A drug used in the diagnosis of adrenal insufficiency and occasionally in the treatment of Cushing’s syndrome.
Blocks cortisol synthesis by inhibiting steroid 11β-hydroxylase.
Blocking cortisol synthesis stimulates ACTH secretion, which in turn increases plasma 11-deoxycortisol levels.
Because it is essentially devoid of glucocorticoid activity, 11-deoxycortisol does not inhibit ACTH secretion.
In normal patients the fall in serum cortisol concentrations leads sequentially to increases in ACTH secretion, adrenal steroidogenesis, and the secretion of cortisol precursors, in particular, 11-deoxycortisol, or 17-hydroxycorticosteroid.
When excess ACTH secretion is the cause of hypercortisolism, the metyrapone test helps clarify if the source of the ACTH is pituitary or ectopic (non-pituitary).
The metyrapone stimulation test-Metyrapone 30mg/kg, maximum dose 3000 mg, is administered at midnight and the plasma cortisol and 11-deoxycortisol are measured the next morning between 8:00 and 9:00 am: a plasma cortisol less than 220nmol/l indicates adequate inhibition of 11β-hydroxylase.
In patients with intact Hypothamalmo-pituitary-adrenal axis, cortico-releasing hormone and ACTH levels rise as a response to the falling cortisol levels: This results in an increase of the steroid precursors in the pathway, so that if 11-deoxycortisol levels do not rise and remains less than 7 mcg/dl then it is highly suggestive of impaired HPA axis.
Most patients with pituitary dysfunction and/or pituitary microadenoma will increase ACTH secretion in response to metyrapone.
Most ectopic ACTH-producing tumors will not increase in response to metyrapone.
Pituitary macroadenomas do not always respond to metyrapone.
The utilization of the metyrapone stimulation test has become less frequent as a result of the larger availability of plasma ACTH assays.