Skip to main content
SpringerLink
Log in

Cushing’s Syndrome and Glucocorticoid Excess

  • Chapter
  • First Online:
Disorders of Blood Pressure Regulation

Part of the book series: Updates in Hypertension and Cardiovascular Protection ((UHCP))

Abstract

Cushing’s syndrome (CS) results from exogenous or endogenous glucocorticoid excess and can exert clinical signs and symptoms to various degrees depending on individual tissue sensitivities determined by the distribution and function of glucocorticoid receptors. Endogenous CS is divided into adrenocorticotropic hormone (ACTH)-dependent or adrenocorticotropic hormone (ACTH)-independent. Among ACTH-dependent CS, the most frequent (~85%) form is Cushing’s disease (CD) caused by an ACTHoma within or outside (ectopic) the pituitary gland. Approximately 5% of ACTH-dependent forms of CS are related to ectopic ACTH secretion from a neuroendocrine tumor, with the remaining 10% of CS cases caused by an adrenal tumor or adrenal hyperplasia oversecreting glucocorticoids including cortisol. Hypertension is a major cardiovascular risk factor and occurs frequently in patients with CS. Such patients also may have other cardiovascular risk factors including insulin resistance, diabetes mellitus, obesity, endothelial dysfunction, and hyperlipidemia. In this chapter, we provide a brief overview on the diagnosis and therapy of CS, including three case study illustrations.

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

Access this chapter

Log in via an institution

Institutional subscriptions

References

  1. Koch CA, Chrousos GP (2003) Cushing’ disease. In: Powell MP, Lightman SL, Laws ER (eds) Management of pituitary tumors: the clinician’s practical guide. Springer, New York, pp 51–75

    Chapter  Google Scholar 

  2. Kantorovich V, Koch CA, Chrousos GP (2013) Hypertension in patients with Cushing’s syndrome. In: Koch CA, Chrousos GP (eds) Endocrine hypertension. Springer, New York

    Google Scholar 

  3. Koch CA, Pamporaki C, Kantorovich V (2015) Endocrine hypertension in patients with chronic kidney disease. In: Weir MR, Lerma EV (eds) Chronic kidney disease and hypertension. Springer, New York

    Google Scholar 

  4. Hannah-Shmouni F, Melcescu E, Koch CA (2016) Testing for Endocrine Hypertension. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A (eds) Endotext [Internet]. South Dartmouth: MDText.com; 2000–2016 Dec 30

    Google Scholar 

  5. Koch CA, Chrousos GP (2016) Overview of endocrine hypertension. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A (eds) Endotext [Internet]. South Dartmouth: MDText.com.; 2000–2016 Oct 26.

  6. Lindholm J, Juul S, Jorgensen JO et al (2001) Incidence and late prognosis of Cushing’s syndrome: a population-based study. J Clin Endocrinol Metab 86(1):117–123

    CAS  PubMed  Google Scholar 

  7. Nieman LK (2015) Cushing’s syndrome: update on signs, symptoms and biochemical screening. Eur J Endocrinol 173(4):M33–M38

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM, Montori VM (2008) The diagnosis of Cushing’s syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 93(5):1526–1540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hall JE, Nieman LK (eds) (2003) Handbook of diagnostic endocrinology. Humana, Totowa

    Google Scholar 

  10. Magiakou MA, Smyrnaki P, Chrousos GP (2006) Hypertension in Cushing’s syndrome. Best Pract Res Clin Endocrinol Metab 20:467–482

    Article  CAS  PubMed  Google Scholar 

  11. León-Justel A, Madrazo-Atutxa A, Alvarez-Rios AI et al; Spanish CRISALIDA Study Group (2016) A probabilistic model for Cushing’s syndrome screening in at-risk populations: a prospective multicenter study. J Clin Endocrinol Metab 101(10):3747–3754

    Article  CAS  Google Scholar 

  12. Lanfranco F, Motta G, Minetto MA et al (2010) Neuroendocrine alterations in obese patients with sleep apnea syndrome. Int J Endocrinol 2010:474518

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Reinehr T, Kulle A, Wolters B et al (2014) Relationships between 24-hour urinary free cortisol concentrations and metabolic syndrome in obese children. J Clin Endocrinol Metab 99(7):2391–2399

    Article  CAS  PubMed  Google Scholar 

  14. Storr HL, Savage MO (2015) Management of endocrine disease: paediatric Cushing’s disease. Eur J Endocrinol 173(1):R35–R45

