Cushing syndrome - Symptoms, Causes, Images, and Treatment Options

Diseases

Highlights & Basics

Key Highlights

Cushing syndrome is the clinical manifestation of pathologic hypercortisolism from any cause.
Exogenous corticosteroid exposure is the most common cause of Cushing syndrome. Cushing disease, which is hypercortisolism caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma, is the most common cause of endogenous Cushing syndrome, and is responsible for 70% to 80% of cases.
It may be difficult to distinguish patients with mild Cushing syndrome from those with the metabolic syndrome (central obesity with insulin resistance, and hypertension). Features more specific to Cushing syndrome include proximal muscle weakness, supraclavicular fat pads, facial plethora, violaceous striae, easy bruising, and premature osteoporosis.
After excluding exogenous corticosteroid use, patients with suspected Cushing syndrome should be tested for hypercortisolism with one of three high-sensitivity tests (late-night salivary cortisol, 1 mg overnight low-dose dexamethasone suppression testing, or 24-hour urinary free cortisol).
At least one additional test should be performed to confirm hypercortisolism in patients with a positive initial screening test.

Abdominal computed scan showing adrenocortical tumor infiltrating the pancreas and left kidney, and metastasized to the liver, spleen, and central nodes

From BMJ Case Reports 2010; doi:10.1136/bcr.07.2009.2100

Quick Reference

History & Exam
- Key Factors
- Other Factors
More information...
Diagnostics Tests
More information...
Treatment Options
More information...

Definition

Epidemiology

Etiology

Pathophysiology

Images

Abdominal computed scan showing adrenocortical tumor infiltrating the pancreas and left kidney, and metastasized to the liver, spleen, and central nodes
Abdominal striae in pregnancy
Algorithm for the treatment of Cushing disease (DST = dexamethasone suppression test. IPSS = inferior petrosal sinus sampling. ACTH = adrenocorticotropic hormone. *Pituitary surgery should be performed by an experienced surgeon. †Absence of ACTH-staining adenoma. §Lifelong monitoring for hypopituitarism and secondary neoplasia in the radiation field required. ¶On maximum tolerated dose of the drug)

Citations

Key Articles

Sharma ST, Nieman LK, Feelders RA. Cushing's syndrome: epidemiology and developments in disease management. Clin Epidemiol. 2015 Apr 17;7:281-93.[Abstract][Full Text]
Fleseriu M, Auchus R, Bancos I, et al. Consensus on diagnosis and management of Cushing's disease: a guideline update. Lancet Diabetes Endocrinol. 2021 Dec;9(12):847-75.[Abstract][Full Text]
Nieman LK, Biller BM, Findling JW, et al. Treatment of Cushing's syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2015 Aug;100(8):2807-31.[Abstract][Full Text]
Feelders RA, Newell-Price J, Pivonello R, et al. Advances in the medical treatment of Cushing's syndrome. Lancet Diabetes Endocrinol. 2019 Apr;7(4):300-12.[Abstract]
Ritzel K, Beuschlein F, Mickisch A, et al. Clinical review: outcome of bilateral adrenalectomy in Cushing's syndrome: a systematic review. J Clin Endocrinol Metab. 2013 Oct;98(10):3939-48.[Abstract][Full Text]

