Synacthen: Uses, Dosage & Side Effects
A synthetic adrenocorticotropic hormone (ACTH) analog used to assess adrenal gland function through the short Synacthen test and, less commonly, in steroid-responsive therapy
Synacthen (international non-proprietary name: tetracosactide; also known as tetracosactrin in the UK and as cosyntropin in the United States) is a synthetic analog of the first 24 amino acids of naturally occurring adrenocorticotropic hormone (ACTH). In the 0.25 mg/ml solution form, it is used primarily as a diagnostic agent in the short Synacthen test (also known as the ACTH stimulation test) to evaluate the function of the adrenal cortex. A rapid rise in plasma cortisol after injection confirms that the adrenal glands can respond to stimulation; a blunted response suggests adrenal insufficiency. Synacthen requires a prescription and is administered in a clinical setting under medical supervision because of the possibility of allergic reactions.
Quick Facts: Synacthen
Key Takeaways
- Synacthen (tetracosactide) is a synthetic polypeptide corresponding to the first 24 amino acids of natural ACTH and has the full biological activity of human corticotropin in stimulating the adrenal cortex to release cortisol.
- Its main clinical role today is as a diagnostic tool in the short Synacthen test, used to diagnose primary adrenal insufficiency (Addison’s disease) and established secondary adrenal insufficiency of pituitary or hypothalamic origin.
- The 0.25 mg/ml solution is a short-acting preparation; a separate depot (zinc-complexed) formulation exists for occasional therapeutic use, but most steroid-responsive conditions are now treated with direct glucocorticoid therapy rather than with ACTH.
- Hypersensitivity reactions, including anaphylaxis, are the most important acute safety concern, especially in patients with asthma, hay fever, or other allergic conditions; resuscitation facilities must always be available.
- The test result can be distorted by many factors, including oral contraceptives and exogenous steroids, so a detailed medication history and the correct timing of sampling are essential for reliable interpretation.
What Is Synacthen and What Is It Used For?
Synacthen contains the active substance tetracosactide hexaacetate, a synthetic peptide identical to the first 24 of the 39 amino acids of natural adrenocorticotropic hormone (ACTH or corticotropin). Despite its shorter length, this 1–24 ACTH fragment retains the full biological activity of the complete hormone: it binds to the melanocortin-2 receptor (MC2R) on the outer zone of the adrenal cortex and rapidly stimulates the synthesis and release of glucocorticoids (principally cortisol), mineralocorticoids (principally aldosterone), and adrenal androgens. Because the final 15 amino acids of native ACTH, which carry most of the immunogenic potential, have been removed, synthetic 1–24 ACTH is less likely to provoke antibody formation than natural porcine or bovine corticotropin, which were used historically.
In clinical practice today, the 0.25 mg/ml Synacthen solution is used overwhelmingly for one indication: the short Synacthen test (SST), also known internationally as the ACTH stimulation test, the cosyntropin test, or the rapid ACTH test. The test evaluates whether the adrenal cortex is able to respond normally to a corticotropic stimulus. It is the cornerstone diagnostic test for suspected adrenal insufficiency of either primary (adrenal) or secondary (pituitary/hypothalamic) origin. A baseline blood cortisol level is taken, 250 micrograms of Synacthen is injected intramuscularly or intravenously, and further blood samples are drawn at 30 and/or 60 minutes. Adequate adrenal reserve is usually defined as a stimulated cortisol concentration above a laboratory-specific threshold (historically 500 nmol/L or 550 nmol/L with older assays, often 430–450 nmol/L with modern mass-spectrometry and monoclonal immunoassays).
Beyond its diagnostic role, Synacthen has, historically, been given therapeutically in a range of steroid-responsive disorders in which an ACTH-driven release of endogenous cortisol was desirable, including certain forms of nephrotic syndrome, dermatological conditions, rheumatic disease, asthma, and multiple sclerosis relapses. For most of these indications it has been largely superseded by direct glucocorticoid therapy, which is easier to dose, better absorbed, and more predictable. In children, a depot form of tetracosactide is still used in some countries as an option for infantile spasms (West syndrome) where high-dose corticosteroids or vigabatrin are not appropriate. The short-acting 0.25 mg/ml solution discussed on this page is not intended for long-term therapeutic use; when longer-lasting ACTH activity is required, a separate depot (zinc-complexed) preparation is used.
