Metopirone (Metyrapone)
Steroidogenesis inhibitor for diagnosis and treatment of Cushing's syndrome
Metopirone (metyrapone) is a prescription medication that inhibits cortisol production in the adrenal glands. It is used both as a diagnostic tool to evaluate pituitary gland function (ACTH secretion) and as a therapeutic agent for managing Cushing's syndrome by reducing excess cortisol levels. This guide covers its uses, dosage, side effects, drug interactions, and important safety information based on international endocrine guidelines.
Quick Facts
Key Takeaways
- Metopirone (metyrapone) blocks the enzyme 11-beta-hydroxylase, reducing cortisol synthesis in the adrenal glands and is used both diagnostically and therapeutically.
- As a diagnostic test, it evaluates pituitary ACTH reserve and helps differentiate types of Cushing's syndrome through single-dose overnight or multi-dose protocols.
- For Cushing's syndrome treatment, doses range from 250 mg to 6 g daily, individualised to achieve target cortisol levels under close medical supervision.
- Regular blood monitoring of cortisol, electrolytes, and blood pressure is essential during treatment to prevent adrenal insufficiency and electrolyte imbalances.
- It is not recommended during pregnancy or breastfeeding, and several drug interactions (especially paracetamol and anticonvulsants) require careful management.
What Is Metopirone and What Is It Used For?
Metopirone (metyrapone) belongs to a class of medicines known as steroidogenesis inhibitors. It works by blocking the enzyme 11-beta-hydroxylase (also called CYP11B1), which is responsible for the final step in cortisol biosynthesis within the adrenal cortex. By preventing the conversion of 11-deoxycortisol to cortisol, metyrapone effectively reduces circulating cortisol concentrations in the blood.
The drug serves two primary clinical purposes. First, it is widely used as a diagnostic tool to evaluate the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis. When cortisol production is blocked by metyrapone, a healthy pituitary gland responds by increasing the secretion of adrenocorticotropic hormone (ACTH). Measuring this ACTH response, along with the accumulation of cortisol precursors such as 11-deoxycortisol, helps clinicians determine whether the pituitary gland is functioning normally or whether an ACTH deficiency is present. The metyrapone test is also used to help differentiate between various causes of Cushing's syndrome, including pituitary adenomas (Cushing's disease), ectopic ACTH production, and adrenal tumours.
Second, metyrapone is used therapeutically for the treatment of endogenous Cushing's syndrome. Cushing's syndrome is a condition that results from chronically elevated cortisol levels, regardless of the underlying cause. Symptoms include central obesity, moon face, purple striae (stretch marks), muscle weakness, hypertension, diabetes, osteoporosis, and increased susceptibility to infections. By reducing cortisol production, metyrapone helps alleviate these symptoms and their associated health risks.
Metyrapone has been used in clinical endocrinology for over five decades and remains a cornerstone of both diagnostic testing and medical management of hypercortisolism. It is endorsed by major endocrine guidelines, including those from the Endocrine Society and the European Society of Endocrinology, as a first-line or adjunctive therapy for Cushing's syndrome, particularly when surgery is not feasible or as a bridging therapy before surgical intervention.
What Should You Know Before Taking Metopirone?
Contraindications
There are specific situations in which Metopirone must not be used. For the diagnostic metyrapone test to assess ACTH deficiency, the drug is contraindicated in patients with known adrenocortical insufficiency (Addison's disease), as further suppression of cortisol production in these patients could precipitate a life-threatening adrenal crisis.
Additionally, Metopirone should not be taken by anyone with a known allergy (hypersensitivity) to metyrapone or any of the other ingredients in the capsule formulation. Allergic reactions may include skin rash, itching, swelling, or difficulty breathing. If you experience any of these symptoms, seek medical attention immediately.
