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库欣综合征诊断的确立

Author
Lynnette K Nieman, MD
Section Editor
André Lacroix, MD
Deputy Editor
Kathryn A Martin, MD
Translators
孙磊, 副主任医师

引言

某些症状和体征提示可能存在库欣综合征。不幸的是，这些症状和体征都不具有疾病特征性，并且许多并不具有特异性(例如，肥胖、高血压、月经不规则和葡萄糖耐受不良)。因此，库欣综合征的诊断必须通过生化试验确认。

确定患者是否存在皮质醇增多症(库欣综合征)的实验室诊断性评估将总结在此。已确定的皮质醇增多症的鉴别诊断方法将单独讨论。(参见“确定库欣综合征的病因”)

排除外源性糖皮质激素

在针对可能的库欣综合征进行评估之前，通过仔细的病史采集排除外源性糖皮质激素摄入是至关重要的。糖皮质激素的摄入可能有以下两种方式：

  • 皮质醇增多症的最常见原因是摄入处方开具的泼尼松，通常是为了治疗非内分泌疾病。然而，库欣综合征也可由其他口服、注射、局部用和吸入型糖皮质激素引起[1-3]，以及由醋酸甲地孕酮(一种含有一定的固有的糖皮质激素活性的黄体酮)引起[4]。利托那韦可能延迟一些吸入型类固醇的清除，从而导致库欣综合征[5]。应用含糖皮质激素的乳膏或中草药制剂也可能引起库欣综合征[6,7]。
  • 人为库欣综合征是一种罕见的疾病，它是指患者暗中摄入糖皮质激素，通常发生于接近医护人员的患者[8,9]。

所有糖皮质激素，包括强效吸入型和局部用糖皮质激素，如倍氯米松和氟轻松，若给予足够的剂量均能够抑制促肾上腺皮质激素(adrenocorticotrophic hormone, ACTH)的分泌。因此，血浆ACTH和血清皮质醇浓度以及尿17-羟皮质类固醇和皮质醇排泄量(除非给予的类固醇是皮质醇或可的松)都可能会很低[9]。相反地，外阴阴道应用氢化可的松可能会导致尿皮质醇排泄量假性升高[10]。

            

