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  • Review Article
  • Published:

Endocrine incidentalomas—challenges imposed by incidentally discovered lesions

Nature Reviews Endocrinology volume 7, pages 668–680 (2011)Cite this article

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Abstract

Endocrine glands are among the organs that most frequently harbor incidentally discovered lesions. Pituitary, thyroid, parathyroid and adrenal incidentalomas are increasingly encountered in everyday practice with variable clinical implications. The major concerns are the risks of malignancy and hormonal hypersecretion mostly in the form of subclinically functioning tumors. Pituitary incidentalomas are usually microadenomas and most of the time clinically unimportant; however, incidentally discovered larger lesions require a more careful diagnostic and therapeutic approach. Thyroid incidentalomas are extremely common; exclusion of malignancy is the main concern in this clinical setting. Although parathyroid adenomas are not uncommon, these lesions are frequently missed owing to their small size and due to clinical unawareness. Adrenal incidentalomas carry a small but finite risk of malignancy. An intriguing challenge regarding incidentally discovered adrenal lesions is that a substantial proportion is associated with hormonal alterations, mainly in the form of subtle cortisol excess. Although still largely controversial, evidence is emerging that so-called subclinical hypercortisolism may not be completely harmless. The best biochemical criterion of subtle cortisol excess remains elusive. Surgical intervention in selected cases results in some beneficial effects, but more data are required in order to routinely support surgery in this clinical setting. This Review provides a brief overview of the prevalence, clinical effect and management of endocrine incidentalomas with a focus on data regarding the diagnostic and therapeutic challenges imposed by incidentally discovered adrenal lesions.

Key Points

  • Most pituitary microincidentalomas are clinically unimportant, whereas macroincidentalomas require a more cautious approach

  • Thyroid incidentalomas carry a substantial risk of malignancy; fine-needle aspiration is the procedure of choice for the management of a substantial number of these patients

  • Parathyroid incidentalomas are not frequently seen

  • In patients with adrenal incidentalomas, hormonal assessment for exclusion of cortisol, aldosterone and catecholamine excess is mandatory

  • Subtle autonomous cortisol secretion is the most common abnormality, and increasing evidence shows that subclinical hypercortisolism is not completely harmless

  • Although surgical removal of cortisol-secreting, incidentally detected adrenal lesions may have some beneficial effects, more studies are required in order to routinely recommend surgery in this clinical setting

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Figure 1: Age-dependent prevalence of adrenal incidentalomas in five autopsy studies.
Figure 2: The post-dexamethasone cortisol level provides a measure of autonomous cortisol secretion.

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References

  1. Black, W. C. & Welch, H. G. Advances in diagnostic imaging and overestimations of disease prevalence and the benefits of therapy. N. Engl. J. Med. 328, 1237–1243 (1993).

    Article  CAS  PubMed  Google Scholar 

  2. Bailey, R. H. & Aron, D. C. The diagnostic dilemma of incidentalomas. Working through uncertainty. Endocrinol. Metab. Clin. North Am. 29, 91–105 (2000).

    Article  CAS  PubMed  Google Scholar 

  3. Chidiac, R. M. & Aron, D. C. Incidentalomas. A disease of modern technology. Endocrinol. Metab. Clin. North Am. 26, 233–253 (1997).

    Article  CAS  PubMed  Google Scholar 

  4. Turner, H. E., Moore, N. R., Byrne, J. V. & Wass, J. A. H. Pituitary, adrenal and thyroid incidentalomas. Endocr. Relat. Cancer 5, 131–150 (1998).

    Article  Google Scholar 

  5. Aron, D. C. & Howlett, T. A. Pituitary incidentalomas. Endocrinol. Metab. Clin. North Am. 29, 205–221 (2000).

    Article  CAS  PubMed  Google Scholar 

  6. Koenig, K. & Kleerekoper, M. How common are functional incidentalomas of the parathyroid gland? Nat. Clin. Pract. Endocrinol. Metab. 2, 316–317 (2006).

    Article  PubMed  Google Scholar 

  7. Griffing, G. T. A-I-D-S: the new endocrine epidemic. J. Clin. Endocrinol. Metab. 79, 1530–1531 (1994).

    CAS  PubMed  Google Scholar 

  8. Dean, D. S. & Gharib, H. Epidemiology of thyroid nodules. Best Pract. Res. Clin. Endocrinol. Metab. 22, 901–911 (2008).

