous depression. Psychiatry Res 1985; 15(4):341–350.

    Article  PubMed  CAS  Google Scholar 

  43. Musselman DL, Evans DL, Nemeroff CB. The relationship of depression to cardiovascular disease: epidemiology, biology, and treatment. Arch Gen Psychiatry 1998; 55(7):580–592.

    Article  PubMed  CAS  Google Scholar 

  44. Cushing H. Psychic disturbances associated with disorders of the ductless glands. Am J of Insanity 1913; 69:965–990.

    Google Scholar 

  45. Gifford S, Gunderson JG. Cushing’s disease as a psychosomatic disorder: A selective review of the clinical and experimental literature and a report of ten cases. Persp Biol Med 1970; 13:169–221.

    CAS  Google Scholar 

  46. Sonino N, Fava GA, Grandi S, Mantero F, Boscaro M. Stressful life events in the pathogenesis of Cushing’s disease. Clin Endocrinol 1988; 29:617–623.

    Article  CAS  Google Scholar 

  47. Isojarvi JI, Myllyla VV, Pakarinen AJ. Effects of carbamazepine on pituitary responsiveness to luteinizing hormone-releasing hormone, thyrotropin-releasing hormone, and metoclopramide in epileptic patients. Epilepsia 1989; 30(1):50–56.

    Article  PubMed  CAS  Google Scholar 

  48. Reus VI. Neuropsychiatric disturbance in endocrine disease. In: Nemeroff CB, Loosen PT, editors. Handbook of Clinical Psychoneuroendocrinology. New York: Guilford Press, 1988: 71–84.

    Google Scholar 

  49. Mazet P, Simon D, Luton JP, Bricaire H. [Psychic symptoms and personality of 50 patients with Cushing’s syndrome (author’s transl)]. Nouv Presse Med 1981; 10(31):2565–2570.

    PubMed  CAS  Google Scholar 

  50. McEwen BS, Angulo J, Cameron H et al. Paradoxical effects ofadrenal steroids on the brain: protection versus degeneration. Biol Psychiatry 1992; 31:177–199.

    Article  PubMed  CAS  Google Scholar 

  51. Kellner C, Rubinow D, Gold P, Post R. Relationship of cortisol hypersecretion and brain CT scan alterations in depressed patients. Psychiat Res 1983; 8:191–197.

    Article  CAS  Google Scholar 

  52. Schlegel S, von Bardeleben U, Wiedemann K, Frommberger U, Holsboer F. Computerized brain tomography measures compared with spontaneous and suppressed cortisol levels in major depression. Psychoneuroendocr 1989; 14:209–216.

    Article  CAS  Google Scholar 

  53. Bentson JR, Reza M, Winter J, Wilson G. Steroids and apparent cerebral atrophy on computed tomography scans. J Comput Assist Tomogr 1978; 2:16–23.

    Article  PubMed  CAS  Google Scholar 

  54. Okuno T, Ito M, Knoishi Y, Yoshioka MK, Nakano Y. Cerebral atrophy following ACTH therapy. J Comput Assist Tomogr 1980; 4:20–23.

    Article  PubMed  CAS  Google Scholar 

  55. Heinz ER, Martinez J, Haenggeli A. Reversibility of cerebral atrophy in anorexia nervosa. J Comput Assist Tomogr 1977; 1:415–418.

    Article  PubMed  CAS  Google Scholar 

  56. Zola-Morgan S, Squire LR, Amaral DG. Human amnesia and the medial temporal region:enduring memory impairment following a bilateral lesion limited to field CAl of the hippocampus. J Neurosci 1986; 6:2950–2967.

    PubMed  CAS  Google Scholar 

  57. Squire LR, Shimamura AP, Amaral DG. Memory and the hippocampus. In: Byrne J, Berry W, editors. Neural Modes of Plasticity. New York: Academic Press, 1989: 208–239.

    Google Scholar 

  58. Sapolsky RM, Uno H, Rebert CS, Finch CE. Hippocampal damage associated with prolonged glucocorticoid exposure in primates. I Neurosci 1990; 10:2897–2902.

    CAS  Google Scholar 

  59. Starkman MN, Gebarski SS, Berent S, Schteingart DE. Hippocampal formation volume, memory dysfunction, and cortisol levels in patients with Cushing’s syndrome. Biol Psychiatry 1992; 32(9):756–765.

    Article  PubMed  CAS  Google Scholar 

  60. Axelson DA, Doraiswamy PM, McDonald WM et al. Hypercortisolemia and hippocampal changes in depression. Psychiatry Res 1993; 47: 163–173.

    Article  PubMed  CAS  Google Scholar 

  61. Krishnan KR, Doraiswamy PM, Figiel GS et al. Hippocampal abnormalities in depression. J Neuropsych & Clin Neurosciences 1991; 3(4):387–391.

    CAS  Google Scholar 

  62. Bremner JD, Randall P, Scott TM et al. MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. Am J Psychiatry 1995; 152(7):973–981.

    PubMed  CAS  Google Scholar 

  63. Ling MHM, Perry PJ, Tsuang MT. Side effects of corticosteroid therapy. Arch Gen Psychiatry 1981; 38:471–477.

    Article  PubMed  CAS  Google Scholar 

  64. The Boston Collaborative Drug Surveillance Program. Acute adverse reactions to prednisone in relation to dosage. Clin Pharmacol Ther 1972; 13:695–698.

    Google Scholar 

  65. Lewis DA, Smith RE. Steroid-induced psychiatric syndromes. J Affect Dis 1994; 5:319–332.

    Article  Google Scholar 

  66. Goolker P, Schein J. Psychic effects of ACTH and cortisone. Psychosom Med 1953; 15:589–613.

    PubMed  CAS  Google Scholar 

  67. Wolkowitz OM, Rubinow D, Doran AR et al. Prednisone effects on neurochemistry and behavior. Preliminary findings. Arch Gen Psychiatry 1990; 47(10):963–968.

    Article  PubMed  CAS  Google Scholar 

  68. Price R. A Whole New Life. An Illness and a Healing. New York: Macmillan, 1994.

    Google Scholar 

  69. Varney NR, Alexander B, McIndoe JH. Reversible steroid dementia in patients without steroid psychoses. Am J Psychiatry 1984; 141:369–372.

    PubMed  CAS  Google Scholar 

  70. Hall RCW, Popkin MK, Stickney SK, Gardner ER. Presentation of the steroid psychoses. J Nerv Ment Dis 1979; 167:229–236.

    Article  PubMed  CAS  Google Scholar 

  71. Reckart MD, Eisendrath SJ. Exogenous corticosteroid effects on mood and cognition: case presentations. Interntl J of Psychosomatics 1990; 37(1–4):57–61.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Springer Science+Business Media New York

About this chapter

Cite this chapter

Loosen, P.T. (2002). Psychiatric Manifestations of Cushing’s Syndrome. In: Blevins, L.S. (eds) Cushing’s Syndrome. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1103-8_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-1103-8_3

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5396-6

  • Online ISBN: 978-1-4615-1103-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics