Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Pros and cons of screening for occult Cushing syndrome

Nature Reviews Endocrinology volume 7, pages 445–455 (2011)Cite this article

Subjects

Abstract

Systematic screening studies performed mainly in patients with diabetes mellitus have revealed an unexpectedly high prevalence of occult Cushing syndrome. Such studies may provide a rationale for systematically screening obese patients with type 2 diabetes mellitus. However, a screening strategy is only justified if it is supported by enough evidence of its efficacy and if the benefits will outweigh drawbacks. To date, the natural history of occult Cushing syndrome and its possible effect on long-term morbidity are unknown. The clinical spectrum of occult Cushing syndrome and its relatively low prevalence may potentially negatively affect the performance of endocrine tests used to diagnose overt Cushing syndrome and generate false positives. Whether the cure of occult Cushing syndrome favorably influences clinical outcomes and is more beneficial than treatment of diabetes mellitus and cardiovascular risk factors with currently available pharmacological tools remains to be demonstrated. Last, the acceptability of a screening program by professionals and the health-care system in terms of workload and costs is highly questionable. Thus, an assessment of the indications for and against screening for occult Cushing syndrome on the basis of currently available data suggests that, to date, the cons surpass the pros.

Key Points

  • Common clinical experience and a few epidemiological studies suggest that endogenous Cushing syndrome is a rare condition

  • Systematic screening studies performed in specific populations that exhibit nonspecific symptoms of Cushing syndrome (mainly patients with diabetes mellitus) reveal a prevalence of occult Cushing syndrome that reaches 3.3%

  • A screening strategy is justified when its efficacy is supported by evidence and if benefits outweigh potential drawbacks

  • Examination of the indications for and against screening for occult Cushing syndrome reveals that the cons exceed the pros

  • Additional studies are needed before we can acknowledge, from an evidence-based perspective, the usefulness of systematic screening for occult Cushing syndrome

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Limitations of physical examination to identify mild Cushing syndrome.
Figure 2: Algorithm used to screen for occult Cushing syndrome in obese patients with type 2 diabetes mellitus.
Figure 3: Influence of the spectrum of the disease on the performance of screening tests.
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Findling, J. W. & Raff, H. Screening and diagnosis of Cushing's syndrome. Endocrinol. Metab. Clin. North Am. 34, 385–402, ix–x (2005).

    Article  PubMed  Google Scholar 

  2. Newell-Price, J., Bertagna, X., Grossman, A. B. & Nieman, L. K. Cushing's syndrome. Lancet 367, 1605–1617 (2006).

    Article  CAS  PubMed  Google Scholar 

  3. Arnaldi, G. et al. Diagnosis and complications of Cushing's syndrome: a consensus statement. J. Clin. Endocrinol. Metab. 88, 5593–5602 (2003).

    Article  CAS  PubMed  Google Scholar 

  4. Cushing's, H. The basophil adenomas of the pituitary body and their clinical manifestations (pituitary basophilism). Obes. Res. 2, 486–508 (1994).

    Article  Google Scholar 

  5. Lindholm, J. et al. Incidence and late prognosis of Cushing's syndrome: a population-based study. J. Clin. Endocrinol. Metab. 86, 117–123 (2001).

    CAS  PubMed  Google Scholar 

  6. Invitti, C., Giraldi, F. P., 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. 84, 440–448 (1999).

    CAS  PubMed  Google Scholar 

  7. Etxabe, J. & Vazquez, J. A. Morbidity and mortality in Cushing's disease: an epidemiological approach. Clin. Endocrinol. (Oxf.) 40, 479–484 (1994).

    Article  CAS  Google Scholar 

  8. Cavagnini, F. & Pecori Giraldi, F. Epidemiology and follow-up of Cushing's disease. Ann. Endocrinol. (Paris) 62, 168–172 (2001).

    CAS  Google Scholar 

  9. 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. 19, 647–672 (1998).

    CAS  PubMed  Google Scholar 

  10. Nieman, L. K. et al. The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline. J. Clin. Endocrinol. Metab. 93, 1526–1540 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Gatta, B. 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. 92, 4290–4293 (2007).

    Article  CAS  PubMed  Google Scholar 

  12. Pecori Giraldi, F. 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.) 66, 251–257 (2007).

    Article  CAS  Google Scholar 

  13. Ross, E. J. & Linch, D. C. Cushing's syndrome—killing disease: discriminatory value of signs and symptoms aiding early diagnosis. Lancet 2, 646–649 (1982).

    Article  CAS  PubMed  Google Scholar 

  14. Minami, I. et al. Subclinical Cushings disease with amelioration of metabolic comorbidities after removal of pituitary tumor. Intern Med. 45, 1231–1235 (2006).

    Article  PubMed  Google Scholar 

  15. Nagai, T., Imamura, M., Misumi, S. & Mori, M. Subclinical Cushing's disease accompanied by malignant hypertension and diabetes mellitus. Intern Med. 41, 566–570 (2002).

    Article  PubMed  Google Scholar 

  16. Roberge, C. et al. Adrenocortical dysregulation as a major player in insulin resistance and onset of obesity. Am. J. Physiol. Endocrinol. Metab. 293, E1465–E1478 (2007).

    Article  CAS  PubMed  Google Scholar 

  17. van Raalte, D. H., Ouwens, D. M. & Diamant, M. Novel insights into glucocorticoid-mediated diabetogenic effects: towards expansion of therapeutic options? Eur. J Clin. Invest. 39, 81–93 (2009).

    Article  CAS  PubMed  Google Scholar 

  18. Alberti, K. G. et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120, 1640–1645 (2009).

    Article  CAS  PubMed  Google Scholar 

  19. Qatanani, M. & Lazar, M. A. Mechanisms of obesity-associated insulin resistance: many choices on the menu. Genes Dev. 21, 1443–1455 (2007).

    Article  CAS  PubMed  Google Scholar 

  20. Arnaldi, G., Mancini, T., Polenta, B. & Boscaro, M. Cardiovascular risk in Cushing's syndrome. Pituitary 7, 253–256 (2004).

    Article  PubMed  Google Scholar 

  21. Faggiano, A. et al. Cardiovascular risk factors and common carotid artery caliber and stiffness in patients with Cushing's disease during active disease and 1 year after disease remission. J. Clin. Endocrinol. Metab. 88, 2527–2533 (2003).

    Article  CAS  PubMed  Google Scholar 

  22. Mancini, T., Kola, B., Mantero, F., Boscaro, M. & Arnaldi, G. High cardiovascular risk in patients with Cushing's syndrome according to 1999 WHO/ISH guidelines. Clin. Endocrinol. (Oxf.) 61, 768–777 (2004).

    Article  Google Scholar 

  23. Pivonello, R., Faggiano, A., Lombardi, G. & Colao, A. The metabolic syndrome and cardiovascular risk in Cushing's syndrome. Endocrinol. Metab. Clin. North Am. 34, 327–339, viii (2005).

    Article  CAS  PubMed  Google Scholar 

  24. Catargi, B. et al. Occult Cushing's syndrome in type-2 diabetes. J. Clin. Endocrinol. Metab. 88, 5808–5813 (2003).

    Article  CAS  PubMed  Google Scholar 

  25. Chiodini, I. et al. Association of subclinical hypercortisolism with type 2 diabetes mellitus: a case–control study in hospitalized patients. Eur. J. Endocrinol. 153, 837–844 (2005).

    Article  CAS  PubMed  Google Scholar 

  26. Leibowitz, G. et al. Pre-clinical Cushing's syndrome: an unexpected frequent cause of poor glycaemic control in obese diabetic patients. Clin. Endocrinol. (Oxf.) 44, 717–722 (1996).

    Article  CAS  Google Scholar 

  27. Reimondo, G. et al. Screening of Cushing's syndrome in adult patients with newly diagnosed diabetes mellitus. Clin. Endocrinol. (Oxf.) 67, 225–229 (2007).

