Laboratory Studies

The diagnosis of Cushing syndrome requires the demonstration of an inappropriately high level of cortisol in the serum or urine. The levels should be measured when cortisol, according to its physiologic circadian rhythm, is supposed to be suppressed, meaning at midnight or when a patient is given exogenous glucocorticoids.

This concept gives rise to the following tests, which have been recommended as screening tests for Cushing syndrome:^{[2, 3]}

Midnight serum or salivary cortisol^{[4, 5, 6]}
24-hour urine free cortisol
Low-dose dexamethasone suppression test (Liddle test)

An adrenocorticotropic hormone (ACTH) level obtained at the same time as the cortisol level can be helpful in identifying the etiology of Cushing syndrome.

Diagnosis of Cushing syndrome.

View Media Gallery

Other Tests

A study by Álvarez-Hernández et al indicated that the clinical severity index of Cushing syndrome, developed by Sonino et al, while useful in endogenous Cushing syndrome, can also effectively be employed in patients with the iatrogenic form of the condition (specifically, in this report, those who had undergone at least 4 weeks of glucocorticoid treatment for rheumatologic disease). Once the definitions of subjective clinical variables had been standardized, the investigators found that the index adequately correlated with clinical manifestations associated with chronic glucocorticoid use.^[33]

Treatment & Management

Chaudhry HS, Singh G. Cushing Syndrome. StatPearls. 2022 Jan. [QxMD MEDLINE Link]. [Full Text].
Eddy RL, Jones AL, Gilliland PF, Ibarra JD Jr, Thompson JQ, MacMurry JF Jr. Cushing's syndrome: a prospective study of diagnostic methods. Am J Med. 1973 Nov. 55(5):621-30. [QxMD MEDLINE Link].
Kaye TB, Crapo L. The Cushing syndrome: an update on diagnostic tests. Ann Intern Med. 1990 Mar 15. 112(6):434-44. [QxMD MEDLINE Link].
Carroll T, Raff H, Findling JW. Late-night salivary cortisol for the diagnosis of Cushing syndrome: a meta-analysis. Endocr Pract. 2009 Jul-Aug. 15(4):335-42. [QxMD MEDLINE Link].
Kidambi S, Raff H, Findling JW. Limitations of nocturnal salivary cortisol and urine free cortisol in the diagnosis of mild Cushing's syndrome. Eur J Endocrinol. 2007 Dec. 157(6):725-31. [QxMD MEDLINE Link].
Raff H. Utility of salivary cortisol measurements in Cushing's syndrome and adrenal insufficiency. J Clin Endocrinol Metab. 2009 Jul 14. [QxMD MEDLINE Link].
Chrousos GP, Gold PW. The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis. JAMA. 1992 Mar 4. 267(9):1244-52. [QxMD MEDLINE Link].
Melmed S, Polonsky KS, Larsen PR, Kronenberg HM. Williams Textbook of Endocrinology. 12th ed. Elsevier Health Sciences; May 12, 2011. 488-491.
Meduri GU, Muthiah MP, Carratu P, Eltorky M, Chrousos GP. Nuclear factor-kappaB- and glucocorticoid receptor alpha- mediated mechanisms in the regulation of systemic and pulmonary inflammation during sepsis and acute respiratory distress syndrome. Evidence for inflammation-induced target tissue resistance to glucocorticoids. Neuroimmunomodulation. 2005. 12(6):321-38. [QxMD MEDLINE Link].
Christ-Crain M, Kola B, Lolli F, Fekete C, Seboek D, Wittmann G, et al. AMP-activated protein kinase mediates glucocorticoid-induced metabolic changes: a novel mechanism in Cushing's syndrome. FASEB J. 2008 Jun. 22(6):1672-83. [QxMD MEDLINE Link].
Jonat C, Rahmsdorf HJ, Park KK, Cato AC, Gebel S, Ponta H, et al. Antitumor promotion and antiinflammation: down-modulation of AP-1 (Fos/Jun) activity by glucocorticoid hormone. Cell. 1990 Sep 21. 62(6):1189-204. [QxMD MEDLINE Link].
Serfling G, Buades-Rotger M, Harbeck B, Kramer UM, Brabant G. The corticosteroid prednisolone increases amygdala and insula reactivity to food approach signals in healthy young men. Psychoneuroendocrinology. 2018 Sep 8. 99:154-65. [QxMD MEDLINE Link].
Liapi C, Chrousos GP. Glucocorticoids. Jaffe SJ, Aranda JV, eds. Therapeutic Principles in Practice. 2nd ed. Philadelphia, Pa: WB Saunders; 1992. 466-475.
Dekkers AJ, Amaya JM, van der Meulen M, Biermasz NR, Meijer OC, Pereira AM. Long-term effects of glucocorticoid excess on the brain. J Neuroendocrinol. 2022 Aug. 34 (8):e13142. [QxMD MEDLINE Link]. [Full Text].
