Cosyntropin

The standard diagnostic dose for adults is 0.25 mg (250 micrograms) administered as a single dose. This can be given as an intramuscular (IM) injection or as an intravenous (IV) bolus. In some specialized clinical settings, a 'low-dose' ACTH stimulation test may be performed using 1 microgram (0.001 mg), although the 0.25 mg dose remains the conventional standard for most diagnostic protocols. For intravenous infusion, 0.25 mg of cosyntropin may be added to glucose or saline solution and infused at a rate of approximately 0.04 mg per hour over a period of 6 hours to observe a more prolonged adrenal response.

Cosyntropin is approved for use in pediatric patients, but the dosage must be carefully adjusted based on age and weight.

• Children (over 2 years of age): The standard adult dose of 0.25 mg is typically used, as the adrenal response capacity is similar to that of adults.
• Infants and Neonates (under 2 years of age): A common dose is 0.125 mg (half of the adult vial) given IM or IV. Some protocols suggest a dose of 0.015 mg/kg of body weight to ensure safety and accuracy in very small infants. Your pediatrician will determine the most appropriate dose based on current clinical guidelines.

Renal Impairment

No specific dosage adjustments are required for patients with renal (kidney) impairment. Because cosyntropin is degraded by peptidases in the blood rather than being excreted primarily by the kidneys, its clearance is not significantly altered by kidney disease. However, the physiological response of the adrenal glands may be subtly affected by the systemic state of uremia.

Hepatic Impairment

No dosage adjustments are necessary for patients with hepatic (liver) impairment. The liver's CYP450 system is not involved in the metabolism of this peptide.

Elderly Patients

Clinical studies have not identified significant differences in the safety or efficacy of cosyntropin between elderly patients and younger adults. Dosage is generally the same, though clinicians should be mindful of the patient's overall cardiovascular health when administering the injection.

Cosyntropin is administered only by healthcare professionals in a clinical setting (hospital, clinic, or laboratory). It is not for self-administration.

1. 1Preparation: The procedure usually begins with a baseline blood draw to measure the 'resting' cortisol level.
2. 2Administration: The healthcare provider will then inject the cosyntropin into a muscle (usually the shoulder or buttock) or directly into a vein.
3. 3Monitoring: After the injection, you will be asked to wait. Further blood samples are typically drawn at 30 minutes and 60 minutes post-injection.
4. 4Storage: Prior to use, vials should be stored at controlled room temperature (20°C to 25°C) or refrigerated, depending on the specific manufacturer's instructions. Once reconstituted, the solution should be used immediately.

Since cosyntropin is administered as a single diagnostic dose by a healthcare provider, a 'missed dose' in the traditional sense is unlikely. If you miss your appointment for the stimulation test, contact your doctor to reschedule. The timing of the test is often important (many doctors prefer to perform it in the morning when natural cortisol levels are highest).

An acute overdose of cosyntropin is highly unlikely to cause significant harm because the drug is cleared from the body so quickly. However, a massive dose could theoretically cause transient fluid retention, high blood pressure, or electrolyte imbalances due to a sudden spike in cortisol and aldosterone. There is no specific antidote; treatment is supportive and involves monitoring the patient until the effects wear off.

> Important: Follow your healthcare provider's dosing instructions. Do not adjust your dose without medical guidance. Ensure you inform the staff of all medications you are currently taking before the test begins.

Because cosyntropin is typically administered as a single, one-time dose for diagnostic purposes, side effects are relatively uncommon. However, some patients may experience:

• Injection Site Reactions: Redness, mild swelling, or a 'stinging' sensation at the site where the needle entered the skin or muscle. This usually resolves within an hour.
• Flushing: A temporary feeling of warmth or redness in the face and neck, often occurring shortly after an intravenous injection.

• Nausea: A brief feeling of stomach upset or the urge to vomit.
• Dizziness: A momentary lightheadedness, which may be related to the procedure itself or a vasovagal response (fainting reflex) to the needle.
• Palpitations: A sensation that the heart is racing or skipping a beat, usually transient.