    Article  CAS  Google Scholar 

  28. Liu, H., Bravata, D. M., Cabaccan, J., Raff, H. & Ryzen, E. Elevated late-night salivary cortisol levels in elderly male type 2 diabetic veterans. Clin. Endocrinol. (Oxf.) 63, 642–649 (2005).

    Article  CAS  Google Scholar 

  29. Mullan, K. et al. Is there value in routine screening for Cushing's syndrome in patients with diabetes? J. Clin. Endocrinol. Metab. 95, 2262–2265 (2010).

    Article  CAS  PubMed  Google Scholar 

  30. Murakami, H. et al. The frequency of type 2 diabetic patients who meet the endocrinological screening criteria of subclinical Cushing's disease. Endocr. J. 57, 267–272 (2010).

    Article  PubMed  Google Scholar 

  31. Newsome, S. et al. Cushing's syndrome in a clinic population with diabetes. Intern. Med. J. 38, 178–182 (2008).

    Article  CAS  PubMed  Google Scholar 

  32. Shaker, J. L. & Lukert, B. P. Osteoporosis associated with excess glucocorticoids. Endocrinol. Metab. Clin. North Am. 34, 341–356, viii–ix (2005).

    Article  CAS  PubMed  Google Scholar 

  33. Chiodini, I. et al. Subclinical hypercortisolism among outpatients referred for osteoporosis. Ann. Intern. Med. 147, 541–548 (2007).

    Article  PubMed  Google Scholar 

  34. Magiakou, M. A., Smyrnaki, P. & Chrousos, G. P. Hypertension in Cushing's syndrome. Best Pract. Res. Clin. Endocrinol. Metab. 20, 467–482 (2006).

    Article  CAS  PubMed  Google Scholar 

  35. Omura, M., Saito, J., Yamaguchi, K., Kakuta, Y. & Nishikawa, T. Prospective study on the prevalence of secondary hypertension among hypertensive patients visiting a general outpatient clinic in Japan. Hypertens. Res. 27, 193–202 (2004).

    Article  PubMed  Google Scholar 

  36. Anderson, G. H. Jr, Blakeman, N. & Streeten, D. H. The effect of age on prevalence of secondary forms of hypertension in 4,429 consecutively referred patients. J. Hypertens. 12, 609–615 (1994).

    Article  PubMed  Google Scholar 

  37. Cooper, M. S. & Stewart, P. M. 11β-hydroxysteroid dehydrogenase type 1 and its role in the hypothalamus–pituitary–adrenal axis, metabolic syndrome, and inflammation. J. Clin. Endocrinol. Metab. 94, 4645–4654 (2009).

    Article  CAS  PubMed  Google Scholar 

  38. Kola, B. et al. Changes in adenosine ([0-9])′-monophosphate-activated protein kinase as a mechanism of visceral obesity in Cushing's syndrome. J. Clin. Endocrinol. Metab. 93, 4969–4973 (2008).

    Article  CAS  PubMed  Google Scholar 

  39. Rockall, A. G. et al. Computed tomography assessment of fat distribution in male and female patients with Cushing's syndrome. Eur. J. Endocrinol. 149, 561–567 (2003).

    Article  CAS  PubMed  Google Scholar 

  40. Ness-Abramof, R. et al. Overnight dexamethasone suppression test: a reliable screen for Cushing's syndrome in the obese. Obes. Res. 10, 1217–1221 (2002).

    Article  CAS  PubMed  Google Scholar 

  41. Tiryakioglu, O. et al. Screening for Cushing's syndrome in obese patients. Clinics (Sao Paulo) 65, 9–13 (2010).

    Article  Google Scholar 

  42. Baid, S. K. et al. Specificity of screening tests for Cushing's syndrome in an overweight and obese population. J. Clin. Endocrinol. Metab. 94, 3857–3864 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Setji, T. L. & Brown, A. J. Polycystic ovary syndrome: diagnosis and treatment. Am. J. Med. 120, 128–132 (2007).

    Article  PubMed  Google Scholar 

  44. Kaltsas, G. A. et al. How common are polycystic ovaries and the polycystic ovarian syndrome in women with Cushing's syndrome? Clin. Endocrinol. (Oxf.) 53, 493–500 (2000).