    Article  CAS  PubMed  Google Scholar 

  15. Stratakis CA (2016) Diagnosis and clinical genetics of Cushing syndrome in pediatrics. Endocrinol Metab Clin North Am 45(2):311–328

    Article  PubMed  PubMed Central  Google Scholar 

  16. Magiakou MA, Mastorakos G, Chrousos GP (1994) Final stature in patients with endogenous Cushing’s syndrome. J Clin Endocrinol Metab 79(4):1082–1085

    CAS  PubMed  Google Scholar 

  17. Robyn JA, Koch CA, Montalto J et al (1997) Cushing’s syndrome in childhood and adolescence. J Paediatr Child Health 33(6):522–527

    Article  CAS  PubMed  Google Scholar 

  18. Güemes M, Murray PG, Brain CE et al (2016) Management of Cushing syndrome in children and adolescents: experience of a single tertiary centre. Eur J Pediatr 175(7):967–976

    Article  PubMed  Google Scholar 

  19. Sharma ST, Nieman LN (2011) Cushing’s syndrome: all variants, detection, and treatment. Endocrinol Metab Clin North Am 40(2):379–391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Isidori AM, Graziadio C, Paragliola RM et al; ABC Study Group (2015) The hypertension of Cushing’s syndrome: controversies in the pathophysiology and focus on cardiovascular complications. J Hypertens 33(1):44–60

    Article  CAS  Google Scholar 

  21. Stratakis CA (2016) Skin manifestation of Cushing syndrome. Rev Endocr Metab Disord 17(3):283–286

    Article  PubMed  PubMed Central  Google Scholar 

  22. Hannah-Shmouni F, Stratakis CA, Koch CA (2016) Flushing in (neuro)endocrinology. Rev Endocr Metab Disord 17(3):373–380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Rahman SH, Papadakis GZ, Keil MF et al (2016) Kidney stones as an underrecognized clinical sign in pediatric Cushing disease. J Pediatr 170:273–277

    Article  PubMed  Google Scholar 

  24. Lodish M, Dunn SV, Sinaii N et al (2012) Recovery of the hypothalamic-pituitary-adrenal axis in children and adolescents after surgical cure of Cushing’s disease. J Clin Endocrinol Metab 97(5):1483–1491

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Zemskova MS, Gundabolu B, Sinaii N et al (2010) Utility of various functional and anatomic imaging modalities for detection of ectopic adrenocorticotropin-secreting tumors. J Clin Endocrinol Metab 95(3):1207–1219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Karageorgiadis AS, Papadakis GZ, Biro J et al (2015) Ectopic adrenocorticotropic hormone and corticotropin-releasing hormone co-secreting tumors in children and adolescents causing cushing syndrome: a diagnostic dilemma and how to solve it. J Clin Endocrinol Metab 100(1):141–148

    Article  CAS  PubMed  Google Scholar 

  27. Singer J, Werner F, Koch CA et al (2010) Ectopic Cushing’s syndrome caused by a well differentiated ACTH-secreting neuroendocrine carcinoma of the ileum. Exp Clin Endocrinol Diabetes 118(8):524–529

    Article  CAS  PubMed  Google Scholar 

  28. Fasshauer M, Lincke T, Witzigmann H et al (2006) Ectopic Cushing’ syndrome caused by a neuroendocrine carcinoma of the mesentery. BMC Cancer 6:108

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Miehle K, Tannapfel A, Lamesch P et al (2004) Pancreatic neuroendocrine tumor with ectopic adrenocorticotropin production upon second recurrence. J Clin Endocrinol Metab 89(8):3731–3736

    Google Scholar 

  30. Trainer PJ, Eastment C, Grossman AB et al (1993) The relationship between cortisol production rate and serial cortisol estimation in patients on medical therapy for Cushing syndrome. Clin Endocrinol (Oxf) 39(4):441–443

    Article  CAS  Google Scholar 

  31. Monaghan PJ, Owen LJ, Trainer PJ et al (2011) Comparison of serum cortisol measurement by immunoassay and liquid chromatography-tandem mass spectrometry in patients receiving the 11beta-hydroxylase inhibitor metyrapone. Ann Clin Biochem 48(Pt 5):441–446

    Article  CAS  PubMed  Google Scholar 

  32. Koch CA, Tsigos C, Patronas NJ, Papanicolaou DA (1999) Cushing’s disease presenting with avascular necrosis of the hip: an orthopedic emergency. J Clin Endocrinol Metab 84(9):3010–3012