Other Online Resources

Algorithm for diagnosis of Cushing syndrome

Referenced Articles

1. Lacroix A, Feelders RA, Stratakis CA, et al. Cushing's syndrome. Lancet. 2015 Aug 29;386(9996):913-27.[Abstract]
2. Costa MH, Lacroix A. Cushing's syndrome secondary to ACTH-independent macronodular adrenal hyperplasia. Arq Bras Endocrinol Metabol. 2007 Nov;51(8):1226-37.[Abstract][Full Text]
3. Beuschlein F, Reincke M, Karl M, et al. Clonal composition of human adrenocortical neoplasms. Cancer Res. 1994 Sep 15;54(18):4927-32.[Abstract][Full Text]
4. Gicquel C, Bertagna X, Le Bouc Y. Recent advances in the pathogenesis of adrenocortical tumours. Eur J Endocrinol. 1995 Aug;133(2):133-44.[Abstract]
5. Stratakis CA. Cushing syndrome caused by adrenocortical tumors and hyperplasias (corticotropin-independent Cushing syndrome). Endocr Dev. 2008;13:117-32.[Abstract][Full Text]
6. Stratakis CA, Kirschner LS, Carney JA. Clinical and molecular features of the Carney complex: diagnostic criteria and recommendations for patient evaluation. J Clin Endocrinol Metab. 2001 Sep;86(9):4041-6.[Abstract][Full Text]
7. Horvath A, Stratakis C. Primary pigmented nodular adrenocortical disease and Cushing's syndrome. Arq Bras Endocrinol Metabol. 2007 Nov;51(8):1238-44.[Abstract][Full Text]
8. Sharma ST, Nieman LK, Feelders RA. Cushing's syndrome: epidemiology and developments in disease management. Clin Epidemiol. 2015 Apr 17;7:281-93.[Abstract][Full Text]
9. Ferrau F, Korbonits M. Metabolic comorbidities in Cushing's syndrome. Eur J Endocrinol. 2015 Oct;173(4):M133-57.[Abstract][Full Text]
10. Fassnacht M, Dekkers OM, Else T, et al. European Society of Endocrinology clinical practice guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2018 Oct 1;179(4):G1-46.[Abstract][Full Text]
11. Hakami OA, Ahmed S, Karavitaki N. Epidemiology and mortality of Cushing's syndrome. Best Pract Res Clin Endocrinol Metab. 2021 Jan;35(1):101521.[Abstract]
12. Anderson GH Jr, Blankeman N, Streeten DH. The effect of age on prevalence of secondary forms of hypertension in 4429 consecutively referred patients. J Hypertens. 1994 May;12(5):609-15.[Abstract]
13. Omura M, Saito J, Yamaguchi K, et al. Prospective study on the prevalence of secondary hypertension among hypertensive patients visiting a general outpatient clinic in Japan. Hypertens Res. 2004 Mar;27(3):193-202.[Abstract][Full Text]
14. Vaidya A, Hamrahian A, Bancos I, et al. The evaluation of incidentally discovered adrenal masses. Endocr Pract. 2019 Feb;25(2):178-92.[Abstract]
15. Chiodini I, Mascia ML, Muscarella S, et al. Subclinical hypercortisolism among outpatients referred for osteoporosis. Ann Intern Med. 2007 Oct 16;147(8):541-8.[Abstract]
16. Mehta GU, Lonser RR. Management of hormone-secreting pituitary adenomas. Neuro Oncol. 2017 Jun 1;19(6):762-73.[Abstract][Full Text]
17. Ben-Shlomo A, Cooper O. Silent corticotroph adenomas. Pituitary. 2018 Apr;21(2):183-93.[Abstract]
18. Perez-Rivas LG, Reincke M. Genetics of Cushing's disease: an update. J Endocrinol Invest. 2016 Jan;39(1):29-35.[Abstract]
19. Duan K, Gomez Hernandez K, Mete O. Clinicopathological correlates of adrenal Cushing's syndrome. J Clin Pathol. 2015 Mar;68(3):175-86.[Abstract][Full Text]
20. Hopkins RL, Leinung MC. Exogenous Cushing's syndrome and glucocorticoid withdrawal. Endocrinol Metab Clin North Am. 2005 Jun;34(2):371-84, ix.[Abstract]
21. Mebrahtu TF, Morgan AW, Keeley A, et al. Dose dependency of iatrogenic glucocorticoid excess and adrenal insufficiency and mortality: a cohort study in England. J Clin Endocrinol Metab. 2019 Apr 22;104(9):3757-67.[Abstract][Full Text]
22. Freda PU, Beckers AM, Katznelson L, et al. Pituitary incidentaloma: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Apr;96(4):894-904.[Abstract][Full Text]
23. 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 May;93(5):1526-40.[Abstract][Full Text]