    Article  CAS  Google Scholar 

  45. Fegan, P. G. et al. Cushing's syndrome in women with polycystic ovaries and hyperandrogenism. Nat. Clin. Pract. Endocrinol. Metab. 3, 778–783 (2007).

    Article  CAS  PubMed  Google Scholar 

  46. Glintborg, D. et al. Prevalence of endocrine diseases and abnormal glucose tolerance tests in 340 Caucasian premenopausal women with hirsutism as the referral diagnosis. Fertil. Steril. 82, 1570–1579 (2004).

    Article  PubMed  Google Scholar 

  47. Cawood, T. J., Hunt, P. J., O'Shea, D., Cole, D. & Soule, S. Recommended evaluation of adrenal incidentalomas is costly, has high false-positive rates and confers a risk of fatal cancer that is similar to the risk of the adrenal lesion becoming malignant; time for a rethink? Eur. J. Endocrinol. 161, 513–527 (2009).

    Article  CAS  PubMed  Google Scholar 

  48. Libè, R. et al. Long-term follow-up study of patients with adrenal incidentalomas. Eur. J. Endocrinol. 147, 489–494 (2002).

    Article  PubMed  Google Scholar 

  49. Mantero, F. et al. A survey on adrenal incidentaloma in Italy. Study Group on Adrenal Tumors of the Italian Society of Endocrinology. J. Clin. Endocrinol. Metab. 85, 637–644 (2000).

    CAS  PubMed  Google Scholar 

  50. Reincke, M. et al. Preclinical Cushing's syndrome in adrenal “incidentalomas”: comparison with adrenal Cushing's syndrome. J. Clin. Endocrinol. Metab. 75, 826–832 (1992).

    CAS  PubMed  Google Scholar 

  51. Tabarin, A. et al. Exploration and management of adrenal incidentalomas. French Society of Endocrinology Consensus. Ann. Endocrinol. (Paris) 69, 487–500 (2008).

    Article  CAS  Google Scholar 

  52. Terzolo, M. et al. Subclinical Cushing's syndrome in adrenal incidentalomas. Endocrinol. Metab. Clin. North Am. 34, 423–439 (2005).

    Article  PubMed  Google Scholar 

  53. Grumbach, M. M. et al. Management of the clinically inapparent adrenal mass (“incidentaloma”). Ann. Intern. Med. 138, 424–429 (2003).

    Article  PubMed  Google Scholar 

  54. Sackett, D. L., Haynes, R. B., Guyatt, G. H. & Tugwell, P. Clinical epidemiology. A basic science for clinical medicine. (Little, Brown and Company, Boston, 1991).

  55. Wilson, J. & Jungner, G. Principles and practice of screening for disease. Public Health Papers No. 34. (WHO, Geneva, 1968).

  56. Adriaanse, M. C. & Snoek, F. J. The psychological impact of screening for type 2 diabetes. Diabetes Metab. Res. Rev. 22, 20–25 (2006).

    Article  PubMed  Google Scholar 

  57. Barton, M. B. et al. Decreasing women's anxieties after abnormal mammograms: a controlled trial. J. Natl Cancer Inst. 96, 529–538 (2004).

    Article  PubMed  Google Scholar 

  58. Brett, J., Austoker, J. & Ong, G. Do women who undergo further investigation for breast screening suffer adverse psychological consequences? A multi-centre follow-up study comparing different breast creening result groups five months after their last breast screening appointment. J. Public Health Med. 20, 396–403 (1998).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  60. Gao, S. Combining binomial data using the logistic normal model. J. Stat. Comput. Simul. 74, 293–306 (2004).

    Article  Google Scholar 

  61. Clayton, R. N. Mortality in Cushing's disease. Neuroendocrinology 92 (Suppl. 1), 71–76 (2010).

    Article  CAS  PubMed  Google Scholar 

  62. Hammer, G. D. et al. Transsphenoidal microsurgery for Cushing's disease: initial outcome and long-term results. J. Clin. Endocrinol. Metab. 89, 6348–6357 (2004).

