2. • Cushing's syndrome reflects a constellation of
clinical features that result from chronic exposure to
excess glucocorticoids of any etiology
• ACTH dependent or ACTH independent
• Cushing's disease refers specifically to Cushing's
syndrome caused by a pituitary corticotrope
adenoma
• Most common cause is supraphysiologic doses of
corticosteroid drugs
4. Establishing diagnosis of Cushing’s syndrome
Determination of the cause
• Requires
• Clinical evaluation
• Investigations
5. • The majority of clinical signs and symptoms
observed in Cushing's syndrome are relatively
nonspecific (such as obesity, diabetes, hypertension,
depression)
• Some clinical features are more specific (such as
fragility of the skin, with easy bruising; broad,
purplish striae; signs of proximal myopathy)
• Thorough history to rule out iatrogenic Cushing's
syndrome
6. • A combination of clinical feature is more specific than
any single feature alone
• excess ACTH can cause hyperpigmentation of the
knuckles, scars, or skin areas exposed to increased
friction (more common in ectopic ACTH)
7. • Clinical suspicion
Establish ACTH
dependent/independent
Screening/confirmation of diagnosis
Clinical suspicion of Cushing's
9. Nature of Adrenal Pathology
(Hyperplasia/Adenoma/Carcinoma)
ACTH independent
Cushing’s syndrome
10. At least 2 tests among available options should
be performed to make the diagnosis
• 24-h urinary free cortisol excretion
• Increased above normal (3x)
• Should be done at least twice
• Overnight dexamethasone suppression test:
• 1mg dexamethasone at 11pm
• Plasma cortisol > 50nmol/L at 8-9am
11. • Midnight plasma cortisol level
• >130nmol/L
• Midnight salivary cortisol
• >5nmol/L
• Should be done at least twice
• Low dose dexamethasone suppression test
• 0.5mg dexamethasone 6 hourly for 2 days
• Plasma cortisol >50 nmol/l
12. • ACTH dependent Cushing’s
• ACTH normal or high > 15pg/ml
• ACTH independent Cushing’s
• ACTH suppressed < 5pg/ml
13. • MRI pituitary
• CRH stimulation test
• IV CRH 100 µg
• Positive for pituitary source if
• ACTH increase >40% at 15-30min
• Cortisol increase >20% at 45-60min
• High dose dexamethasone suppression test
• 2mg dexamethasone 6 hourly for 48 hours
• Positive for pituitary source if >50% cortisol
suppression
14. • Inferior petrosal sinus sampling
• For equivocal results
• Positive for pituitary source if
• ACTH ratio (venous sinus/peripheral blood) >2
at base line
• >3 at 3-5min after CRH 100 µg IV