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Literature review current through: 2017-06 . | This topic last updated: 2015-06-19.
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References
Top
  1. Weber SL. Cushing'S syndrome attributable to topical use of lotrisone. Endocr Pract 1997; 3:140.
  2. Nutting CM, Page SR. Iatrogenic Cushing's syndrome due to nasal betamethasone: a problem not to be sniffed at! Postgrad Med J 1995; 71:231.
  3. Hughes JM, Hichens M, Booze GW, Thorner MO. Cushing's syndrome from the therapeutic use of intramuscular dexamethasone acetate. Arch Intern Med 1986; 146:1848.
  4. Mann M, Koller E, Murgo A, et al. Glucocorticoidlike activity of megestrol. A summary of Food and Drug Administration experience and a review of the literature. Arch Intern Med 1997; 157:1651.
  5. Samaras K, Pett S, Gowers A, et al. Iatrogenic Cushing's syndrome with osteoporosis and secondary adrenal failure in human immunodeficiency virus-infected patients receiving inhaled corticosteroids and ritonavir-boosted protease inhibitors: six cases. J Clin Endocrinol Metab 2005; 90:4394.
  6. Olumide YM, Akinkugbe AO, Altraide D, et al. Complications of chronic use of skin lightening cosmetics. Int J Dermatol 2008; 47:344.
  7. Oldenburg-Ligtenberg PC, van der Westerlaken MM. A woman with Cushing's syndrome after use of an Indonesian herb: a case report. Neth J Med 2007; 65:150.
  8. Cizza G, Nieman LK, Doppman JL, et al. Factitious Cushing syndrome. J Clin Endocrinol Metab 1996; 81:3573.
  9. Quddusi S, Browne P, Toivola B, Hirsch IB. Cushing syndrome due to surreptitious glucocorticoid administration. Arch Intern Med 1998; 158:294.
  10. Kelly CJ, Ogilvie A, Evans JR, et al. Raised cortisol excretion rate in urine and contamination by topical steroids. BMJ 2001; 322:594.
  11. Lin CL, Wu TJ, Machacek DA, et al. Urinary free cortisol and cortisone determined by high performance liquid chromatography in the diagnosis of Cushing's syndrome. J Clin Endocrinol Metab 1997; 82:151.
  12. Workman RJ, Nicholson WE, McCammon DK. Factitious hypercortisoluria. J Clin Endocrinol Metab 1995; 80:3050.
  13. LIDDLE GW. Tests of pituitary-adrenal suppressibility in the diagnosis of Cushing's syndrome. J Clin Endocrinol Metab 1960; 20:1539.
  14. Loosen PT, Chambliss B, DeBold CR, et al. Psychiatric phenomenology in Cushing's disease. Pharmacopsychiatry 1992; 25:192.
  15. Pfohl B, Sherman B, Schlechte J, Winokur G. Differences in plasma ACTH and cortisol between depressed patients and normal controls. Biol Psychiatry 1985; 20:1055.
  16. Pfohl B, Sherman B, Schlechte J, Stone R. Pituitary-adrenal axis rhythm disturbances in psychiatric depression. Arch Gen Psychiatry 1985; 42:897.
  17. Gold PW, Loriaux DL, Roy A, et al. 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.
  18. Amsterdam JD, Maislin G, Winokur A, et al. The oCRH stimulation test before and after clinical recovery from depression. J Affect Disord 1988; 14:213.
  19. Kirkman S, Nelson DH. Alcohol-induced pseudo-Cushing's disease: a study of prevalence with review of the literature. Metabolism 1988; 37:390.
  20. Groote Veldman R, Meinders AE. On the mechanism of alcohol-induced pseudo-Cushing's syndrome. Endocr Rev 1996; 17:262.
  21. Yanovski JA, Nieman LK, Doppman JL, et al. Plasma levels of corticotropin-releasing hormone in the inferior petrosal sinuses of healthy volunteers, patients with Cushing's syndrome, and patients with pseudo-Cushing states. J Clin Endocrinol Metab 1998; 83:1485.
  22. Arnaldi G, Angeli A, Atkinson AB, et al. Diagnosis and complications of Cushing's syndrome: a consensus statement. J Clin Endocrinol Metab 2003; 88:5593.
  23. Tsagarakis S, Vassiliadi D, Thalassinos N. Endogenous subclinical hypercortisolism: Diagnostic uncertainties and clinical implications. J Endocrinol Invest 2006; 29:471.
  24. Newell-Price J, Trainer P, Besser M, Grossman A. The diagnosis and differential diagnosis of Cushing's syndrome and pseudo-Cushing's states. Endocr Rev 1998; 19:647.
  25. Nieman LK, Biller BM, Findling JW, et al. The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2008; 93:1526.
  26. Baid SK, Rubino D, Sinaii N, et al. Specificity of screening tests for Cushing's syndrome in an overweight and obese population. J Clin Endocrinol Metab 2009; 94:3857.
  27. Crapo L. Cushing's syndrome: a review of diagnostic tests. Metabolism 1979; 28:955.
  28. Mengden T, Hubmann P, Müller J, et al. Urinary free cortisol versus 17-hydroxycorticosteroids: a comparative study of their diagnostic value in Cushing's syndrome. Clin Investig 1992; 70:545.
  29. Hellman L, Weitzman ED, Roffwarg H, et al. Cortisol is secreted episodically in Cushing's syndrome. J Clin Endocrinol Metab 1970; 30:686.
  30. Sederberg-Olsen P, Binder C, Kehlet H, et al. Episodic variation in plasma corticosteroids in subjects with Cushing's syndrome of differing etiology. J Clin Endocrinol Metab 1973; 36:906.
  31. Van Cauter E, Refetoff S. Evidence for two subtypes of Cushing's disease based on the analysis of episodic cortisol secretion. N Engl J Med 1985; 312:1343.
  32. Elamin MB, Murad MH, Mullan R, et al. Accuracy of diagnostic tests for Cushing's syndrome: a systematic review and metaanalyses. J Clin Endocrinol Metab 2008; 93:1553.
  33. 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; 269:2232.
  34. Batista DL, Riar J, Keil M, Stratakis CA. Diagnostic tests for children who are referred for the investigation of Cushing syndrome. Pediatrics 2007; 120:e575.
  35. Corcuff JB, Tabarin A, Rashedi M, et al. Overnight urinary free cortisol determination: a screening test for the diagnosis of Cushing's syndrome. Clin Endocrinol (Oxf) 1998; 48:503.