    CAS  PubMed  Google Scholar 

  33. Koch CA (2017) Parathyroid hormone resistance and bilateral Macronodular adrenocortical disease: does partial loss of methylation at the GNAS exon 1 differentially methylated region (DMR) play a role? Horm Metab Res. 2017;49(7):558–560

    Google Scholar 

  34. East HE, Subauste JS, Gandhi A, Koch CA (2012) About secondary causes of diabetes mellitus. J Miss State Med Assoc 53(11):380–383

    PubMed  Google Scholar 

  35. Lopez D, Luque-Fernandez MA, Steele A et al (2016) “Nonfunctional” adrenal tumors and the risk for incident diabetes and cardiovascular outcomes: a cohort study. Ann Intern Med 165(8):533–542

    Article  PubMed  PubMed Central  Google Scholar 

  36. Fassnacht M, Arlt W, Bancos I et al (2016) 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 175(2):G1–G34

    Article  CAS  PubMed  Google Scholar 

  37. Koch CA, Bornstein SR, Chrousos GP, Stratakis CA (2000) Primary pigmented nodular adrenocortical dysplasia (PPNAD) within the scope of Carney complex as the etiology of Cushing’s syndrome. Med Klin (Munich) 95(4):224–230

    Article  CAS  Google Scholar 

  38. Kirkby-Bott J, Brunaud L, Mathonet M et al (2012) Ectopic hormone-secreting pheochromocytoma: a Francophone observational study. World J Surg 36(6):1382–1388

    Article  PubMed  Google Scholar 

  39. Falhammar H, Calissendorff J, Höybye C (2017) Frequency of Cushing’s syndrome due to ACTH-secreting adrenal medullary lesions: a retrospective study over 10 years from a single center. Endocrine 55(1):296–302

    Article  CAS  PubMed  Google Scholar 

  40. Bancos I, Alahdab F, Crowley RK et al (2016) Therapy of endocrine disease: improvement of cardiovascular risk factors after adrenalectomy in patients with adrenal tumors and subclinical Cushing syndrome: a systematic review and meta-analysis. Eur J Endocrinol 175(6):R283–R295

    Article  CAS  PubMed  Google Scholar 

  41. Lodish M, Stratakis CA (2016) A genetic and molecular update on adrenocortical causes of Cushing syndrome. Nat Rev Endocrinol 12(5):255–262

    Article  CAS  PubMed  Google Scholar 

  42. Kirschner MA, Powell RD Jr, Lipsett MB (1964) Cushing’s syndrome: nodular cortical hyperplasia of adrenal glands with clinical and pathological features suggesting adrenocortical tumor. J Clin Endocrinol Metab 24:947–955

    Article  CAS  PubMed  Google Scholar 

  43. Fragoso MC, Alencar GA, Lerario AM et al (2015) Genetics of primary macronodular adrenal hyperplasia. J Endocrinol 224(1):R31–R43

    Article  CAS  PubMed  Google Scholar 

  44. Alencar GA, Lerario AM, Nishi MY et al (2014) ARMC5 mutations are a frequent cause of primary macronodular adrenal hyperplasia. J Clin Endocrinol Metab 99(8):E1501–E1509

    Article  CAS  PubMed  Google Scholar 

  45. Assie G, Libe R, Espiard S et al (2013) ARMC5 mutations in macronodular adrenal hyperplasia with Cushing’s syndrome. N Engl J Med 369(22):2105–2114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Faucz FR, Zilbermint M, Lodish MB et al (2014) Macronodular adrenal hyperplasia due to mutations in an armadillo repeat containing 5 (ARMC5) gene: a clinical and genetic investigation. J Clin Endocrinol Metab 99(6):E1113–E1119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Liu H, Bravata DM, Cabaccan J et al (2005) Elevated late-night salivary cortisol levels in elderly male type 2 diabetic veterans. Clin Endocrinol (Oxf) 63(6):642–649

    Article  CAS  Google Scholar 

  48. Meikle AW (1982) Dexamethasone suppression tests: usefulness of simultaneous measurement of plasma cortisol and dexamethasone. Clin Endocrinol (Oxf) 16(4):401–408

    Article  CAS  Google Scholar 

  49. Nieman LK, Oldfield EH, Wesley R et al (1993) A simplified morning ovine corticotropin-releasing hormone stimulation test for the differential diagnosis of adrenocorticotropin-dependent Cushing’s syndrome. J Clin Endocrinol Metab 77(5):1308–1312

