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Laboratorial Diagnosis of Cushing’s Syndrome: Differential Diagnosis with Pseudo Cushing’s Conditions as Obesity, Alcoholism and Depression

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Cushing's Syndrome

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

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Summary

The diagnosis of Cushing’s syndrome requires a high degree of suspicion and this may lead to testing of patients with some, but not all, features of hypercortisolism due to causes other than adrenal/pituitary dysfunction. Indeed, conditions such as depression, alcoholism, obesity and polycystic ovary syndrome may be accompanied by Cushing’s-like physical and biochemical changes and are therefore grouped under the heading of “pseudoCushing”.

This review will summarize clinical and biochemical findings in pseudoCushing’s states and describe the differential diagnosis with Cushing’s syndrome.

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References

  1. Newell-Price J, Trainer PJ, Besser GM, Grossman AB. The diagnosis and differential diagnosis of Cushing’s syndrome and Pseudo-Cushing’s states. Endocrine Rev. 1998;19:647–672.

    Article  CAS  Google Scholar 

  2. Invitti C, Pecori Giraldi F, De Martin M, Cavagnini F, and the Study Group of the Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic-Pituitary-Adrenal Axis. Diagnosis and management of Cushing’s syndrome: results of an Italian multicentre study. J Clin Endocrinol Metab. 1999;84:440–448.

    Article  PubMed  CAS  Google Scholar 

  3. 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;92:4123–4129.

    Article  PubMed  CAS  Google Scholar 

  4. Chan KCA, Lit LCW, Law ELK, Tai MHL, Yung CU, Chan MHM, et al. Diminished urinary free cortisol excretion in patients with moderate and severe renal impairment. Clin Chem 2004;50:757–759.

    Article  PubMed  CAS  Google Scholar 

  5. Putignano P, Dubini A, Cavagnini F. Urinary free cortisol is unrelated to physiological changes in urine volume in healthy women. Clin Chem 2000;46:879.

    PubMed  CAS  Google Scholar 

  6. Fenske M. Urinary free cortisol and cortisone excretion in healthy individuals: influence of water loading. Steroids 2006;71:1014–1018.

    Article  PubMed  CAS  Google Scholar 

  7. Findling JW, Pinkstaff SM, Shaker JL, Raff H, Nelson JC. Pseudohypercortisoluria: spurious elevation of urinary cortisol due to carbamazepine. Endocrinologist 1998;8:51–54.

    Article  Google Scholar 

  8. Meikle AW, Findling J, Kushnir MM, Rockwood AL, Nelson GJ, Terry AH. Pseudo-Cushing syndrome caused by fenofibrate interference with urinary cortisol assayed by high-performance liquid chromatography. J Clin Endocrinol Metab 2003;88:3521–3524.

    Article  PubMed  CAS  Google Scholar 

  9. Newell-Price J, Trainer PJ, Perry L, Wass JAH, Grossman AB, Besser GM. A single sleeping midnight cortisol has 100% sensitivity for the diagnosis of Cushing’s syndrome. Clin Endocrinol 1995;43:545–550.

    Article  CAS  Google Scholar 

  10. Papanicolaou DA, Yanovski, JA, Cutler GBJr., Chrousos GP, Nieman LK. A single midnight serum cortisol measurement distinguishes Cushing’s syndrome from pseudo-Cushing states. J Clin Endocrinol Metab 1998;83:1163–1167.

    Article  PubMed  CAS  Google Scholar 

  11. van Cauter E, Leproult R, Kupfer DJ. Effects of gender and age on the levels and circadian rhythmicity of plasma cortisol. J Clin Endocrinol Metab 1996;81:2468–2473.

    Article  PubMed  CAS  Google Scholar 

  12. Viardot A, Huber P, Puder JJ, Zulewski H, Keller U, Müller B. Reproducibility of nighttime salivary cortisol and its use in the diagnosis of hypercortisolism compared with urinary free cortisol and overnight dexamethasone suppression test. J Clin Endocrinol Metab 2005;90:5730–5736.

    Article  PubMed  CAS  Google Scholar 

  13. Brien TG. Human corticosteroid binding globulin. Clin Endocrinol 1981;14:193–212.

    Article  CAS  Google Scholar 

  14. Raff H, Raff JL, Findling JW. Late-night salivary cortisol as a screening test for Cushing’s syndrome. J Clin Endocrinol Metab 1998;83:2681–2686.

    Article  PubMed  CAS  Google Scholar 

  15. Nunes ML, Vattaut S, Corcuff JB, Rault A, Loiseau H, Gatta B, et al. Late-night salivary cortisol for diagnosis of overt and subclinical Cushing’s syndrome in hospitalized and ambulatory patients. J Clin Endocrinol Metab 2009;94:456–462.

    Article  PubMed  CAS  Google Scholar 

  16. Papanicolaou DA, Mullen N, Kyrou I, Nieman LK. Nighttime salivary cortisol: a useful test for the diagnosis of Cushing’s syndrome. J Clin Endocrinol Metab 2002;87:4515–4521.

    Article  PubMed  CAS  Google Scholar 

  17. Putignano P, Toja PM, Dubini A, Pecori Giraldi F, Corsello SM, Cavagnini F. Midnight salivary cortisol versus urinary free and midnight cortisol as screening tests for Cushing’s syndrome. J Clin Endocrinol Metab 2003;88:4153–4157.

    Article  PubMed  CAS  Google Scholar 

  18. Liu H, Bravata DM, Cabaccan J, Raff H, Ryzen E. Elevated late-night salivary cortisol levels in elderly male type 2 diabetic veterans. Clin Endocrinol 2005;63:642–649.

