Skip to main content
Log in

Psychiatric Disorders Associated with Cushing’s Syndrome

Epidemiology, Pathophysiology and Treatment

  • Therapy in Practice
  • Published:
CNS Drugs Aims and scope Submit manuscript

Abstract

Cushing’s syndrome is caused by a chronic excess of glucocorticoids. A number of psychiatric and psychological disturbances may be associated with the condition, regardless of its aetiology. Major depression is the most common co-morbid disorder. Other psychopathological aspects of Cushing’s syndrome in adults include mania, anxiety disorders and cognitive dysfunction.

The presence of depression connotes a severe clinical presentation and, in patients with hypothalamic-pituitary forms of Cushing’s syndrome, is prognostically useful. Inhibitors of corticosteroid production (e.g. ketoconazole, metyrapone, aminoglutethimide), rather than antidepressant drugs, are generally successful in relieving depressive symptoms, as well as other disabling symptoms. These drugs can be used to control symptoms prior to surgical treatment of Cushing’s syndrome.

Long-standing hypercortisolism may cause some degree of irreversible pathological damage and induce highly individualised affective responses based on each patient’s psychological assets and liabilities. As a result, upon normalisation of cortisol levels, treatment may still be required, and should encompass both psychotherapeutic strategies (particularly cognitive-behavioural therapies that have been found to be effective in affective disorders) and psychotropic drug treatment [antidepressants such as tricyclic agents and selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors]. In patients with severe anxiety, benzodiazepines (e.g. clonazepam in small doses) may also be helpful.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Table I
Table II
Table III
Table IV

Similar content being viewed by others

References

  1. Sonino N, Fava GA. Psychological aspects of endocrine disease. Clin Endocrinol (Oxf) 1998; 49: 1–7

    Article  CAS  Google Scholar 

  2. Sonino N, Fava GA. Psychosomatic aspects of Cushing’s disease. Psychother Psychosom 1998; 67: 140–6

    Article  PubMed  CAS  Google Scholar 

  3. Boscaro M, Barzon L, Sonino N. The diagnosis of Cushing’s syndrome: atypical presentations and laboratory pitfalls. Arch Intern Med 2000; 160: 3045–53

    Article  PubMed  CAS  Google Scholar 

  4. Boscaro M, Barzon L, Fallo F, et al. Update on Cushing’s syndrome. Lancet 2001; 357: 783–91

    Article  PubMed  CAS  Google Scholar 

  5. Crosby SR, Steward MF, Ratcliffe JD, et al. Direct measurement of the precursors of adrenocorticotropin in human plasma by two-site immunoradiometric assay. J Clin Endocrinol Metab 1998; 67: 1272–7

    Article  Google Scholar 

  6. Lowry PJ, Linton EA, Hodgkinson SC. Analysis of peptide hormones of the hypothalamic pituitary adrenal axis using ‘two-site’ immunoradiometric assays. Horm Res 1989; 32: 25–9

    Article  PubMed  CAS  Google Scholar 

  7. Samuels MH, Loriaux LD. Cushing’ s syndrome and the nodular adrenal gland. Endocrinol Metab Clin North Am 1994; 23: 555–69

    PubMed  CAS  Google Scholar 

  8. Lacroix A, Boite E, Tremblay J, et al. Gastric inhibitory polypeptide-dependent Cortisol hypersecretion: a new cause of Cushing’s syndrome. N Engl J Med 1992; 327: 974–80

    Article  PubMed  CAS  Google Scholar 

  9. Reznik Y, Allali-Zerah V, Chayavialle JA, et al. Food dependent Cushing’s syndrome mediated by aberrant adrenal sensitivity to gastric inhibitory polypeptide. N Engl J Med 1992; 327: 981–6

    Article  PubMed  CAS  Google Scholar 

  10. Oldfield EH, Doppman JL, Nieman LK, et al. Petrosal sinus sampling with and without corticotrophin-releasing hormone for the differential diagnosis of Cushing’s syndrome. N Engl J Med 1991; 325: 897–905

    Article  PubMed  CAS  Google Scholar 

  11. White FE, White MC, Drury PL, et al. Value of computed tomography of the abdomen and chest in investigations of Cushing’s syndrome. BMJ 1982; 284: 771–4

    Article  PubMed  CAS  Google Scholar 

  12. Buchfelder M, Nistor R, Fahlbusch R, et al. The accuracy of CT and MR evaluation of the sella turcica for detection of adrenocorticotropin hormone-secreting adenomas in Cushing’s disease. Am J Neuroradiol 1993; 4: 1183–90

    Google Scholar 

  13. Colombo L, Loli P, Vignati F, et al. MR of corticotropin-secreting pituitary microadenomas. Am J Neuroradiol 1994; 15: 1591–5

    PubMed  CAS  Google Scholar 

  14. James RA. Octreotide and ectopic Cushing’s syndrome: a commentary. Clin Endocrinol 1998; 49: 419–20

    Article  CAS  Google Scholar 

  15. de Herder WW, Lamberts SWJ. Tumor localization: the ectopic ACTH syndrome. J Clin Endocrinol Metab 1999; 84: 1184–5

    Article  PubMed  Google Scholar 

  16. Urbanic RC, George JM. Cushing’s disease: 18 years experience. Medicine 1981; 60: 14–24

    Article  PubMed  CAS  Google Scholar 

  17. Ross EJ, Linch DC. Cushing’s syndrome — killing disease: discriminatory value of signs and symptoms aiding early diagnosis. Lancet 1982; II: 646–9

    Article  Google Scholar 

  18. Sonino N, Boscaro M, Fallo F, et al. A clinical index for rating severity in Cushing’s syndrome. Psychother Psychosom 2000; 69: 216–0

    Article  PubMed  CAS  Google Scholar 

  19. Sonino N, Zielezny M, Fava GA, et al. Risk factors and long-term outcome in pituitary-dependent Cushing’s disease. J Clin Endocrinol Metab 1996; 81: 2647–52

    Article  PubMed  CAS  Google Scholar 

  20. Sonino N, Boscaro M. Medical therapy for Cushing’s disease. Endocrinol Metab Clin North Am 1999; 28: 211–2

    Article  PubMed  CAS  Google Scholar 

  21. Sonino N, Fava GA, Fallo F, et al. Effect of serotonin antagonists ritanserin and ketanserin in Cushing’s disease. Pituitary 2000; 3: 55–60

    Article  PubMed  CAS  Google Scholar 

  22. Sonino N. The use of ketoconazole as an inhibitor of steroid production. N Engl J Med 1987; 317: 812–18

    Article  PubMed  CAS  Google Scholar 

  23. Whitlock FA. Symptomatic affective disorders. Sydney: Academic Press, 1982

    Google Scholar 

  24. Haskett RF. Diagnostic categorization of psychiatric disturbance in Cushing’s syndrome. Am J Psychiatry 1985; 142: 911–16

    PubMed  CAS  Google Scholar 

  25. Hudson JI, Hudson MS, Griffing GT, et al. Phenomenology and family history of affective disorder in Cushing’ s disease. Am J Psychiatry 1987; 144: 951–3

    PubMed  CAS  Google Scholar 

  26. Loosen PT, Chambliss B, de Bold CR, et al. Psychiatric phenomenology in Cushing’s disease. Pharmacopsychiatry 1992; 25: 192–8

    Article  PubMed  CAS  Google Scholar 

  27. Sonino N, Fava GA, Belluardo P, et al. Course of depression in Cushing’s syndrome: response to treatment and comparison with Graves’ disease. Horm Res 1993; 39: 202–6

    Article  PubMed  CAS  Google Scholar 

  28. Kelly WF. Psychiatric aspects of Cushing’s syndrome. Q J Med 1996; 89: 543–1

    Article  CAS  Google Scholar 

  29. Sonino N, Fava GA, Raffi AR, et al. Clinical correlates of major depression in Cushing’s disease. Psychopathology 1998; 31: 302–6

    Article  PubMed  CAS  Google Scholar 

  30. Dorn LD, Burgess ES, Dubbert B, et al. Psychopathology in patients with endogenous Cushing’s syndrome: atypical or melancholic features. Clin Endocrinol 1995; 43: 433–2

    Article  CAS  Google Scholar 

  31. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994

    Google Scholar 

  32. Fava GA. Affective disorders and endocrine disease. Psychosomatics 1994; 35: 341–53

    Article  PubMed  CAS  Google Scholar 

  33. Fava GA, Sonino N. Depression associated with medical illness. CNS Drugs 1996; 5: 175–89

    Article  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  35. Lam RW, Stewart JN. The validity of atypical depression in DSM-IV. Compr Psychiatry 1996; 37: 375–83

    Article  PubMed  CAS  Google Scholar 

  36. Fava GA. Subclinical symptoms in mood disorders. Psychol Med 1999; 29: 47–61

    Article  PubMed  CAS  Google Scholar 

  37. Fava GA, Mangelli L. Subclinical symptoms of panic disorder. Psychother Psychosom 1999; 68: 281–9

    Article  PubMed  CAS  Google Scholar 

  38. Schneider G, Kruse A, Nehen HG, et al. The prevalence and differential diagnosis of subclinical depressive syndromes in inpatients 60 years old and older. Psychother Psychosom 2000; 69: 251–60

    Article  PubMed  CAS  Google Scholar 

  39. Fava GA, Sonino N. Psychosomatic medicine: emerging trends and perspectives. Psychother Psychosom 2000; 69: 184–97

    Article  PubMed  CAS  Google Scholar 

  40. Meyer T, Klemme H, Herrmann C. Depression but not anxiety is a significant predictor of physicians’ assessment of medical status in physically ill patients. Psychother Psychosom 2000; 69: 147–54

    Article  PubMed  CAS  Google Scholar 

  41. Fava M, Rankin MA, Wright JE, et al. Anxiety disorders in major depression. Comp Psychiatry 2000; 41: 97–102

    Article  CAS  Google Scholar 

  42. Starkman MN, Schteingart DE, Schork MA. Correlation of bedside cognitive and neuropsychological tests in patients with Cushing’s syndrome. Psychosomatics 1986; 27: 508–11

    Article  PubMed  CAS  Google Scholar 

  43. Mauri M, Sinforiani E, Bono G, et al. Memory impairment in Cushing’s disease. Acta Neurol Scand 1993; 87: 52–5

    Article  PubMed  CAS  Google Scholar 

  44. Forget H, Lacroix A, Somma M, et al. Cognitive decline in patients with Cushing’s syndrome. J Internat Neuropsychol Soc 2000; 6: 20–9

    CAS  Google Scholar 

  45. Simmons NE, Do HM, Lipper MH, et al. Cerebral atrophy in Cushing’s disease. Surg Neurol 2000; 53: 72–6

    Article  PubMed  CAS  Google Scholar 

  46. Sonino N. From the lesson of Harvey Cushing to current knowledge: psychosocial aspects of endocrine disease. Psychother Psychosom 1997; 66: 113–6

    Article  PubMed  CAS  Google Scholar 

  47. Cushing H. Psychic disturbances associated with disorders of the ductless glands. Am J Insanity 1913; 69: 965–0

    Google Scholar 

  48. Trethowan WH, Cobb S. Neuropsychiatric aspects of Cushing’s syndrome. AMA Arch Neurol Psychiat 1952; 67: 283–309

    Article  CAS  Google Scholar 

  49. Gifford S, Gunderson JG. Cushing’ s disease as a psychosomatic disorder. Medicine 1970; 49: 397–409

    Article  PubMed  CAS  Google Scholar 

  50. Cohen SI. Cushing’ s syndrome. A psychiatric study of 29 patients. Br J Psychiatry 1988; 120–4

  51. Sonino N, Fava GA, Grandi S, et al. Stressful life events in the pathogenesis of Cushing’s syndrome. Clin Endocrinol 1988; 29: 617–23