    CAS  PubMed  Google Scholar 

  50. Lindholm J (2014) Cushing disease, pseudo-Cushing states, and the dexamethasone test: a historical and critical review. Pituitary 17(4):374–380

    Article  CAS  PubMed  Google Scholar 

  51. Auchus RJ (2015) Is it time to emancipate plasma cortisol? Endocr Pract 21(12):1445–1447

    Article  PubMed  Google Scholar 

  52. Manetti L, Rossi G, Grasso L et al (2013) Usefulness of salivary cortisol in the diagnosis of hypercortisolism: comparison with serum and urinary cortisol. Eur J Endocrinol 168(3):315–321

    Article  CAS  PubMed  Google Scholar 

  53. Ceccato F, Barbot M, Zilio M et al (2015) Screening tests for Cushing’s syndrome: urinary free cortisol role measured by LC-MS/MS. J Clin Endocrinol Metab 100(10):3856–3861

    Article  CAS  PubMed  Google Scholar 

  54. Caimari F, Valassi E, Garbayo P et al (2016) Cushing’s syndrome and pregnancy outcomes: a systematic review of published cases. Endocrine 55(2):555–563

    Article  PubMed  CAS  Google Scholar 

  55. Lindsay JR, Jonklaas J, Oldfield EH, Nieman LK (2005) Cushing’s syndrome during pregnancy: personal experience and review of the literature. J Clin Endocrinol Metab 90(5):3077–3083

    Article  CAS  PubMed  Google Scholar 

  56. Velez DA, Mayberg MR, Ludlam WH (2007) Cyclic Cushing syndrome: definitions and treatment implications. Neurosurg Focus 23(3):E4; discussion E4a

    Google Scholar 

  57. N’Gankam V, Uehlinger D, Dick B et al (2002) Increased cortisol metabolites and reduced activity of 11beta-hydroxysteroid dehydrogenase in patients on hemodialysis. Kidney Int 61(5):1859–1866

    Article  PubMed  Google Scholar 

  58. Wallace EZ, Rosman P, Toshav N et al (1980) Pituitary-adrenocortical function in chronic renal failure: studies of episodic secretion of cortisol and dexamethasone suppressibility. J Clin Endocrinol Metab 50(1):46–51

    Article  CAS  PubMed  Google Scholar 

  59. Ramirez G, Gomez-Sanchez C, Meikle WA, Jubiz W (1982) Evaluation of the hypothalamic hypophyseal adrenal axis in patients receiving long-term hemodialysis. Arch Intern Med 142(8):1448–1452

    Article  CAS  PubMed  Google Scholar 

  60. Workman RJ, Vaughn WK, Stone WJ (1986) Dexamethasone suppression testing in chronic renal failure: pharmacokinetics of dexamethasone and demonstration of a normal hypothalamic-pituitary-adrenal axis. J Clin Endocrinol Metab 63(3):741–746

    Article  CAS  PubMed  Google Scholar 

  61. Cooke CR, Whelton PK, Moore MA et al (1979) Dissociation of the diurnal variation of aldosterone and cortisol in anephric subjects. Kidney Int 15(6):669–675

    Article  CAS  PubMed  Google Scholar 

  62. Chan KC, Lit LC, Law EL et al (2004) Diminished urinary free cortisol excretion in patients with moderate and severe renal impairment. Clin Chem 50(4):757–759

    Article  CAS  PubMed  Google Scholar 

  63. Cardoso EM, Arregger AL, Budd D et al (2016) Dynamics of salivary cortisol in chronic kidney disease patients at stages 1 through 4. Clin Endocrinol (Oxf) 85(2):313–319

    Article  CAS  Google Scholar 

  64. Raff H, Trivedi H (2012) Circadian rhythm of salivary cortisol, plasma cortisol, and plasma ACTH in end-stage renal disease. Endocr Connect 2(1):23–31

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Mise K, Ubara Y, Sumida K et al (2013) Cushing’s syndrome after hemodialysis for 21 years. J Clin Endocrinol Metab 98(1):13–19

    Article  CAS  PubMed  Google Scholar 

  66. Fleseriu M, Hamrahian AH, Hoffman AR, Kelly DF, Katznelson L; AACE Neuroendocrine and Pituitary Scientific Committee (2016) American Association of Clinical Endocrinologists and American College of Endocrinology Disease State Clinical Review: Diagnosis Of Recurrence In Cushing Disease Endocr Pract 22(12):1436–1448

    Google Scholar 

  67. Carroll TB, Javorsky BR, Findling JW (2016) Postsurgical recurrent cushing disease: clinical benefit of early intervention in patients with normal urinary free cortisol. Endocr Pract 22(10):1216–1223