  36. Invitti C, Pecori Giraldi F, de Martin M, Cavagnini F. Diagnosis and management of Cushing's syndrome: results of an Italian multicentre study. Study Group of the Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic-Pituitary-Adrenal Axis. J Clin Endocrinol Metab 1999; 84:440.
  37. Carroll BJ, Curtis GC, Davies BM, et al. Urinary free cortisol excretion in depression. Psychol Med 1976; 6:43.
  38. Mericq MV, Cutler GB Jr. High fluid intake increases urine free cortisol excretion in normal subjects. J Clin Endocrinol Metab 1998; 83:682.
  39. Kidambi S, Raff H, Findling JW. Limitations of nocturnal salivary cortisol and urine free cortisol in the diagnosis of mild Cushing's syndrome. Eur J Endocrinol 2007; 157:725.
  40. Meinardi JR, Wolffenbuttel BH, Dullaart RP. Cyclic Cushing's syndrome: a clinical challenge. Eur J Endocrinol 2007; 157:245.
  41. Blethen SL, Chasalow FI. Overnight dexamethasone suppression test: normal responses and the diagnosis of Cushing's syndrome. Steroids 1989; 54:185.
  42. Findling JW, Raff H, Aron DC. The low-dose dexamethasone suppression test: a reevaluation in patients with Cushing's syndrome. J Clin Endocrinol Metab 2004; 89:1222.
  43. Meikle AW. Dexamethasone suppression tests: usefulness of simultaneous measurement of plasma cortisol and dexamethasone. Clin Endocrinol (Oxf) 1982; 16:401.
  44. Borcherding SM, Baciewicz AM, Self TH. Update on rifampin drug interactions. II. Arch Intern Med 1992; 152:711.
  45. Castro M, Elias PC, Quidute AR, et al. Out-patient screening for Cushing's syndrome: the sensitivity of the combination of circadian rhythm and overnight dexamethasone suppression salivary cortisol tests. J Clin Endocrinol Metab 1999; 84:878.
  46. Laudat MH, Cerdas S, Fournier C, et al. Salivary cortisol measurement: a practical approach to assess pituitary-adrenal function. J Clin Endocrinol Metab 1988; 66:343.
  47. Bonnin R, Villabona C, Rivera A, et al. Is salivary cortisol a better index than free cortisol in serum or urine for diagnosis of Cushing syndrome? Clin Chem 1993; 39:1353.
  48. 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.
  49. Putignano P, Toja P, Dubini A, et al. Midnight salivary cortisol versus urinary free and midnight serum cortisol as screening tests for Cushing's syndrome. J Clin Endocrinol Metab 2003; 88:4153.
  50. 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.
  51. Yaneva M, Mosnier-Pudar H, Dugué MA, et al. Midnight salivary cortisol for the initial diagnosis of Cushing's syndrome of various causes. J Clin Endocrinol Metab 2004; 89:3345.
  52. Viardot A, Huber P, Puder JJ, et al. 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.
  53. Raff H, Homar PJ, Burns EA. Comparison of two methods for measuring salivary cortisol. Clin Chem 2002; 48:207.
  54. Liu H, Bravata DM, Cabaccan J, et al. Elevated late-night salivary cortisol levels in elderly male type 2 diabetic veterans. Clin Endocrinol (Oxf) 2005; 63:642.
  55. Newell-Price J, Trainer P, Perry L, et al. A single sleeping midnight cortisol has 100% sensitivity for the diagnosis of Cushing's syndrome. Clin Endocrinol (Oxf) 1995; 43:545.
  56. Papanicolaou DA, Yanovski JA, Cutler GB Jr, et al. A single midnight serum cortisol measurement distinguishes Cushing's syndrome from pseudo-Cushing states. J Clin Endocrinol Metab 1998; 83:1163.
  57. O'Brien, JT, Ames, D, Schweitzer, I. HPA axis function in depression and dementia: a review. Int J Geriatr Psychiatry 1993; 8:887.
  58. Duclos M, Corcuff JB, Pehourcq F, Tabarin A. Decreased pituitary sensitivity to glucocorticoids in endurance-trained men. Eur J Endocrinol 2001; 144:363.
  59. Duclos M, Corcuff JB, Roger P, Tabarin A. The dexamethasone-suppressed corticotrophin-releasing hormone stimulation test in anorexia nervosa. Clin Endocrinol (Oxf) 1999; 51:725.
  60. Martin NM, Dhillo WS, Banerjee A, et al. Comparison of the dexamethasone-suppressed corticotropin-releasing hormone test and low-dose dexamethasone suppression test in the diagnosis of Cushing's syndrome. J Clin Endocrinol Metab 2006; 91:2582.
  61. Gatta B, Chabre O, Cortet C, 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.
  62. Erickson D, Natt N, Nippoldt T, et al. Dexamethasone-suppressed corticotropin-releasing hormone stimulation test for diagnosis of mild hypercortisolism. J Clin Endocrinol Metab 2007; 92:2972.
  63. Pecori Giraldi F, Pivonello R, Ambrogio AG, 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 (Oxf) 2007; 66:251.
  64. Valassi E, Swearingen B, Lee H, et al. Concomitant medication use can confound interpretation of the combined dexamethasone-corticotropin releasing hormone test in Cushing's syndrome. J Clin Endocrinol Metab 2009; 94:4851.
  65. Reimondo G, Bovio S, Allasino B, et al. The combined low-dose dexamethasone suppression corticotropin-releasing hormone test as a tool to rule out Cushing's syndrome. Eur J Endocrinol 2008; 159:569.
  66. Jackson RV, Grice JE, Jackson AJ, Hockings GI. Naloxone-induced ACTH release in man is inhibited by clonidine. Clin Exp Pharmacol Physiol 1990; 17:179.
  67. Torpy DJ, Jackson RV, Grice JE, et al. Naloxone stimulation of ACTH secretion during petrosal sinus sampling in Cushing's syndrome. Clin Exp Pharmacol Physiol 1993; 20:299.
  68. Davis, BC, Gaitan, D, Loosen, PT, Orth, DN. Naloxone test distinguishes pituitary ACTH-dependent Cushing's disease (CD) from major depressive disorder (MDD) and chronic alcoholism (ALC). J Invest Med 1995; 43(Suppl):259A.
  69. Besser, GM, Edwards, CRW. Cushing's syndrome. Clin Endocrinol Metab 1972; 1:451.
  70. Samuels MH, Brandon DD, Isabelle LM, et al. Cortisol production rates in subjects with suspected Cushing's syndrome: assessment by stable isotope dilution methodology and comparison to other diagnostic methods. J Clin Endocrinol Metab 2000; 85:22.