Warnings and Precautions
Before starting Metopirone, it is important to discuss several factors with your doctor to ensure safe use of the medication:
- Adrenal insufficiency risk: Metopirone can temporarily reduce cortisol levels below the normal range, causing adrenal insufficiency. Symptoms include weakness, fatigue, dizziness, loss of appetite, nausea, vomiting, diarrhoea, and abdominal pain. Your doctor will monitor your cortisol levels and may prescribe glucocorticoid replacement therapy (such as hydrocortisone) to prevent this complication.
- Liver disease: If you have liver disease or liver damage, the metabolism of metyrapone may be slowed, potentially leading to increased drug levels and a higher risk of side effects. Your doctor may need to adjust your dose accordingly.
- Concurrent corticosteroid therapy: If you are taking corticosteroids (such as cortisone or hydrocortisone), your doctor may decide not to perform the metyrapone test, as these medications interfere with test results and must be discontinued beforehand.
- Infection risk: Patients with Cushing's syndrome who are being treated with metyrapone may have an increased risk of infections, including serious lung infections. If you develop breathlessness, persistent fever, or signs of infection, contact your doctor promptly.
- Blood pressure: Long-term use of Metopirone may lead to elevated blood pressure (hypertension), which will need to be monitored and managed.
- Electrolyte monitoring: Regular blood tests are essential to check potassium, sodium, and blood glucose levels, as metyrapone can cause electrolyte disturbances. Depending on your cardiac risk factors, your doctor may also order an electrocardiogram (ECG) before or during treatment.
Contact your doctor immediately if you experience a combination of: weakness, dizziness, fatigue, loss of appetite, nausea, vomiting, abdominal pain, or diarrhoea. These may be signs of adrenal insufficiency (dangerously low cortisol), which requires urgent medical attention. Also seek immediate care for unusual bleeding, bruising, or persistent fatigue, which may indicate blood cell abnormalities.
Pregnancy and Breastfeeding
Metopirone is not recommended for women of childbearing potential who are not using effective contraception. If you are pregnant, think you may be pregnant, or are planning to become pregnant, inform your doctor as soon as possible so a decision can be made regarding whether to continue or discontinue the medication.
If Metopirone must be used during pregnancy, the treating physician will closely monitor the infant's cortisol levels during the first week after birth, as the drug's cortisol-suppressing effects may affect the newborn's adrenal function.
Breastfeeding must be discontinued during treatment with Metopirone, as metyrapone may pass into breast milk and potentially affect the nursing infant.
Driving and Operating Machinery
Metopirone may cause dizziness or drowsiness in some patients. If you experience these effects, you should not drive, operate heavy machinery, or perform tasks requiring full alertness until the symptoms have resolved. You are responsible for assessing your own fitness to drive or operate machinery while taking this medication.
Important Information About Excipients
Metopirone capsules contain sodium ethyl parahydroxybenzoate (E215) and sodium propyl parahydroxybenzoate (E217), which may cause allergic reactions (possibly delayed). The capsules contain less than 1 mmol (23 mg) sodium per capsule, making them essentially sodium-free.
How Does Metopirone Interact with Other Drugs?
Several categories of medications can interact with metyrapone, either by altering its effectiveness, changing its metabolism, or interfering with the results of the diagnostic metyrapone test. It is essential to inform your doctor or pharmacist about all medicines you are currently taking, have recently taken, or may be planning to take.