    Article  PubMed  Google Scholar 

  68. Abdelmannan D, Chaiban J, Selman WR, Arafah BM (2013) Recurrences of ACTH-secreting adenomas after pituitary adenomectomy can be accurately predicted by perioperative measurements of plasma ACTH levels. J Clin Endocrinol Metab 98(4):1458–1465

    Article  CAS  PubMed  Google Scholar 

  69. Khan MI, Habra MA, McCutcheon IE et al (2011) Random postoperative day-3 cortisol concentration as a predictor of hypothalamic-pituitary-adrenal axis integrity after transsphenoidal surgery. Endocr Pract 17(5):717–726

    Article  PubMed  Google Scholar 

  70. Azad TD, Veeravagu A, Kumar S, Katznelson L (2015) Nelson syndrome: update on therapeutic approaches. World Neurosurg 83(6):1135–1134

    Article  PubMed  Google Scholar 

  71. Clayton RN, Jones PW, Reulen RC et al (2016) Mortality in patients with Cushing’s disease more than 10 years after remission: a multicentre, multinational, retrospective cohort study. Lancet Diabetes Endocrinol 4(7):569–576

    Article  PubMed  Google Scholar 

  72. Clayton RN, Raskauskiene D, Reulen RC, Jones PW (2011) Mortality and morbidity in Cushing’s disease over 50 years in Stoke-on-Trent, UK: audit and meta-analysis of literature. J Clin Endocrinol Metab 96:632–642

    Article  CAS  PubMed  Google Scholar 

  73. Bolland MJ, Holdaway IM, Berkeley JE et al (2011) Mortality and morbidity in Cushing’s syndrome in New Zealand. Clin Endocrinol (Oxf) 75:436–442

    Article  Google Scholar 

  74. Yaneva M, Kalinov K, Zacharieva S (2013) Mortality in Cushing’s syndrome: data from 386 patients from a single tertiary referral center. Eur J Endocrinol 169(5):621–627

    Article  CAS  PubMed  Google Scholar 

  75. Patronas N, Bulakbasi N, Stratakis CA et al (2003) Spoiled gradient recalled acquisition in the steady state technique is superior to conventional postcontrast spin echo technique for magnetic resonance imaging detection of adrenocorticotropin-secreting pituitary tumors. J Clin Endocrinol Metab 88(4):1565–1569

    Article  CAS  PubMed  Google Scholar 

  76. Hall WA, Luciano MG, Doppman JL et al (1994) Pituitary magnetic resonance imaging in normal human volunteers: occult adenomas in the general population. Ann Intern Med 120(10):817–820

    Article  CAS  PubMed  Google Scholar 

  77. Hodish I, Giordano TJ, Starkman MN, Schteingart DE (2009) Location of ectopic adrenocortical hormone-secreting tumors causing Cushing’s syndrome in the paranasal sinuses. Head Neck 31(5):699–706

    Article  PubMed  Google Scholar 

  78. Zerikly RK, Eray E, Faiman C et al (2009) Cyclic Cushing syndrome due to an ectopic pituitary adenoma. Nat Clin Pract Endocrinol Metab 5(3):174–179

    Article  PubMed  Google Scholar 

  79. Findling JW, Kehoe ME, Raff H (2004) Identification of patients with Cushing’s disease with negative pituitary adrenocorticotropin gradients during inferior petrosal sinus sampling: prolactin as an index of pituitary venous effluent. J Clin Endocrinol Metab 89(12):6005–6009

    Article  CAS  PubMed  Google Scholar 

  80. Sharma ST, Nieman LK (2013) Is prolactin measurement of value during inferior petrosal sinus sampling in patients with adrenocorticotropic hormone-dependent Cushing’s syndrome? J Endocrinol Invest 36(11):1112–1116

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Escourolle H, Abecassis JP, Bertagna X et al (1993) Comparison of computerized tomography and magnetic resonance imaging for the examination of the pituitary gland in patients with Cushing’s disease. Clin Endocrinol (Oxf) 39(3):307–313

    Article  CAS  Google Scholar 

  82. Suzuki Y, Sasagawa SH et al (2001) The role of ultrasonography in the detection of adrenal masses: comparison with computed tomography and magnetic resonance imaging. Int Urol Nephrol 32(3):303–306