• Bradycardia: An unusually slow heart rate has been reported in rare instances following cosyntropin administration.
• Tachycardia: Conversely, some patients may experience a rapid heart rate.
• Hypersensitivity Reactions: While much rarer than with natural ACTH, some individuals may develop a rash, hives, or itching.

> Warning: Stop the procedure and alert your healthcare provider immediately if you experience any of the following symptoms of a severe allergic reaction (anaphylaxis):

• Difficulty Breathing: Shortness of breath, wheezing, or a feeling of tightness in the chest.
• Swelling (Angioedema): Swelling of the lips, tongue, throat, or face.
• Severe Hypotension: A sudden, sharp drop in blood pressure that can lead to fainting or shock.
• Generalized Hives: A widespread, itchy red rash that develops rapidly over the body.

In the clinical setting where cosyntropin is administered, medical staff are trained to recognize and treat these emergencies immediately with epinephrine and other supportive measures.

Cosyntropin is not intended for long-term therapeutic use. Therefore, the side effects associated with chronic corticosteroid excess (such as weight gain, osteoporosis, skin thinning, or 'Cushingoid' features) are not expected from a single diagnostic dose. If cosyntropin were to be used repeatedly over a long period (which is not standard practice), it could theoretically lead to adrenal hyperplasia or the suppression of the natural pituitary-adrenal axis.

As of 2026, there are no FDA black box warnings for cosyntropin. It is generally considered a safe diagnostic tool when used under appropriate medical supervision. However, the primary risk remains hypersensitivity, particularly in patients who have had previous reactions to ACTH or other synthetic peptides.

Report any unusual symptoms to your healthcare provider. Even if a symptom seems minor, it is important for the clinical team to document it as part of your diagnostic record.

Cosyntropin is a diagnostic agent and must only be used by qualified healthcare professionals. The most critical safety consideration is the risk of a hypersensitivity reaction. Although cosyntropin is synthetic and lacks the animal proteins that caused many reactions in the past, it is still a peptide and can trigger an immune response in susceptible individuals. Patients with a known history of asthma or significant allergies should be monitored closely during and after the injection.

No FDA black box warnings for Cosyntropin.

• Allergic Reactions / Anaphylaxis Risk: Patients who have previously reacted poorly to natural ACTH (porcine-derived) may still be at risk for a reaction to cosyntropin, though the risk is lower. Facilities where the test is performed must have emergency resuscitation equipment and medications (like epinephrine) readily available.
• Adrenal Hemorrhage: There have been extremely rare reports of adrenal hemorrhage (bleeding into the adrenal glands) following the administration of ACTH-like agents. This is more common in patients with pre-existing coagulation disorders or those taking anticoagulant medications.
• Interpretation Errors: Many factors can lead to a 'false' result. For example, patients taking estrogens (including birth control pills) may have elevated baseline cortisol levels, which can make the adrenal response appear abnormal when it is not.
• Infection: As with any injection, there is a very minor risk of localized infection at the site of administration.

The primary monitoring during a cosyntropin test is the measurement of plasma cortisol levels.

• Baseline: Blood is drawn immediately before the injection.
• Post-Stimulation: Blood is drawn at 30 and 60 minutes.
• Vital Signs: In patients with a history of heart disease or allergies, the healthcare provider may monitor blood pressure and heart rate throughout the procedure.

Cosyntropin itself does not typically cause sedation or cognitive impairment. However, some patients may feel slightly dizzy or faint after an injection or blood draw. It is generally advised to wait a few minutes after the procedure before driving to ensure you feel stable.

There are no direct chemical interactions between alcohol and cosyntropin. However, chronic alcohol consumption can affect the hypothalamic-pituitary-adrenal (HPA) axis and may interfere with the accuracy of the cortisol response. It is best to avoid alcohol for at least 24 hours prior to the diagnostic test.

Because cosyntropin is a one-time diagnostic dose, there is no 'discontinuation' process or tapering required. There is no risk of withdrawal syndrome.

> Important: Discuss all your medical conditions, especially any history of allergies or asthma, with your healthcare provider before starting the Cosyntropin stimulation test.