The distinction between Synacthen and tetracosactide depot is clinically important. The plain 0.25 mg/ml aqueous solution, sometimes also referred to as “Synacthen ampoules”, has a plasma half-life of around 15 minutes and a duration of pharmacological action of approximately 1–2 hours — perfect for the short Synacthen test but unsuitable for chronic therapy. The depot preparation, by contrast, slowly releases tetracosactide over 12–24 hours or longer, allowing for less frequent dosing when therapeutic ACTH activity is clinically indicated.
The short Synacthen test itself is recognized in international guidelines (Endocrine Society, European Society of Endocrinology, NICE, and others) as the first-line dynamic test when adrenal insufficiency is suspected. It is safer, faster, and much more widely used than the insulin tolerance test, which was the historical reference standard but carries a risk of hypoglycemia and requires close medical supervision.
ACTH is the pituitary hormone that drives the adrenal cortex to produce cortisol, an essential stress and survival hormone. Diseases that destroy the adrenal cortex (primary adrenal insufficiency, e.g., autoimmune Addison’s disease) or reduce ACTH release from the pituitary (secondary adrenal insufficiency, e.g., after pituitary surgery or prolonged steroid therapy) lead to cortisol deficiency and can progress to a life-threatening adrenal crisis. The short Synacthen test probes this ACTH–cortisol axis from the adrenal side and is central to modern endocrine diagnostics.
What Should You Know Before Taking Synacthen?
Synacthen is a potent hormonal agent and, despite its short duration of action, can provoke serious hypersensitivity reactions. A complete medical history is therefore always needed before the test. The guidance below covers absolute and relative contraindications as well as the practical precautions observed in most hospitals and outpatient clinics worldwide.
Contraindications
There are several situations in which Synacthen must not be used, or used only with extreme caution under specialist supervision:
- Hypersensitivity: Do not use Synacthen if you are allergic to tetracosactide, natural corticotropin (ACTH), or any of the other ingredients in the product. Previous severe allergic or anaphylactic reactions to any ACTH preparation are an absolute contraindication.
- Allergic disorders: Active allergic diseases such as uncontrolled asthma, eczema, atopic dermatitis, or allergic rhinitis significantly increase the risk of anaphylactic reactions to Synacthen. In some summary of product characteristics these are listed as contraindications; in others as strong precautions. The decision should be taken by a specialist.
- Untreated Cushing’s syndrome: Synacthen will further increase circulating cortisol in patients who already have excess cortisol production and is contraindicated.
- Adrenogenital syndrome (congenital adrenal hyperplasia): Synacthen may precipitate a steep rise in adrenal androgens and is generally contraindicated, although low-dose provocative testing with Synacthen is sometimes used in specialized endocrine investigations under expert supervision.
- Active or recent peptic ulcer disease: Endogenous corticosteroid release may aggravate gastric or duodenal ulceration.
- Refractory heart failure: Sodium and water retention caused by endogenous corticosteroids may worsen decompensated heart failure.
- Acute psychosis: Increased cortisol production may exacerbate psychotic symptoms.
- Severe systemic infection: Unless adequately treated, systemic bacterial, viral, or fungal infections may be worsened by the immunomodulatory effects of endogenous corticosteroid release. Live vaccines should not be administered concurrently.
Warnings and Precautions
Severe allergic reactions, including anaphylactic shock, have been reported after administration of Synacthen, particularly in patients with asthma or other allergic conditions and in those previously exposed to corticotropic hormones. Synacthen must always be given in a setting where emergency resuscitation equipment, adrenaline (epinephrine), oxygen, and trained staff are immediately available. Patients should be observed closely for at least 30 minutes after the injection.
Even in otherwise healthy individuals, caution is required for the following situations:
- Asthma and atopy: A personal or family history of asthma, hay fever, eczema, chronic urticaria, or other atopic disease increases the risk of hypersensitivity reactions. A careful risk–benefit assessment must be made before testing.
- Diabetes mellitus: The cortisol released after Synacthen stimulation can transiently raise blood glucose, which may require short-term adjustment of hypoglycemic therapy. Long-term use can unmask or worsen diabetes.
- Hypertension: Sodium and water retention may transiently raise blood pressure, especially with repeated doses.
- Liver or kidney impairment: Hepatic cirrhosis and renal disease predispose patients to fluid retention and electrolyte disturbance; monitoring is advised.
