Cushing’s Syndrome

Cushing’s Syndrome

·        = Chronic glucocorticoid excess, either exogenous or endogenous (adrenal or pituitary neoplasm, or ectopic ACTH secretion)

·        Signs: Tissue wasting, myopathy, thin skin, purple abdominal striae, easy bruising, osteoporosis, water retention, supraclavicular fat-pad (“buffalo hump”), predisposition to infection, bad wound healing, hirsutism, amenorrhoea, hyperglycaemia (30%)

·        Tests:

o   Confirm source biochemically before looking radiologically. CT adrenal „incidentalomas‟ are common Þ does not prove adrenal source of cortisol excess

o   Screening tests:

§  24h urinary free cortisol (normal < 280 nmol/24 hr). If positive then high dose dexamethasone suppression test.

§  Alternative is low dose dexamethasone suppression test: give 1 mg po at midnight, check cortisol at 8 am (normal 450 – 700 nmol/L). False positives with depression, obesity and drugs affecting metabolism of dexamethasone (eg phenytoin, phenobarbitone)

§  Midnight cortisol nearly as good: but must do as an inpatient (need to wake to do it and be unstressed) – midnight is low point of diurnal cycle, if high then diurnal cycle depressed

o   Do high dose dexamethasone test (8mg) to determine type of Cushing‟s or if obese

·        Causes and treatment:

o   Exogenous corticosteroid administration: reduce as much as possible. In asthma, use inhaled steroids

o   Cushing‟s Disease: (adrenal hyperplasia secondary to pituitary tumour, F > M, peak age 30 – 50).

o   Some, but not normal, suppression of cortisol with high dose dexamethasone. Treatment: Surgical removal of pituitary adenoma

o   Adrenal gland adenoma or carcinoma: No suppression of cortisol with high dose.  Undetectable

o   ACTH. Treatment: surgical removal

·        Ectopic ACTH production: especially small cell carcinoma of the lung and carcinoid. No suppression of cortisol with high dose dexamethasone. Plasma ACTH generally >250 ng/L. Hypokalaemic alkalosis is common. CT relevant areas (lung, pancreas, mediastinum, thyroid)

·        Can block adrenal cortisol production with ketoconazole