The clinical manifestation of pathological hypercortisolism from any cause.
Cushing's disease, which is hypercortisolism caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma, is the most common cause of Cushing's syndrome, and is responsible for 70% to 80% of cases.
Though uncommon, the prevalence of endogenous Cushing syndrome is greater than previously thought.
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 pathological 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, dyslipidaemia, metabolic bone disease, and hypertension. Cushing syndrome can be caused by adrenocorticotropic hormone (ACTH)-secreting pituitary tumours (termed Cushing's disease), by autonomous adrenal cortisol overproduction, and, rarely, by ectopic ACTH-secreting tumours.
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
- plasma dehydroepiandrosterone sulphate (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
- PET scan
- octreotide scanning
Professor of Medicine (Endocrinology) and Neurological Surgery
Oregon Health & Science University
MF is the Pituitary Society's President Elect, and sits on it's Board of Directors. She holds a research grant to the University for Clinical Studies as Principal Investigator for Novartis and Strongbridge, and is Scientific Consultant for Novartis and Strongbridge. MF is an author of several references cited in this monograph.
Dr Maria Fleseriu would like to gratefully acknowledge Dr Ty Carroll and Dr James Finding, previous contributors to this monograph. TC is an author of a number of references cited in this monograph. He is an investigator in clinical trials sponsored by Corcept. JF is an author of a number of references cited in this monograph. 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.
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