    Article  CAS  Google Scholar 

  19. Tiong K, Falhammar H. Carbamazepine and falsely positive screening tests for Cushing’s syndrome. N Z Med J 2009;122:100–102.

    PubMed  Google Scholar 

  20. Jubiz W, Meikle AW, Levison RA, Mizutani S, West CD, Tyler FH. Effect of diphenylhydantoin on the metabolism of dexamethasone. N Engl J Med 1970;2:11–14.

    Article  Google Scholar 

  21. Reimondo G, Pia A, Bovio S, Allasino B, Daffara F, Paccotti P, et al. Laboratory differentiation of Cushing’s syndrome. Clin Chim Acta 2008;388:5–14.

    Article  PubMed  CAS  Google Scholar 

  22. Wood PJ, Barth JH, Freedman DB, Perry L, Sheridan B. Evidence of the low dose dexamethasone suppression test to screen for Cushing’s syndrome - recommendations for a protocol for biochemistry laboratories. Ann Clin Biochem 1997;34:222–229.

    PubMed  CAS  Google Scholar 

  23. Fok ACK, Tan KT, Jacob E, Sum CF. Overnight (1 mg) dexamethasone suppression testing reliably distinguishes non-cushingoid obesity from Cushing’s syndrome. Steroids 1991;56:549–561.

    Article  PubMed  CAS  Google Scholar 

  24. Nieman LK, Biller BMK, Findling JW, Newell-Price J, Savage MO, Stewart PM, et al. Diagnosis of Cushing’s syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2008;93:1526–1540.

    Article  PubMed  CAS  Google Scholar 

  25. Coenen CM, Thomas CM, Borm GF, Hollanders JM, Rolland R. Changes in androgens during treatment with four low-dose contraceptives. Contraception 1996;53:171–176.

    Article  PubMed  CAS  Google Scholar 

  26. Yanovski JA, Cutler, GBJr, Chrousos GP, Nieman LK. Corticotropin-releasing hormone stimulation following low-dose dexamethasone administration. JAMA 1993;269: 2232–2238.

    Article  PubMed  CAS  Google Scholar 

  27. Batista D, Courkoutsakis NA, Riar J, Keil MF, Stratakis CA. Severe obesity confounds the interpretation of low dose dexamethasone test with the administration of ovine corticotrophin releasing hormone in childhood Cushing syndrome. J Clin Endocrinol Metab 2008;93:4323–4330.

    Article  PubMed  CAS  Google Scholar 

  28. Erickson D, Natt N, Nippoldt TB, Young WFJr, Carpenter PC, Petterson T, et al. Dexamethasone-suppressed corticotropin-releasing hormone stimulation test for diagnosis of mild hypercortisolism. J Clin Endocrinol Metab 2007;92:2972–2976.

    Article  PubMed  CAS  Google Scholar 

  29. Martin NM, Dhillo WS, Banerjee A, Abdulali A, Jayasena CN, Donaldson M, et al. Comparison of the dexamethasone-suppressed corticotrophin-releasing hormone test and low-dose dexamethasone suppression test in the diagnosis of Cushing’s syndrome. J Clin Endocrinol Metab 2006;91:2582–2586.

    Article  PubMed  CAS  Google Scholar 

  30. Gatta B, Chabre O, Cortet C, Martinie M, Corcuff JB, Roger P, et al. Reevaluation of the combined dexamethasone suppression-corticotropin-releasing hormone test for differentiation of mild Cushing’s disease from pseudo-Cushing’s syndrome. J Clin Endocrinol Metab 2007;92:4290–4293.

    Article  PubMed  CAS  Google Scholar 

  31. Pecori Giraldi F, Pivonello R, Ambrogio AG, De Martino MC, De Martin M, Scacchi M, et al. The dexamethasone-suppressed corticotropin-releasing hormone stimulation test and the desmopressin test to distinguish Cushing’s syndrome from pseudo-Cushing’s states. Clin Endocrinol 2006;66:251–257.

    Google Scholar 

  32. Moro M, Putignano P, Losa M, Invitti C, Maraschini C, Cavagnini F. The desmopressin test in the differential diagnosis between Cushing’s disease and pseudoCushing states. J Clin Endocrinol Metab 2000;85:3569–3574.

    Article  PubMed  CAS  Google Scholar 

  33. Malerbi DA, Bilharinho de Mendonça B, Liberman B, Toledo SPA, Corradini MCM, Cunha-Neto MB, et al. The desmopressin stimulation test in the differential diagnosis of Cushing’s syndrome. Clin Endocrinol 1993;38:463–472.

    Article  CAS  Google Scholar 

  34. Dahia PLM, Ahmed-Shuaib A, Jacobs RA, Chew SL, Honegger J, Fahlbusch R, et al. Vasopressin receptor expression and mutation analysis in corticotropin-secreting tumors. J Clin Endocrinol Metab 1996;81:1768–1771.

    Article  PubMed  CAS  Google Scholar 

  35. De Keyzer Y, René P, Beldjord C, Lenne F, Bertagna X. Overexpression of vasopressin (V3) and corticotrophin-releasing hormone receptor genes in corticotroph tumours. Clin Endocrinol 1998;49:475–482.

    Article  CAS  Google Scholar 

  36. Pecori Giraldi F, Marini E, Torchiana E, Mortini P, Dubini A, Cavagnini F. Corticotrophin-releasing activity of desmopressin in Cushing’s disease. Lack of correlation between in vivo and in vitro responsiveness. J Endocrinol 2003;177:373–379.

