Cushing Syndrome Differential Diagnoses

Author: Gail K Adler, MD, PhD; Chief Editor: George T Griffing, MD more...

Updated: Feb 22, 2012

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Diagnostic Considerations

Renal failure

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Psychiatric illness

Differentiation of Cushing syndrome from pseudo–Cushing syndrome can sometimes be a challenge. A pseudo-Cushing state is defined as having some of the clinical features and biochemical evidence of Cushing syndrome. However, resolution of the primary condition results in disappearance of the cushingoid features and biochemical abnormalities.

In patients who chronically abuse alcohol, clinical and biochemical findings suggestive of Cushing syndrome are often encountered. Discontinuation of alcohol causes disappearance of these abnormalities, and, therefore, this syndrome is often specifically referred to as alcohol-induced pseudo-Cushing syndrome.

Patients with depression often have perturbation of the HPA axis, with abnormal cortisol hypersecretion. These patients rarely develop clinical Cushing syndrome. Because excess glucocorticoids can lead to emotional liability and depression, distinguishing between depression and mild Cushing syndrome is often a diagnostic challenge.

Differential Diagnoses

Proceed to Workup

Contributor Information and Disclosures

Author

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

Gail K Adler, MD, PhD is a member of the following medical societies: American Heart Association and Endocrine Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Frederick H Ziel, MD Associate Professor of Medicine, University of California, Los Angeles, David Geffen School of Medicine; Physician-In-Charge, Endocrinology/Diabetes Center, Director of Medical Education, Kaiser Permanente Woodland Hills; Chair of Endocrinology, Co-Chair of Diabetes Complete Care Program, Southern California Permanente Medical Group

Frederick H Ziel, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Federation for Medical Research, American Medical Association, American Society for Bone and Mineral Research, California Medical Association, Endocrine Society, and International Society for Clinical Densitometry

Disclosure: Nothing to disclose.

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

Disclosure: Medscape Salary Employment

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.

Mark Cooper, MBBS, PhD, FRACP Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD Professor of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

We wish to thank Susanna L Dipp, MD, Fellow, Department of Medicine, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, for her previous contributions to this entry.