    Article  CAS  PubMed  Google Scholar 

  83. Blake MA, Kalra MK, Sweeney AT et al (2006) Distinguishing benign from malignant adrenal masses: multi-detector row CT protocol with 10-minute delay. Radiology 238(2):578–585

    Article  PubMed  Google Scholar 

  84. Young WF Jr (2011) Conventional imaging in adrenocortical carcinoma: update and perspectives. Horm Cancer 2(6):341–347

    Article  PubMed  Google Scholar 

  85. Rockall AG, Babar SA, Sohaib SA et al (2004) CT and MR imaging of the adrenal glands in ACTH-independent cushing syndrome. Radiographics 24(2):435–452

    Article  PubMed  Google Scholar 

  86. Lumachi F, Marchesi P, Miotto D, Motta R (2011) CT and MR imaging of the adrenal glands in cortisol-secreting tumors. Anticancer Res 31(9):2923–2926

    PubMed  Google Scholar 

  87. Hamrahian AH, Ioachimescu AG, Remer EM et al (2005) Clinical utility of noncontrast computed tomography attenuation value (Hounsfield units) to differentiate adrenal adenomas/hyperplasias from nonadenomas: Cleveland Clinic experience. J Clin Endocrinol Metab 90(2):871–877

    Article  CAS  PubMed  Google Scholar 

  88. Caoili EM, Korobkin M, Francis IR et al (2002) Adrenal masses: characterization with combined unenhanced and delayed enhanced CT. Radiology 222(3):629–633

    Article  PubMed  Google Scholar 

  89. Korobkin M, Brodeur FJ, Francis IR et al (1998) CT time-attenuation washout curves of adrenal adenomas and nonadenomas. AJR Am J Roentgenol 170(3):747–752

    Article  CAS  PubMed  Google Scholar 

  90. Pena CS, Boland GW, Hahn PF et al (2000) Characterization of indeterminate (lipid-poor) adrenal masses: use of washout characteristics at contrast-enhanced CT. Radiology 217(3):798–802

    Article  CAS  PubMed  Google Scholar 

  91. Patel D, Gara SK, Ellis RJ et al (2016) FDG PET/CT scan and functional adrenal tumors: a pilot study for lateralization. World J Surg 40(3):683–689

    Article  PubMed  Google Scholar 

  92. Tenenbaum F, Groussin L, Foehrenbach H et al (2004) 18F-fluorodeoxyglucose positron emission tomography as a diagnostic tool for malignancy of adrenocortical tumours? Preliminary results in 13 consecutive patients. Eur J Endocrinol 150(6):789–792

    Article  CAS  PubMed  Google Scholar 

  93. Nieman LK, Biller BM, Findling JW et al; Endocrine Society (2015) Treatment of Cushing’s syndrome: An Endocrine Society Clinical Practice Guideline J Clin Endocrinol Metab 100(8):2807–2831

    Google Scholar 

  94. Sheehan JP, Xu Z, Salvetti DJ et al (2013) Results of gamma knife surgery for Cushing’s disease. J Neurosurg 119(6):1486–1492

    Article  PubMed  Google Scholar 

  95. Budyal S, Lila AR, Jalali R et al (2014) Encouraging efficacy of modern conformal fractionated radiotherapy in patients with uncured Cushing’s disease. Pituitary 17(1):60–67

    Article  PubMed  Google Scholar 

  96. Sheehan JM, Lopes MB, Sheehan JP et al (2000) Results of transsphenoidal surgery for Cushing’s disease in patients with no histologically confirmed tumor. Neurosurgery 47(1):33–36

    CAS  PubMed  Google Scholar 

  97. Ratliff JK, Oldfield EH (2000) Multiple pituitary adenomas in Cushing’s disease. J Neurosurg 93(5):753–761

    Article  CAS  PubMed  Google Scholar 

  98. Oldfield EH, Vance ML, Louis RG et al (2015) Crooke’s changes in Cushing’s syndrome depends on degree of hypercortisolism and individual susceptibility. J Clin Endocrinol Metab 100(8):3165–3171

    Article  CAS  PubMed  Google Scholar 

  99. Mallappa A, Debono M (2016) Recent advances in hydrocortisone replacement treatment. Endocr Dev 30:42–53

    Article  PubMed  Google Scholar 

  100. Bornstein SR, Allolio B, Arlt W et al (2016) Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 101(2):364–389

    Article  CAS  PubMed  Google Scholar 

  101. Ritzel K, Beuschlein F, Mickisch A et al (2013) Clinical review: outcome of bilateral adrenalectomy in Cushing’s syndrome: a systematic review. J Clin Endocrinol Metab 98(10):3939–3948