    Article  PubMed  CAS  Google Scholar 

  37. Terzolo M, Reimondo G, Alì A, Borretta G, Cesario F, Pia A, et al. The limited value of the desmopressin test in the diagnostic approach to Cushing’s syndrome. Clin Endocrinol 2001;54:609–616.

    Article  CAS  Google Scholar 

  38. Malerbi DA, Villares Fragoso MCB, Vieira Filho AHG, Brenlha EML, Bilharinho de Mendonça B. Cortisol and adrenocorticotropin response to desmopressin in women with Cushing’s disease compared with depressive illness. J Clin Endocrinol Metab 1996;81: 2233–2237.

    Article  PubMed  CAS  Google Scholar 

  39. Coiro V, Volpi R, Capretti L, Caffarri G, Chiodera P. Desmopressin and hexarelin tests in alcohol-induced pseudo-Cushing’s syndrome. J Intern Med 2000;247:667–673.

    Article  PubMed  CAS  Google Scholar 

  40. Tsagarakis S, Vasiliou V, Kokkoris P, Stavropoulos G, Thalassinos N. Assessment of cortisol and ACTH responses to the desmopressin test in patients with Cushing’s syndrome and simple obesity. Clin Endocrinol 1999;51:473–477.

    Article  CAS  Google Scholar 

  41. Andersson KE, Arner B, Hedner P, Mulder JL. Effects of 8-lysine-vasopressin and synthetic analogues on release of ACTH. Acta Endocrinol (Copenh) 1972;69:640–648.

    CAS  Google Scholar 

  42. Gaillard RC, Riondel AM, Ling N, Muller AF. Corticotropin releasing factor activity of CRF-41 in normal man is potentiated by angiotensin II and vasopressin but not by desmopressin. Life Sci 1988;43:1935–1944.

    Article  PubMed  CAS  Google Scholar 

  43. Colombo P, Passini E, Re T, Faglia G, Ambrosi B. Effect of desmopressin on ACTH and cortisol secretion in states of ACTH excess. Clin Endocrinol 1997;46:661–668.

    Article  CAS  Google Scholar 

  44. Sakai Y, Horiba N, Tozawa F, Sakai K, Kuwayama A, Demura H, et al. Desmopressin stimulation test for diagnosis of ACTH-dependent Cushing’s syndrome. Endocr J 1997;44: 687–695.

    Article  PubMed  CAS  Google Scholar 

  45. Contreras P, Araya V. Overnight dexamethasone pre-treatment improves the performance of the lysine-vasopressin test in the diagnosis of Cushing’s syndrome. Clin Endocrinol 1996;44:703–710.

    Article  CAS  Google Scholar 

  46. Besser GM, Edwards CRW. Cushing’s syndrome. Clin Endocrinol Metab 1972;1:451–490.

    Article  Google Scholar 

  47. Lopez JF, Kathol RG, Jaeckle RS, Meiler W. The HPA axis response to insulin hypoglycemia in depression. Biol Psychiatry 1987;22:153–166.

    Article  PubMed  CAS  Google Scholar 

  48. Weaver JU, Kopelman PG, McLoughlin L, Forsling ML, Grossman AB. Hyperactivity of the hypothalamo pituitary adrenal axis in obesity - a study of ACTH, AVP, beta-lipotrophin and cortisol responses to insulin-induced hypoglycaemia. Clin Endocrinol 1993;39:345–350.

    Article  CAS  Google Scholar 

  49. Grottoli S, Arvat E, Gauna C, Maccagno B, Ramunni J, Giordano R, et al. Effects of alprazolam, a benzodiazepine, on the ACTH-, GH- and PRL-releasing activity of hexarelin, a synthetic peptidyl GH secretagogue (GHS), in patients with simple obesity and in patients with Cushing’s disease. Pituitary 1999;2:197–204.

    Article  PubMed  CAS  Google Scholar 

  50. Hickey GJ, Drisko J, Faidley T, Chang C, Anderson LL, Nicolich S, et al. Mediation by the central nervous system is critical to the in vivo activity of the GH secretagogue L-692,585. J Endocrinol 1996;148:371–380.

    Article  PubMed  CAS  Google Scholar 

  51. Jackson RV, Hockings GI, Torpy DJ, Grice JE, Crosbie GV, Walters MM, et al. New diagnostic tests for Cushing’s syndrome: uses of naloxone, vasopressin and alprazolam. Clin Exp Pharmacol Physiol 1996;23:579–581.

    Article  PubMed  CAS  Google Scholar 

  52. Ambrosi B, Bochicchio D, Ferrario R, Colombo P, Faglia G. Effects of the opiate agonist loperamide on pituitary adrenal function in patients with supected hypercortisolism. J Endocrinol Invest 1989;12:31–35.

    PubMed  CAS  Google Scholar 

  53. Nemeroff CB, Krishnan KRR, Reed D, Leder R, Beam C, Dunnick NR. Adrenal gland enlargement in major depression. A computed tomographic study. Arch Gen Psychiatry 1992;49:384–387.

    Article  PubMed  CAS  Google Scholar 

  54. Rubin RT, Phillips JJ, Sadow TF, McCracken JT. Adrenal gland volume in major depression. Increase during the depressive episode and decrease with successful treatment. Arch Gen Psychiatry 1995;52:213–218.

    Article  PubMed  CAS  Google Scholar 

  55. Jaeckle RS, Kathol RG, Lopez JF, Meller WH, Krummel SJ. Enhanced adrenal sensitivity to exogenous cosyntropin (ACTH alfa 1–24) stimulation in major depression. Relationship to dexamethasone suppression test results. Arch Gen Psychiatry 1987;44:233–240.