References

Ilias I, Torpy DJ, Pacak K, Mullen N, Wesley RA, Nieman LK. Cushing's syndrome due to ectopic corticotropin secretion: twenty years' experience at the National Institutes of Health. J Clin Endocrinol Metab. Aug 2005;90(8):4955-62. [Medline].
Pereira AM, Delgado V, Romijn JA, et al. Cardiac dysfunction is reversed upon successful treatment of Cushing's syndrome. Eur J Endocrinol. Feb 2010;162(2):331-40. [Medline].
Brown RJ, Kelly MH, Collins MT. Cushing Syndrome in the McCune-Albright Syndrome. J Clin Endocrinol Metab. Feb 15 2010;[Medline].
Flack MR, Oldfield EH, Cutler GB Jr, et al. Urine free cortisol in the high-dose dexamethasone suppression test for the differential diagnosis of the Cushing syndrome. Ann Intern Med. Feb 1 1992;116(3):211-7. [Medline].
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. Dec 2007;157(6):725-31. [Medline].
Tyrrell JB, Findling JW, Aron DC, Fitzgerald PA, Forsham PH. An overnight high-dose dexamethasone suppression test for rapid differential diagnosis of Cushing's syndrome. Ann Intern Med. Feb 1986;104(2):180-6. [Medline].
Raff H. Utility of salivary cortisol measurements in Cushing's syndrome and adrenal insufficiency. J Clin Endocrinol Metab. Jul 14 2009;[Medline].
Carroll T, Raff H, Findling JW. Late-night salivary cortisol for the diagnosis of Cushing syndrome: a meta-analysis. Endocr Pract. Jul-Aug 2009;15(4):335-42. [Medline].
Chrousos GP, Gold PW. The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis. JAMA. Mar 4 1992;267(9):1244-52. [Medline].
Mulligan GB, Eray E, Faiman C, et al. Reduction of false-negative results in inferior petrosal sinus sampling with simultaneous prolactin and corticotropin measurement. Endocr Pract. Jan-Feb 2011;17(1):33-40. [Medline].
Donadille B, Groussin L, Waintrop C, et al. Management of Cushing's syndrome due to ectopic adrenocorticotropin secretion with 1,ortho-1, para'-dichloro-diphenyl-dichloro-ethane: findings in 23 patients from a single center. J Clin Endocrinol Metab. Feb 2010;95(2):537-44. [Medline].
Johanssen S, Allolio B. Mifepristone (RU 486) in Cushing's syndrome. Eur J Endocrinol. Nov 2007;157(5):561-9. [Medline].
Lila AR, Gopal RA, Acharya SV, George J, Sarathi V, Bandgar T, et al. Efficacy of cabergoline in uncured (persistent or recurrent) Cushing disease after pituitary surgical treatment with or without radiotherapy. Endocr Pract. Nov-Dec 2010;16(6):968-76. [Medline].
Batista DL, Oldfield EH, Keil MF, et al. Postoperative testing to predict recurrent Cushing disease in children. J Clin Endocrinol Metab. Aug 2009;94(8):2757-65. [Medline].
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. Nov 1973;55(5):621-30. [Medline].
Findling JW, Doppman JL. Biochemical and radiologic diagnosis of Cushing's syndrome. Endocrinol Metab Clin North Am. Sep 1994;23(3):511-37. [Medline].
Kaye TB, Crapo L. The Cushing syndrome: an update on diagnostic tests. Ann Intern Med. Mar 15 1990;112(6):434-44. [Medline].
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. Oct 1998;19(5):647-72. [Medline].
Nieman L, Cutler GB Jr. Cushing's syndrome. In: Degroot LJ, Besser M, Burger HG, et al, eds. Endocrinology. 3^rd ed. Philadelphia, Pa: WB Saunders; 1995:1741-69.
Pavlatos FC, Smilo RP, Forsham PH. A rapid screening test for Cushing's syndrome. JAMA. Aug 30 1965;193:720-3. [Medline].
Plotz CM, Knowlton AI, Ragan C. The natural history of Cushing's syndrome. Am J Med. Nov 1952;13(5):597-614. [Medline].
Raff H, Findling JW. A physiologic approach to diagnosis of the Cushing syndrome. Ann Intern Med. Jun 17 2003;138(12):980-91. [Medline].
Yanovski JA, Cutler GB Jr. Glucocorticoid action and the clinical features of Cushing's syndrome. Endocrinol Metab Clin North Am. Sep 1994;23(3):487-509. [Medline].
Corcept Therapeutics Incorporated announces FDA approval of Korlym (mifepristone) 300 mg tablets: First and only approved medication for Cushing's Syndrome Patients. Corcept Therapeutics. Available at http://www.corcept.com/news_events/pr_1329524335. Accessed February 21, 2012.

Physical findings in Cushing syndrome.

Diagnosis of Cushing syndrome.

Etiology of Cushing syndrome.

Table. States of Increased and Decreased HPA Activity

Table. States of Increased and Decreased HPA Activity

States of Increased HPA Activity	States of Decreased HPA Activity
Chronic stress^[9] Melancholic depression Anorexia nervosa Obsessive-compulsive disorder Panic disorder Excessive exercise Chronic active alcoholism Alcohol and nicotine withdrawal Diabetes mellitus Central obesity Sexual abuse Hyperthyroidism Premenstrual tension syndrome Cushing syndrome Pregnancy	Adrenal insufficiency Atypical/seasonal depression Chronic fatigue syndrome Fibromyalgia Hypothyroidism Nicotine withdrawal Post glucocorticoid therapy Post-Cushing syndrome Postpartum period Post-chronic stress^[9] Rheumatoid arthritis

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