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 excluding exogenous corticosteroid use, patients with suspected Cushing syndrome should be tested for hypercortisolism with one of three high-sensitivity tests (late-night salivary cortisol, 1 mg overnight low-dose dexamethasone suppression testing, or 24-hour urinary free cortisol).
At least one additional test should be performed 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.
Surgical resection of the pituitary or adrenal adenoma that is causing hypercortisolism is the primary treatment of choice in the vast majority of patients with endogenous Cushing syndrome.
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 exogenous corticosteroid exposure, 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
Key diagnostic factors
- facial plethora
- supraclavicular fullness
- violaceous striae
- absence of pregnancy
- menstrual irregularities
- absence of malnutrition
- absence of alcoholism
- absence of physiologic stress
- linear growth deceleration in children
Other diagnostic factors
- 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
- exogenous corticosteroid use
- pituitary adenoma
- adrenal adenoma
- adrenal carcinoma
- neuroendocrine tumors
- thoracic or bronchogenic carcinoma
1st investigations to order
- urine pregnancy test
- serum glucose
- late-night salivary cortisol
- 1 mg overnight dexamethasone suppression test
- 24-hour urinary free cortisol
- 48-hour 2 mg (low-dose) dexamethasone suppression test
Investigations to consider
- plasma dehydroepiandrosterone sulfate (DHEAS) level
- morning plasma adrenocorticotropic hormone (ACTH)
- pituitary MRI
- adrenal CT
- high-dose dexamethasone suppression test
- inferior petrosal sinus sampling (IPSS)
- CT of chest, abdomen, and pelvis
- MRI chest
- octreotide scanning
- gallium-68 DOTATATE PET/CT
Cushing disease (adrenocorticotropic hormone [ACTH]-secreting pituitary tumor)
ectopic ACTH or corticotropin-releasing hormone (CRH) syndrome
ACTH-independent due to unilateral adrenal carcinoma or adenoma
ACTH-independent due to bilateral adrenal disease (hyperplasia or adenoma)
- Metabolic syndrome
- Diagnosis, management, and followup of the incidentally discovered adrenal mass
- American Association of Endocrine Surgeons guidelines for adrenalectomy
Cushing syndrome caused by an internal problem
Cushing syndrome caused by medicationMore Patient leaflets
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