    Article  PubMed  CAS  Google Scholar 

  56. Ehrhart-Bornstein M, Hinson JP, Bornstein SR, Scherbaum WA, Vinson GP. Intraadrenal interactions in the regulation of adrenocortical steroidogenesis. Endocrine Rev 1998;19:101–143.

    Article  CAS  Google Scholar 

  57. Kling MA, Roy A, Doran AR, Calabrese JR, Rubinow DR, Whitfield HJ, et al. Cerebrospinal fluid immunoreactive corticotropin-releasing hormone and adrenocorticotropin secretion in Cushing’s disease and major depression: potential clinical implications. J Clin Endocrinol Metab 1991;72:260–271.

    Article  PubMed  CAS  Google Scholar 

  58. Nemeroff CB, Widerlöv E, Bissette G, Walléus H, Karlsson I, Eklund K, et al. Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients. Science 1984;226:1342–1344.

    Article  PubMed  CAS  Google Scholar 

  59. Zobel AW, Nickel T, Künzel HE, Ackl N, Sonntag A, Ising M, et al. Effects of the high-affinity corticotropin-releasing hormone receptor 1 antagonist R121919 in major depression: in the first 20 patients treated. J Psychiat Res 2000;34:171–181.

    Article  PubMed  CAS  Google Scholar 

  60. Young EA, Lopez JF, Murphy-Weinberg V, Watson SJ, Akil H. Mineralcorticoid receptor function in major depression. Arch Gen Psychiatry 2003;60:24–28.

    Article  PubMed  CAS  Google Scholar 

  61. Calfa G, Kademian S, Ceschin D, Vega G, Rabinovich GA, Volosin M. Characterization and functional significance of glucocorticoid receptors in patients with major depression: modulation by antidepressant treatment. Psychoneuroendocrinology 2003;28:687–701.

    Article  PubMed  CAS  Google Scholar 

  62. Pariante CM, Miller AH. Glucocorticoid receptors in major depression: relevance to pathophysiology and treatment. Biol Psychiatry 2009;49:391–404.

    Article  Google Scholar 

  63. Brady LS, Whitfield HJ, Fox RJ, Gold PW, Herkenham M. Long-term antidepressant administration alters corticotropin-releasing hormone, tyrosine hydroxylase, and mineralcorticoid receptor gene expression in rat brain. J Clin Invest 1991;87:831–837.

    Article  PubMed  CAS  Google Scholar 

  64. Seckl JR, Fink G. Antidepressants increase glucocorticoid and mineralcorticoid receptor mRNA expression in rat hippocampus in vivo. Neuroendocrinology 1992;55:621–626.

    Article  PubMed  CAS  Google Scholar 

  65. Reul JM, Stec I, Soder M, Holsboer F. Chronic treatment of rats with the antidepressant amitriptyline attenuates the activity of the hypothalamic-pituitary-adrenocortical system. Endocrinology 1993;133:312–320.

    Article  PubMed  CAS  Google Scholar 

  66. Schüle C. Neuroendocrinological mechanisms of actions of antidepressant drugs. J Neuroendocrinol 2006;19:213–226.

    Article  CAS  Google Scholar 

  67. Antonijevic IA, Murck H, Frieboes RM, Horn R, Brabant G, Steiger A. Elevated nocturnal profiles of serum leptin in patients with depression. J Psychiat Res 1998;32:403–410.

    Article  PubMed  CAS  Google Scholar 

  68. Raadsheer FC, Hoogendijk WJG, Stam FC, Tilders FJH, Swaab DF. Increased numbers of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of depressed patients. Neuroendocrinology 1994;60:436–444.

    Article  PubMed  CAS  Google Scholar 

  69. Gold PW, Loriaux DL, Roy A, Kling MA, Calabrese JR, Kellner CH, et al. (1986) Responses to corticotropin-releasing hormone in the hypercortisolism of depression and Cushing’s disease. Pathophysiologic and diagnostic implications. N Engl J Med 1986;314:1329–1335.

    Article  PubMed  CAS  Google Scholar 

  70. Krishnan KR, Rayasam K, Reed DR, Smith M, Chappell P, Saunders WB, et al. The corticotropin-releasing factor stimulation test in patients with major depression: relationship to dexamethasone suppression test results. Depression 1993;1:133–136.

    Article  Google Scholar 

  71. von Bardeleben U, Stalla GK, Müller OA, Holsboer F. Blunting of ACTH response to human CRH in depressed patients is avoided by metyrapone pretreatment. Biol Psychiatry 1988;24:782–786.

    Article  PubMed  CAS  Google Scholar 

  72. Young EA, Haskett RF, Grunhaus L, Pande A, Weinberg MV, Watson SJ, et al. Increased evening activation of the hypothalamic-pituitary-adrenal axis in depressed patients. Arch Gen Psychiatry 1994;51:701–707.

    Article  PubMed  CAS  Google Scholar 

  73. Murphy BEP. Antiglucocorticoid therapies in major depression: a review. Psychoneuroendocrinology 1997;22:S125–S132.

    Article  PubMed  Google Scholar 

  74. Kling MA, Coleman VH, Schulkin J. Glucocorticoid inhibition in the treatment of depression: can we think outside the endocrine hypothalamus? Depress Anxiety 2009;doi, 10.1002/da.20546.

    Google Scholar 

  75. Young EA, Carlson NE, Brown MB. Twenty-four-hour ACTH and cortisol pulsatility in depressed women. Neuropsychopharmacology 2001;25:267–276.

    Article  PubMed  CAS  Google Scholar 

  76. Carroll BJ, Curtis GC, Davies BM, Mendels J, Sugerman AA. Urinary free cortisol excretion in depression. Psychol Med 1976;6:43–50.