- Osteoporosis: Prolonged or repeated therapeutic use of ACTH analogs can accelerate bone loss, similar to long-term corticosteroid therapy.
- Concurrent live vaccines: Because Synacthen causes release of immunosuppressive glucocorticoids, live vaccines (MMR, varicella, BCG, live attenuated influenza, yellow fever) should be avoided during treatment and, conservatively, for several weeks afterwards.
- Myasthenia gravis: Corticotropin-driven steroid release may worsen muscle weakness in the early phase.
- Known or suspected tuberculosis: As with direct corticosteroid therapy, Synacthen can reactivate latent tuberculosis.
- Children: The standard 0.25 mg/ml solution is used in diagnostic tests in children with age- and weight-adjusted doses; safety and efficacy of long-term therapeutic use are limited and should be managed by a pediatric specialist only.
During the short Synacthen test, patients may experience transient flushing, dizziness, or a feeling of warmth. These are usually harmless, but any sign of a progressing hypersensitivity reaction — widespread rash, swelling of the face or tongue, wheezing, chest tightness, fainting, or collapse — must be treated immediately as anaphylaxis.
Pregnancy and Breastfeeding
Data from controlled clinical trials of Synacthen in pregnant women are limited. Tetracosactide crosses the placenta in small amounts, and long-term corticotropin exposure can theoretically lead to adrenal suppression in the fetus, similar to the effects of chronic maternal corticosteroid use. For a single diagnostic dose (250 micrograms) in the short Synacthen test, the exposure is very small and the risk is generally considered low when the test is clinically essential, particularly in pregnancy-associated adrenal insufficiency. Nevertheless, the decision should always be made by an endocrinologist or obstetrician who weighs the diagnostic benefit against any theoretical risk.
It is not known whether tetracosactide is excreted in human breast milk; any excretion would likely be as small peptides that are digested in the infant’s gut. Because of the limited data, breastfeeding women are usually asked to discuss a short interruption in feeding (e.g., for 24 hours after the test) with their doctor, although for most women this precaution is not strictly necessary.
Men and women of reproductive age do not need to change contraceptive or fertility plans because of a single diagnostic test. With repeated or prolonged therapeutic ACTH administration, the same long-term considerations apply as for systemic corticosteroids.
Driving and Operating Machinery
Synacthen has no known direct effect on reaction time or concentration. However, the injection can cause transient dizziness, flushing or, rarely, fainting. Patients are advised to remain seated or lying for a short time after administration and to delay driving if they feel unwell. Because the short Synacthen test is brief and usually done in a morning outpatient appointment, most patients can resume normal activities the same day.
Important Information About Ingredients
Synacthen 0.25 mg/ml solution for injection contains, in addition to the active substance tetracosactide hexaacetate, pharmacologically inactive excipients such as acetic acid, sodium acetate trihydrate, mannitol, and sodium chloride in water for injections. The product contains only small amounts of sodium (less than 1 mmol per ampoule), and the packaging is generally latex free; however, patients with a known allergy to any excipient should inform the prescribing physician.
How Does Synacthen Interact with Other Drugs?
Clinically relevant interactions with Synacthen fall into four main categories: drugs that alter measured cortisol levels independent of true adrenal function, drugs that suppress the hypothalamic–pituitary–adrenal (HPA) axis, drugs whose pharmacology is modified by elevated endogenous glucocorticoids, and drugs that amplify specific adverse effects. The following tables summarize the most important of these interactions; your doctor will review your full medication list before performing the short Synacthen test.
