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Adrenal Steroidogenesis Inhibitor Pregnancy: Avoid — risk of adrenal insufficiency in mother and fetus; androgen precursor accumulation may cause virilisation of female fetus. Seek specialist advice.

Metyrapone

Brand names: Metopirone

Adult dose

Dose: Cushing's syndrome (medical management): 250mg–1g TDS initially; titrate based on urinary free cortisol and serum cortisol; usual dose 2.25–6g daily in divided doses. Diagnostic test (metyrapone test for ACTH reserve): 750mg orally every 4 hours for 6 doses (30mg/kg max; administered at midnight for standard protocol).
Route: Oral (take with food — reduces nausea)
Frequency: Three to four times daily (treatment); every 4 hours (diagnostic test)
Max: 6g daily (treatment); weight-based for diagnostic test
Inhibits 11-beta-hydroxylase (CYP11B1) — the final step in cortisol synthesis. Cortisol falls but 11-deoxycortisol accumulates. ACTH rises reactively (in pituitary-dependent Cushing's). Used as bridging therapy before pituitary surgery or radiotherapy. Not a cure — cortisol will return to high levels if stopped.

Paediatric dose

Dose: 15 mg/kg
Route: Oral
Frequency: Three times daily
Max: Individualised
BNFc: 15mg/kg TDS (minimum 250mg TDS). Used under specialist paediatric endocrinology supervision for Cushing's syndrome in children. Seek specialist opinion.

Dose adjustments

Renal

No specific dose adjustment — use with caution; monitor cortisol closely.

Hepatic

Hepatic impairment may reduce metyrapone clearance — monitor carefully.

Paediatric weight-based calculator

BNFc: 15mg/kg TDS (minimum 250mg TDS). Used under specialist paediatric endocrinology supervision for Cushing's syndrome in children. Seek specialist opinion.

Clinical pearls

  • Adrenal crisis risk: over-treatment drops cortisol too low — patients must carry hydrocortisone for emergency self-administration; sick day rules essential
  • Mineralocorticoid excess: accumulating 11-deoxycorticosterone (a mineralocorticoid precursor) causes hypertension and hypokalaemia — monitor BP and potassium; may need potassium supplementation or antihypertensive
  • Diagnostic metyrapone test: phenytoin invalidates the test (accelerated metabolism) — check medications before performing
  • Used in combination with pasireotide, cabergoline, or mifepristone in severe/refractory Cushing's — multi-drug blockade approach under specialist guidance

Contraindications

  • Primary adrenal insufficiency (Addison's disease — metyrapone reduces cortisol further, precipitating adrenal crisis)
  • Hypersensitivity to metyrapone

Side effects

  • Nausea and vomiting (take with food)
  • Dizziness
  • Hypotension
  • Adrenal insufficiency / adrenal crisis (over-treatment — cortisol falls too low)
  • Oedema (accumulation of mineralocorticoid precursors — 11-deoxycorticosterone)
  • Hypertension and hypokalaemia (from mineralocorticoid precursor accumulation)
  • Hirsutism and acne (androgen precursor accumulation)

Interactions

  • Phenytoin — accelerates metyrapone metabolism (CYP3A4 induction) — higher doses required; invalidates diagnostic test
  • Paracetamol — metyrapone reduces paracetamol sulfation; theoretical increased hepatotoxicity risk at high doses
  • Cyproheptadine — may reduce efficacy

Monitoring

  • Urinary free cortisol / serum cortisol (guide dose titration)
  • Serum potassium and blood pressure (mineralocorticoid excess monitoring)
  • ACTH levels
  • Symptoms of adrenal insufficiency (fatigue, hypotension, nausea)

Reference: BNFc; BNF 90; Endocrine Society Cushing's Syndrome Guidelines 2015; BNF 90 Chapter 6. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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