    Article  PubMed  CAS  Google Scholar 

  77. Anton RF. Urinary free cortisol in psychotic depression. Biol Psychiatry 1987;22:24–34.

    Article  PubMed  CAS  Google Scholar 

  78. Keller J, Flores B, Gomez RG, Sovason HB, Kenna H, Williams GH, et al. Cortisol circadian rhythm alterations in psychotic major depression. Biol Psychiatry 2005;60:275–281.

    Article  CAS  Google Scholar 

  79. Nelson JC, Davis JM. DST studies in psychotic depression: a meta-analysis. Am J Psychiatry 1997;154:1497–1503.

    PubMed  CAS  Google Scholar 

  80. Young EA, Haskett RF, Murphy-Weinberg V, Watson SJ, Akil H. Loss of glucocorticoid fast feedback in depression. Arch Gen Psychiatry 1991;48:693–699.

    Article  PubMed  CAS  Google Scholar 

  81. Zobel AW, Nickel T, Sonntag A, Uhr M, Holsboer F, Ising M. Cortisol response in the combined dexamethasone/CRH test as predictor of relapse in patients with remitted depression: a prospective study. J Psychiat Res 2001;35:83–94.

    Article  PubMed  CAS  Google Scholar 

  82. Appelhof BC, Huyser J, Verweij M, Brouwer JP, van Dyck R, Fliers E, et al. Glucocorticoids and relapse of major depression. Biol Psychiatry 2006;59:696–701.

    Article  PubMed  CAS  Google Scholar 

  83. Holsboer F, Lauer CJ, Schreiber W, Krieg JC. Altered hypothamic-pituitary-adrenocortical regulation in healthy subjects at high familial risk for affective disorders. Neuroendocrinology 1995;62:340–347.

    Article  PubMed  CAS  Google Scholar 

  84. Kathol RG, Gehris TL, Carroll BT, Samuelson SD, Pitts AF, Meller WH, et al. Blunted ACTH response to hypoglicemic stress in depressed patients but not in patients with schizophrenia. J Psychiat Res 1992;26:103–116.

    Article  PubMed  CAS  Google Scholar 

  85. Bernini GP, Argenio GF, Cerri F, Franchi F. Comparison between the suppressive effects of dexamethasone and loperamide on cortisol and ACTH secretion in some pathological conditions. J Endocrinol Invest 1994;17:799–804.

    PubMed  CAS  Google Scholar 

  86. Ambrogio AG, Pecori Giraldi F, Cavagnini F. Drugs and the HPA axis. Pituitary 2008;11:219–229.

    Article  PubMed  CAS  Google Scholar 

  87. Gibbons L. Cortisol secretion rate in depressive illness. Arch Gen Psychiatry 1964;10: 572–575.

    Article  PubMed  CAS  Google Scholar 

  88. Heuser I, Yassouridis A, Holsboer F. The combined dexamethasone/CRH test: a refined laboratory test for psychiatric disorders. J Psychiat Res 1994;28:341–356.

    Article  PubMed  CAS  Google Scholar 

  89. Zobel AW, Yassouridis A, Frieboes RM, Holsboer F. Prediction of medium-term outcome by cortisol response to the combined dexamethasone-CRH test in patients with remitted depression. Am J Psychiatry 1999;156:949–951.

    PubMed  CAS  Google Scholar 

  90. Wand GS, Dobs AS. Alterations in the hypothalamic-pituitary-adrenal axis in actively drinking alcoholics. J Clin Endocrinol Metab 1991;72:1290–1295.

    Article  PubMed  CAS  Google Scholar 

  91. Groote Veldman R, Meinders AE. On the mechanism of alcohol-induced pseudo-Cushing’s syndrome. Endocrine Rev 1996;17:262–268.

    Article  CAS  Google Scholar 

  92. Rivier C. Alcohol stimulates ACTH secretion in the rat: mechanisms of action and interactions with other stimuli. Alcohol Clin Exp Res 1996;20:240–254.

    Article  PubMed  CAS  Google Scholar 

  93. Ogilvie K, Lee S, Weiss B, Rivier C. Mechanisms mediating the influence of alcohol on the hypothalamic-pituitary-adrenal axis responses to immune and nonimmune signals. Alcohol Clin Exp Res 1998;22:243S–247S.

    Article  PubMed  CAS  Google Scholar 

  94. Ellis F. Effect of ethanol on plasma corticosterone levels. J Pharmacol Exp Ther 1966;153: 121–128.

    PubMed  CAS  Google Scholar 

  95. Rivier C, Bruhn T, Vale W. Effect of ethanol on the hypothalamic-pituitary axis in the rat: role of CRH. J Pharmacol Exp Ther 1984;229:127–131.

    PubMed  CAS  Google Scholar 

  96. Wand G, Froehlich J. Alterations in hypothalamo-hypophyseal function by ethanol. In: McCleod, R, Müller, EE, eds. Neuroendocrine perspectives., New York: Spinger Verlag, 1990;45–122.

    Google Scholar 

  97. Mendelson JH, Ogata M, Mello NK. Adrenal function and alcoholism. I. Serum cortisol. Psychosom Med 1971;33:145–157.

    PubMed  CAS  Google Scholar 

  98. Dave JR, Eiden LE, Karanian JW, Eskay RL. Ethanol exposure decreases pituitary corticotropin-releasing factor binding, adenylate cyclase activity, proopiomelanocortin biosyntesis, and plasma beta-endorphin levels in the rat. Endocrinology 1986;118:280–286.

    Article  PubMed  CAS  Google Scholar 

  99. Rivier C, Lee S. Acute alcohol administration stimulates the activity of hypothalamic neurons that express corticotropin-releasing factor and vasopressin. Brain Res 1996;726:1–10.

    Article  PubMed  CAS  Google Scholar 

  100. Costa A, Bono G, Martignoni E, Merlo P, Sances G, Nappi G. An assessment of hypothalamo-pituitary-adrenal axis functioning in non-depressed, early abstinent alcoholics. Psychoneuroendocrinology 1996;21:263–275.

    Article  PubMed  CAS  Google Scholar 

  101. Ahmed A, Saksena S, Sherlock M, Olliff SP, Elias E, Stewart PM. Induction of hepatic 11-hydroxysteroid dehydrogenase type 1 in patients with alcoholic liver disease. Clin Endocrinol 2008;68:898–903.

    Article  CAS  Google Scholar 

  102. Stewart PM, Burra P, Shackleton CHL, Sheppard MC, Elias E. 11hydroxysteroid dehydrogenase deficiency and glucocorticoid status in patients with alcoholic and non-alcoholic chronic liver disease. J Clin Endocrinol Metab 1993;76:748–751.

    Article  PubMed  CAS  Google Scholar 

  103. Adinoff B, Anton R, Linnoila M, Guidotti A, Nemeroff CB, Bissette G. Cerebrospinal fluid concentrations of corticotropin-releasing hormone (CRH) and diazepam-binding inhibitor (DBI) during alcohol withdrawal and abstinence. Neuropsychopharmacology 1996;15:288–295.

    Article  PubMed  CAS  Google Scholar 

  104. Wilkins JN, Gorelick DA, Nademanee K, Taylor A, Herzberg DS. Hypothalamic-pituitary function during alcohol exposure and withdrawal and cocaine exposure. Recent Dev Alcohol 1992;10:57–71.

    PubMed  CAS  Google Scholar 

  105. Berman JD, Cook DM, Buchman M, Keith LD. Diminished adrenocorticotropin response to insulin-induced hypoglycemia in nondepressed, actively drinking male alcoholics. J Clin Endocrinol Metab 1990;71:712–717.

    Article  PubMed  CAS  Google Scholar 

  106. Stokes PE. Adrenocortical activation in alcoholics during chronic drinking. Ann NY Acad Sci 1973;215:77–83.

    Article  PubMed  CAS  Google Scholar 

  107. Fonzi S, Murialdo G, Bo P, Filippi U, Costelli P, Parodi C, et al. The neuroendocrine aspects of chronic alcoholism: the effect of alcohol intake and its withdrawal. Ann Ital Med Int 1992;7:87–94.

    PubMed  CAS  Google Scholar 

  108. Bertello P, Agrimonti F, Gurioli L, Frairia R, Fornaro D, Angeli A. Circadian patterns of plasma cortisol and testosterone in chronic male alcoholics. Alcohol Clin Exp Res 1982;6:475–481.

    Article  PubMed  CAS  Google Scholar 

  109. Hasselbach H, Selmer J, Sestoft L, Kehlet H. Hypothalamic-pituitary-adrenocortical function in chronic alcoholism. Clin Endocrinol 1982;16:73–76.

    Article  Google Scholar 

  110. Meikle AW. Dexamethasone suppression tests: usefulness of simultaneous measurement of plasma cortisol and dexamethasone. Clin Endocrinol 1982;16:401–408.

    Article  CAS  Google Scholar 

  111. Kirkman S, Nelson DH. Alcohol-induced pseudo-Cushing’s disease: a study of prevalence with review of the literature. Metabolism 1988;37:390–394.

    Article  PubMed  CAS  Google Scholar 

  112. Jeffcoate WJ. Alcohol-induced pseudo-Cushing’s syndrome. Lancet 1993;341:676–677.

    Article  PubMed  CAS  Google Scholar 

  113. Waltman C, McCaul ME, Wand GS. Adrenocorticotropin responses following administration of ethanol and ovine corticotropin-releasing hormone in the sons of alcoholics and control subjects. Alcohol Clin Exp Res 1994;18:826–830.

    Article  PubMed  CAS  Google Scholar 

  114. Sher L, Cooper TB, Mann JJ, Oquendo MA. Modified dexamethasone suppression-corticotropin-releasing hormone stimulation test: a pilot study of young healthy volunteers and implications for alcoholism research in adolescents and young adults. Int J Adolesc Med Health 2006;18:133–137.

    PubMed  Google Scholar 

  115. Dai X, Thavundayil J, Santella S, Gianoulakis C. Response of the HPA-axis to alcohol and stress as a function of alcohol dependence and family history of alcoholism. Psychoneuroendocrinology 2007;32:293–305.

    Article  PubMed  CAS  Google Scholar 

  116. Ehrenreich H, Schuck J, Stender N, Pilz J, Gefeller O, Schilling L, et al. Endocrine and hemodynamic effects of stress versus systemic CRF in alcoholics during early and medium term abstinence. Alcohol Clin Exp Res 1997;21:1285–1293.

    Article  PubMed  CAS  Google Scholar 

  117. Dunkelman SS, Fairhurst B, Plager J, Waterhouse C. Cortisol metabolism in obesity. J Clin Endocrinol Metab 1964;24:832–841.

    Article  PubMed  CAS  Google Scholar 

  118. Andrew R, Phillips DIW, Walker BR. Obesity and gender influence cortisol secretion and metabolism in man. J Clin Endocrinol Metab 1998;83:1806–1809.