Major Interactions
| Drug / Class | Type of Interaction | Clinical Significance |
|---|---|---|
| Paracetamol (Acetaminophen) | Pharmacokinetic interaction | Do not take concurrently without medical advice. May alter drug metabolism and increase risk of adverse effects. |
| Phenytoin, Barbiturates | CYP enzyme induction | Anticonvulsants may accelerate metyrapone metabolism, reducing its effectiveness and interfering with diagnostic test results. |
| Corticosteroids (cortisone, hydrocortisone) | Pharmacological interference | Exogenous corticosteroids directly interfere with cortisol measurements. Must be discontinued before diagnostic testing; dose adjustments needed during treatment. |
| ACTH, Tetracosactide | HPA axis modulation | Hormones affecting the hypothalamic-pituitary-adrenal axis can confound diagnostic results and alter treatment response. |
Other Notable Interactions
| Drug / Class | Effect | Recommendation |
|---|---|---|
| Antidepressants (amitriptyline, alprazolam) | May affect diagnostic test results | Inform your doctor; timing adjustments may be needed for diagnostic testing. |
| Antipsychotics (chlorpromazine) | May affect HPA axis function and test interpretation | Doctor may need to account for these effects when interpreting test results. |
| Antithyroid medications (carbimazole, thyroxine) | Thyroid function affects cortisol metabolism | Thyroid status should be assessed and stabilised before metyrapone testing. |
| Cyproheptadine | May reduce ACTH secretion | Can interfere with the metyrapone diagnostic test; discuss with your doctor. |
The above lists are not exhaustive. Always provide your healthcare provider with a complete list of all prescription medications, over-the-counter drugs, herbal supplements, and vitamins you are taking before undergoing metyrapone testing or starting Metopirone treatment.
What Is the Correct Dosage of Metopirone?
The dosing of Metopirone differs significantly depending on whether it is being used for diagnostic testing or for the treatment of Cushing's syndrome. Always follow your doctor's specific instructions and never alter the dose without medical guidance.
Diagnostic Use
Single-Dose Overnight Test (Pituitary Function Assessment)
The recommended dose is 30 mg/kg body weight, administered as a single dose at approximately midnight. The capsules should be swallowed with yoghurt or milk to reduce gastrointestinal discomfort. A blood sample is taken the following morning (typically at 8 AM) to measure plasma 11-deoxycortisol, cortisol, and ACTH levels. The same dose applies to both adults and children.
Multi-Dose Test (Pituitary Function and Cushing's Syndrome Differential Diagnosis)
Adults: 500-750 mg (2-3 capsules) every 4 hours for 24 hours. The capsules should be taken with milk or after a meal. Urine collection begins 24 hours before dosing and continues for 24 hours after the final dose for measurement of urinary steroid metabolites.
Children: 15 mg/kg body weight (minimum 250 mg) every 4 hours during the test period.
Treatment of Cushing's Syndrome
Adults
The dose is individualised and may range from 250 mg (1 capsule) to 6,000 mg (24 capsules) per day, divided into three or four equally spaced doses. Treatment typically begins at a lower dose, which is gradually titrated upward based on cortisol measurements. The target is to normalise cortisol levels while avoiding adrenal insufficiency. Your doctor will periodically adjust the dose based on blood test results.
Children and Adolescents
For treatment of Cushing's syndrome in children, the dose is adjusted individually based on cortisol levels and tolerability. There is no fixed paediatric dosing protocol; the treating endocrinologist will determine the appropriate regimen.
Missed Dose
If you accidentally miss a dose, take it as soon as you remember. If it is nearly time for your next scheduled dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to compensate for a missed one. If you have questions about missed doses, consult your doctor or pharmacist.
Overdose
If you take too much Metopirone, or if a child accidentally ingests it, seek emergency medical attention immediately. Symptoms of overdose may include nausea, vomiting, abdominal pain, diarrhoea, dizziness, fatigue, headache, excessive sweating, and elevated blood pressure. Treatment may include activated charcoal and intravenous hydrocortisone administration.
What Are the Side Effects of Metopirone?
Like all medicines, Metopirone can cause side effects, although not everyone will experience them. The likelihood and severity of side effects often depend on the dose and duration of treatment. Many side effects are related to the drug's mechanism of action — specifically, the reduction in cortisol levels and compensatory changes in other adrenal hormones.
