Evaluation and Treatment of Patients With Hypercortisolism: A Review.

Importance With the potential for severe adverse effects of hypercortisolism, the need to limit the development and unrecognized persistence of sequelae from cortisol excess is of great importance on individual and population health levels. This review discusses the evaluation and treatment of patients with hypercortisolism. Pathophysiology; pitfalls in the diagnosis of hypercortisolism; and preoperative, perioperative, and postoperative management considerations are discussed. The association of hypercortisolism with population health and the potential role surgeons and surgery can play in the future of patients with hypercortisolism are also discussed. Higher-level considerations are put forth to encourage a long-term view of future work needed to optimally care for these patients. Observations Although classic signs and symptoms of hypercortisolism are evident in some patients, mild autonomous cortisol secretion is likely more prevalent and more difficult to detect despite having the potential to cause significant adverse effects, such as increased risk of mortality, and overt hypercortisolism. With treatment, some adverse effects of hypercortisolism may resolve, although not in all patients. Thus, the need for early diagnosis and treatment is of great importance. Conclusions and Relevance More attention in the future on early treatment of hypercortisolism, whether subclinical or overt, and prevention of adverse effects is warranted for the sake of the individual and the population.

[1]  I. Bancos,et al.  Cardiovascular risk and mortality in patients with active and treated hypercortisolism. , 2020, Gland surgery.

[2]  B. S. Miller,et al.  Adrenal Crisis. , 2019, The New England journal of medicine.

[3]  S. Taler,et al.  New-onset resistant hypertension in a newly diagnosed prostate cancer patient. , 2019, American journal of hypertension.

[4]  I. Bryngelsson,et al.  Overall and Disease-Specific Mortality in Patients With Cushing Disease: A Swedish Nationwide Study. , 2019, The Journal of clinical endocrinology and metabolism.

[5]  H. Raff,et al.  Assay-Specific Spurious ACTH Results Lead to Misdiagnosis, Unnecessary Testing, and Surgical Misadventure—A Case Series , 2019, Journal of the Endocrine Society.

[6]  F. Kober,et al.  Cushing Syndrome Is Associated With Subclinical LV Dysfunction and Increased Epicardial Adipose Tissue. , 2018, Journal of the American College of Cardiology.

[7]  I. Chiodini,et al.  Cardiovascular mortality in patients with subclinical Cushing. , 2018, Annales d'endocrinologie.

[8]  Viju Raghupathi,et al.  An Empirical Study of Chronic Diseases in the United States: A Visual Analytics Approach to Public Health , 2018, International journal of environmental research and public health.

[9]  Weihong Guo,et al.  Effect of hypercortisolism on bone mineral density and bone metabolism: A potential protective effect of adrenocorticotropic hormone in patients with Cushing’s disease , 2017, The Journal of international medical research.

[10]  H. Stoddart Low dehydroepiandrosterone sulphate: a sensitive and specific test for the detection of subclinical hypercortisolism in adrenal incidentalomas , 2017, Annals of clinical biochemistry.

[11]  A. Comlekçi,et al.  Interference in ACTH immunoassay negatively impacts the management of subclinical hypercortisolism , 2017, Endocrine.

[12]  A. Lowery,et al.  Posterior retroperitoneoscopic adrenal surgery for clinical and subclinical Cushing’s syndrome in patients with bilateral adrenal disease , 2017, Langenbeck's Archives of Surgery.

[13]  M. Bufi,et al.  Clinical Benefits of Unilateral Adrenalectomy in Patients with Subclinical Hypercortisolism Due to Adrenal Incidentaloma: Results from a Single Center , 2017, High Blood Pressure & Cardiovascular Prevention.

[14]  W. Inder Towards a universally accepted definition of subclinical Cushing's syndrome – subclinical autonomous hypercortisolism , 2017, Clinical endocrinology.

[15]  C. Lombardi,et al.  Outcome of adrenalectomy for subclinical hypercortisolism and Cushing syndrome , 2017, Surgery.

[16]  A. Pontecorvi,et al.  Factors predicting the duration of adrenal insufficiency in patients successfully treated for Cushing disease and nonmalignant primary adrenal Cushing syndrome , 2017, Endocrine.

[17]  Fares Alahdab,et al.  THERAPY OF ENDOCRINE DISEASE: Improvement of cardiovascular risk factors after adrenalectomy in patients with adrenal tumors and subclinical Cushing's syndrome: a systematic review and meta-analysis. , 2016, European journal of endocrinology.

[18]  A. Tabarin,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. , 2016, European journal of endocrinology.

[19]  Niki Karavitaki,et al.  Mortality in patients with Cushing's disease more than 10 years after remission: a multicentre, multinational, retrospective cohort study. , 2016, The lancet. Diabetes & endocrinology.

[20]  I. Chiodini,et al.  Adrenalectomy reduces the risk of vertebral fractures in patients with monolateral adrenal incidentalomas and subclinical hypercortisolism. , 2016, European journal of endocrinology.

[21]  Douglas B. Evans,et al.  Cosyntropin stimulation testing on postoperative day 1 allows for selective glucocorticoid replacement therapy after adrenalectomy for hypercortisolism: Results of a novel, multidisciplinary institutional protocol. , 2016, Surgery.

[22]  S. Tsagarakis,et al.  Biochemical and clinical benefits of unilateral adrenalectomy in patients with subclinical hypercortisolism and bilateral adrenal incidentalomas. , 2015, European journal of endocrinology.