    Article  CAS  PubMed  Google Scholar 

  102. Reincke M, Ritzel K, Oßwald A et al (2015) A critical reappraisal of bilateral adrenalectomy for ACTH-dependent Cushing’s syndrome. Eur J Endocrinol 173(4):M23–M32

    Article  CAS  PubMed  Google Scholar 

  103. Oßwald A, Plomer E, Dimopoulou C et al (2014) Favorable long-term outcomes of bilateral adrenalectomy in Cushing’s disease. Eur J Endocrinol 171(2):209–215

    Article  PubMed  CAS  Google Scholar 

  104. Gadelha MR, Vieira Neto L (2014) Efficacy of medical treatment in Cushing’s disease: a systematic review. Clin Endocrinol (Oxf) 80(1):1–12

    Article  CAS  Google Scholar 

  105. Trementino L, Cardinaletti M, Concettoni C et al (2015) Salivary cortisol is a useful tool to assess the early response to pasireotide in patients with Cushing’s disease. Pituitary 18(1):60–67

    Article  CAS  PubMed  Google Scholar 

  106. Fleseriu M, Biller BM, Findling JW, Molitch ME, Schteingart DE, Gross C; SEISMIC Study Investigators (2012) Mifepristone, a glucocorticoid receptor antagonist, produces clinical and metabolic benefits in patients with Cushing’s syndrome. J Clin Endocrinol Metab 97(6):2039–2049

    Article  CAS  Google Scholar 

  107. Wallia A, Colleran K, Purnell JQ et al (2013) Improvement in insulin sensitivity during mifepristone treatment of Cushing syndrome: early and late effects. Diabetes Care 36(9):e147–e148

    Article  PubMed  PubMed Central  Google Scholar 

  108. Newell-Price J (2014) Ketoconazole as an adrenal steroidogenesis inhibitor: effectiveness and risks in the treatment of Cushing’s disease. J Clin Endocrinol Metab 99(5):1586–1588

    Article  CAS  PubMed  Google Scholar 

  109. Zacharia BE, Gulati AP, Bruce JN et al (2014) High response rates and prolonged survival in patients with corticotroph pituitary tumors and refractory Cushing disease from capecitabine and temozolomide (CAPTEM): a case series. Neurosurgery 74(4):E447–E455

    Article  PubMed  Google Scholar 

  110. Uwaifo GI, Koch CA, Hirshberg B et al (2003) Is there a therapeutic role for octreotide in patients with ectopic Cushing’s syndrome? J Endocrinol Invest 26(8):710–717

    Article  CAS  PubMed  Google Scholar 

  111. Krakoff J, Koch CA, Calis KA et al (2001) Use of a parenteral propylene glycol-containing etomidate preparation for the long-term management of ectopic Cushing’s syndrome. J Clin Endocrinol Metab 86(9):4104–4108

    CAS  PubMed  Google Scholar 

  112. Vilar L, Naves LA, Machado MC, Bronstein MD (2015) Medical combination therapies in Cushing’s disease. Pituitary 18(2):253–262

    Article  CAS  PubMed  Google Scholar 

  113. Koch CA, Pacak K, Chrousos GP (2002) The molecular pathogenesis of hereditary and sporadic adrenocortical and adrenomedullary tumors. J Clin Endocrinol Metab 87(12):5367–5384

    Article  CAS  PubMed  Google Scholar 

  114. Dworakowska D, Grossman AB (2012) The molecular pathogenesis of corticotroph tumours. Eur J Clin Invest 42(6):665–676

    Article  CAS  PubMed  Google Scholar 

  115. Perez-Rivas LG, Reincke M (2016) Genetics of Cushing’s disease: an update. J Endocrinol Invest 39(1):29–35

    Article  CAS  PubMed  Google Scholar 

  116. Beuschlein F, Fassnacht M, Assié G et al (2014) Constitutive activation of PKA catalytic subunit in adrenal Cushing’s syndrome. N Engl J Med 370(11):1019–1028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Goh G, Scholl UI, Healy JM et al (2014) Recurrent activating mutation in PRKACA in cortisol-producing adrenal tumors. Nat Genet 46(6):613–617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Bourdeau I, Oble S, Magne F et al (2016) ARMC5 mutations in a large French-Canadian family with cortisol-secreting β-adrenergic/vasopressin responsive bilateral macronodular adrenal hyperplasia. Eur J Endocrinol 174(1):85–96