    Article  CAS  Google Scholar 

  52. Sonino N, Fava GA, Boscaro M. A role for life events in the pathogenesis of Cushing’s disease. Clin Endocrinol 1993; 38: 261–4

    Article  CAS  Google Scholar 

  53. Paykel ES. The interview for recent life events. Psychol Med 1997; 27: 301–10

    Article  PubMed  CAS  Google Scholar 

  54. Mazet Ph, Simon D, Luton JP, et al. Syndrome de Cushing: Symptomatologie psychique et personalité de 50 malades. Nouv Press Med 1988; 10: 2565–70

    Google Scholar 

  55. Fava GA, Munari F, Pavan L, et al. Life events and depression. J Affect Disord 1981; 3: 159–65

    Article  PubMed  CAS  Google Scholar 

  56. Sonino N, Girelli ME, Boscaro M, et al. Life events in the pathogenesis of Graves’ disease. Acta Endocrinol 1993; 128: 293–6

    PubMed  CAS  Google Scholar 

  57. Radosavljevic VR, Jankovic SN, Marinkovic JM. Stressful life events in the pathogenesis of Graves’ disease. Eur J Endocrinol 1996; 134: 699–701

    Article  PubMed  CAS  Google Scholar 

  58. Kung AWC. Life events, daily stresses and coping in patients with Graves’ disease. Clin Endocrinol 1995; 42: 303–8

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  60. Biondi M, Picardi A. Psychological stress and neuroendocrine function in humans. Psychother Psychosom 1999; 68: 114–50

    Article  PubMed  CAS  Google Scholar 

  61. Sonino N, Fava GA. Serotonin, Cushing’s disease and depression. Psychother Psychosom 1996; 65: 63–5

    Article  PubMed  CAS  Google Scholar 

  62. de Kloet ER, Rots NY, Cools AR. Brain-corticosteroid hormone dialogue: slow and persistent. Cell Mol Neurobiol 1996; 16: 345–56

    Article  Google Scholar 

  63. Seeman T, McEwen BS. Impact of social environment characteristics on neuroendocrine regulation. Psychosom Med 1996; 58:459–71

    PubMed  CAS  Google Scholar 

  64. Heim C, Owens MJ, Plotsky PM, et al. Persistent changes in corticotrophin-releasing factor systems due to early life stress. Psychopharmacol Bull1997; 33: 185–92

    PubMed  CAS  Google Scholar 

  65. Burgess E, Dorn LD, Haaga DAF, et al. Sociotropy, autonomy, stress, and depression in Cushing syndrome. J Nerv Ment Dis 1996; 184: 362–7

    Article  PubMed  CAS  Google Scholar 

  66. Patten SB, Love EJ. Drug-induced depression. Psychother Psychosom 1997; 66: 63–73

    Article  PubMed  CAS  Google Scholar 

  67. Kelly WF, Kelly MJ, Faragher B. A prospective study of psychiatric and psychological aspects of Cushing’s syndrome. Clin Endocrinol 1996; 45: 715–20

    Article  CAS  Google Scholar 

  68. Dorn LD, Burgess ES, Friedman TC, et al. The longitudinal course of psychopathology in Cushing’s syndrome after correction of hypercortisolism. J Clin Endocrinol Metab 1997; 82: 912–9

    Article  PubMed  CAS  Google Scholar 

  69. Voigt KH, Bossert S, Bretschneider S, et al. Disturbed Cortisol secretion in man. Psychiatry Res 1985; 15: 341–50

    Article  PubMed  CAS  Google Scholar 

  70. Taft P, Martin FIR, Melick R. Cushing’ s syndrome. A review of the response to treatment in 42 patients. Australas Ann Med 1970; 4: 295–303

    Google Scholar 

  71. Sonino N, Fallo F, Opocher G, et al. Hypertension in Cushing’s syndrome. Med Sci Res 1992; 20: 431–4

    Google Scholar 

  72. Fallo F, Sonino N, Barzon L, et al. Effects of surgical treatment on hypertension in Cushing’s syndrome. Am JHypertens 1996; 9: 77–80

    Article  CAS  Google Scholar 

  73. Regenstein QR, Rose LI, Williams GH. Psychopathology in Cushing’s syndrome. Arch Intern Med 1972; 130: 114–7

    Article  Google Scholar 

  74. Jacobs BL, van Praag H, Gage FH. Adult brain neurogenesis and psychiatry: a novel theory of depression. Mol Psychiatry 2000; 5: 262–9

    Article  PubMed  CAS  Google Scholar 

  75. Starkman MN, Giordani B, Gerbaski SS, et al. Decrease in cortical reverses human hippocampal atrophy following treatment of Cushing’s disease. Biol Psychiatry 1999; 46: 1595–602

    Article  PubMed  CAS  Google Scholar 

  76. Jeffcoate WJ, Silverstone JT, Edwards CRW, et al. Psychiatric manifestations of Cushing’s syndrome: response to lowering of plasma cortisol. Q J Med 1979, 48: 465–72

    PubMed  CAS  Google Scholar 

  77. Kramlinger KG, Peterson GC, Watson PK,et al. Metyrapone for depression and delirium secondary to Cushing’s syndrome. Psychosomatics 1985; 26: 67–71

    Article  PubMed  CAS  Google Scholar 

  78. van der Lely AJ, Foeken K, van der Mast RC, et al. Rapid reversal of acute psychosis in the Cushing’s syndrome with the cortisol-receptor antagonist mifepristone (RU 486). Ann Intern Med 1991; 114: 143–4

    PubMed  Google Scholar 

  79. Sonino N, Boscaro M, Ambroso G, et al. Prolonged treatment of Cushing’s disease with metyrapone and aminoglutethimide. IRCS Med Sci 1986; 14: 485–6

    Google Scholar 

  80. Pelton GH. Antiglucocorticoidid medication for the treatment of depression. Psychiat Ann 2000; 30: 139–46

    Google Scholar 

  81. Starkman MN, Schteingart DE, Schork MA. Cushing’s syndrome after treatment. Psychiatry Res 1986; 17: 177–8

    Article  Google Scholar 

  82. Starkman MN, Gebarski SS, Berent S, et al. Hippocampal formation volume, memory dysfunction, and Cortisol levels in patients with Cushing’s syndrome. Biol Psychiatry 1992; 32: 756–65

    Article  PubMed  CAS  Google Scholar 

  83. Momose KJ, Kjellberg RN, Kliman B. High incidence of cortical atrophy of the cerebral and cerebellar hemispheres in Cushing’s disease. Radiology 1971; 99: 341–8

    PubMed  CAS  Google Scholar 

  84. Dubrovsky B. Effects of adrenal cortex hormones on limbic structures. J Psychiat Neurosci 1993; 18: 4–16

    CAS  Google Scholar 

Download references

Acknowledgements

This paper has been supported in part by grants from the Ministero dell’Università e della Ricerca Scientifica e Tecnologica (MURST), Rome, Italy to Dr Sonino and Dr Fava.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sonino, N., Fava, G.A. Psychiatric Disorders Associated with Cushing’s Syndrome. Mol Diag Ther 15, 361–373 (2001). https://doi.org/10.2165/00023210-200115050-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00023210-200115050-00003

Keywords

Navigation