Major Interactions
| Interacting Drug | Effect | Clinical Significance |
|---|---|---|
| Oestrogens / combined oral contraceptives | Increase cortisol-binding globulin (CBG), falsely elevating measured total cortisol | Discontinue 4–6 weeks before the test where possible, or use free-cortisol / salivary cortisol assays |
| Glucocorticoids (prednisolone, hydrocortisone, dexamethasone) | Suppress the HPA axis; hydrocortisone also cross-reacts in cortisol assays | Hydrocortisone must be withheld for at least 24 hours before the test; long-acting steroids may require specialist withdrawal |
| Barbiturates, phenytoin, carbamazepine, rifampicin (enzyme inducers) | Accelerate cortisol metabolism; may lower measured cortisol and unmask partial insufficiency | Interpretation must take enzyme induction into account; the result may not reflect baseline adrenal capacity |
| Potassium-depleting diuretics (furosemide, thiazides) | Additive hypokalaemia when combined with ACTH-driven cortisol release | Monitor serum potassium; avoid repeated doses of Synacthen in patients with ongoing diuretic therapy |
| Cardiac glycosides (digoxin) | Hypokalaemia increases risk of digoxin toxicity and arrhythmia | Check potassium before and after repeated administration; avoid unnecessary retesting |
| Live attenuated vaccines | Increased risk of infection with vaccine strain during steroid-like immunosuppression | Avoid during prolonged therapeutic ACTH use; a single diagnostic dose is not normally clinically significant |
Minor Interactions
| Interacting Drug | Effect | Clinical Significance |
|---|---|---|
| Insulin and oral antidiabetic drugs | Hyperglycaemic effect of endogenous cortisol may reduce their efficacy | Monitor blood glucose after the test; dose adjustment rarely needed for a single test |
| Salicylates (aspirin) | Glucocorticoids increase renal clearance of salicylate; levels may drop and rise again on withdrawal | Relevant mainly with repeated therapeutic ACTH use, not single diagnostic doses |
| Anticoagulants (warfarin, coumarins) | Variable effect — both increased and decreased anticoagulant response have been reported | Monitor INR during repeated therapeutic ACTH exposure |
| Mitotane, metyrapone, ketoconazole (adrenolytic/enzyme inhibitors) | Blunt the cortisol response to ACTH stimulation | Results unreliable; withhold where clinically safe, or use alternative testing |
| Carbenoxolone and glycyrrhizin (liquorice) | Potentiate mineralocorticoid effects, increase risk of hypokalaemia and hypertension | Avoid large amounts of liquorice-containing products around the test |
Because Synacthen itself has a very short plasma half-life, most interactions are either indirect (via cortisol) or concern the interpretation of the test rather than safety of a single injection. Nonetheless, even subtle interactions may cause the test to be misinterpreted, leading either to a missed diagnosis of adrenal insufficiency or, conversely, to unnecessary steroid replacement. Providing a complete and accurate medication history is therefore as important as the injection itself.
What Is the Correct Dosage of Synacthen?
The dose and schedule of Synacthen depend entirely on the indication. For the overwhelming majority of patients — those undergoing the short Synacthen test — a single 250 microgram dose is used. Therapeutic regimens require individual specialist planning, usually with the tetracosactide depot formulation rather than the aqueous 0.25 mg/ml solution described here. Your doctor will calculate the most appropriate dose for you based on your age, weight, kidney function, and indication.
Adults
Short Synacthen Test (Standard Dose)
Indication: Diagnosis of primary or secondary adrenal insufficiency
Dose: 250 micrograms (1 ml of the 0.25 mg/ml solution) intramuscularly or intravenously
Timing of blood samples: Baseline cortisol immediately before injection; stimulated cortisol at 30 minutes, with optional sampling at 60 minutes
Interpretation: A stimulated cortisol above the assay-specific cut-off (typically around 430–500 nmol/L with modern monoclonal assays, 500–550 nmol/L with older polyclonal assays) excludes primary adrenal insufficiency. An inadequate rise suggests adrenal cortex dysfunction and warrants further work-up, including a basal ACTH measurement to differentiate primary from secondary causes.
Low-Dose Short Synacthen Test (Research / Selected Centers)
Indication: Detection of subtle or evolving secondary adrenal insufficiency (e.g., early pituitary failure, suspected tertiary insufficiency after glucocorticoid withdrawal)
Dose: 1 microgram of tetracosactide diluted in saline, given intravenously
Interpretation: Similar cortisol response thresholds are used, but the test has lower specificity and is more demanding to perform. It is not a substitute for the standard 250 microgram test in routine practice.
Therapeutic Use (Outside the Scope of the 0.25 mg/ml Solution)
When ACTH activity is needed for more than a few hours — for example, in infantile spasms or, in some countries, in acute multiple sclerosis relapses — a separate tetracosactide depot preparation is usually chosen. Doses and schedules for these indications are individualized and are not covered in detail on this page, since they involve a different product. Always rely on your specialist’s instructions for therapeutic use.
Children
The short Synacthen test can be performed in children of all ages, including neonates. Pediatric protocols vary, but commonly:
- Neonates and infants under 6 months: 62.5 micrograms (0.25 ml of the 0.25 mg/ml solution) intravenously or intramuscularly.
