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 exclusion of exogenous corticosteroid use, patients with suspected Cushing syndrome should be tested for hypercortisolism with 1 of 4 high-sensitivity tests (late-night salivary cortisol; 1 mg overnight low-dose dexamethasone suppression testing, 24-hour urinary free cortisol; or 48-hour 2 mg dexamethasone suppression testing).
At least one additional test should be used to confirm hypercortisolism in patients with a positive initial screening test.
Once endogenous hypercortisolism is confirmed, plasma ACTH should be measured. If ACTH is suppressed, diagnostic testing should focus on the adrenal glands. If ACTH is not suppressed, pituitary or ectopic disease should be sought.
In the vast majority of cases of endogenous Cushing syndrome, surgical resection of the pituitary adenoma or adrenal adenoma that is causing hypercortisolism is the primary treatment of choice.
Cushing syndrome is the clinical manifestation of pathologic hypercortisolism from any cause. Patients often display weight gain with central obesity, facial rounding and plethora, proximal muscle weakness, and thinning of the skin. They also develop metabolic complications including diabetes mellitus, dyslipidemia, metabolic bone disease, and hypertension. Cushing syndrome can be caused by adrenocorticotropic hormone (ACTH)-secreting pituitary tumors (termed Cushing disease), by autonomous adrenal cortisol overproduction, and, rarely, by ectopic ACTH-secreting tumors.
History and exam
- female sex
- glucose intolerance or diabetes mellitus
- premature osteoporosis or unexplained fractures
- weight gain and central obesity
- psychiatric symptoms
- decreased libido
- easy bruisability
- facial rounding
- dorsocervical fat pads
- unexplained nephrolithiasis
- venothrombolic event
- plasma dehydroepiandrosterone sulfate (DHEAS) level
- morning plasma adrenocorticotropic hormone (ACTH)
- high-dose dexamethasone suppression test
- pituitary MRI
- adrenal CT
- inferior petrosal sinus sampling
- CT of chest, abdomen, and pelvis
- MRI chest
- octreotide scanning
- gallium-68 DOTATATE PET/CT
Professor of Medicine (Endocrinology) and Neurological Surgery
Oregon Health & Science University
MF is the Pituitary Society's President and sits on its Board of Directors. She holds a research grant to the University for Clinical Studies as Principal Investigator for Novartis, Millendo, and Strongbridge, and is an occasional Scientific Consultant for Novartis and Strongbridge. MF is an author of several references cited in this topic.
Dr Maria Fleseriu would like to gratefully acknowledge Dr Ty Carroll and Dr James Findling, previous contributors to this topic.
TC is an author of a number of references cited in this topic. He is an investigator in clinical trials sponsored by Corcept. JF is an author of a number of references cited in this topic. He is a consultant for, and investigator in, clinical trials sponsored by Corcept and Novartis.
Professor of Medicine
Director of Research
College of Medical and Dental Sciences
University of Birmingham
Honorary Consultant Physician
Queen Elizabeth Hospital
PMS declares that he has no competing interests.
Department of Endocrinology
University Hospital of Bordeaux
AT declares that he has no competing interests.
Endocrine Research Department
Instituto de Investigaciones Médicas A. Lanari
University of Buenos Aires and IDIM-CONICET
LC declares that she has no competing interests.
Professor of Medicine
Division of Endocrinology, Diabetes & Metabolism
University of Texas Medical School
PRO declares that he has no competing interests.
Department of Endocrine Neoplasia and Hormonal Disorders
Division of Internal Medicine
University of Texas MD Anderson Cancer Center
MAH declares that he has no competing interests.
Use of this content is subject to our disclaimer