    Article  PubMed  Google Scholar 

  9. Ezzat, S. et al. The prevalence of pituitary adenomas: a systematic review. Cancer 101, 613–619 (2004).

    Article  PubMed  Google Scholar 

  10. Ezzat, S., Sarti, D. A., Cain, D. R. & Braunstein, G. D. Thyroid incidentalomas. Prevalence by palpation and ultrasonography. Arch. Intern. Med. 154, 1838–1840 (1994).

    Article  CAS  PubMed  Google Scholar 

  11. Young, W. F. Jr. Management approaches to adrenal incidentalomas. A view from Rochester, Minnesota. Endocrinol. Metab. Clin. North Am. 29, 159–185 (2000).

    Article  PubMed  Google Scholar 

  12. Molitch, M. E. Pituitary tumours: pituitary incidentalomas. Best Pract. Res. Clin. Endocrinol. Metab. 23, 667–675 (2009).

    Article  CAS  PubMed  Google Scholar 

  13. Chambers, E. F., Turski, P. A., LaMasters, D. & Newton, T. H. Regions of low density in the contrast-enhanced pituitary gland: normal and pathologic processes. Radiology 144, 109–113 (1982).

    Article  CAS  PubMed  Google Scholar 

  14. Krikorian, A. & Aron, D. Evaluation and management of pituitary incidentalomas—revisiting an acquaintance. Nat. Clin. Pract. Endocrinol. Metab. 2, 138–145 (2006).

    Article  CAS  PubMed  Google Scholar 

  15. Connor, S. E. & Penney, C. C. MRI in the differential diagnosis of a sellar mass. Clin. Radiol. 58, 20–31 (2003).

    Article  CAS  PubMed  Google Scholar 

  16. Nammour, G. M., Ybarra, J., Naheedy, M. H., Romeo, J. H. & Aron, D. C. Incidental pituitary macroadenoma: a population-based study. Am. J. Med. Sci. 314, 287–291 (1997).

    CAS  PubMed  Google Scholar 

  17. Yue, N. C. et al. Clinically serious abnormalities found incidentally at MR imaging of the brain: data from the Cardiovascular Health Study. Radiology 202, 41–46 (1997).

    Article  CAS  PubMed  Google Scholar 

  18. Chacko, A. G. & Chandy, M. J. Incidental pituitary macroadenomas. Br. J. Neurosurg. 6, 233–236 (1992).

    Article  CAS  PubMed  Google Scholar 

  19. Buurman, H. & Saeger, W. Subclinical adenomas in postmortem pituitaries: classification and correlations to clinical data. Eur. J. Endocrinol. 154, 753–758 (2006).

    Article  CAS  PubMed  Google Scholar 

  20. Kontogeorgos, G., Kovacs, K., Horvath, E. & Scheithauer, B. W. Multiple adenomas of the human pituitary. A retrospective autopsy study with clinical implications. J. Neurosurg. 74, 243–247 (1991).

    Article  CAS  PubMed  Google Scholar 

  21. Chong, B. W., Kucharczyk, W., Singer, W. & George, S. Pituitary gland MR: a comparative study of healthy volunteers and patients with microadenomas. AJNR Am. J. Neuroradiol. 15, 675–679 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Hall, W. A., Luciano, M. G., Doppman, J. L., Patronas, N. J. & Oldfield, E. H. Pituitary magnetic resonance imaging in normal human volunteers: occult adenomas in the general population. Ann. Intern. Med. 120, 817–820 (1994).

    Article  CAS  PubMed  Google Scholar 

  23. Jeong, S. Y. et al. Incidental pituitary uptake on whole-body 18F-FDG PET/CT: a multicentre study. Eur. J. Nucl. Med. Mol. Imaging 37, 2334–2343 (2010).

    Article  PubMed  Google Scholar 

  24. Molitch, M. E. Clinical review 65. Evaluation and treatment of the patient with a pituitary incidentaloma. J. Clin. Endocrinol. Metab. 80, 3–6 (1995).

    CAS  PubMed  Google Scholar 

  25. Feldkamp, J. et al. Incidentally discovered pituitary lesions: high frequency of macroadenomas and hormone-secreting adenomas—results of a prospective study. Clin. Endocrinol. (Oxf.) 51, 109–113 (1999).

