Metyrapone

How it works

It inhibits the 11-beta-hydroxylase enzyme, blocking the final step of cortisol synthesis and thereby lowering circulating cortisol.

Prescribing in practice

• Over-suppression of cortisol can precipitate acute adrenal insufficiency, so cortisol must be monitored and patients counselled on recognising and managing adrenal crisis.
• Accumulation of steroid precursors with androgenic and mineralocorticoid activity can cause hirsutism, hypertension, oedema and hypokalaemia.
• It is also used as a diagnostic test of pituitary-adrenal axis function, where careful timing and interpretation are required.

Monitoring

Monitor serum or urinary cortisol, blood pressure, potassium and clinical signs of both under- and over-treatment.

Counselling the patient

• Take exactly as directed, usually with food to reduce nausea.
• Seek urgent help for symptoms of adrenal insufficiency such as severe fatigue, dizziness, nausea or low blood pressure.
• Attend all blood tests so the dose can be adjusted accurately.

Evidence & guidelines

Metyrapone is a long-established agent for controlling cortisol excess in Cushing's syndrome and for assessing pituitary-adrenal reserve.