    Article  CAS  PubMed  Google Scholar 

  63. Storr, H. L., Chan, L. F., Grossman, A. B. & Savage, M. O. Paediatric Cushing's syndrome: epidemiology, investigation and therapeutic advances. Trends Endocrinol. Metab. 18, 167–174 (2007).

    Article  CAS  PubMed  Google Scholar 

  64. Pecori Giraldi, F., Moro, M. & Cavagnini, F. Gender-related differences in the presentation and course of Cushing's disease. J. Clin. Endocrinol. Metab. 88, 1554–1558 (2003).

    Article  CAS  PubMed  Google Scholar 

  65. Wajngot, A., Giacca, A., Grill, V., Vranic, M. & Efendic, S. The diabetogenic effects of glucocorticoids are more pronounced in low- than in high-insulin responders. Proc. Natl Acad. Sci. USA 89, 6035–6039 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. van Rossum, E. F. & Lamberts, S. W. Polymorphisms in the glucocorticoid receptor gene and their associations with metabolic parameters and body composition. Recent Prog. Horm. Res. 59, 333–357 (2004).

    Article  CAS  PubMed  Google Scholar 

  67. Devenport, L., Knehans, A., Sundstrom, A. & Thomas, T. Corticosterone's dual metabolic actions. Life Sci. 45, 1389–1396 (1989).

    Article  CAS  PubMed  Google Scholar 

  68. Sonino, N., Boscaro, M., Fallo, F. & Fava, G. A. A clinical index for rating severity in Cushing's syndrome. Psychother. Psychosom. 69, 216–220 (2000).

    Article  CAS  PubMed  Google Scholar 

  69. Sarlis, N. J., Chanock, S. J. & Nieman, L. K. Cortisolemic indices predict severe infections in Cushing's syndrome due to ectopic production of adrenocorticotropin. J. Clin. Endocrinol. Metab. 85, 42–47 (2000).

    CAS  PubMed  Google Scholar 

  70. Sonino, N., Fava, G. A., Raffi, A. R., Boscaro, M. & Fallo, F. Clinical correlates of major depression in Cushing's disease. Psychopathology 31, 302–306 (1998).

    Article  CAS  PubMed  Google Scholar 

  71. Strack, A. M., Horsley, C. J., Sebastian, R. J., Akana, S. F. & Dallman, M. F. Glucocorticoids and insulin: complex interaction on brown adipose tissue. Am. J. Physiol. 268, R1209–R1216 (1995).

    CAS  PubMed  Google Scholar 

  72. Webb, S. M. et al. Evaluation of health-related quality of life in patients with Cushing's syndrome with a new questionnaire. Eur. J. Endocrinol. 158, 623–630 (2008).

    Article  CAS  PubMed  Google Scholar 

  73. Garrapa, G. G., Pantanetti, P., Arnaldi, G., Mantero, F. & Faloia, E. Body composition and metabolic features in women with adrenal incidentaloma or Cushing's syndrome. J. Clin. Endocrinol. Metab. 86, 5301–5306 (2001).

    CAS  PubMed  Google Scholar 

  74. Tauchmanova, L. et al. Patients with subclinical Cushing's syndrome due to adrenal adenoma have increased cardiovascular risk. J. Clin. Endocrinol. Metab. 87, 4872–4878 (2002).

    Article  CAS  PubMed  Google Scholar 

  75. Terzolo, M. et al. Adrenal incidentaloma: a new cause of the metabolic syndrome? J. Clin. Endocrinol. Metab. 87, 998–1003 (2002).

    Article  CAS  PubMed  Google Scholar 

  76. Giordano, R. et al. Long-term morphological, hormonal, and clinical follow-up in a single unit on 118 patients with adrenal incidentalomas. Eur. J. Endocrinol. 162, 779–785 (2010).

    Article  CAS  PubMed  Google Scholar 

  77. Sereg, M. et al. Atherosclerotic risk factors and complications in patients with non-functioning adrenal adenomas treated with or without adrenalectomy: a long-term follow-up study. Eur. J. Endocrinol. 160, 647–655 (2009).