    Article  CAS  PubMed  Google Scholar 

  119. Zilbermint M, Stratakis CA (2015) Protein kinase A defects and cortisol-producing adrenal tumors. Curr Opin Endocrinol Diabetes Obes 22(3):157–162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Thiel A, Reis AC, Haase M et al (2015) PRKACA mutations in cortisol-producing adenomas and adrenal hyperplasia: a single-center study of 60 cases. Eur J Endocrinol 172(6):677–685

    Article  CAS  PubMed  Google Scholar 

  121. Nakamura Y, Yamazaki Y, Felizola SJ et al (2015) Adrenocortical carcinoma: review of the pathologic features, production of adrenal steroids, and molecular pathogenesis. Endocrinol Metab Clin North Am 44(2):399–410

    Article  PubMed  Google Scholar 

  122. Reincke M, Sbiera S, Hayakawa A et al (2015) Mutations in the deubiquitinase gene USP8 cause Cushing’s disease. Nat Genet 47(1):31–38

    Article  CAS  PubMed  Google Scholar 

  123. Mancia G, Oparil S, Whelton PK et al (2017) The technical report on sodium intake and cardiovascular disease in low- and middle-income countries by the joint working group of the World Heart Federation, the European Society of Hypertension and the European Public Health Association. Eur Heart J 38(10):712–719

    PubMed  Google Scholar 

  124. Mariampillai JE, Eskås PA, Heimark S et al (2016) A case for less intensive blood pressure control: it matters to achieve target blood pressure early and sustained below 140/90mmHg. Prog Cardiovasc Dis 59(3):209–218

    Article  PubMed  Google Scholar 

  125. Mangat BK, Campbell N, Mohan S et al (2015) Resources for blood pressure screening programs in low resource settings: a guide from the World Hypertension League. J Clin Hypertens (Greenwich) 17(6):418–420

    Article  Google Scholar 

  126. Baid S, Nieman LK (2004) Glucocorticoid excess and hypertension. Curr Hypertens Rep 6:493–499

    Article  PubMed  Google Scholar 

  127. Magiakou MA, Mastorakos G, Zachman K, Chrousos GP (1997) Blood pressure in children and adolescents with Cushing’s syndrome before and after surgical cure. J Clin Endocrinol Metab 82:1734–1737

    CAS  PubMed  Google Scholar 

  128. Lodish MB, Sinaii N, Patronas N et al (2009) Blood pressure in pediatric patients with Cushing’s syndrome. J Clin Endocrinol Metab 94:2002–2008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Pirpiris M, Yeung S, Dewar E et al (1993) Hydrocortisone-induced hypertension in men. The role of cardiac output. Am J Hypertens 6:287–294

    Article  CAS  PubMed  Google Scholar 

  130. Connell JM, Whitworth JA, Davies DL et al (1987) Effects of ACTH and cortisol administration on blood pressure, electrolyte metabolism, atrial natriuretic peptide and renal function in normal man. J Hypertens 5:425–433

    Article  CAS  PubMed  Google Scholar 

  131. Grassi G, Seravalle G, Dell’Oro R et al (2001) Participation of the hypothalamus-hypophysis axis in the sympathetic activation of human obesity. Hypertension 38(6):1316–1320

    Article  CAS  PubMed  Google Scholar 

  132. Cicala MV, Mantero F (2010) Hypertension in Cushing’s syndrome: from pathogenesis to treatment. Neuroendocrinology 92:44–49

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Mississippi Medical Center, Jackson, MS, 39216, USA

    Christian A. Koch

  2. G.V. (Sonny) Montgomery VA Medical Center, Jackson, MS, USA

    Christian A. Koch

  3. Department of Medicine, Med Klinik 3, University of Dresden, Dresden, Germany

    Christian A. Koch

Authors
  1. Christian A. Koch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christian A. Koch .

Editor information

Editors and Affiliations

  1. Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon

    Adel E. Berbari

  2. Emeritus Professor of Medicine, University of Milano-Bicocca, Monza, Italy

    Giuseppe Mancia

Ethics declarations

Conflict of Interest

The author declares that he has no conflict of interest related to this work.

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Koch, C.A. (2018). Cushing’s Syndrome and Glucocorticoid Excess. In: Berbari, A., Mancia, G. (eds) Disorders of Blood Pressure Regulation. Updates in Hypertension and Cardiovascular Protection. Springer, Cham. https://doi.org/10.1007/978-3-319-59918-2_28

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-59918-2_28

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-59917-5

  • Online ISBN: 978-3-319-59918-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation