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# Adrenal steroid synthesis inhibitors

Drugs that block enzymes of the adrenal cortex to lower cortisol in Cushing syndrome or to test the pituitary-adrenal axis.

Updated 2026-11-01

## What they are

Inhibitors of the cytochrome P450 enzymes that make cortisol (and sometimes aldosterone and androgens). They control severe cortisol excess while the cause is being treated, or are used as diagnostic tools.

## Mechanism of action

Cortisol is made from cholesterol in a chain of P450 steps; the last is 11β-hydroxylation of 11-deoxycortisol by CYP11B1. Metyrapone blocks that step, ketoconazole and osilodrostat act at other or the same points, and mitotane damages the adrenal cortex. With less cortisol, the pituitary raises ACTH, and the precursor before the block builds up.

Target: Adrenal cytochrome P450 enzymes, especially 11β-hydroxylase (CYP11B1)

## Key points

- Metyrapone blocks 11β-hydroxylase: cortisol falls and 11-deoxycortisol rises.
- The metyrapone test checks pituitary ACTH reserve: a normal pituitary raises ACTH and 11-deoxycortisol.
- Excess 11-deoxycortisol has mineralocorticoid action, so salt and water retention can occur.
- Any of these drugs can tip a patient into adrenal insufficiency.

## Drugs in this class

- [**Metyrapone** A blocker of the last step of cortisol synthesis. It tests pituitary ACTH reserve and can lower cortisol in Cushing… Steroid 11β-hydroxylase (CYP11B1)](https://durgical.com/en/pharmacology/metyrapone/)

## Others in the class

- Ketoconazole
- Osilodrostat
- Mitotane
- Etomidate

## Test yourself

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

## Which enzyme does metyrapone inhibit, and which precursor accumulates?

11β-hydroxylase (CYP11B1); 11-deoxycortisol accumulates because it is not converted to cortisol.

## What does a rise in 11-deoxycortisol after metyrapone show?

That the pituitary responded to falling cortisol by raising ACTH: the pituitary-adrenal axis has reserve.

## What is the main risk of all adrenal synthesis inhibitors?

Adrenal insufficiency from too much cortisol suppression.

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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](https://atcddd.fhi.no/atc_ddd_index/?code=V04CD01) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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