[23]  Martin Reincke,et al.  Subclinical hypercortisolism: a state, a syndrome, or a disease? , 2015, European journal of endocrinology.

[24]  A. Lacroix,et al.  Multiple aberrant hormone receptors in Cushing's syndrome. , 2015, European journal of endocrinology.

[25]  A. Tabarin,et al.  Treatment of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline. , 2015, The Journal of clinical endocrinology and metabolism.

[26]  L. Nieman Update on subclinical Cushing's syndrome , 2015, Current opinion in endocrinology, diabetes, and obesity.

[27]  A. Fassina,et al.  An analysis of different therapeutic options in patients with Cushing's syndrome due to bilateral macronodular adrenal hyperplasia: a single‐centre experience , 2015, Clinical endocrinology.

[28]  O. Dekkers,et al.  Management of endocrine disease: Mortality remains increased in Cushing's disease despite biochemical remission: a systematic review and meta-analysis. , 2015, European journal of endocrinology.

[29]  F. Beuschlein,et al.  Time to recovery of adrenal function after curative surgery for Cushing's syndrome depends on etiology. , 2015, The Journal of clinical endocrinology and metabolism.

[30]  D. Nitti,et al.  Systematic review of surgical treatment of subclinical Cushing's syndrome , 2015, The British journal of surgery.

[31]  H. Raff,et al.  Urine free cortisol in the diagnosis of Cushing's syndrome: is it worth doing and, if so, how? , 2015, The Journal of clinical endocrinology and metabolism.

[32]  A. Comlekçi,et al.  DHEAS for the prediction of subclinical Cushing’s syndrome: perplexing or advantageous? , 2015, Endocrine.

[33]  Jing Shen,et al.  Nonconformity in the clinical practice guidelines for subclinical Cushing's syndrome: which guidelines are trustworthy? , 2014, European journal of endocrinology.

[34]  M. Bradburn,et al.  Cortisol as a marker for increased mortality in patients with incidental adrenocortical adenomas. , 2014, The Journal of clinical endocrinology and metabolism.

[35]  F. Beuschlein,et al.  Adrenal function after adrenalectomy for subclinical hypercortisolism and Cushing's syndrome: a systematic review of the literature. , 2014, The Journal of clinical endocrinology and metabolism.

[36]  R. Golfieri,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. , 2014, The lancet. Diabetes & endocrinology.

[37]  S. Fried,et al.  Deconstructing the roles of glucocorticoids in adipose tissue biology and the development of central obesity. , 2014, Biochimica et biophysica acta.

[38]  E. Horváth-Puhó,et al.  Multisystem morbidity and mortality in Cushing's syndrome: a cohort study. , 2013, The Journal of clinical endocrinology and metabolism.

[39]  D. Nitti,et al.  Adrenalectomy may improve cardiovascular and metabolic impairment and ameliorate quality of life in patients with adrenal incidentalomas and subclinical Cushing's syndrome. , 2012, Surgery.

[40]  G. Gamble,et al.  Mortality and morbidity in Cushing’s syndrome in New Zealand , 2011, Clinical endocrinology.

[41]  Miklós Tóth,et al.  The European Registry on Cushing's syndrome: 2-year experience. Baseline demographic and clinical characteristics. , 2011, European journal of endocrinology.

[42]  E. Papini,et al.  AME position statement on adrenal incidentaloma. , 2011, European journal of endocrinology.

[43]  J. Jørgensen,et al.  Epidemiology of Cushing’s Syndrome , 2010, Neuroendocrinology.

[44]  J. Mullins,et al.  Mineralocorticoid and Glucocorticoid Receptors Stimulate Epithelial Sodium Channel Activity in a Mouse Model of Cushing Syndrome , 2009, Hypertension.

[45]  Q. Duh,et al.  Waiting for change: symptom resolution after adrenalectomy for Cushing's syndrome. , 2008, Surgery.

[46]  V. Montori,et al.  The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline. , 2008, The Journal of clinical endocrinology and metabolism.

[47]  Charles B. Wilson,et al.  Transsphenoidal microsurgery for Cushing's disease: initial outcome and long-term results. , 2004, The Journal of clinical endocrinology and metabolism.

[48]  M. Quinkler,et al.  Hypertension and the cortisol-cortisone shuttle. , 2003, The Journal of clinical endocrinology and metabolism.

[49]  C Hagen,et al.  Incidence and late prognosis of cushing's syndrome: a population-based study. , 2001, The Journal of clinical endocrinology and metabolism.

[50]  L. del Viscovo,et al.  Subclinical Cushing's syndrome in patients with adrenal incidentaloma: clinical and biochemical features. , 2000, The Journal of clinical endocrinology and metabolism.

[51]  A. Klibanski,et al.  Long-term mortality after transsphenoidal surgery for Cushing disease. , 1999 .

[52]  B. Walker,et al.  11 beta-Hydroxysteroid dehydrogenase activity in Cushing's syndrome: explaining the mineralocorticoid excess state of the ectopic adrenocorticotropin syndrome. , 1995, The Journal of clinical endocrinology and metabolism.

[53]  J. Norton,et al.  Time to recovery of the hypothalamic-pituitary-adrenal axis after curative resection of adrenal tumors in patients with Cushing's syndrome. , 1990, Surgery.