24. Brzana J, Yedinak CG, Hameed N, et al. Polycystic ovarian syndrome and Cushing's syndrome: a persistent diagnostic quandary. Eur J Obstet Gynecol Reprod Biol. 2014 Apr;175:145-8.[Abstract]
25. 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 Jul-Aug;15(5):450-3.[Abstract][Full Text]
26. Fleseriu M, Auchus R, Bancos I, et al. Consensus on diagnosis and management of Cushing's disease: a guideline update. Lancet Diabetes Endocrinol. 2021 Dec;9(12):847-75.[Abstract][Full Text]
27. Nieman L. Cushing's: update on signs, symptoms and biochemical screening. Eur J Endocrinol. 2015 Oct;173(4):M33-8.[Abstract][Full Text]
28. Galm BP, Qiao N, Klibanski A, et al. Accuracy of laboratory tests for the diagnosis of Cushing syndrome. J Clin Endocrinol Metab. 2020 Jun 1;105(6):2081-94.[Abstract][Full Text]
29. Carroll TB, Raff H, Findling JW. Late-night salivary cortisol for the diagnosis of Cushing syndrome: a meta-analysis. Endocr Pract. 2009 May-Jun;15(4):335-42.[Abstract]
30. Raff H. Utility of salivary cortisol measurements in Cushing's syndrome and adrenal insufficiency. J Clin Endocrinol Metab. 2009 Oct;94(10):3647-55.[Abstract][Full Text]
31. Zhang Q, Dou J, Gu W, et al. Reassessing the reliability of the salivary cortisol assay for the diagnosis of Cushing syndrome. J Int Med Res. 2013 Oct;41(5):1387-94.[Abstract][Full Text]
32. Petersenn S, Newell-Price J, Findling JW, et al. High variability in baseline urinary free cortisol values in patients with Cushing's disease. Clin Endocrinol (Oxf). 2014 Feb;80(2):261-9.[Abstract][Full Text]
33. Elias PC, Martinez EZ, Barone BF, et al. Late-night salivary cortisol has a better performance than urinary free cortisol in the diagnosis of Cushing's syndrome. J Clin Endocrinol Metab. 2014 Jun;99(6):2045-51.[Abstract][Full Text]
34. Sandouk Z, Johnston P, Bunch D, et al. Variability of late-night salivary cortisol in Cushing disease: a prospective study. J Clin Endocrinol Metab. 2018 Mar 1;103(3):983-90.[Abstract][Full Text]
35. Keller J, Flores B, Gomez RG, et al. Cortisol circadian rhythm alterations in psychotic major depression. Biol Psychiatry. 2006 Aug 1;60(3):275-81.[Abstract]
36. Carroll BJ, Cassidy F, Naftolowitz D, et al. Pathophysiology of hypercortisolism in depression. Acta Psychiatr Scand Suppl. 2007;(433):90-103.[Abstract]
37. Raff H, Raff JL, Findling JW. Late-night salivary cortisol as a screening test for Cushing's syndrome. J Clin Endocrinol Metab. 1998 Aug;83(8):2681-6.[Abstract][Full Text]
38. Grober Y, Grober H, Wintermark M, et al. Comparison of MRI techniques for detecting microadenomas in Cushing's disease. J Neurosurg. 2017 Apr 28:1-7.[Abstract]
39. Newell-Price J, Trainer P, Besser M, et al. The diagnosis and differential diagnosis of Cushing's syndrome and pseudo-Cushing's states. Endocr Rev. 1998 Oct;19(5):647-72.[Abstract][Full Text]
40. Aron DC, Raff H, Findling JW. Effectiveness versus efficacy: the limited value in clinical practice of high dose dexamethasone suppression testing in the differential diagnosis of adrenocorticotropin-dependent Cushing's syndrome. J Clin Endocrinol Metab. 1997 Jun;82(6):1780-5.[Abstract][Full Text]
41. Raff H, Findling JW. A physiologic approach to diagnosis of the Cushing syndrome. Ann Intern Med. 2003 Jun 17;138(12):980-91.[Abstract]
42. Oldfield EH, Doppman JL, Nieman LK, et al. Petrosal sinus sampling with and without corticotropin-releasing hormone for the differential diagnosis of Cushing's syndrome. N Engl J Med. 1991 Sep 26;325(13):897-905.[Abstract][Full Text]
43. Findling JW, Kehoe ME, Shaker JL, et al. Routine inferior petrosal sinus sampling in the differential diagnosis of adrenocorticotropin (ACTH)-dependent Cushing's syndrome: early recognition of the occult ectopic ACTH syndrome. J Clin Endocrinol Metab. 1991 Aug;73(2):408-13.[Abstract]
44. Doppman JL, Pass HI, Nieman LK, et al. Detection of ACTH-producing bronchial carcinoid tumors: MR imaging vs CT. AJR Am J Roentgenol. 1991 Jan;156(1):39-43.[Abstract][Full Text]
45. Pacak K, Ilias I, Chen CC, et al. The role of (18)F-fluorodeoxyglucose positron emission tomography and (111)In-diethylenetriaminepentaacetate-D-Phe-pentetreotide scintigraphy in the localization of ectopic adrenocorticotropin-secreting tumors causing Cushing's syndrome. J Clin Endocrinol Metab. 2004 May;89(5):2214-21.[Abstract][Full Text]
46. Panagiotidis E, Alshammari A, Michopoulou S, et al. Comparison of the impact of 68Ga-DOTATATE and 18F-FDG PET/CT on clinical management in patients with neuroendocrine tumors. J Nucl Med. 2017 Jan;58(1):91-6.[Abstract][Full Text]
47. Santhanam P, Taieb D, Giovanella L, et al. PET imaging in ectopic Cushing syndrome: a systematic review. Endocrine. 2015 Nov;50(2):297-305.[Abstract]
48. Barrio M, Czernin J, Fanti S, et al. The impact of somatostatin receptor-directed PET/CT on the management of patients with neuroendocrine tumor: a systematic review and meta-analysis. J Nucl Med. 2017 May;58(5):756-61.[Abstract]
49. Delivanis DA, Athimulam S, Bancos I. Modern management of mild autonomous cortisol secretion. Clin Pharmacol Ther. 2019 Dec;106(6):1209-21.[Abstract]
50. Masserini B, Morelli V, Bergamaschi S, et al. The limited role of midnight salivary cortisol levels in the diagnosis of subclinical hypercortisolism in patients with adrenal incidentaloma. Eur J Endocrinol. 2009 Jan;160(1):87-92.[Abstract][Full Text]
51. Pivonello R, De Martino MC, Colao A. How should patients with adrenal incidentalomas be followed up? Lancet Diabetes Endocrinol. 2014 May;2(5):352-4.[Abstract]
52. 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 Aug;175(2):G1-34.[Abstract][Full Text]
53. Paschou SA, Kandaraki E, Dimitropoulou F, et al. Subclinical Cushing's syndrome in patients with bilateral compared to unilateral adrenal incidentalomas: a systematic review and meta-analysis. Endocrine. 2016 Feb;51(2):225-35.[Abstract]
54. Scaroni C, Zilio M, Foti M, et al. Glucose metabolism abnormalities in Cushing syndrome: from molecular basis to clinical management. Endocr Rev. 2017 Jun 1;38(3):189-219.[Abstract][Full Text]
55. Steffensen C, Pereira AM, Dekkers OM, et al. Diagnosis of endocrine disease: prevalence of hypercortisolism in type 2 diabetes patients: a systematic review and meta-analysis. Eur J Endocrinol. 2016 Dec;175(6):R247-53.[Abstract][Full Text]
56. Pivonello R, Isidori AM, De Martino MC, et al. Complications of Cushing's syndrome: state of the art. Lancet Diabetes Endocrinol. 2016 Jul;4(7):611-29.[Abstract]
57. Dorn LD, Burgess ES, Dubbert B, et al. Psychopathology in patients with endogenous Cushing's syndrome: 'atypical' or melancholic features. Clin Endocrinol (Oxf). 1995 Oct;43(4):433-42.[Abstract]
58. Bourdeau I, Bard C, Forget H, et al. Cognitive function and cerebral assessment in patients who have Cushing's syndrome. Endocrinol Metab Clin North Am. 2005 Jun;34(2):357-69;ix.[Abstract]
59. van der Pas R, Leebeek FW, Hofland LJ, et al. Hypercoagulability in Cushing's syndrome: prevalence, pathogenesis and treatment. Clin Endocrinol (Oxf). 2013 Apr;78(4):481-8.[Abstract][Full Text]
60. Stuijver DJ, van Zaane B, Feelders RA, et al. Incidence of venous thromboembolism in patients with Cushing's syndrome: a multicenter cohort study. J Clin Endocrinol Metab. 2011 Nov;96(11):3525-32.[Abstract][Full Text]
61. Stratakis CA. Skin manifestations of Cushing's syndrome. Rev Endocr Metab Disord. 2016 Sep;17(3):283-6.[Abstract][Full Text]
62. Pecori Giraldi F, Moro M, Cavagnini F, et al. Gender-related differences in the presentation and course of Cushing's disease. J Clin Endocrinol Metab. 2003 Apr;88(4):1554-8.[Abstract][Full Text]
63. Carroll T, Raff H, Findling JW. Late-night salivary cortisol measurement in the diagnosis of Cushing's syndrome. Nat Clin Pract Endocrinol Metab. 2008 Jun;4(6):344-50.[Abstract]
64. Elamin MB, Murad MH, Mullan R, et al. Accuracy of diagnostic tests for Cushing's syndrome: a systematic review and metaanalyses. J Clin Endocrinol Metab. 2008 May;93(5):1553-62.[Abstract][Full Text]
65. Invitti C, Pecori Giraldi F, Dubini A, et al. Increased urinary free cortisol and decreased serum corticosteroid-binding globulin in polycystic ovary syndrome. Acta Endocrinol (Copenh). 1991 Jul;125(1):28-32.[Abstract]
66. Rowe NE, Kumar RM, Schieda N, et al. Canadian Urological Association guideline: diagnosis, management, and followup of the incidentally discovered adrenal mass. Can Urol Assoc J. 2023 Feb;17(2):12-24.[Abstract][Full Text]
67. American College of Radiology. ACR appropriateness criteria: adrenal mass evaluation. 2021 [internet publication].[Full Text]
68. Nieman LK, Biller BM, Findling JW, et al. Treatment of Cushing's syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2015 Aug;100(8):2807-31.[Abstract][Full Text]
69. Swearingen B, Biller BM, Barker FG 2nd, et al. Long-term mortality after transsphenoidal surgery for Cushing disease. Ann Intern Med. 1999 May 18;130(10):821-4.[Abstract]
70. Hammer GD, Tyrrell JB, Lamborn KR, et al. Transsphenoidal microsurgery for Cushing's disease: initial outcome and long-term results. J Clin Endocrinol Metab. 2004 Dec;89(12):6348-57.[Abstract][Full Text]
71. Pivonello R, De Leo M, Cozzolino A, et al. The treatment of Cushing's disease. Endocr Rev. 2015 Aug;36(4):385-486.[Abstract][Full Text]
72. Broersen LHA, Biermasz NR, van Furth WR, et al. Endoscopic vs. microscopic transsphenoidal surgery for Cushing's disease: a systematic review and meta-analysis. Pituitary. 2018 Oct;21(5):524-34.[Abstract][Full Text]
73. Abu Dabrh AM, Singh Ospina NM, Al Nofal A, et al. Predictors of biochemical remission and recurrence after surgical and radiation treatments of Cushing disease: a systematic disease: a systematic review and meta-analysis. Endocr Pract. 2016 Apr;22(4):466-75.[Abstract]
74. Patil CG, Prevedello DM, Lad SP, et al. Late recurrences of Cushing's disease after initial successful transsphenoidal surgery. J Clin Endocrinol Metab. 2008 Feb;93(2):358-62.[Abstract][Full Text]
75. Fleseriu M, Hamrahian AH, Hoffman AR, et al; AACE Neuroendocrine and Pituitary Scientific Committee. American Association of Clinical Endocrinologists and American College of Endocrinology Disease State Clinical Review: diagnosis of recurrence in Cushing disease. Endocr Pract. 2016 Dec;22(12):1436-48.[Abstract]
76. Sughrue ME, Shah JK, Devin JK, et al. Utility of the immediate postoperative cortisol concentrations in patients with Cushing's disease. Neurosurgery. 2010 Sep;67(3):688-95.[Abstract]
77. Hameed N, Yedinak CG, Brzana J, et al. Remission rate after transsphenoidal surgery in patients with pathologically confirmed Cushing's disease, the role of cortisol, ACTH assessment and immediate reoperation: a large single center experience. Pituitary. 2013 Dec;16(4):452-8.[Abstract]
78. Danet-Lamasou M, Asselineau J, Perez P, et al. Accuracy of repeated measurements of late-night salivary cortisol to screen for early-stage recurrence of Cushing's disease following pituitary surgery. Clin Endocrinol (Oxf). 2015 Feb;82(2):260-6.[Abstract]
79. Braun LT, Rubinstein G, Zopp S, et al. Recurrence after pituitary surgery in adult Cushing's disease: a systematic review on diagnosis and treatment. Endocrine. 2020 Nov;70(2):218-31.[Abstract][Full Text]
80. Reincke M, Ritzel K, Osswald A, et al. A critical re-appraisal of bilateral adrenalectomy for ACTH-dependent Cushing's syndrome. Eur J Endocrinol. 2015 Oct;173(4):M23-32.[Abstract][Full Text]
81. Cuevas-Ramos D, Fleseriu M. Treatment of Cushing's disease: a mechanistic update. J Endocrinol. 2014 Nov;223(2):R19-39.[Abstract][Full Text]
82. Friedman RB, Oldfield EH, Nieman LK, et al. Repeat transsphenoidal surgery for Cushing's disease. J Neurosurg. 1989 Oct;71(4):520-7.[Abstract]