Tuel SM, Meythaler JM, Cross LL. Cushing's syndrome from epidural methylprednisolone. Pain. 1990 Jan. 40(1):81-4. [QxMD MEDLINE Link].
Matos AC, Srirangalingam U, Barry T, Grossman AB. Cushing's syndrome with low levels of serum cortisol: the role of inhaled steroids. Clin Med. 2011 Aug. 11(4):404-5. [QxMD MEDLINE Link].
Dutta D, Shivaprasad KS, Ghosh S, Mukhopadhyay S, Chowdhury S. Iatrogenic Cushing's syndrome following short-term intranasal steroid use. J Clin Res Pediatr Endocrinol. 2012 Sep. 4(3):157-9. [QxMD MEDLINE Link]. [Full Text].
Gen R, Akbay E, Sezer K. Cushing syndrome caused by topical corticosteroid: a case report. Am J Med Sci. 2007 Mar. 333(3):173-4. [QxMD MEDLINE Link].
Bolland MJ, Bagg W, Thomas MG, Lucas JA, Ticehurst R, Black PN. Cushing's syndrome due to interaction between inhaled corticosteroids and itraconazole. Ann Pharmacother. 2004 Jan. 38(1):46-9. [QxMD MEDLINE Link].
Samaras K, Pett S, Gowers A, McMurchie M, Cooper DA. Iatrogenic Cushing's syndrome with osteoporosis and secondary adrenal failure in human immunodeficiency virus-infected patients receiving inhaled corticosteroids and ritonavir-boosted protease inhibitors: six cases. J Clin Endocrinol Metab. 2005 Jul. 90(7):4394-8. [QxMD MEDLINE Link].
Kedem E, Shahar E, Hassoun G, Pollack S. Iatrogenic Cushing's syndrome due to coadministration of ritonavir and inhaled budesonide in an asthmatic human immunodeficiency virus infected patient. J Asthma. 2010 Sep. 47(7):830-1. [QxMD MEDLINE Link].
Celik O, Niyazoglu M, Soylu H, Kadioglu P. Iatrogenic Cushing's syndrome with inhaled steroid plus antidepressant drugs. Multidiscip Respir Med. 2012 Aug 29. 7(1):26. [QxMD MEDLINE Link]. [Full Text].
Duman AK, Fulco PP. Adrenal Insufficiency With Voriconazole and Inhaled/Intranasal Corticosteroids: Case Report and Systematic Review. J Pharm Pract. 2016 May 4. [QxMD MEDLINE Link].
Epperla N, McKiernan F. Iatrogenic Cushing syndrome and adrenal insufficiency during concomitant therapy with ritonavir and fluticasone. Springerplus. 2015. 4:455. [QxMD MEDLINE Link]. [Full Text].
Joshi RR, Maresh A. Iatrogenic Cushing's syndrome and adrenal insufficiency in infants on intranasal dexamethasone drops for nasal obstruction - Case series and literature review. Int J Pediatr Otorhinolaryngol. 2018 Feb. 105:123-6. [QxMD MEDLINE Link].
Yeoh SW. Iatrogenic Cushing Syndrome from Interaction Between Ritonavir and Oral Budesonide During Direct Acting Antiviral Hepatitis C Therapy. J Clin Exp Hepatol. 2016 Sep. 6 (3):246-9. [QxMD MEDLINE Link].
Mann M, Koller E, Murgo A, Malozowski S, Bacsanyi J, Leinung M. Glucocorticoidlike activity of megestrol. A summary of Food and Drug Administration experience and a review of the literature. Arch Intern Med. 1997 Aug 11-25. 157(15):1651-6. [QxMD MEDLINE Link].
Krapf R. Development of Cushing's syndrome after use of a herbal remedy. Lancet. 2002 Dec 7. 360(9348):1884. [QxMD MEDLINE Link].
Abuchaibe C, Akhtar ON. SAT-0776:Exogenous Cushing's Syndrome after Use of OTC Joint Supplement. Adrenal Case Reports 1 - CAH and Adrenal Insufficiency. Endocrine Society's 96th Annual Meeting and Expo, June 21–24, 2014 – Chicago. Available at http://press.endocrine.org/doi/abs/10.1210/endo-meetings.2014.AHPAA.1.SAT-0776. Accessed: 4/2/15.
Newell-Price J, Trainer P, Besser M, Grossman A. The diagnosis and differential diagnosis of Cushing's syndrome and pseudo-Cushing's states. Endocr Rev. 1998 Oct. 19(5):647-72. [QxMD MEDLINE Link].
Findling JW, Doppman JL. Biochemical and radiologic diagnosis of Cushing's syndrome. Endocrinol Metab Clin North Am. 1994 Sep. 23(3):511-37. [QxMD MEDLINE Link].
Anastasopoulou C. Pseudo-Cushing Syndrome. Medscape Drugs & Diseases. Available at http://emedicine.medscape.com/article/124718-overview. Accessed: 4/3/15.
Alvarez-Hernandez E, Mercado-Molina G, Barrera-Guerra RC. Validity of the Cushing's Syndrome Severity Index in Patients with Iatrogenic Cushing's Syndrome. Reumatol Clin. 2019 Dec 13. [QxMD MEDLINE Link].

