Diagnosis of Cushings Syndrome

This is a summary of the Endocrine Society guideline in JCEM 2008; 93: 1526.

Whom To Investigate?

Other conditions with hypercortisolism

Some clinical features of Cushings may be present Clinical features of Cushings unlikely to be present
Pregnancy Physical stress pain
Depression and other psychiatric conditions Malnutrition, anorexia nervosa
Alcohol dependence Excessive exercise
Glucocorticoid resistance Hypothalamic amenorrhea
Morbid obesity CBG excess (increased total serum cortisol)
Poorly controlled diabetes  
Features suggestive of Cushing's syndrome

Most discriminatory features Other signs Overlapping conditions
NB most do not have high sensitivity Common and less discriminatory Other diagnoses that may suggest Cushing's syndrome
Easy bruising Buffalo hump Hypertension
Facial plethora Facial fullness Adrenal lump
Proximal myopathy Obesity Vertebral osteoporosis
Striae (esp. livid and >1 cm wide) Thin skin PCOS
In children, weight gain & decreasing growth velocity Acne Type 2 diabetes
  Hirsutism or female balding Hypokalaemia

Screening tests

Algorithm for suspected Cushing's syndrome
Conditions affecting screening tests

Condition Effect
Oral contraceptive use
Oestrogens increase cortisol binding globulin
Serum measurements of total cortisol are increased
Urinary free cortisol measurement is recommended
Enzyme inducers (phenytoin, carbamazepine, rifampicin, phenobarbitone, alcohol) Accelerate dexamethasone clearance
Suppressed cortisol measurements are unreliable
Unsuppressed urine or saliva measurement recommended
Renal failure Overnight DST recommended
Urinary free cortisol not recommended

Notes on dexamethasone suppression test

1mg overnight dexamethasone suppression test
Criterion <50 nmol/l Sensitivity 95%, specificity 80%
Criterion <140 nmol/l Sensitivity 85%, specificity 95%
48hr, 2mg/day dexamethasone suppression test
  • 0.5mg dex at 0900-0300-1500-0300, test at 0900
  • when other conditions may cause hypercortisolism, e.g. diabetes, morbid obesity, alcoholism
  • serum cortisol is more accurate and simpler than UFC
Criterion <50 nmol/l Sensitivity 95%, specificity about 70%
High-dose dexamethasone suppression test
  • used in Metabolic Unit protocol
  • 0.5mg qds, then 2mg qds
Suppression of UFC with high but not low-dose dex Typical of pituitary disease
CRH test
Where Cushings syndrome confirmed
100mcg CRH IV, samples at 15,30,45,60,120 min
Peak cortisol >20% over baseline Typical of pituitary disease
Peak ACTH >15% over baseline Typical of pituitary disease