83. Benveniste RJ, King WA, Walsh J, et al. Repeated transsphenoidal surgery to treat recurrent or residual pituitary adenoma. J Neurosurg. 2005 Jun;102(6):1004-12.[Abstract]
84. Hofmann BM, Hlavac M, Kreutzer J, et al. Surgical treatment of recurrent Cushing's disease. Neurosurgery. 2006 Jun;58(6):1108-18.[Abstract]
85. Sonino N, Zielezny M, Fava GA, et al. Risk factors and long-term outcome in pituitary-dependent Cushing's disease. J Clin Endocrinol Metab. 1996 Jul;81(7):2647-52.[Abstract][Full Text]
86. Castinetti F, Nagai M, Dufour H, et al. Gamma knife radiosurgery is a successful adjunctive treatment in Cushing's disease. Eur J Endocrinol. 2007 Jan;156(1):91-8.[Abstract][Full Text]
87. Devin JK, Allen GS, Cmelak AJ, et al. The efficacy of linear accelerator radiosurgery in the management of patients with Cushing's disease. Stereotact Funct Neurosurg. 2004;82(5-6):254-62.[Abstract]
88. Estrada J, Boronat M, Mielgo M, et al. The long-term outcome of pituitary irradiation after unsuccessful transsphenoidal surgery in Cushing's disease. N Engl J Med. 1997 Jan 16;336(3):172-7.[Abstract][Full Text]
89. Starke RM, Williams BJ, Vance ML, et al. Radiation therapy and stereotactic radiosurgery for the treatment of Cushing's disease: an evidence-based review. Curr Opin Endocrinol Diabetes Obes. 2010 Aug;17(4):356-64.[Abstract]
90. Varlamov EV, McCartney S, Fleseriu M. Functioning pituitary adenomas - current treatment options and emerging medical therapies. Eur Endocrinol. 2019 Apr;15(1):30-40.[Abstract][Full Text]
91. Feelders RA, Newell-Price J, Pivonello R, et al. Advances in the medical treatment of Cushing's syndrome. Lancet Diabetes Endocrinol. 2019 Apr;7(4):300-12.[Abstract]
92. Hinojosa-Amaya JM, Cuevas-Ramos D, Fleseriu M. Medical management of Cushing's syndrome: current and emerging treatments. Drugs. 2019 Jun;79(9):935-56.[Abstract]
93. Broersen LHA, Jha M, Biermasz NR, et al. Effectiveness of medical treatment for Cushing's syndrome: a systematic review and meta-analysis. Pituitary. 2018 Dec;21(6):631-41.[Abstract][Full Text]
94. Colao A, Petersenn S, Newell-Price J, et al. A 12-month phase 3 study of pasireotide in Cushing's disease. N Engl J Med. 2012 Mar 8;366(10):914-24.[Abstract][Full Text]
95. Lacroix A, Gu F, Gallardo W, et al. Efficacy and safety of once-monthly pasireotide in Cushing's disease: a 12 month clinical trial. Lancet Diabetes Endocrinol. 2018 Jan;6(1):17-26.[Abstract]
96. Simeoli C, Auriemma RS, Tortora F, et al. The treatment with pasireotide in Cushing's disease: effects of long-term treatment on tumor mass in the experience of a single center. Endocrine. 2015 Dec;50(3):725-40.[Abstract]
97. Findling JW, Fleseriu M, Newell-Price J, et al. Late-night salivary cortisol may be valuable for assessing treatment response in patients with Cushing's disease: 12-month, phase III pasireotide study. Endocrine. 2016 Nov;54(2):516-23.[Abstract][Full Text]
98. Trementino L, Michetti G, Angeletti A, et al. A single-center 10-year experience with pasireotide in Cushing's disease: patients' characteristics and outcome. Horm Metab Res. 2016 May;48(5):290-8.[Abstract][Full Text]
99. Petersenn S, Fleseriu M. Pituitary-directed medical therapy in Cushing's disease. Pituitary. 2015 Apr;18(2):238-44.[Abstract]
100. Palui R, Sahoo J, Kamalanathan S, et al. Effect of cabergoline monotherapy in Cushing's disease: an individual participant data meta-analysis. J Endocrinol Invest. 2018 Dec;41(12):1445-55.[Abstract]
101. Pivonello R, Fleseriu M, Newell-Price J, et al. Efficacy and safety of osilodrostat in patients with Cushing's disease (LINC 3): a multicentre phase III study with a double-blind, randomised withdrawal phase. Lancet Diabetes Endocrinol. 2020 Sep;8(9):748-61.[Abstract]
102. Castinetti F, Guignat L, Giraud P, et al. Ketoconazole in Cushing's disease: is it worth a try? J Clin Endocrinol Metab. 2014 May;99(5):1623-30.[Abstract][Full Text]