Media Gallery

Physical findings in Cushing syndrome.
Diagnosis of Cushing syndrome.

of 2

Table 1. Glucocorticoid Equivalencies^[13]

Table 1. Glucocorticoid Equivalencies ^[13]

Type	Drug	Dose	Relative Glucocorticoid Potency	Relative Mineralocorticoid Potency	Plasma Half-Life (mg)	Biologic Half-Life (h)
Short-acting	Cortisol	20	1.0	2	90	8-12
Short-acting	Hydrocortisone^‡	25	0.8	2	80-118	8-12
Intermediate-acting	Prednisone	5	4	1	60	18-36
	Prednisolone	5	4	1	115-200	18-36
	Triamcinolone	4	5	0	30	18-36
	Methylprednisolone	4	5	0	180	18-36
Long-acting	Dexamethasone	0.5	25-50	0	200	36-54
Long-acting	Betamethasone	0.6	25-50	0	300	36-54
Mineralocorticoid	Aldosterone	0.3	0	300	15-20	8-12
	Fludrocortisone	2	15	150	200	18-36
	Desoxycorticosterone acetate	0	0	20	70	…

Back to List

Author

Ha Cam Thuy Nguyen, MD Fellow, Department of Endocrinology, University of Pittsburgh Medical Center

Ha Cam Thuy Nguyen, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Medical Association, Endocrine Society

Disclosure: Nothing to disclose.

Coauthor(s)

Catherine Anastasopoulou, MD, PhD, FACE Associate Professor of Medicine, The Steven, Daniel and Douglas Altman Chair of Endocrinology, Sidney Kimmel Medical College of Thomas Jefferson University; Einstein Endocrine Associates, Einstein Medical Center

Catherine Anastasopoulou, MD, PhD, FACE is a member of the following medical societies: American Association of Clinical Endocrinologists, American Society for Bone and Mineral Research, Endocrine Society, Philadelphia Endocrine Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Romesh Khardori, MD, PhD, FACP (Retired) Professor, Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.

Acknowledgements

Gail K Adler, MD, PhD, Associate Professor of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School.

Disclosure: Nothing to disclose.

Susanna L Dipp, MD Fellow, Department of Medicine, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School

Disclosure: Nothing to disclose

Don S Schalch, MD Professor Emeritus, Department of Internal Medicine, Division of Endocrinology, University of Wisconsin Hospitals and Clinics

Don S Schalch, MD is a member of the following medical societies: American Diabetes Association, American Federation for Medical Research, Central Society for Clinical Research, and Endocrine Society

Disclosure: Nothing to disclose