Recent Updates on the Diagnosis and Management of Cushing's Syndrome

다국어 초록 (Multilingual Abstract)

Cushing’s syndrome, a potentially lethal disorder characterized by endogenous hypercortisolism, may be difficult to recognize, especially when it is mild and the presenting features are common in the general population. However, there is a need to identify the condition at an early stage, as it tends to progress, accruing additional morbidity and increasing mortality rates. Once a clinical suspicion is raised, screening tests involve timed measurement of urine, serum or salivary cortisol at baseline or after administration of dexamethasone, 1 mg. Each test has caveats, so that the choice of tests must be individualized for each patient. Once the diagnosis is established, and the cause is determined, surgical resection of abnormal tumor/tissue is the optimal treatment. When this cannot be achieved, medical treatment (or bilateral adrenalectomy) must be used to normalize cortisol production. Recent updates in screening for and treating Cushing’s syndrome are reviewed here.

참고문헌 (Reference)

1 Atkinson B, "What is the best approach to suspected cyclical Cushing syndrome? Strategies for managing Cushing's syndrome with variable laboratory data" 75 : 27-30, 2011

2 Nieman LK, "Treatment of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline" 100 : 2807-2831, 2015

3 Alexandraki KI, "The prevalence and characteristic features of cyclicity and variability in Cushing's disease" 160 : 1011-1018, 2009

4 Findling JW, "The low-dose dexamethasone suppression test: a reevaluation in patients with Cushing's syndrome" 89 : 1222-1226, 2004

5 Lindsay JR, "The hypothalamic-pituitary-adrenal axis in pregnancy: challenges in disease detection and treatment" 26 : 775-799, 2005

6 Peltzer K, "The globalization of whitening: prevalence of skin lighteners (or bleachers) use and its social correlates among university students in 26 countries" 55 : 165-172, 2016

7 Nieman LK, "The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline" 93 : 1526-1540, 2008

8 Baid SK, "Specificity of screening tests for Cushing's syndrome in an overweight and obese population" 94 : 3857-3864, 2009

9 Kritikou I, "Sleep apnoea and the hypothalamic-pituitary-adrenal axis in men and women: effects of continuous positive airway pressure" 47 : 531-540, 2016

10 Paez-Pereda M, "Retinoic acid prevents experimental Cushing syndrome" 108 : 1123-1131, 2001

11 Corcuff JB, "Rapid control of severe neoplastic hypercortisolism with metyrapone and ketoconazole" 172 : 473-481, 2015

12 Pecori Giraldi F, "Potential role for retinoic acid in patients with Cushing's disease" 97 : 3577-3583, 2012

13 Pivonello R, "Pasireotide treatment significantly improves clinical signs and symptoms in patients with Cushing's disease: results from a phase III study" 81 : 408-417, 2014

14 Fleseriu M, "Osilodrostat, a potent oral $11{\beta}$-hydroxylase inhibitor: 22-week, prospective, phase II study in Cushing's disease" 19 : 138-148, 2016

15 Clayton RN, "Mortality in patients with Cushing's disease more than 10 years after remission: a multicentre, multinational, retrospective cohort study" 4 : 569-576, 2016

16 Kamenicky P, "Mitotane, metyrapone, and ketoconazole combination therapy as an alternative to rescue adrenalectomy for severe ACTH-dependent Cushing's syndrome" 96 : 2796-2804, 2011

17 Fleseriu M, "Mifepristone, a glucocorticoid receptor antagonist, produces clinical and metabolic benefits in patients with Cushing's syndrome" 97 : 2039-2049, 2012

18 Riedl M, "Long term control of hypercortisolism with fluconazole: case report and in vitro studies" 154 : 519-524, 2006

19 Kidambi S, "Limitations of nocturnal salivary cortisol and urine free cortisol in the diagnosis of mild Cushing's syndrome" 157 : 725-731, 2007

20 Bertagna X, "LCI699, a potent 1$1{\beta}$-hydroxylase inhibitor, normalizes urinary cortisol in patients with Cushing's disease: results from a multicenter, proof-of-concept study" 99 : 1375-1383, 2014

21 van der Pas R, "Hypercoagulability in Cushing's syndrome: prevalence, pathogenesis and treatment" 78 : 481-488, 2013

22 Mericq MV, "High fluid intake increases urine free cortisol excretion in normal subjects" 83 : 682-684, 1998

23 van der Pas R, "Fluconazole inhibits human adrenocortical steroidogenesis in vitro" 215 : 403-412, 2012

24 Raff H, "Elevated salivary cortisol in the evening in healthy elderly men and women: correlation with bone mineral density" 54 : 479-483, 1999

25 Liu H, "Elevated late-night salivary cortisol levels in elderly male type 2 diabetic veterans" 63 : 642-649, 2005

26 Vilar L, "Effectiveness of cabergoline in monotherapy and combined with ketoconazole in the management of Cushing's disease" 13 : 123-129, 2010

27 Chan KC, "Diminished urinary free cortisol excretion in patients with moderate and severe renal impairment" 50 : 757-759, 2004

28 Alwani RA, "Differentiating between Cushing's disease and pseudo-Cushing's syndrome: comparison of four tests" 170 : 477-486, 2014

29 Creemers SG, "Cushing's syndrome: an update on current pharmacotherapy and future directions" 16 : 1829-1844, 2015

30 Lacroix A, "Cushing's syndrome" 386 : 913-927, 2015

31 Sarlis NJ, "Cortisolemic indices predict severe infections in Cushing syndrome due to ectopic production of adrenocorticotropin" 85 : 42-47, 2000

32 Chong YK, "Corticosteroid adulteration in proprietary Chinese medicines: a recurring problem" 21 : 411-416, 2015

33 Valassi E, "Concomitant medication use can confound interpretation of the combined dexamethasone-corticotropin releasing hormone test in Cushing's syndrome" 94 : 4851-4859, 2009

34 Olumide YM, "Complications of chronic use of skin lightening cosmetics" 47 : 344-353, 2008

35 Miller R, "Comparison of salivary cortisol as measured by different immunoassays and tandem mass spectrometry" 38 : 50-57, 2013

36 Maneli MH, "Combinations of potent topical steroids, mercury and hydroquinone are common in internationally manufactured skin-lightening products: a spectroscopic study" 41 : 196-201, 2016

37 Barbot M, "Combination therapy for Cushing's disease: effectiveness of two schedules of treatment: should we start with cabergoline or ketoconazole?" 17 : 109-117, 2014

38 Godbout A, "Cabergoline monotherapy in the long-term treatment of Cushing's disease" 163 : 709-716, 2010

39 Besemer F, "Alcohol-induced Cushing syndrome. Hypercortisolism caused by alcohol abuse" 69 : 318-323, 2011

40 Luger A, "Acute hypothalamic-pituitary-adrenal responses to the stress of treadmill exercise. Physiologic adaptations to physical training" 316 : 1309-1315, 1987

41 Biller BM, "Abnormal cortisol secretion and responses to corticotropin-releasing hormone in women with hypothalamic amenorrhea" 70 : 311-317, 1990

42 Colao A, "A 12-month phase 3 study of pasireotide in Cushing's disease" 366 : 914-924, 2012