103. US Food and Drug Administration. FDA drug safety communication: FDA warns that prescribing of Nizoral (ketoconazole) oral tablets for unapproved uses including skin and nail infections continues; linked to patient death. May 2016 [internet publication].[Full Text]
104. Fleseriu M, Castinetti F. Updates on the role of adrenal steroidogenesis inhibitors in Cushing's syndrome: a focus on novel therapies. Pituitary. 2016 Dec;19(6):643-53.[Abstract][Full Text]
105. Fleseriu M, Pivonello R, Elenkova A, et al. Efficacy and safety of levoketoconazole in the treatment of endogenous Cushing's syndrome (SONICS): a phase 3, multicentre, open-label, single-arm trial. Lancet Diabetes Endocrinol. 2019 Nov;7(11):855-65.[Abstract]
106. Zacharieva SZ, Pivonello R, Elenkova A, et al. MON-332 safety and efficacy of levoketoconazole in the treatment of endogenous Cushing's syndrome (LOGICS): a double-blind, placebo-controlled, withdrawal study. J Endocr Soc. 2020 May 8;4(suppl 1):MON-332.[Full Text]
107. Fleseriu M, Findling JW, Koch CA, et al. Changes in plasma ACTH levels and corticotroph tumor size in patients with Cushing's disease during long-term treatment with the glucocorticoid receptor antagonist mifepristone. J Clin Endocrinol Metab. 2014 Oct;99(10):3718-27.[Abstract][Full Text]
108. Fleseriu M, Biller BM, Findling JW, et al; SEISMIC Study Investigators. Mifepristone, a glucocorticoid receptor antagonist, produces clinical and metabolic benefits in patients with Cushing's syndrome. J Clin Endocrinol Metab. 2012 Jun;97(6):2039-49.[Abstract][Full Text]
109. Neychev V, Steinberg SM, Yang L, et al. Long-term outcome of bilateral laparoscopic adrenalectomy measured by disease-specific questionnaire in a unique group of patients with Cushing's syndrome. Ann Surg Oncol. 2015 Dec;22 Suppl 3:S699-706.[Abstract]
110. Ritzel K, Beuschlein F, Mickisch A, et al. Clinical review: outcome of bilateral adrenalectomy in Cushing's syndrome: a systematic review. J Clin Endocrinol Metab. 2013 Oct;98(10):3939-48.[Abstract][Full Text]
111. Fleseriu M, Hashim IA, Karavitaki N, et al. Hormonal replacement in hypopituitarism in adults: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016 Nov;101(11):3888-921.[Abstract][Full Text]
112. Bancos I, Alahdab F, Crowley RK, 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. Eur J Endocrinol. 2016 Dec;175(6):R283-95.[Abstract][Full Text]
113. Cohan P, East HE, Galati SJ, et al. Mifepristone treatment in four cases of primary bilateral macronodular adrenal hyperplasia (BMAH). J Clin Endocrinol Metab. 2019 Dec 1;104(12):6279-90.[Abstract][Full Text]
114. Fleseriu M, Petersenn S. Medical management of Cushing's disease: what is the future? Pituitary. 2012 Sep;15(3):330-41.[Abstract][Full Text]
115. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: neuroendocrine and adrenal tumors [internet publication].[Full Text]
116. Yip L, Duh QY, Wachtel H, et al. American Association of Endocrine Surgeons guidelines for adrenalectomy: executive summary. JAMA Surg. 2022 Oct 1;157(10):870-7.[Abstract]
117. De Tommasi C, Vance ML, Okonkwo DO, et al. Surgical management of adrenocorticotropic hormone-secreting macroadenomas: outcome and challenges in patients with Cushing's disease or Nelson's syndrome. J Neurosurg. 2005 Nov;103(5):825-30.[Abstract]
118. Faggiano A, Pivonello R, Spiezia S, 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. 2003 Jun;88(6):2527-33.[Abstract][Full Text]
119. Van der Klaauw AA, Kars M, Biermasz NR, et al. Disease-specific impairments in quality of life during long-term follow-up of patients with different pituitary adenomas. Clin Endocrinol (Oxf). 2008 Nov;69(5):775-84.[Abstract]
120. Knoble N, Nayroles G, Cheng C, et al. Illustration of patient-reported outcome challenges and solutions in rare diseases: a systematic review in Cushing's syndrome. Orphanet J Rare Dis. 2018 Dec 19;13(1):228.[Abstract][Full Text]