There are no drugs that are strictly 'contraindicated' in the sense of causing a lethal chemical reaction with cosyntropin. However, certain drugs must be stopped before the test because they make the results impossible to interpret.

• Exogenous Glucocorticoids: Medications like hydrocortisone, prednisone, or dexamethasone will interfere with the cortisol assay. If a patient is taking these, the test will measure the medication in the blood rather than the body's natural response. Most clinicians require these to be held for 24-48 hours prior to the test (with the exception of dexamethasone, which does not cross-react with most cortisol assays, though it still suppresses the HPA axis).

• Estrogens and Oral Contraceptives: Estrogens increase the level of Cortisol-Binding Globulin (CBG) in the blood. This can lead to abnormally high total cortisol levels, potentially masking a case of adrenal insufficiency. Healthcare providers may suggest stopping estrogen therapy for 4-6 weeks before the test for the most accurate results.
• Spironolactone: This diuretic can interfere with some cortisol assays, leading to falsely elevated readings.

• Phenytoin and Phenobarbital: These anti-seizure medications can increase the metabolism of cortisol in the liver, which might subtly affect the results of the stimulation test.
• Rifampin: Like phenytoin, this antibiotic induces liver enzymes and can lower the circulating levels of cortisol, potentially complicating the interpretation of the adrenal response.
• Ketoconazole: This antifungal medication inhibits steroid synthesis in the adrenal gland. If a patient is taking ketoconazole, their response to cosyntropin will be artificially blunted.

There are no known food interactions with cosyntropin. Unlike oral medications, its absorption is not affected by the presence of food in the stomach. However, patients are often asked to fast or avoid caffeine on the morning of the test to ensure baseline cortisol levels are not artificially spiked by dietary stimulants.

• St. John's Wort: This herbal supplement can induce liver enzymes (CYP3A4), which may increase the clearance of the cortisol produced during the test, though the clinical significance is minor.
• Licorice Root: Real licorice contains glycyrrhizic acid, which inhibits the enzyme that breaks down cortisol (11β-HSD2). This can lead to falsely high cortisol readings and should be avoided for several days before the test.

Cosyntropin is specifically designed to interact with lab tests (it is the stimulus for the test). However, it can also cause a transient increase in blood glucose levels (hyperglycemia) and a decrease in circulating eosinophils (a type of white blood cell) as a secondary effect of the cortisol spike it induces.

For each major interaction, the primary concern is not toxicity, but rather diagnostic inaccuracy. If the test results are skewed by other medications, a patient might be misdiagnosed with a life-threatening hormone deficiency or, conversely, a true deficiency might be missed.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, especially any steroid creams, inhalers, or pills.

Cosyntropin must NEVER be used in the following circumstances:

• Known Hypersensitivity to Cosyntropin: If a patient has had a prior documented allergic reaction or anaphylaxis to cosyntropin or any component of the formulation, the drug is strictly contraindicated.
• Known Hypersensitivity to ACTH: Patients who have reacted to natural adrenocorticotropic hormone in the past are at high risk for a cross-reaction and should not receive cosyntropin.

Conditions requiring careful risk-benefit analysis include:

• Acute Myocardial Infarction: The transient increase in cortisol and heart rate could theoretically put stress on a heart that has recently suffered a heart attack.
• Active Peptic Ulcer Disease: High levels of cortisol can exacerbate ulcers, though a single diagnostic dose is unlikely to cause significant damage.
• Severe Systemic Infection: Cortisol has immunosuppressive properties, but again, the duration of the spike from cosyntropin is very brief.
• Pregnancy: While not strictly contraindicated, the test should only be performed if the diagnostic information is essential for the management of the pregnancy.

Patients who are allergic to other synthetic peptides or those with a history of multiple drug allergies should be approached with caution. There is no evidence of cross-sensitivity between cosyntropin and non-peptide drugs like penicillin or sulfa drugs.

> Important: Your healthcare provider will evaluate your complete medical history, including any history of asthma or allergic rhinitis, before prescribing Cosyntropin for diagnostic testing.

Cosyntropin is classified as FDA Pregnancy Category C. This means that animal reproduction studies have not been conducted, and it is not known whether cosyntropin can cause fetal harm when administered to a pregnant woman. However, diagnosing adrenal insufficiency during pregnancy is critical, as untreated Addison's disease carries a high risk of maternal and fetal morbidity. If a pregnant woman is suspected of having adrenal insufficiency, the benefits of performing the cosyntropin stimulation test usually outweigh the theoretical risks. Clinicians should interpret the results carefully, as pregnancy naturally increases cortisol-binding globulin and total cortisol levels.

It is not known whether cosyntropin is excreted in human milk. However, because cosyntropin is a peptide with a very short half-life (15 minutes) and would be digested in the infant's stomach if any were present in the milk, it is considered highly unlikely to affect a nursing infant. Most experts believe breastfeeding can be continued normally after a cosyntropin test.

Cosyntropin is safe and effective for use in the pediatric population, including neonates. It is the preferred agent for diagnosing adrenal insufficiency in children. The primary consideration is the dosage adjustment for infants under 2 years of age (typically 0.125 mg). Growth effects are not a concern with a single diagnostic dose.

In patients over 65, the cosyntropin stimulation test is generally safe. There is no evidence of reduced clearance in the elderly since the drug is broken down by blood enzymes. However, elderly patients are more likely to be taking multiple medications (polypharmacy), such as estrogens or corticosteroids, which can interfere with the interpretation of the test results.

No dose adjustment is required for patients with kidney disease. The drug's metabolism is independent of renal function. However, patients on dialysis should ideally have the test performed on a non-dialysis day to ensure the most stable physiological environment.

No dose adjustment is required for patients with liver disease. The liver does not play a primary role in the clearance of cosyntropin.

> Important: Special populations require individualized medical assessment to ensure that the diagnostic results are both safe to obtain and accurate to interpret.

Cosyntropin is a synthetic 1-24 amino acid residue of the natural adrenocorticotropic hormone (ACTH). Its molecular mechanism involves binding to the Melanocortin 2 Receptor (MC2R) on the plasma membrane of the adrenal cortical cells. This binding stimulates the G-protein coupled receptor to activate adenylate cyclase, increasing intracellular cAMP. This increase in cAMP activates protein kinase A, which promotes the transport of cholesterol into the mitochondria via the Steroidogenic Acute Regulatory (StAR) protein. Inside the mitochondria, cholesterol is converted to pregnenolone, the precursor for cortisol synthesis. The result is a rapid increase in the synthesis and secretion of cortisol into the systemic circulation.

Following a 0.25 mg dose of cosyntropin, a measurable increase in plasma cortisol levels is usually seen within 5 to 10 minutes. In healthy individuals, cortisol levels typically peak between 45 and 60 minutes. The effect is transient; because the half-life of cosyntropin is so short, the stimulation of the adrenal glands ceases quickly once the drug is cleared, and cortisol levels return to baseline within a few hours. There is no evidence of tolerance development because the drug is not used chronically.

| Parameter | Value |

|---|---|

| Bioavailability | 100% (IV/IM) |

| Protein Binding | Minimal (peptide) |

| Half-life | 15 minutes |

| Tmax | 0.5 - 1 hour (for cortisol response) |

| Metabolism | Rapid enzymatic degradation by serum peptidases |

| Excretion | Minimal renal excretion of intact peptide |

The molecular formula of cosyntropin is C136H210N40O31S, with a molecular weight of approximately 2933.44 Daltons. It is a white to off-white lyophilized powder that is soluble in water. Structurally, it is identical to the first 24 amino acids of human ACTH, starting with Serine at the N-terminus and ending with Tyrosine at the 24th position.

Cosyntropin is classified as a diagnostic agent and a synthetic analogue of Adrenocorticotropic Hormone (ACTH). It is the only synthetic ACTH analogue currently used for diagnostic purposes in the United States. Related medications include natural ACTH (Acthar), though cosyntropin is preferred for diagnosis due to its purity and lower allergenicity.