    Article  PubMed  CAS  Google Scholar 

  119. Copinschi G, Cornil A, Leclercq R, Franckson JR. Cortisol secretion rate and urinary corticoid excretion in normal and obese subjects. Acta Endocrinol 1966;51:186–192.

    PubMed  CAS  Google Scholar 

  120. Trainer PJ, Grossman AB. The diagnosis and differential diagnosis of Cushing’s syndrome. Clin Endocrinol 1991;34:317–330.

    Article  CAS  Google Scholar 

  121. Pasquali R, Cantorelli S, Casimirri F, Capelli M, Bortoluzzi L, Flamia R, et al. The hypothalamic-pituitary-adrenal axis in obese women with different patterns of body fat distribution. J Clin Endocrinol Metab 1993;77:341–346.

    Article  PubMed  CAS  Google Scholar 

  122. Gomez MT, Malozowski S, Winterer J, Vamvakopoulos NC, Chrousos GP. Urinary free cortisol values in normal children and adolescents. J Pediatr 1991;118:256–258.

    Article  PubMed  CAS  Google Scholar 

  123. Jones KL. The Cushing syndrome. Pediatr Clin North Am 1990;37:1313–1329.

    PubMed  CAS  Google Scholar 

  124. Migeon CJ, Green OC, Eckert JP. Study of adrenocortical function in obesity. Metabolism 1963;12:718–739.

    PubMed  CAS  Google Scholar 

  125. Vicennati V, Pasquali R. Abnormalities of the hypothalamic-pituitary-adrenal axis in nondepressed women with abdominal obesity and relations with insulin resistence: evidence for a central and a peripheral alteration. J Clin Endocrinol Metab 2000;85:4093–4098.

    Article  PubMed  CAS  Google Scholar 

  126. Lanzone A, Cucinelli F, Fulghesu AM, Caruso A, Guido M, Mancuso S. Somatostatin treatment reduces the exaggerated response of adrenocorticotropin hormone and cortisol to corticotropin- releasing hormone in polycystic ovary syndrome. Fertil Steril 1997;67:34–39.

    Article  PubMed  CAS  Google Scholar 

  127. Ljung T, Holm G, Friberg P, Andersson B, Bengtsson BA, Svensson J, et al. The activity of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system in relation to waist/hip circumference ratio in men. Obes Res 2000;8:487–495.

    Article  PubMed  CAS  Google Scholar 

  128. Kopelman PG, Grossman A, Lavender P, Besser GM, Rees LH, Coy D. The cortisol response to corticotrophin-releasing factor is blunted in obesity. Clin Endocrinol 1988;28: 15–18.

    Article  CAS  Google Scholar 

  129. Luboshitzky R, Ishai A, Shen-Or Z, Herer P. Evaluation of the pituitary-adrenal axis in hyperandrogenic women with polycystic ovary syndrome. Neuro Endocrinol Lett 2003;24: 249–254.

    PubMed  CAS  Google Scholar 

  130. Katz JR, Taylor NF, Goodrick S, Perry L, Yudkin JS, Coppack SW. Central obesity, depression and the hypothalamo-pituitary-adrenal axis in men and postmenopausal women. Int J Obes Relat Metab Disord 2000;24:246–251.

    Article  PubMed  CAS  Google Scholar 

  131. Ward AMV, Syddall HE, Wood PJ, Dennison EM, Phillips DIW. Central hypothalamic-pituitary-adrenal activity and the metabolic syndrome: studies using the corticotropin-releasing hormone test. Metabolism 2004;53:720–726.

    Article  PubMed  CAS  Google Scholar 

  132. Putignano P, Pecori Giraldi F, Cavagnini F. Tissue-specific dysregulation of 11-hydroxysteroid dehydrogenase type 1 and pathogenesis of the metabolic syndrome. J Endocrinol Invest 2004;27:969–974.

    PubMed  CAS  Google Scholar 

  133. Bujalska IK, Kumar S, Stewart PM. Does central obesity reflect “Cushing’s disease of the omentum”? Lancet 1997;349:1210–1213.

    Article  PubMed  CAS  Google Scholar 

  134. Masuzaki H, Paterson J, Shinyama H, Morton NM, Mullins JJ, Seckl JR, et al. A transgenic model of visceral obesity and the metabolic syndrome. Science 2001;294:2166–2170.

    Article  PubMed  CAS  Google Scholar 

  135. Morton NM, Paterson JM, Masuzaki H, Holmes MC, Staels B, Fievet C, et al. Novel adipose tissue-mediated resistance to diet-induced visceral obesity in 11 beta-hydroxysteroid dehydrogenase type 1-deficient mice. Diabetes 2004;53:931–938.

    Article  PubMed  CAS  Google Scholar 

  136. Mariniello B, Ronconi C, Rilli S, Bernante P, Boscaro M, Mantero F, et al. Adipose tissue 11-hydroxysteroid dehydrogenase type 1 expression in obesity and Cushing’s syndrome. Eur J Endocrinol 2006;155:435–441.

    Article  PubMed  CAS  Google Scholar 

  137. Ferrannini E, Natali A, Bell P, Cavallo-Perin P, Lalic N, Mingrone G, et al. Insulin resistance and hypersecretion in obesity. J Clin Invest 1997;100:1166–1173.

    Article  PubMed  CAS  Google Scholar 

  138. Fruehwald-Schultes B, Kern W, Born J, Fehm HL, Peters A. Hyperinsulinemia causes activation of the hypothalamus-pituitary-adrenal axis in humans. Int J Obes Relat Metab Disord 2001;25:S38–S40.