Very Common
Affects more than 1 in 10 patients
- Adrenal insufficiency (low cortisol levels)
- Loss of appetite
- Headache
- Dizziness
- Hypertension (high blood pressure)
- Nausea
- Abdominal pain
- Diarrhoea
- Allergic skin reactions (hives, rash, itching)
- Joint pain (arthralgia)
- Peripheral oedema (swelling of hands, feet, arms, or legs)
- Fatigue and exhaustion
Common
Affects up to 1 in 10 patients
- Hypokalaemia (low potassium levels)
- Drowsiness or somnolence
- Hypotension (low blood pressure)
- Vomiting
- Acne
- Hirsutism (excessive hair growth)
- Muscle pain (myalgia)
Not Known Frequency
Frequency cannot be estimated from available data
- Abnormal liver function (elevated liver enzymes)
- Leukopenia (low white blood cell count)
- Anaemia (low red blood cell count)
- Thrombocytopenia (low platelet count)
- Alopecia (hair loss)
- Lung infection (pneumonia)
Contact your doctor immediately if you experience two or more of these symptoms together: weakness, dizziness, fatigue, loss of appetite, nausea, vomiting, abdominal pain, or diarrhoea — these may indicate adrenal insufficiency. Also seek urgent care for unusual bleeding, bruising lasting longer than normal, blood in the gums or nose, or persistent tiredness, which may suggest blood cell abnormalities (leukopenia, anaemia, or thrombocytopenia).
Many of the very common side effects, particularly adrenal insufficiency and its associated symptoms, are more likely to occur during periods of dose escalation or during times of increased physiological stress (such as illness or surgery). Your doctor can manage these effects by adjusting your Metopirone dose and, if necessary, providing temporary glucocorticoid replacement therapy.
The hirsutism and acne seen in some patients are caused by the accumulation of adrenal androgen precursors when cortisol synthesis is blocked. These effects are generally reversible upon dose reduction or discontinuation of the medication.
How Should You Store Metopirone?
Proper storage of Metopirone is essential to maintain its effectiveness and safety. Follow these storage guidelines:
- Temperature: Store at or below 25°C (77°F). Do not refrigerate or freeze.
- Moisture protection: Keep the container tightly closed, as the capsules are moisture-sensitive.
- After opening: Use within 2 months of first opening the container.
- Expiry date: Do not use after the expiry date printed on the container and carton. The expiry date refers to the last day of the stated month.
- Child safety: Keep out of sight and reach of children at all times.
- Disposal: Do not dispose of medications via household waste or wastewater. Return unused medicines to your pharmacist for proper disposal to help protect the environment.
What Does Metopirone Contain?
Each Metopirone capsule is a white to yellowish-white, oblong, opaque, soft gelatin capsule printed with "HRA" in red ink. The capsule measures approximately 18.5 mm in length and 7.5 mm in diameter, containing a slightly yellowish viscous to jelly-like substance.
Active Ingredient
Each capsule contains 250 mg metyrapone.
Inactive Ingredients (Excipients)
- Ethylvanillin
- Gelatin
- Glycerol
- Macrogol 400
- Macrogol 4000
- p-Methoxyacetophenone
- Sodium ethyl parahydroxybenzoate (E215)
- Sodium propyl parahydroxybenzoate (E217)
- Titanium dioxide (E171)
- Purified water
Printing ink (red): Carminic acid (E120), aluminium chloride hexahydrate, sodium hydroxide, hypromellose, and propylene glycol.
Packaging: Each plastic container holds 50 capsules.
Marketing Authorisation Holder
Esteve Pharmaceuticals S.A., Barcelona, Spain. Metopirone is manufactured by Delpharm Lille SAS, France, and is approved within the European Economic Area under the brand names Metopirone, Metycor, Metyrapone Esteve, Metopiron, and Cormeto, depending on the country.
Frequently Asked Questions About Metopirone
Metopirone (metyrapone) is used both as a diagnostic test to evaluate pituitary gland function (specifically ACTH secretion) and as a treatment for Cushing's syndrome. As a diagnostic tool, it helps determine whether the pituitary is producing adequate ACTH by measuring the body's response to blocked cortisol production. As a treatment, it reduces excessive cortisol levels in patients with Cushing's syndrome by inhibiting the enzyme 11-beta-hydroxylase in the adrenal cortex.
