Pharmacology · Adrenal steroid synthesis inhibitors

Metyrapone !

A blocker of the last step of cortisol synthesis. It tests pituitary ACTH reserve and can lower cortisol in Cushing syndrome.

Updated 2026-11-01

Class: Adrenal steroid synthesis inhibitors
Enzyme: Steroid 11β-hydroxylase (CYP11B1)
ATC code: V04CD01

Steroid 11β-hydroxylase (CYP11B1)Metyrapone

The figure shows metyrapone itself bound to the heme of human CYP11B1 (an engineered mutant used for crystallisation).

Target in 3D: Steroid 11β-hydroxylase (CYP11B1). PDB structure 7E7F (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Metyrapone binds the heme iron of 11β-hydroxylase (CYP11B1), the mitochondrial enzyme that turns 11-deoxycortisol into cortisol in the adrenal cortex. Cortisol and corticosterone fall. With a normal pituitary, ACTH rises and drives more 11-deoxycortisol, which is measured in the test of pituitary reserve. The accumulating precursors have mineralocorticoid and androgen effects.

Metyrapone binds the heme of 11β-hydroxylase (CYP11B1)
11-deoxycortisol is not converted to cortisol
Cortisol falls; a normal pituitary raises ACTH
11-deoxycortisol accumulates and can be measured

Pharmacokinetics

Absorption: Given by mouth as capsules

Indications

Test of pituitary ACTH reserve (metyrapone test)
Control of severe cortisol excess in Cushing syndrome while the cause is treated Cushing syndrome →

Adverse effects

Common

Dizziness and sedation
Nausea and abdominal discomfort
Headache
Hirsutism and acne with longer use

Contraindications

Adrenal cortical insufficiency
Hypersensitivity to metyrapone

Key interactions

Anticonvulsants, psychotropic drugs, hormone preparations, corticosteroids, antithyroid drugs and cyproheptadine: Can distort the result of the metyrapone test
Paracetamol (acetaminophen): Metyrapone inhibits its glucuronidation

What is monitored

Cortisol (and 11-deoxycortisol) levels
Symptoms of adrenal insufficiency
Blood pressure and potassium

Administration and safety

Given by mouth; drugs that distort the test are reviewed beforehand
Before the test, the adrenal glands' ability to respond to ACTH is confirmed

Nursing care

Watch for weakness, dizziness, low blood pressure, nausea and vomiting (adrenal insufficiency)
Warn about drowsiness and dizziness: no driving until it passes
Time the blood samples exactly as the test protocol states

Pregnancy and breastfeeding

It is the adrenal inhibitor that can be used in pregnant women with Cushing syndrome, with specialist follow-up.

Test yourself

Think of the answer, then tap the question to see it.

In a metyrapone test, what result shows a normal pituitary reserve?

Cortisol falls while ACTH and 11-deoxycortisol rise, showing the pituitary responded to low cortisol.

Why can metyrapone cause hypertension and hypokalaemia?

Precursors such as 11-deoxycorticosterone build up behind the block and act as mineralocorticoids.

Which adrenal inhibitor can be used in pregnancy for Cushing syndrome?

Metyrapone.

Add to my cards (3)

Hydrocortisone

Cushing syndrome

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Farmacología básica y clínica (Katzung), 16.ª ed., cap. 39 (McGraw Hill, 2025); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); Human CYP11B1 mutant in complex with metyrapone (RCSB Protein Data Bank, 2021).

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Representative model, for educational purposes only.