    Article  CAS  Google Scholar 

  26. Oyama, K., Sanno, N., Tahara, S. & Teramoto, A. Management of pituitary incidentalomas: according to a survey of pituitary incidentalomas in Japan. Semin. Ultrasound CT MR 26, 47–50 (2005).

    Article  PubMed  Google Scholar 

  27. Daems, T. et al. Modification of hormonal secretion in clinically silent pituitary adenomas. Pituitary 12, 80–86 (2009).

    Article  CAS  PubMed  Google Scholar 

  28. Fainstein Day, P. et al. Retrospective multicentric study of pituitary incidentalomas. Pituitary 7, 145–148 (2004).

    Article  Google Scholar 

  29. Reincke, M., Allolio, B., Saeger, W., Menzel, J. & Winkelmann, W. The 'incidentaloma' of the pituitary gland. Is neurosurgery required? JAMA 263, 2772–2776 (1990).

    Article  CAS  PubMed  Google Scholar 

  30. King, J. T. Jr, Justice, A. C. & Aron, D. C. Management of incidental pituitary microadenomas: a cost-effectiveness analysis. J. Clin. Endocrinol. Metab. 82, 3625–3632 (1997).

    CAS  PubMed  Google Scholar 

  31. Donovan, L. E. & Corenblum, B. The natural history of the pituitary incidentaloma. Arch. Intern. Med. 155, 181–183 (1995).

    Article  CAS  PubMed  Google Scholar 

  32. Yuen, K. C. et al. Prevalence of GH and other anterior pituitary hormone deficiencies in adults with nonsecreting pituitary microadenomas and normal serum IGF-1 levels. Clin. Endocrinol. (Oxf.) 69, 292–298 (2008).

    Article  CAS  Google Scholar 

  33. Arita, K. et al. Natural course of incidentally found nonfunctioning pituitary adenoma, with special reference to pituitary apoplexy during follow-up examination. J. Neurosurg. 104, 884–891 (2006).

    Article  PubMed  Google Scholar 

  34. Karavitaki, N. et al. What is the natural history of nonoperated nonfunctioning pituitary adenomas? Clin. Endocrinol. (Oxf.) 67, 938–943 (2007).

    Article  CAS  Google Scholar 

  35. Dekkers, O. M. et al. The natural course of non-functioning pituitary macroadenomas. Eur. J. Endocrinol. 156, 217–224 (2007).

    Article  CAS  PubMed  Google Scholar 

  36. Kay, J. & Czirják, L. Gadolinium and systemic fibrosis: guilt by association. Ann. Rheum. Dis. 69, 1895–1897 (2010).

    Article  PubMed  Google Scholar 

  37. Molitch, M. E. Nonfunctioning pituitary tumors and pituitary incidentalomas. Endocrinol. Metab. Clin. North. Am. 37, 151–171, xi (2008).

    Article  PubMed  Google Scholar 

  38. Tomimori, E., Pedrinola, F., Cavaliere, H., Knobel, M. & Medeiros-Neto, G. Prevalence of incidental thyroid disease in a relatively low iodine intake area. Thyroid 5, 273–276 (1995).

    Article  CAS  PubMed  Google Scholar 

  39. Mortensen, J. D., Woolner, L. B. & Bennett, W. A. Gross and microscopic findings in clinically normal thyroid glands. J. Clin. Endocrinol. Metab. 15, 1270–1280 (1955).

    Article  CAS  PubMed  Google Scholar 

  40. Wang, C. & Crapo, L. M. The epidemiology of thyroid disease and implications for screening. Endocrinol. Metab. Clin. North Am. 26, 189–218 (1997).

    Article  CAS  PubMed  Google Scholar 

  41. Reiners, C. et al. Prevalence of thyroid disorders in the working population of Germany: ultrasonography screening in 96,278 unselected employees. Thyroid 14, 926–932 (2004).

    Article  PubMed  Google Scholar 

  42. Chu, Q. D. et al. Positron emission tomography (PET) positive thyroid incidentaloma: the risk of malignancy observed in a tertiary referral center. Am. Surg. 72, 272–275 (2006).

    PubMed  Google Scholar 

  43. Are, C. et al. FDG-PET detected thyroid incidentalomas: need for further investigation? Ann. Surg. Oncol. 14, 239–247 (2007).

    Article  PubMed  Google Scholar 

  44. Kang, K. W. et al. Prevalence and risk of cancer of focal thyroid incidentaloma identified by 18F-fluorodeoxyglucose positron emission tomography for metastasis evaluation and cancer screening in healthy subjects. J. Clin. Endocrinol. Metab. 88, 4100–4104 (2003).

    Article  CAS  PubMed  Google Scholar 

  45. Minamimoto, R. et al. Performance profile of FDG-PET and PET/CT for cancer screening on the basis of a Japanese Nationwide Survey. Ann. Nucl. Med. 21, 481–498 (2007).

    Article  PubMed  Google Scholar 

  46. Van den Bruel, A. et al. Clinical relevance of thyroid fluorodeoxyglucose-whole body positron emission tomography incidentaloma. J. Clin. Endocrinol. Metab. 87, 1517–1520 (2002).

    Article  CAS  PubMed  Google Scholar 

  47. Kim, T. Y. et al. 18F-fluorodeoxyglucose uptake in thyroid from positron emission tomogram (PET) for evaluation in cancer patients: high prevalence of malignancy in thyroid PET incidentaloma. Laryngoscope 115, 1074–1078 (2005).

    Article  PubMed  Google Scholar 

  48. Gharib, H. & Papini, E. Thyroid nodules: clinical importance, assessment, and treatment. Endocrinol. Metab. Clin. North Am. 36, 707–735 (2007).

    Article  CAS  PubMed  Google Scholar 

  49. Kang, H. W. et al. Prevalence, clinical and ultrasonographic characteristics of thyroid incidentalomas. Thyroid 14, 29–33 (2004).

    Article  PubMed  Google Scholar 

  50. Davies, L. & Welch, H. G. Increasing incidence of thyroid cancer in the United States, 1973–2002. JAMA 295, 2164–2167 (2006).

    Article  CAS  PubMed  Google Scholar 

  51. Bernet, V. Approach to the patient with incidental papillary microcarcinoma. J. Clin. Endocrinol. Metab. 95, 3586–3592 (2010).

    Article  CAS  PubMed  Google Scholar 

  52. Hay, I. D. et al. Papillary thyroid microcarcinoma: a study of 900 cases observed in a 60-year period. Surgery 144, 980–987 (2008).

    Article  PubMed  Google Scholar 

  53. Gharib, H. et al. American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association medical guidelines for clinical practice for the diagnosis and management of thyroid nodules. Endocr. Pract. 16 (Suppl. 1), 1–43 (2010).

    Article  PubMed  Google Scholar 

  54. Cosgrove, D. Future prospects for SonoVue and CPS. Eur. Radiol. 14 (Suppl. 8), P116–P124 (2004).

    PubMed  Google Scholar 

  55. Asteria, C. et al. US-elastography in the differential diagnosis of benign and malignant thyroid nodules. Thyroid 18, 523–531 (2008).

    Article  PubMed  Google Scholar 

  56. Cooper, D. S. et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 19, 1167–1214 (2009).

    Article  PubMed  Google Scholar 

  57. Kim, S. W. et al. BRAFV600E mutation analysis in fine-needle aspiration cytology specimens for evaluation of thyroid nodule: a large series in a BRAFV600E-prevalent population. J. Clin. Endocrinol. Metab. 95, 3693–3700 (2010).

    Article  CAS  PubMed  Google Scholar 

  58. Boelaert, K. The association between serum TSH concentration and thyroid cancer. Endocr. Relat. Cancer 16, 1065–1072 (2009).

    Article  CAS  PubMed  Google Scholar 

  59. Boelaert, K. et al. Serum thyrotropin concentration as a novel predictor of malignancy in thyroid nodules investigated by fine-needle aspiration. J. Clin. Endocrinol. Metab. 91, 4295–4301 (2006).

    Article  CAS  PubMed  Google Scholar 

  60. Fiore, E. et al. Lower levels of TSH are associated with a lower risk of papillary thyroid cancer in patients with thyroid nodular disease: thyroid autonomy may play a protective role. Endocr. Relat. Cancer 16, 1251–1260 (2009).

    Article  CAS  PubMed  Google Scholar 

  61. Valle, L. A. & Kloos, R. T. The prevalence of occult medullary thyroid carcinoma at autopsy. J. Clin. Endocrinol. Metab. 96, E109–E113 (2011).

    Article  CAS  PubMed  Google Scholar 

  62. Wilhelm, S. M., Robinson, A. V., Krishnamurthi, S. S. & Reynolds, H. L. Evaluation and management of incidental thyroid nodules in patients with another primary malignancy. Surgery 142, 581–586 (2007).

    Article  PubMed  Google Scholar 

  63. Ohba, K. et al. High incidence of thyroid cancer in focal thyroid incidentaloma detected by 18F-fluorodexyglucose positron emission tomography in relatively young healthy subjects: results of 3-year follow-up. Endocr. J. 57, 395–401 (2010).

    Article  CAS  PubMed  Google Scholar 

  64. Shroff, P., McGrath, G. A. & Pezzi, C. M. Incidentalomas of the parathyroid gland: multiple presentations, variable function, and review of the literature. Endocr. Pract. 11, 363–369 (2005).

    Article  PubMed  Google Scholar 

  65. Katz, A. D. & Kong, L. B. Incidental preclinical hyperparathyroidism identified during thyroid operations. Am. Surg. 58, 747–749 (1992).

    CAS  PubMed  Google Scholar 

  66. Kwak, J. Y. et al. Parathyroid incidentalomas detected on routine ultrasound-directed fine-needle aspiration biopsy in patients referred for thyroid nodules and the role of parathyroid hormone analysis in the samples. Thyroid 19, 743–748 (2009).

    CAS  PubMed  Google Scholar 

  67. Akerström, G. et al. Histologic parathyroid abnormalities in an autopsy series. Hum. Pathol. 17, 520–527 (1986).

    Article  PubMed  Google Scholar 

  68. Yu, N., Donnan, P. T. & Leese, G. P. A record linkage study of outcomes in patients with mild primary hyperparathyroidism: The Parathyroid Epidemiology and Audit Research Study (PEARS). Clin. Endocrinol. (Oxf.) doi:10.1111/j.1365–2265.2010.03958.x.

  69. Bilezikian, J. P., Khan, A. A. & Potts, J. T. Jr. Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the third international workshop. J. Clin. Endocrinol. Metab. 94, 335–339 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Barzon, L., Sonino, N., Fallo, F., Palu, G. & Boscaro, M. Prevalence and natural history of adrenal incidentalomas. Eur. J. Endocrinol. 149, 273–285 (2003).

    Article  CAS  PubMed  Google Scholar 

  71. Kloos, R. T., Gross, M. D., Francis, I. R., Korobkin, M. & Shapiro, B. Incidentally discovered adrenal masses. Endocr. Rev. 16, 460–484 (1995).

    CAS  PubMed  Google Scholar 

  72. Spain, D. M. & Weinsaft, P. Solitary adrenal cortical adenoma in elderly female; frequency. Arch. Pathol. 78, 231–233 (1964).

    CAS  PubMed  Google Scholar 

  73. Dévényi, I. Possibility of normokalaemic primary aldosteronism as reflected in the frequency of adrenal cortical adenomas. J. Clin. Pathol. 20, 49–51 (1967).

    Article  PubMed  PubMed Central  Google Scholar 

  74. Dobbie, J. W. Adrenocortical nodular hyperplasia: the ageing adrenal. J. Pathol. 99, 1–18 (1969).

    Article  CAS  PubMed  Google Scholar 

  75. Bovio, S. et al. Prevalence of adrenal incidentaloma in a contemporary computerized tomography series. J. Endocrinol. Invest. 29, 298–302 (2006).

    Article  CAS  PubMed  Google Scholar 

  76. Bülow, B. et al. Adrenal incidentaloma—follow-up results from a Swedish prospective study. Eur. J. Endocrinol. 154, 419–423 (2006).

    Article  CAS  PubMed  Google Scholar 

  77. Kasperlik-Zeluska, A. A. et al. Incidentally discovered adrenal mass (incidentaloma): investigation and management of 208 patients. Clin. Endocrinol. (Oxf.) 46, 29–37 (1997).

    Article  CAS  Google Scholar 

  78. Barzon, L. et al. Incidentally discovered adrenal tumors: endocrine and scintigraphic correlates. J. Clin. Endocrinol. Metab. 83, 55–62 (1998).

    CAS  PubMed  Google Scholar 

  79. Caplan, R. H., Strutt, P. J. & Wickus, G. G. Subclinical hormone secretion by incidentally discovered adrenal masses. Arch. Surg. 129, 291–296 (1994).

    Article  CAS  PubMed  Google Scholar 

  80. Herrera, M. F., Grant, C. S., van Heerden, J. A., Sheedy, P. F. & Ilstrup, D. M. Incidentally discovered adrenal tumors: an institutional perspective. Surgery 110, 1014–1021 (1991).

    CAS  PubMed  Google Scholar 

  81. 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 

  82. Buurman, H. & Saeger, W. Abnormalities in incidentally removed adrenal glands. Endocr. Pathol. 17, 277–282 (2006).

    Article  CAS  PubMed  Google Scholar 

  83. Funder, J. W. et al. Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 93, 3266–3281 (2008).

    Article  CAS  PubMed  Google Scholar 

  84. 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 

  85. Bernini, G. P. et al. Frequency of pheochromocytoma in adrenal incidentalomas and utility of the glucagon test for the diagnosis. J. Endocrinol. Invest. 20, 65–71 (1997).

    Article  CAS  PubMed  Google Scholar 

  86. Tsagarakis, S., Vassiliadi, D. & Thalassinos, N. Endogenous subclinical hypercortisolism: Diagnostic uncertainties and clinical implications. J. Endocrinol. Invest. 29, 471–482 (2006).

    Article  CAS  PubMed  Google Scholar 

  87. 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 

  88. Nieman, L. K. Approach to the patient with an adrenal incidentaloma. J. Clin. Endocrinol. Metab. 95, 4106–4113 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Pantalone, K. M. et al. Change in adrenal mass size as a predictor of a malignant tumor. Endocr. Pract. 16, 577–587 (2010).

    Article  PubMed  Google Scholar 

  90. Johnson, P. T., Horton, K. M. & Fishman, E. K. Adrenal mass imaging with multidetector CT: pathologic conditions, pearls, and pitfalls. Radiographics 29, 1333–1351 (2009).

    Article  PubMed  Google Scholar 

  91. Ilias, I., Sahdev, A., Reznek, R. H., Grossman, A. B. & Pacak, K. The optimal imaging of adrenal tumours: a comparison of different methods. Endocr. Relat. Cancer 14, 587–599 (2007).

    Article  PubMed  Google Scholar 

  92. Yun, M. et al. 18F-FDG PET in characterizing adrenal lesions detected on CT or MRI. J. Nucl. Med. 42, 1795–1799 (2001).

    CAS  PubMed  Google Scholar 

  93. Kopetschke, R. et al. Frequent incidental discovery of phaeochromocytoma: data from a German cohort of 201 phaeochromocytoma. Eur. J. Endocrinol. 161, 355–361 (2009).

    Article  CAS  PubMed  Google Scholar 

  94. Pacak, K. et al. Pheochromocytoma: recommendations for clinical practice from the First International Symposium. October 2005. Nat. Clin. Pract. Endocrinol. Metab. 3, 92–102 (2007).

    Article  PubMed  Google Scholar 

  95. Vierhapper, H. Determination of the aldosterone/renin ratio in 269 patients with adrenal incidentaloma. Exp. Clin. Endocrinol. Diabetes 115, 518–521 (2007).

    Article  CAS  PubMed  Google Scholar 

  96. 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 

  97. Tsagarakis, S. et al. Elevated post-dexamethasone suppression cortisol concentrations correlate with hormonal alterations of the hypothalamo-pituitary adrenal axis in patients with adrenal incidentalomas. Clin. Endocrinol. (Oxf.) 49, 165–171 (1998).

    Article  CAS  Google Scholar 

  98. Terzolo, M. et al. Midnight serum cortisol as a marker of increased cardiovascular risk in patients with a clinically inapparent adrenal adenoma. Eur. J. Endocrinol. 153, 307–315 (2005).

    Article  CAS  PubMed  Google Scholar 

  99. Fernández-Real, J. M., Engel, W. R., Simó, R., Salinas, I. & Webb, S. M. Study of glucose tolerance in consecutive patients harbouring incidental adrenal tumours. Study Group of Incidental Adrenal Adenoma. Clin. Endocrinol. (Oxf.) 49, 53–61 (1998).

    Article  Google Scholar 

  100. Young, W. F. Jr. Clinical practice. The incidentally discovered adrenal mass. N. Engl. J. Med. 356, 601–610 (2007).

    Article  CAS  PubMed  Google Scholar 

  101. Zeiger, M. A. et al. American Association of Clinical Endocrinologists and American Association of Endocrine Surgeons Medical Guidelines for the Management of Adrenal Incidentalomas: executive summary of recommendations. Endocr. Pract. 15, 450–453 (2009).

    Article  PubMed  Google Scholar 

  102. 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 

  103. 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 

  104. Bardet, S. et al. 131I-6 beta-iodomethylnorcholesterol scintigraphy: an assessment of its role in the investigation of adrenocortical incidentalomas. Clin. Endocrinol. (Oxf.) 44, 587–596 (1996).

    Article  CAS  Google Scholar 

  105. Radiation dose to patients from radiopharmaceuticals (addendum 2 to ICRP publication 53). Ann. ICRP 28, 1–126 (1998).

  106. 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 

  107. 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 

  108. Rossi, R. et al. Subclinical Cushing's syndrome in patients with adrenal incidentaloma: clinical and biochemical features. J. Clin. Endocrinol. Metab. 85, 1440–1448 (2000).

    CAS  PubMed  Google Scholar 

  109. Tauchmanovà, 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 

  110. Bernini, G. et al. Anthropometric, haemodynamic, humoral and hormonal evaluation in patients with incidental adrenocortical adenomas before and after surgery. Eur. J. Endocrinol. 148, 213–219 (2003).

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  112. Tsuiki, M., Tanabe, A., Takagi, S., Naruse, M. & Takano, K. Cardiovascular risks and their long-term clinical outcome in patients with subclinical Cushing's syndrome. Endocr. J. 55, 737–745 (2008).

    Article  CAS  PubMed  Google Scholar 

  113. 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 

  114. Kasperlik-Zaluska, A. A. et al. Incidentally discovered adrenal tumors: a lesson from observation of 1,444 patients. Horm. Metab. Res. 40, 338–341 (2008).

    Article  CAS  PubMed  Google Scholar 

  115. 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 

  116. Emral, R. et al. Prevalence of subclinical Cushing's syndrome in 70 patients with adrenal incidentaloma: clinical, biochemical and surgical outcomes. Endocr. J. 50, 399–408 (2003).

    Article  PubMed  Google Scholar 

  117. Comlekci, A. et al. Adrenal incidentaloma, clinical, metabolic, follow-up aspects: single centre experience. Endocrine 37, 40–46 (2010).

    Article  CAS  PubMed  Google Scholar 

  118. Morelli, V. et al. Subclinical hypercortisolism: correlation between biochemical diagnostic criteria and clinical aspects. Clin. Endocrinol. (Oxf.) 73, 161–166 (2010).

    CAS  Google Scholar 

  119. 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 

  120. Fernández-Real, J. M., Gonzalbez, J. & Ricart, W. Metabolic abnormalities in patients with adrenal incidentaloma. J. Clin. Endocrinol. Metab. 86, 950–952 (2001).

    Article  PubMed  Google Scholar 

  121. Tauchmanovà, L. et al. Bone loss determined by quantitative ultrasonometry correlates inversely with disease activity in patients with endogenous glucocorticoid excess due to adrenal mass. Eur. J. Endocrinol. 145, 241–247 (2001).

    Article  PubMed  Google Scholar 

  122. Chiodini, I. et al. Spinal volumetric bone mineral density and vertebral fractures in female patients with adrenal incidentalomas: the effects of subclinical hypercortisolism and gonadal status. J. Clin. Endocrinol. Metab. 89, 2237–2241 (2004).

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  124. Chiodini, I. et al. Bone mineral density, prevalence of vertebral fractures, and bone quality in patients with adrenal incidentalomas with and without subclinical hypercortisolism: an Italian multicenter study. J. Clin. Endocrinol. Metab. 94, 3207–3214 (2009).

    Article  CAS  PubMed  Google Scholar 

  125. Chiodini, I. et al. Bone involvement in eugonadal male patients with adrenal incidentaloma and subclinical hypercortisolism. J. Clin. Endocrinol. Metab. 87, 5491–5494 (2002).

    Article  CAS  PubMed  Google Scholar 

  126. Chiodini, I. et al. Eugonadal male patients with adrenal incidentalomas and subclinical hypercortisolism have increased rate of vertebral fractures. Clin. Endocrinol. (Oxf.) 70, 208–213 (2009).

    Article  CAS  Google Scholar 

  127. Osella, G. et al. Serum markers of bone and collagen turnover in patients with Cushing's syndrome and in subjects with adrenal incidentalomas. J. Clin. Endocrinol. Metab. 82, 3303–3307 (1997).

    CAS  PubMed  Google Scholar 

  128. Bardet, S. et al. Bone mineral density and biological markers of bone repair in patients with adrenal incidentaloma: effect of subclinical hypercortisolism [French]. Rev. Med. Interne 23, 508–517 (2002).

    Article  CAS  PubMed  Google Scholar 

  129. Hadjidakis, D. et al. Does subclinical hypercortisolism adversely affect the bone mineral density of patients with adrenal incidentalomas? Clin. Endocrinol. (Oxf.) 58, 72–77 (2003).

    Article  CAS  Google Scholar 

  130. Torlontano, M. et al. Altered bone mass and turnover in female patients with adrenal incidentaloma: the effect of subclinical hypercortisolism. J. Clin. Endocrinol. Metab. 84, 2381–2385 (1999).

    Article  CAS  PubMed  Google Scholar 

  131. 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 

  132. Erbil, Y. et al. Cardiovascular risk in patients with nonfunctional adrenal incidentaloma: myth or reality? World J. Surg. 33, 2099–2105 (2009).

    Article  PubMed  Google Scholar 

  133. Yilmaz, H., Tütüncü, N. B. & Sahin, M. Two-year follow-up of thirty-two non-functional benign adrenal incidentalomas. J. Endocrinol. Invest. 32, 913–916 (2009).

    Article  CAS  PubMed  Google Scholar 

  134. Erbil, Y. et al. Evaluation of the cardiovascular risk in patients with subclinical Cushing syndrome before and after surgery. World J. Surg. 30, 1665–1671 (2006).

    Article  PubMed  Google Scholar 

  135. Vasiliadi, D. et al. Glucocortidoid sensitivity assessed in peripheral blood cells do not correlate with the feedback sensitivity of the hypothalamo-pituitary adrenal axis. Hormones (Athens) 1, 233–238 (2002).

    Article  Google Scholar 

  136. Huizenga, N. A. et al. Interperson variability but intraperson stability of baseline plasma cortisol concentrations, and its relation to feedback sensitivity of the hypothalamo-pituitary-adrenal axis to a low dose of dexamethasone in elderly individuals. J. Clin. Endocrinol. Metab. 83, 47–54 (1998).

    CAS  PubMed  Google Scholar 

  137. Mitchell, I. C. et al. “Subclinical Cushing's syndrome” is not subclinical: improvement after adrenalectomy in 9 patients. Surgery 142, 900–905 (2007).

    Article  PubMed  Google Scholar 

  138. 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 

  139. Midorikawa, S., Sanada, H., Hashimoto, S., Suzuki, T. & Watanabe, T. The improvement of insulin resistance in patients with adrenal incidentaloma by surgical resection. Clin. Endocrinol. (Oxf.) 54, 797–804 (2001).

    Article  CAS  Google Scholar 

  140. 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 

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Acknowledgements

C. P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape, LLC-accredited continuing medical education activity associated with this article.

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  1. 2nd Department of Internal Medicine, Endocrine Unit, “Attikon” University Hospital, 1 Rimini Street, Athens, 12462, Greece

    Dimitra A. Vassiliadi

  2. Department of Endocrinology, Diabetes and Metabolism, Evangelismos Hospital, 45–47 Ypsilantou Street, Athens, 10676, Greece

    Stylianos Tsagarakis

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Vassiliadi, D., Tsagarakis, S. Endocrine incidentalomas—challenges imposed by incidentally discovered lesions. Nat Rev Endocrinol 7, 668–680 (2011). https://doi.org/10.1038/nrendo.2011.92

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