- Children 6 months to 2 years: 62.5–125 micrograms.
- Children over 2 years: 250 micrograms, as in adults.
Sampling is usually at baseline and 30 minutes; age- and assay-specific normal ranges should be used for interpretation, as cortisol responses differ across infancy, childhood, and puberty.
Elderly
There is no specific dose reduction recommended for older adults undergoing the short Synacthen test. However, elderly patients are more likely to have comorbidities (hypertension, heart failure, diabetes, chronic kidney disease) that amplify the indirect effects of cortisol release. They should be observed carefully and blood pressure, glucose, and electrolytes monitored if repeated testing is needed.
Missed Dose
Because Synacthen is administered by a healthcare professional as part of a scheduled test or treatment plan, there is no concept of a “missed dose” taken at home. If an appointment is missed, the test should be rescheduled. If the test is interrupted (for example, by loss of IV access between baseline and 30-minute sampling), the test should be restarted on another day after appropriate preparation. Do not attempt to self-administer Synacthen.
Overdose
Accidental overdose of Synacthen is extremely unlikely in supervised clinical practice. Because the peptide has a short half-life, even substantially higher-than-intended doses are usually cleared within hours. Symptoms of overdose or rapid repeated dosing mirror those of excessive endogenous cortisol: high blood pressure, salt and water retention, hypokalaemia, hyperglycaemia, mood changes, and, rarely, psychotic symptoms. Treatment is supportive (IV fluids, potassium replacement, blood pressure management) and the adverse effects typically resolve spontaneously as the drug is cleared. Severe hypersensitivity reactions are treated with adrenaline, oxygen, antihistamines, and corticosteroids.
How Synacthen Is Given
Synacthen 0.25 mg/ml is a clear, colorless solution supplied in glass ampoules. It is administered by a doctor, nurse, or trained healthcare professional. It can be given by slow intravenous injection (over 1–2 minutes), as a short intravenous infusion, or as an intramuscular injection; the intramuscular route is most common for the standard short Synacthen test. The site should be observed for any local reaction, and the patient should remain in the clinical area for at least 30 minutes after the injection so that any hypersensitivity reaction can be recognized and treated promptly.
The short Synacthen test is usually performed in the morning (often between 08:00 and 10:00) when cortisol levels are at their physiological peak, but timing can be flexible — especially in suspected acute adrenal insufficiency where stable high levels rule out the diagnosis at any time of day. Patients are generally asked to avoid glucocorticoid tablets for at least 24 hours before the test; long-acting steroids (prednisolone, dexamethasone) may need to be withheld for longer under specialist supervision.
Synacthen must not be self-administered. It is prepared, stored, and injected by trained healthcare staff in a setting where emergency treatment for anaphylaxis is immediately available. The dose, route, and timing are individualized by the prescribing physician based on the clinical question and patient characteristics.
What Are the Side Effects of Synacthen?
As with all medicines, Synacthen may cause side effects. In routine clinical practice the short Synacthen test is one of the most common endocrine investigations worldwide and is generally very well tolerated, with clinically significant reactions occurring in only a small minority of patients. Reported frequencies below reflect both single-dose (diagnostic) use and the broader experience with repeated and therapeutic ACTH administration. Frequencies follow the Council for International Organizations of Medical Sciences (CIOMS) convention.
Side Effects Organized by Frequency
Very Common
May affect more than 1 in 10 people
- Transient flushing or warmth shortly after injection
- Mild injection-site reaction (pain, redness, or itching at the site)
- Feeling of mild dizziness lasting a few minutes
Common
May affect up to 1 in 10 people
- Nausea, occasionally vomiting
- Headache
- Mild itching (pruritus) at or away from the injection site
- Transient rise in blood pressure
- Transient rise in blood glucose, especially in people with diabetes or glucose intolerance
- Mood changes (anxiety, restlessness), usually short-lived
Uncommon
May affect up to 1 in 100 people
- Urticaria (hives) or more extensive rash
- Bronchospasm, especially in patients with asthma or atopy
- Hypokalaemia (low potassium)
- Fluid retention and mild peripheral oedema
- Menstrual irregularities with repeated therapeutic use
- Insomnia
- Transient tachycardia (rapid heartbeat)
Rare
May affect up to 1 in 1,000 people
- Severe hypersensitivity reaction / anaphylactic shock with breathing difficulty, swelling of the face or tongue, and circulatory collapse
- Angioedema
- Severe bronchospasm in people with asthma
- Psychiatric disturbance (agitation, paranoia, psychosis) with repeated or prolonged exposure
- Clinically significant peptic ulcer or gastrointestinal bleeding with prolonged therapeutic use
- Osteoporosis, aseptic bone necrosis, growth retardation (children) with long-term therapeutic use
- Cataracts, increased intra-ocular pressure, glaucoma with prolonged therapeutic use
Not Known
Frequency cannot be estimated from available data
- Delayed hypersensitivity reactions appearing hours after the injection
- Adrenal haemorrhage in patients on anticoagulants (reported as isolated cases)
- Reactivation of latent tuberculosis with prolonged therapeutic use
Seek emergency medical help immediately if, during or after a Synacthen injection, you develop any of the following: sudden shortness of breath, wheezing, chest tightness, swelling of the face, lips, tongue, or throat, a widespread rash with itching, severe dizziness, collapse, loss of consciousness, or a feeling of impending doom. These may be signs of anaphylaxis, which requires immediate treatment with adrenaline (epinephrine), oxygen, intravenous fluids, and other supportive measures.
If you experience any side effects, including those not listed here, tell your doctor or nurse. You can also report suspected adverse drug reactions through your national pharmacovigilance system (for example, the EMA EudraVigilance database in Europe, the FDA MedWatch program in the United States, the MHRA Yellow Card Scheme in the United Kingdom, or the corresponding system in your country). Reporting side effects helps regulators continuously monitor the benefit–risk balance of Synacthen.
How Should Synacthen Be Stored?
Keep this medicine out of the sight and reach of children. Do not use after the expiry date printed on the ampoule and outer carton after “EXP” — this refers to the last day of the month stated. Synacthen is for single use only; it does not contain a preservative, so any solution that remains in the ampoule after the dose has been drawn up must be discarded rather than reused.
- Unopened ampoules: Store in a refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze.
- Light protection: Keep ampoules inside the outer carton to protect from light until just before use.
- Transport: Can tolerate short periods out of the refrigerator during transport; refer to the manufacturer’s specific stability information.
- After opening: Draw up the required dose, administer immediately, and discard any leftover solution.
- Inspection: Before use, inspect the solution visually; it should be clear and colorless. Do not use if the solution is cloudy, discolored, or contains visible particles, or if the ampoule is damaged.
- Disposal: Unused medicine and waste material must be disposed of in accordance with local requirements for medicinal products and sharps.
Because Synacthen is prepared and administered in a clinical setting, storage will be handled by your healthcare team and pharmacy. Do not dispose of medicines via wastewater or household waste. Appropriate disposal helps protect the environment and ensures no one else is exposed to the product.
What Does Synacthen Contain?
Active Substance
The active substance in Synacthen 0.25 mg/ml solution for injection is tetracosactide (also spelled tetracosactrin; in the United States, the INN cosyntropin is used), formulated as tetracosactide hexaacetate. Tetracosactide is a synthetic polypeptide with 24 amino acids corresponding to positions 1–24 of the 39-amino-acid sequence of human adrenocorticotropic hormone (ACTH). This fragment carries the complete corticotropic biological activity of the natural hormone but lacks the species-specific C-terminal sequence that is responsible for most immunogenic reactions to extract-based ACTH preparations.
Each ampoule contains 1 ml of solution and provides 0.25 mg (250 micrograms) of tetracosactide. Pack sizes vary by country and typically contain a small number of ampoules per carton (e.g., 1, 6, or 10 ampoules).
Inactive Ingredients (Excipients)
The typical formulation of Synacthen 0.25 mg/ml solution for injection includes the following excipients:
- Acetic acid (for pH adjustment)
- Sodium acetate trihydrate (buffer component)
- Mannitol (tonicity agent)
- Sodium chloride (tonicity agent)
- Water for injections (solvent)
The exact composition can vary slightly between national formulations. Always consult the package leaflet supplied with your specific product for a country-accurate list of excipients.
Appearance
Synacthen 0.25 mg/ml is a clear, colorless, aqueous solution supplied in small glass ampoules. The solution is isotonic and has a pH in the slightly acidic range. It should not be used if you can see any particles, haze, or discoloration.
Manufacturer and Marketing Authorization
Synacthen is marketed internationally under several trademarks and generic names; the most widely recognized brand is Synacthen. In the United States, the equivalent product is marketed as Cortrosyn (cosyntropin). Marketing authorization holders and manufacturers differ by country; see the package leaflet for the current holder in your region. Independently of the brand name used, all approved products must meet pharmacopoeial standards for identity, potency, purity, and sterility.
Frequently Asked Questions About Synacthen
Synacthen (tetracosactide) is most commonly used as a diagnostic tool in the short Synacthen test, also known as the ACTH stimulation test or cosyntropin test, to evaluate how well the adrenal glands produce cortisol. It helps diagnose primary adrenal insufficiency (Addison’s disease), established secondary adrenal insufficiency from pituitary disease, and congenital adrenal hyperplasia. Less commonly, Synacthen has been used therapeutically for certain steroid-responsive conditions, but this use has largely been replaced by direct glucocorticoid therapy.
A baseline blood sample is taken to measure your starting cortisol level. Then 250 micrograms of Synacthen are injected, usually into a muscle or a vein. A second blood sample is drawn 30 minutes after the injection, and sometimes a third sample at 60 minutes. If your adrenal glands are functioning normally, cortisol will rise significantly above an assay-specific threshold — typically around 430–500 nmol/L with modern assays. A blunted response suggests adrenal insufficiency and further investigation is usually needed to determine the cause.
For the large majority of patients, the test is uncomplicated. The injection itself feels similar to other intramuscular or intravenous shots. Minor side effects such as flushing, mild nausea, or brief dizziness can occur but usually resolve within minutes. The most important risk is an allergic reaction, including anaphylaxis, which is rare but serious. The test is therefore performed in a setting where staff and equipment are ready to recognize and treat such reactions immediately.
Most centers do not require fasting for the short Synacthen test itself. However, glucocorticoid medications (especially hydrocortisone) should be withheld for at least 24 hours before the test because they can distort the result, and dexamethasone or prednisolone may need to be stopped earlier under specialist guidance. If you are unsure, contact the clinic performing the test. Water and essential non-steroid medications (for example, insulin, antihypertensives, or levothyroxine) are usually continued as normal.
Synacthen should only be used in pregnancy if the expected benefit clearly outweighs the potential risk. Tetracosactide crosses the placenta in small amounts and chronic corticotropin exposure can have corticosteroid-like effects on the fetus. For a single diagnostic dose in the short Synacthen test, the risk is generally considered low when the test is clinically essential. It is not known whether tetracosactide passes into human breast milk; some centers advise a short interruption of breastfeeding, but this is not always necessary. Discuss your individual situation with your doctor.
Synacthen 0.25 mg/ml is a short-acting aqueous solution designed primarily for diagnostic testing; its pharmacological action lasts only 1–2 hours. Synacthen Depot is a different formulation in which tetracosactide is complexed with zinc to form a slow-release depot lasting 12–24 hours or more. Depot is used for therapeutic purposes — for example, in some protocols for infantile spasms (West syndrome) or for acute exacerbations of certain autoimmune diseases — while the plain solution is not suitable for chronic therapy. The two products must not be used interchangeably.
References
- European Medicines Agency (EMA) / National Regulatory Authorities. Summary of Product Characteristics for Synacthen (tetracosactide) 0.25 mg/ml solution for injection. Current version 2025.
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- Fleseriu M, Hashim IA, Karavitaki N, et al. Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(11):3888–3921.
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- Joint Formulary Committee. British National Formulary (BNF) – Tetracosactide. London: BMJ Group and Pharmaceutical Press; 2025 edition.
- U.S. Food and Drug Administration (FDA). Cortrosyn (cosyntropin) Prescribing Information. Revised 2024.
- World Health Organization (WHO). ATC/DDD Index: Tetracosactide – H01AA02. Oslo: WHO Collaborating Centre for Drug Statistics Methodology; 2025.
- Oelkers W. Adrenal insufficiency. N Engl J Med. 1996;335(16):1206–1212.
- Kazlauskaite R, Evans AT, Villabona CV, et al. Corticotropin tests for hypothalamic-pituitary-adrenal insufficiency: a metaanalysis. J Clin Endocrinol Metab. 2008;93(11):4245–4253. doi:10.1210/jc.2008-0710.
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This article was written and reviewed by the iMedic Medical Editorial Team, comprising licensed specialist physicians with expertise in endocrinology, internal medicine, and clinical pharmacology.
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