    Article  PubMed  CAS  Google Scholar 

  139. Chan O, Inouye K, Akirav E, Park E, Riddell MC, Vranic M, et al. Insulin alone increases hypothalamo-pituitary-adrenal activity, and diabetes lowers peak stress responses. Endocrinology 2005;146:1382–1390.

    Article  PubMed  CAS  Google Scholar 

  140. Stewart PM, Shackleton CH, Beastall GH, Edwards CR. 5 alpha-reductase activity in polycystic ovary syndrome. Lancet 1990;335:431–433.

    Article  PubMed  CAS  Google Scholar 

  141. Fernandez-Real JM, Grasa M, Casamitjana R, Pugeat M, Barret C, Ricart W. Plasma total and glycosylated corticosteroid-binding globulin levels are associated with insulin secretion. J Clin Endocrinol Metab 1999;84:3192–3196.

    Article  PubMed  CAS  Google Scholar 

  142. Invitti C, Pecori Giraldi F, Dubini A, De Martin M, Cavagnini F. Increased urinary free cortisol and decreased serum corticosteroid-binding globulin in polycystic ovary syndrome. Acta Endocrinol (Copenh) 1991;125:28–32.

    CAS  Google Scholar 

  143. Pirich K, Vierhapper H. 24-hour serum concentration profile of cortisol in patients with Cushing’s disease. Exp Clin Endocrinol 1988;92:275–279.

    Article  PubMed  CAS  Google Scholar 

  144. Corcuff JB, Tabarin A, Rashedi M, Duclos M, Roger P, Ducassou D. Overnight urinary free cortisol determination: a screening test for the diagnosis of Cushing’s syndrome. Clin Endocrinol 1998;48:503–508.

    Article  CAS  Google Scholar 

  145. Ness-Abramof R, Nabriski D, Apovian CM, Niven M, Weiss E, Shapito MS, et al. Overnight dexamethasone suppression test: a reliable screen for Cushing’s syndrome in the obese. Obes Res 2002;10:1217–1221.

    Article  PubMed  CAS  Google Scholar 

  146. Crapo L. Cushing’s syndrome: a review of diagnostic tests. Metabolism 1979;28:955–977.

    Article  PubMed  CAS  Google Scholar 

  147. Sahin M, Kebapcilar L, Taslipinar A, Azal O, Ozgurtas T, Corakci A, et al. Comparison of 1 mg and 2 mg overnight dexamethasone suppression tests for the screening of Cushing’s syndrome in obese patients. Intern Med 2009;48:33–39.

    Article  PubMed  Google Scholar 

  148. Zoppini G, Targher G, Venturi C, Zamboni C, Muggeo M. Relationship of nonalcoholic hepatic steatosis to overnight low-dose dxamethasone suppression test in obese individuals. Clin Endocrinol 2004;61:711–715.

    Article  Google Scholar 

  149. Ljung T, Andersson B, Bengtsson BA, Björntorp P, Mårin P. Inhibition of cortisol secretion by dexamethasone in relation to body fat distribution: a dose-response study. Obes Res 1996;4:277–282.

    Article  PubMed  CAS  Google Scholar 

  150. Fleseriu M, Ludlam WH, Teh SH, Yedinak CG, Deveney C, Sheppard BC. Cushing’s syndrome might be underappreciated in patients seeking bariatric surgery: a plea for screening. Surg Obes Relat Dis 2009;5:116–122.

    Article  PubMed  Google Scholar 

  151. Taniguchi, T., Hamasaki, A., and Okamoto, M. (2008) Subclinical hypercortisolism in hospitalized patients with type 2 diabetes mellitus. Endocr J 55, 429–432.

    Article  PubMed  CAS  Google Scholar 

  152. Reimondo G, Pia A, Allasino B, Tassone F, Bovio S, Borretta G, et al. Screening of Cushing’s syndrome in adult patients with newly diagnosed diabetes mellitus. Clin Endocrinol 2007;67:225–229.

    Article  CAS  Google Scholar 

  153. Catargi B, Rigalleau V, Poussin A, Ronci-Chaix N, Bex V, Vergnot V, et al. Occult Cushing’s syndrome in type-2 diabetes. J Clin Endocrinol Metab 2003;88:5808–5813.

    Article  PubMed  CAS  Google Scholar 

  154. Chiodini I, Torlontano M, Scillitani A, Arosio M, Bacci S, Di Lembo S, et al. Association of subclinical hypercortisolism with type 2 diabetes mellitus: a case-control study in hospitalized patients. Eur J Endocrinol 2005;153:837–844.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Ospedale San Luca, Istituto Auxologico Italiano IRCCS, Università di Milano, Milan, Italy

    Martina De Martin MD (Chair of Endocrinology)

  2. Ospedale San Luca, Istituto Auxologico Italiano, Università di Milano, Milan, Italy

    Francesca Pecori Giraldi MD (Chair of Endocrinology)

  3. Ospedale San Luca, Istituto Auxologico Italiano IRCCS, Università di Milano, Via Spagnoletto 3, Milano, 20149, Milan, Italy

    Francesco Cavagnini MD (Chair of Endocrinology)

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  1. Martina De Martin MD
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  3. Francesco Cavagnini MD
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  1. , Division of Endocrinology and Metabolism, Hospital das Clínicas, University of Sao, Sao Paulo, 05403-000, Brazil

    Marcello D. Bronstein

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De Martin, M., Giraldi, F.P., Cavagnini, F. (2010). Laboratorial Diagnosis of Cushing’s Syndrome: Differential Diagnosis with Pseudo Cushing’s Conditions as Obesity, Alcoholism and Depression. In: Bronstein, M. (eds) Cushing's Syndrome. Contemporary Endocrinology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-449-4_6

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