Skip to main content

Advertisement

SpringerLink
Log in

Surgical Considerations in Subclinical Cushing’s Syndrome. When is it Time to Operate?

  • Original Article
  • Published:
Hellenic Journal of Surgery

Abstract

Subclinical Cushing’s syndrome (SCS) is a disorder characterized by autonomous cortisol secretion and the presence of an adrenal incidentaloma, in the absence of clinical features of Cushing’s syndrome. SCS is of special interest because it has been associated with several disorders, such as atherosclerosis and arterial hypertension. Despite decades of research, SCS continues to generate controversy regarding its diagnosis and subsequent management. Several issues remain to be resolved. A universal agreement on the hormonal diagnosis of the syndrome remains elusive. Autonomous cortisol secretion has been ill defined and several definitions have been offered. The heterogeneity in diagnostic criteria creates heterogeneity in studies evaluating optimal management. Minimally invasive adrenalectomy has been documented to ameliorate SCS associated disorders in certain patients. Identifying these patients should be the focus of future research on the subject. In this review we summarize current concepts regarding SCS and indications for its surgical management.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Brown JM, Robinson-Cohen C, Luque-Fernandez MA, et al. The spectrum of subclinical primary aldosteronism and incident hypertension: A cohort study. Ann Intern Med 2017;167:630–41.

    Article  PubMed  Google Scholar 

  2. Mannelli M, Lenders JW, Pacak K, et al. Subclinical phaeochromocytoma. Best Pract Res Clin Endocrinol Metab 2012;26:507–15.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Reincke M. Subclinical Cushing's syndrome. Endocrinol Metab Clin North Am 2000;29:43–56.

    Article  CAS  PubMed  Google Scholar 

  4. Torrejon S, Webb SM, Rodriguez-Espinosa J, et al. Longlasting subclinical Addison's disease. Exp Clin Endocrinol Diabetes 2007;115:530–2.

    Article  CAS  PubMed  Google Scholar 

  5. Conzo G, Pasquali D, Colantuoni V, et al. Current concepts of pheochromocytoma. Int J Surg 2014;12:469–74.

    Article  PubMed  Google Scholar 

  6. Nixon AM, Provatopoulou X, Kalogera E, et al. Circulating thyroid cancer biomarkers: Current limitations and future prospects. Clin Endocrinol (Oxf) 2017;87:117–26.

    Article  CAS  Google Scholar 

  7. Beierwaltes WH, Sturman MF, Ryo U, et al. Imaging functional nodules of the adrenal glands with 131-I-19-iodocholesterol. J Nucl Med 1974;15:246–51.

    CAS  PubMed  Google Scholar 

  8. Charbonnel B, Chatal JF, Ozanne P. Does the corticoadrenal adenoma with "pre-Cushing's syndrome" exist? J Nucl Med 1981;22:1059–61.

    CAS  PubMed  Google Scholar 

  9. Debono M, Bradburn M, Bull M, et al. Cortisol as a marker for increased mortality in patients with incidental adrenocortical adenomas. J Clin Endocrinol Metab 2014;99:4462–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Di Dalmazi G, Vicennati V, Garelli S, et al. Cardiovascular events and mortality in patients with adrenal incidentalomas that are either non-secreting or associated with intermediate phenotype or subclinical Cushing's syndrome: a 15-year retrospective study. Lancet Diabetes Endocrinol 2014;2:396–405.

    Article  PubMed  Google Scholar 

  11. Tauchmanova L, Rossi R, Biondi B, et al. Patients with subclinical Cushing's syndrome due to adrenal adenoma have increased cardiovascular risk. J Clin Endocrinol Metab 2002;87:4872–8.

    Article  CAS  PubMed  Google Scholar 

  12. Chiodini I, Albani A, Ambrogio AG, et al. Six controversial issues on subclinical Cushing's syndrome. Endocrine 2017;56:262–6.

    Article  CAS  PubMed  Google Scholar 

  13. Fassnacht M, Arlt W, Bancos I, et al. Management of adrenal incidentalomas: European society of endocrinology clinical practice guideline in collaboration with the european network for the study of adrenal tumors. Eur J Endocrinol 2016;175:G1–G34.

    Article  CAS  PubMed  Google Scholar 

  14. Barzon L, Sonino N, Fallo F, et al. Prevalence and natural history of adrenal incidentalomas. Eur J Endocrinol 2003;149:273–85.

    Article  CAS  PubMed  Google Scholar 

  15. Barzon L, Scaroni C, Sonino N, et al. Risk factors and longterm follow-up of adrenal incidentalomas. J Clin Endocrinol Metab 1999;84:520–6.

    CAS  PubMed  Google Scholar 

  16. Chiodini I. Clinical review: Diagnosis and treatment of subclinical hypercortisolism. J Clin Endocrinol Metab 2011;96:1223–36.

    Article  CAS  PubMed  Google Scholar 

  17. Kohara K. Sarcopenic obesity in aging population: Current status and future directions for research. Endocrine 2014;45:15–25.

    Article  CAS  PubMed  Google Scholar 

  18. NIH sta te-of-the-science statement on management of the clinically inapparent adrenal mass ("incidentaloma"). NIH Consens State Sci Statements 2002;19:1-25.

  19. 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;93:1526–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Tabarin A, Bardet S, Bertherat J, et al. Exploration and management of adrenal incidentalomas. French society of endocrinology consensus. Ann Endocrinol (Paris) 2008;69:487–500.