Very common side effects (affecting more than 1 in 10 patients) include adrenal insufficiency (low cortisol levels), loss of appetite, headache, dizziness, high blood pressure, nausea, abdominal pain, diarrhoea, allergic skin reactions (hives, rash, itching), joint pain, swelling of the extremities, and fatigue. Common side effects (up to 1 in 10 patients) include low potassium, drowsiness, low blood pressure, vomiting, acne, excess hair growth, and muscle pain. Most side effects are dose-dependent and improve with dose adjustment.
Metopirone is not recommended for women of childbearing potential who are not using contraception. If you become pregnant while taking Metopirone, you should contact your doctor as soon as possible to discuss whether to continue or stop treatment. If the medication must be continued during pregnancy, your doctor will monitor the baby's cortisol levels during the first week after birth. Breastfeeding should be discontinued during treatment, as metyrapone may pass into breast milk.
The metyrapone test evaluates pituitary-adrenal function by blocking cortisol production. In the single-dose overnight test, the patient takes 30 mg/kg at midnight with yoghurt or milk, and a blood sample is taken at 8 AM to measure 11-deoxycortisol and ACTH. In a person with normal pituitary function, cortisol blockade triggers a compensatory rise in ACTH and accumulation of 11-deoxycortisol. An inadequate response suggests ACTH deficiency. The multi-dose test (over 24 hours) is used to differentiate between types of Cushing's syndrome. This test must be performed under medical supervision in a healthcare facility.
Yes, metyrapone can be used in children. For the single-dose overnight diagnostic test, the same weight-based dose as adults (30 mg/kg) is used. For the multi-dose test, children receive 15 mg/kg body weight with a minimum of 250 mg every four hours. For the treatment of Cushing's syndrome in children, the dose is individualised based on cortisol levels and tolerability, under the guidance of a paediatric endocrinologist.
If you take more Metopirone than prescribed, or if a child accidentally ingests the medication, seek emergency medical attention immediately. Symptoms of overdose may include nausea, abdominal pain, diarrhoea, dizziness, fatigue, headache, excessive sweating, and elevated blood pressure. Emergency treatment may include administration of activated charcoal and intravenous hydrocortisone.
References
- Nieman LK, et al. Treatment of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline. Journal of Clinical Endocrinology & Metabolism. 2015;100(8):2807-2831. doi:10.1210/jc.2015-1818
- Pivonello R, et al. The Treatment of Cushing's Disease. Endocrine Reviews. 2015;36(4):385-486. doi:10.1210/er.2013-1048
- European Medicines Agency (EMA). Metopirone Summary of Product Characteristics. Updated 2025.
- Fleseriu M, et al. Consensus on diagnosis and management of Cushing's disease: a guideline update. The Lancet Diabetes & Endocrinology. 2021;9(12):847-875.
- British National Formulary (BNF). Metyrapone. National Institute for Health and Care Excellence (NICE). 2025.
- World Health Organization (WHO). WHO Model List of Essential Medicines. 23rd List, 2023.
- Daniel E, Newell-Price JDC. Therapy of endocrine disease: steroidogenesis enzyme inhibitors in Cushing's syndrome. European Journal of Endocrinology. 2015;172(6):R263-R280. doi:10.1530/EJE-14-1014
- Ceccato F, et al. Metyrapone treatment in Cushing's syndrome: a real-life study. Endocrine. 2018;62(3):701-711.
Medical Editorial Team
This article was written and reviewed by the iMedic Medical Editorial Team, comprising board-certified specialists in endocrinology, clinical pharmacology, and internal medicine.
iMedic Medical Content Team — specialists in endocrinology and pharmacology with experience in peer-reviewed medical publishing.
iMedic Medical Review Board — independent panel following Endocrine Society, EMA, and WHO guidelines with GRADE evidence framework.
Disclosure: iMedic receives no commercial funding and has no financial relationships with pharmaceutical companies. All content is independently produced based on peer-reviewed evidence.