121. Petersenn S, Beckers A, Ferone D, et al. Therapy of endocrine disease: outcomes in patients with Cushing's disease undergoing transsphenoidal surgery: systematic review assessing criteria used to define remission and recurrence. Eur J Endocrinol. 2015 June;172(6):R227-39.[Abstract][Full Text]
122. Blevins LS Jr, Christy JH, Khajavi M, et al. Outcomes of therapy for Cushing's disease due to adrenocorticotropin-secreting pituitary macroadenomas. J Clin Endocrinol Metab. 1998 Jan;83(1):63-7.[Abstract][Full Text]
123. Qiao N. Outcome of endoscopic vs microsurgical transsphenoidal resection for Cushing's disease. Endocr Connect. 2018 Jan;7(1):R26-37.[Abstract][Full Text]
124. Dhandapani S, Narayanan R, Jayant SS, et al. Endonasal endoscopic versus microscopic transsphenoidal surgery in pituitary tumors among the young: a comparative study & meta-analysis. Clin Neurol Neurosurg. 2021 Jan;200:106411.[Abstract]
125. Park J, De Luca A, Dutton H, et al. Cardiovascular outcomes in autonomous cortisol secretion and nonfunctioning adrenal adenoma: a systematic review. J Endocr Soc. 2019 May 1;3(5):996-1008.[Abstract][Full Text]
126. Arnaldi G, Angeli A, Atkinson AB, et al. Diagnosis and complications of Cushing's syndrome: a consensus statement. J Clin Endocrinol Metab. 2003 Dec;88(12):5593-602.[Abstract][Full Text]
127. St-Jean M, Lim DST, Langlois F. Hypercoagulability in Cushing's syndrome: from arterial to venous disease. Best Pract Res Clin Endocrinol Metab. 2021 Mar;35(2):101496.[Abstract]
128. Chee GH, Mathias DB, James RA, et al. Transsphenoidal pituitary surgery in Cushing's disease: can we predict outcome? Clin Endocrinol (Oxf). 2001 May;54(5):617-26.[Abstract]
129. McCance DR, Gordon DS, Fannin TF, et al. Assessment of endocrine function after transsphenoidal surgery for Cushing's disease. Clin Endocrinol (Oxf). 1993 Jan;38(1):79-86.[Abstract]
130. Assié G, Bahurel H, Coste J, et al. Corticotroph tumor progression after adrenalectomy in Cushing's disease: a reappraisal of Nelson's syndrome. J Clin Endocrinol Metab. 2007 Jan;92(1):172-9.[Abstract][Full Text]
131. Cote DJ, Alzarea A, Acosta MA, et al. Predictors and rates of delayed symptomatic hyponatremia after transsphenoidal surgery: a systematic review. World Neurosurg. 2016 Apr;88:1-6. [Erratum in: World Neurosurg. 2016 May 31;S1878-8750(16)30270-4.][Abstract]
132. Rees DA, Hanna FW, Davies JS, et al. Long-term follow-up results of transsphenoidal surgery for Cushing's disease in a single centre using strict criteria for remission. Clin Endocrinol (Oxf). 2002 Apr;56(4):541-51.[Abstract]
133. Yap LB, Turner HE, Adams CB, et al. Undetectable postoperative cortisol does not always predict long-term remission in Cushing's disease: a single centre audit. Clin Endocrinol (Oxf). 2002 Jan;56(1):25-31.[Abstract]
134. Burke CW, Adams CB, Esiri MM, et al. Transsphenoidal surgery for Cushing's disease: does what is removed determine the endocrine outcome? Clin Endocrinol (Oxf). 1990 Oct;33(4):525-37.[Abstract]
135. Trainer PJ, Lawrie HS, Verhelst JA, et al. Transsphenoidal resection in Cushing's disease: undetectable serum cortisol as the definition of successful treatment. Clin Endocrinol (Oxf). 1993 Jan;38(1):73-8.[Abstract]
136. Semple CG, Thomson JA, Teasdale GM. Transsphenoidal microsurgery for Cushing's disease. Clin Endocrinol (Oxf). 1984 Dec;21(6):621-9.[Abstract]
137. Smith TR, Hulou MM, Huang KT, et al. Complications after transsphenoidal surgery for patients with Cushing's disease and silent corticotroph adenomas. Neurosurg Focus. 2015 Feb;38(2):E12.[Abstract][Full Text]
138. Prete A, Corsello SM, Salvatori R. Current best practice in the management of patients after pituitary surgery. Ther Adv Endocrinol Metab. 2017 Mar;8(3):33-48.[Abstract][Full Text]