    Article  CAS  Google Scholar 

  21. Zeiger MA, Thompson GB, Duh QY, 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 2009;15:450–3.

    Article  PubMed  Google Scholar 

  22. Piaditis GP, Kaltsas GA, Androulakis, II, et al. High prevalence of autonomous cortisol and aldosterone secretion from adrenal adenomas. Clin Endocrinol (Oxf) 2009;71:772–8.

    Article  CAS  Google Scholar 

  23. Lee JM, Kim MK, Ko SH, et al. Clinical guidelines for the management of adrenal incidentaloma. Endocrinol Metab (Seoul) 2017;32:200–18.

    Article  Google Scholar 

  24. Mantero F, Terzolo M, Arnaldi G, et al. A survey on adrenal incidentaloma in Italy. Study group on adrenal tumors of the italian society of endocrinology. J Clin Endocrinol Metab 2000;85:637–44.

    CAS  Google Scholar 

  25. Hamrahian AH, Ioachimescu AG, Remer EM, et al. Clinical utility of noncontrast computed tomography attenuation value (hounsfield units) to differentiate adrenal adenomas/ hyperplasias from nonadenomas: Cleveland Clinic experience. J Clin Endocrinol Metab 2005;90:871–7.

    Article  CAS  PubMed  Google Scholar 

  26. Iacobone M, Citton M, Scarpa M, et al. Systematic review of surgical treatment of subclinical Cushing's syndrome. Br J Surg 2015;102:318–30.

    Article  CAS  PubMed  Google Scholar 

  27. Perysinakis I, Marakaki C, Avlonitis S, et al. Laparoscopic adrenalectomy in patients with subclinical Cushing syndrome. Surg Endosc 2013;27:2145–8.

    Article  PubMed  Google Scholar 

  28. Vassiliadi DA, Ntali G, Vicha E, et al. High prevalence of subclinical hypercortisolism in patients with bilateral adrenal incidentalomas: a challenge to management. Clin Endocrinol (Oxf) 2011;74:438–44.

    Article  Google Scholar 

  29. Iacobone M, Albiger N, Scaroni C, et al. The role of unilateral adrenalectomy in ACTH-independent macronodular adrenal hyperplasia (AIMAH). World J Surg 2008;32:882–9.

    Article  PubMed  Google Scholar 

  30. Zografos GN, Perysinakis I, Vassilatou E. Subclinical Cushing's syndrome: Current concepts and trends. Hormones (Athens) 2014;13:323–37.

    Article  Google Scholar 

  31. Stefanidis D, Goldfarb M, Kercher KW, et al. SAGES guidelines for minimally invasive treatment of adrenal pathology. Surg Endosc 2013;27:3960–80.

    Article  PubMed  Google Scholar 

  32. Lee CR, Walz MK, Park S, et al. A comparative study of the transperitoneal and posterior retroperitoneal approaches for laparoscopic adrenalectomy for adrenal tumors. Ann Surg Oncol 2012;19:2629–34.

    Article  PubMed  Google Scholar 

  33. Alesina PF, Hommeltenberg S, Meier B, et al. Posterior retroperitoneoscopic adrenalectomy for clinical and subclinical Cushing's syndrome. World J Surg 2010;34:1391–7.

    Article  PubMed  Google Scholar 

  34. Walz MK, Alesina PF, Wenger FA, et al. Posterior retroperitoneoscopic adrenalectomy—results of 560 procedures in 520 patients. Surgery 2006;140:943–8; discussion 8-50.

    Article  PubMed  Google Scholar 

  35. Callender GG, Kennamer DL, Grubbs EG, et al. Posterior retroperitoneoscopic adrenalectomy. Adv Surg 2009;43:147–57.

    Article  PubMed  Google Scholar 

  36. Lowery AJ, Seeliger B, Alesina PF, et al. Posterior retroperitoneoscopic adrenal surgery for clinical and subclinical Cushing's syndrome in patients with bilateral adrenal disease. Langenbecks Arch Surg 2017;402:775–85.

    Article  PubMed  Google Scholar 

  37. Hwang I, Jung SI, Yu SH, et al. Is larger tumor size a contraindication to retroperitoneal laparoscopic adrenalectomy? World J Urol 2014;32:723–8.

    Article  PubMed  Google Scholar 

  38. Nigri G, Rosman AS, Petrucciani N, et al. Meta-analysis of trials comparing laparoscopic transperitoneal and retroperitoneal adrenalectomy. Surgery 2013;153:111–9.

    Article  PubMed  Google Scholar 

  39. Conzo G, Tartaglia E, Gambardella C, et al. Minimally invasive approach for adrenal lesions: Systematic review of laparoscopic versus retroperitoneoscopic adrenalectomy and assessment of risk factors for complications. Int J Surg 2016;28 Suppl 1:S118–23.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. 3rd Department of Surgery, Athens General Hospital, “Georgios Gennimatas”, Athens, Greece

    Alexander M. Nixon, C Aggeli, C Tserkezis & GN Zografos

Authors
  1. Alexander M. Nixon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C Aggeli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C Tserkezis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. GN Zografos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alexander M. Nixon.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nixon, A.M., Aggeli, C., Tserkezis, C. et al. Surgical Considerations in Subclinical Cushing’s Syndrome. When is it Time to Operate?. Hellenic J Surg 90, 27–32 (2018). https://doi.org/10.1007/s13126-018-0431-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13126-018-0431-9

Keywords

Search

Navigation