    Article  CAS  PubMed  Google Scholar 

  78. Barzon, L. et al. Risk factors and long-term follow-up of adrenal incidentalomas. J. Clin. Endocrinol. Metab. 84, 520–526 (1999).

    CAS  PubMed  Google Scholar 

  79. Bernini, G. P. et al. Long-term morphological and hormonal follow-up in a single unit on 115 patients with adrenal incidentalomas. Br. J. Cancer 92, 1104–1109 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Fagour, C. et al. Usefulness of adrenal scintigraphy in the follow-up of adrenocortical incidentalomas: a prospective multicenter study. Eur. J. Endocrinol. 160, 257–264 (2009).

    Article  CAS  PubMed  Google Scholar 

  81. Elamin, M. B. et al. Accuracy of diagnostic tests for Cushing's syndrome: a systematic review and metaanalyses. J. Clin. Endocrinol. Metab. 93, 1553–1562 (2008).

    Article  CAS  PubMed  Google Scholar 

  82. Lijmer, J. G. et al. Empirical evidence of design-related bias in studies of diagnostic tests. JAMA 282, 1061–1066 (1999).

    Article  CAS  PubMed  Google Scholar 

  83. Grimes, D. A. & Schulz, K. F. Refining clinical diagnosis with likelihood ratios. Lancet 365, 1500–1505 (2005).

    Article  PubMed  Google Scholar 

  84. Higgins, J. P. T., Thompson, S. G., Deeks, J. J. & Altman, D. G. Measuring inconsistency in meta-analyses. BMJ 327, 557–560 (2003).

    Article  PubMed  PubMed Central  Google Scholar 

  85. Carroll, T., Raff, H. & Findling, J. W. Late-night salivary cortisol for the diagnosis of Cushing's syndrome: a meta-analysis. Endocr. Pract. 15, 335–342 (2009).

    Article  PubMed  Google Scholar 

  86. Yanovski, J. A., Cutler, G. B. Jr, Chrousos, G. P. & Nieman, L. K. Corticotropin-releasing hormone stimulation following low-dose dexamethasone administration. A new test to distinguish Cushing's syndrome from pseudo-Cushing's states. JAMA 269, 2232–2238 (1993).

    Article  CAS  PubMed  Google Scholar 

  87. Oltmanns, K. M. et al. Cortisol correlates with metabolic disturbances in a population study of type 2 diabetic patients. Eur. J. Endocrinol. 154, 325–331 (2006).

    Article  CAS  PubMed  Google Scholar 

  88. Roy, M. S. et al. The ovine corticotropin-releasing hormone-stimulation test in type I diabetic patients and controls: suggestion of mild chronic hypercortisolism. Metabolism 42, 696–700 (1993).

    Article  CAS  PubMed  Google Scholar 

  89. Tsigos, C., Young, R. J. & White, A. Diabetic neuropathy is associated with increased activity of the hypothalamic–pituitary–adrenal axis. J. Clin. Endocrinol. Metab. 76, 554–558 (1993).

    CAS  PubMed  Google Scholar 

  90. Papanicolaou, D. A., Yanovski, J. A., Cutler, G. B. Jr, Chrousos, G. P. & Nieman, L. K. A single midnight serum cortisol measurement distinguishes Cushing's syndrome from pseudo-Cushing's states. J. Clin. Endocrinol. Metab. 83, 1163–1167 (1998).

    CAS  PubMed  Google Scholar 

  91. Putignano, P. et al. Midnight salivary cortisol versus urinary free and midnight serum cortisol as screening tests for Cushing's syndrome. J. Clin. Endocrinol. Metab. 88, 4153–4157 (2003).

    Article  CAS  PubMed  Google Scholar 

  92. Raff, H., Raff, J. L. & Findling, J. W. Late-night salivary cortisol as a screening test for Cushing's syndrome. J. Clin. Endocrinol. Metab. 83, 2681–2686 (1998).

    CAS  PubMed  Google Scholar 

  93. Masserini, B. et al. The limited role of midnight salivary cortisol levels in the diagnosis of subclinical hypercortisolism in patients with adrenal incidentaloma. Eur. J. Endocrinol. 160, 87–92 (2009).

    Article  CAS  PubMed  Google Scholar 

  94. Nunes, M. L. et al. Late-night salivary cortisol for diagnosis of overt and subclinical Cushing's syndrome in hospitalized and ambulatory patients. J. Clin. Endocrinol. Metab. 94, 456–462 (2009).

    Article  CAS  PubMed  Google Scholar 

  95. Streiner, D. L. & Norman, G. R. Health measurement scales. A practical guide to their development and use (Oxford Medical Publications, Oxford, 1995).

  96. Stewart, P. M. Is subclinical Cushing's syndrome an entity or a statistical fallout from diagnostic testing? Consensus surrounding the diagnosis is required before optimal treatment can be defined. J. Clin. Endocrinol. Metab. 95, 2618–2620 (2010).

    Article  CAS  PubMed  Google Scholar 

  97. Vassilatou, E. et al. Hormonal activity of adrenal incidentalomas: results from a long-term follow-up study. Clin. Endocrinol. (Oxf.) 70, 674–679 (2009).

    Article  CAS  Google Scholar 

  98. Eller-Vainicher, C. et al. Post-surgical hypocortisolism after removal of an adrenal incidentaloma: is it predictable by an accurate endocrinological work-up before surgery? Eur. J. Endocrinol. 162, 91–99 (2010).

    Article  PubMed  Google Scholar 

  99. Gross, K. L. & Cidlowski, J. A. Tissue-specific glucocorticoid action: a family affair. Trends Endocrinol. Metab. 19, 331–339 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Chiodini, I. et al. Beneficial metabolic effects of prompt surgical treatment in patients with an adrenal incidentaloma causing biochemical hypercortisolism. J. Clin. Endocrinol. Metab. 95, 2736–2745 (2010).

    Article  CAS  PubMed  Google Scholar 

  101. Guerrieri, M. et al. Primary adrenal hypercortisolism: minimally invasive surgical treatment or medical therapy? A retrospective study with long-term follow-up evaluation. Surg. Endosc. 24, 2542–2546 (2010).

    Article  PubMed  Google Scholar 

  102. Toniato, A. et al. Surgical versus conservative management for subclinical Cushing's syndrome in adrenal incidentalomas: a prospective randomized study. Ann. Surg. 249, 388–391 (2009).

    Article  PubMed  Google Scholar 

  103. Barahona, M. J., Resmini, E., Sucunza, N. & Webb, S. M. Diagnosis of cure in Cushing's syndrome: lessons from long-term follow-up. Front. Horm. Res. 38, 152–157 (2010).

    Article  CAS  PubMed  Google Scholar 

  104. Fagan, T. J. Letter: Nomogram for Bayes theorem. N. Engl. J. Med. 293, 257 (1975).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors are indebted to V. Bouteloup (INSERM U 897, University of Bordeaux 2, France) for statistical analysis.

Author information

Authors and Affiliations

  1. Department of Endocrinology, Université Bordeaux 2, Centre Hospitalier Universitaire de Bordeaux, 146 Rue Léo Saignat, F–33076, Bordeaux CEDEX, France

    Antoine Tabarin

  2. Clinical Epidemiology Unit (USMR) & CIC-EC7, INSERM, Université Bordeaux 2, Centre Hospitalier Universitaire de Bordeaux, 146 Rue Léo Saignat, F–33076, Bordeaux CEDEX, France

    Paul Perez

Authors
  1. Antoine Tabarin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul Perez
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Both authors researched the data for the article, provided a substantial contribution to discussions of the content, contributed equally to writing the article and reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Antoine Tabarin.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tabarin, A., Perez, P. Pros and cons of screening for occult Cushing syndrome. Nat Rev Endocrinol 7, 445–455 (2011). https://doi.org/10.1038/nrendo.2011.51

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrendo.2011.51

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing