ACTH Dosage Guide: Cosyntropin Protocols, Diagnostic Testing & Clinical Use

ACTH (Adrenocorticotropic Hormone) is a 39-amino-acid peptide hormone produced by the anterior pituitary gland that serves as the principal regulator of adrenal cortex function. Cosyntropin, its synthetic analog comprising the first 24 amino acids (ACTH 1-24), retains full biological activity and is the standard form used in clinical medicine. Unlike most peptides covered in research-oriented dosage guides, ACTH and cosyntropin are FDA-approved medications used primarily in diagnostic testing and select therapeutic applications under direct medical supervision.

ACTH binds the melanocortin 2 receptor (MC2R) on the adrenal cortex, stimulating the synthesis and release of cortisol and other corticosteroids. This mechanism underpins its two major clinical roles: the cosyntropin stimulation test for diagnosing adrenal insufficiency, and therapeutic use of repository corticotropin (Acthar Gel) for conditions including infantile spasms, nephrotic syndrome, and multiple sclerosis exacerbations. This guide covers diagnostic and therapeutic protocols, reconstitution, administration, and safety. Use our Peptide Dosage Calculator for reconstitution math if working with lyophilized cosyntropin.

Important: ACTH (cosyntropin) is an FDA-approved prescription medication. It must be administered under the supervision of a qualified healthcare provider. This article is for educational purposes only. Do not self-administer ACTH without medical oversight.

What Is ACTH?

Adrenocorticotropic hormone (ACTH) is a 39-amino-acid polypeptide hormone synthesized and secreted by corticotroph cells in the anterior pituitary gland. It is cleaved from a larger precursor protein called proopiomelanocortin (POMC), which also gives rise to beta-endorphin and melanocyte-stimulating hormones. ACTH is the primary endocrine driver of the adrenal cortex, controlling the synthesis of cortisol, corticosterone, and adrenal androgens via activation of the melanocortin 2 receptor (MC2R).

Key characteristics:

39-amino-acid peptide — full-length endogenous ACTH; the biologically active region resides in the first 24 amino acids (ACTH 1-24)
Cosyntropin (ACTH 1-24) — synthetic analog retaining full MC2R agonist activity, used as the standard diagnostic agent (brand names: Cortrosyn, Synacthen)
MC2R agonist — binds melanocortin 2 receptors on adrenal cortical cells, stimulating steroidogenesis (cortisol, aldosterone, adrenal androgens)
HPA axis effector — serves as the intermediate signal between hypothalamic CRH (corticotropin-releasing hormone) and adrenal cortisol output
Short half-life — approximately 15 minutes in circulation, which is ideal for diagnostic testing but necessitates depot formulations (Acthar Gel) for therapeutic use
FDA-approved applications — cosyntropin stimulation test (diagnostic); Acthar Gel for infantile spasms, nephrotic syndrome, MS exacerbations, and select rheumatologic conditions

For a complete overview, see our full ACTH profile. New to peptides? Start with the Beginner's Guide to Peptides.

How ACTH Dosage Is Determined

ACTH dosing is firmly established through decades of clinical research, FDA-approved labeling, and endocrine society guidelines. Unlike many research peptides where dosing is extrapolated from animal studies or community experience, ACTH protocols are grounded in large-scale clinical data and standardized diagnostic procedures.

Diagnostic Dose Determination

The standard-dose cosyntropin stimulation test (250 mcg) was established in the 1960s and has remained the gold-standard screening test for adrenal insufficiency for over five decades. This supraphysiologic dose maximally stimulates the adrenal cortex, providing a reliable assessment of adrenal reserve. The 250 mcg dose was chosen because it produces maximal cortisol output in healthy adrenals, creating a clear threshold for distinguishing normal from insufficient adrenal function.

Low-Dose Test Development

The low-dose cosyntropin test (1 mcg) was developed in the 1990s as a potentially more sensitive alternative. Researchers hypothesized that the standard 250 mcg dose — which is approximately 100-fold greater than the physiologic ACTH surge — might stimulate partially damaged adrenals that would fail under physiologic stress. The 1 mcg dose more closely approximates the physiologic ACTH peak during stress, potentially detecting milder degrees of adrenal insufficiency, particularly secondary adrenal insufficiency.

Therapeutic Dose Determination

Therapeutic dosing of repository corticotropin (Acthar Gel) is based on clinical trials for specific FDA-approved indications. Doses are expressed in USP units rather than micrograms because Acthar Gel contains a purified porcine-derived ACTH preparation in a gelatin matrix designed for prolonged absorption. The 40-80 USP unit range was established through controlled trials demonstrating efficacy across infantile spasms, nephrotic syndrome, and inflammatory conditions.

Endocrine Society Guidelines

The Endocrine Society's clinical practice guidelines recommend the 250 mcg cosyntropin stimulation test as the first-line diagnostic test for primary adrenal insufficiency. The test's interpretation — cortisol response above 18 mcg/dL (500 nmol/L) at 30 or 60 minutes — is based on population studies of healthy controls and patients with confirmed adrenal disease.

Strength of evidence: Very strong. ACTH dosing for diagnostic and therapeutic use is supported by decades of clinical trials, FDA-approved labeling, and international endocrine society consensus guidelines. This is among the most well-established dosing protocols in all of peptide medicine.

Standard ACTH (Cosyntropin) Dosage Ranges

ACTH dosing differs fundamentally between diagnostic and therapeutic applications. Diagnostic cosyntropin doses are standardized and weight-independent. Therapeutic Acthar Gel doses vary by indication and clinical response.

Diagnostic Cosyntropin Stimulation Test

Test Type	Dose	Route	Notes
Standard-dose test	250 mcg	IV bolus or IM	Gold standard; supraphysiologic stimulation; measure cortisol at 0, 30, 60 min
Low-dose test	1 mcg	IV bolus only	More physiologic; may detect milder adrenal insufficiency; requires dilution from 250 mcg vial

Therapeutic Acthar Gel (Repository Corticotropin)

Indication	Dose	Frequency	Notes
Infantile spasms	150 USP units/m2/day	Divided BID, IM	FDA-approved; 2-week initial course; taper over 2 weeks
Nephrotic syndrome	80 USP units	BIW (twice weekly), IM/SC	For patients refractory to or intolerant of standard immunosuppression
MS exacerbations	80-120 USP units	Daily for 2-3 weeks, IM	Alternative to IV methylprednisolone for acute relapses
Rheumatologic conditions	40-80 USP units	Every 24-72 hours, IM/SC	For gout flares, rheumatoid arthritis, lupus exacerbations

Clinical Administration Only: ACTH (cosyntropin) and Acthar Gel are prescription medications that must be administered under medical supervision. The cosyntropin stimulation test requires baseline and timed blood draws interpreted by an endocrinologist. Acthar Gel therapy requires ongoing monitoring of blood glucose, blood pressure, electrolytes, and signs of hypercortisolism. Do not self-administer these medications.

Calculate Your Exact Cosyntropin Dose

Cosyntropin for diagnostic use is supplied as a lyophilized powder (250 mcg per vial) that is reconstituted before administration. For the standard 250 mcg test, the entire vial is used. For the 1 mcg low-dose test, serial dilution is required.

Worked Example

Vial: 250 mcg cosyntropin (lyophilized)
Reconstitution: Add 1 mL sterile normal saline
Concentration: 250 mcg/mL
Standard test (250 mcg): Draw entire 1 mL and administer IV or IM
Low-dose test (1 mcg): Draw 0.1 mL (25 mcg) into a 10 mL syringe, add 9.9 mL normal saline (= 2.5 mcg/mL), then draw 0.4 mL (= 1 mcg) from this dilution and administer IV

Quick Reference Table

Test Type	Vial	Reconstitution	Draw Volume	Route
Standard (250 mcg)	250 mcg	1 mL NS	1 mL (entire vial)	IV bolus or IM
Low-dose (1 mcg)	250 mcg	Serial dilution (see above)	0.4 mL of 2.5 mcg/mL solution	IV bolus only

The Peptide Dosage Calculator can assist with reconstitution math for any vial size and concentration. The low-dose test dilution must be prepared fresh and administered within 30 minutes due to peptide adsorption to plastic surfaces.

How to Reconstitute Cosyntropin

Cosyntropin reconstitution follows standard clinical peptide preparation procedures. The lyophilized powder must be dissolved in sterile normal saline (0.9% NaCl) immediately before use. For the low-dose test, a serial dilution technique is required to achieve the 1 mcg dose from the 250 mcg vial.

Supplies Needed

Cosyntropin 250 mcg lyophilized vial (Cortrosyn)
Sterile normal saline (0.9% NaCl) for injection
Syringes (1 mL and 10 mL for low-dose dilution)
Needles (21-25 gauge for drawing, appropriate gauge for injection)
Alcohol swabs
Vacutainer tubes for cortisol blood draws (SST or heparin per lab protocol)

Steps

Verify the cosyntropin vial label, expiration date, and lot number
Swab the vial stopper with an alcohol pad and allow to dry
Draw 1 mL of sterile normal saline into a syringe
Inject the saline into the cosyntropin vial, directing the stream against the glass wall
Gently swirl until the powder is completely dissolved — do not shake
For the standard 250 mcg test: draw the full 1 mL and administer IV or IM
For the 1 mcg low-dose test: perform serial dilution as described in the dose calculation section
Administer the reconstituted solution within 30 minutes of preparation

Storage

Unreconstituted: Store at controlled room temperature (15-30 C / 59-86 F); protect from light
Reconstituted: Use within 30 minutes of preparation — do not store reconstituted solution
Low-dose dilution: Prepare immediately before use; cosyntropin adsorbs to plastic surfaces, reducing concentration over time
Acthar Gel: Refrigerate at 2-8 C (36-46 F); do not freeze; protect from light

For a complete walkthrough, see our Reconstitution Guide.

ACTH Dosage by Clinical Application

ACTH is used across several distinct clinical scenarios, each with its own dosing protocol, administration route, and monitoring requirements. All applications require physician supervision.

Adrenal Insufficiency Diagnosis (Standard Cosyntropin Test)

The gold-standard screening test for primary adrenal insufficiency (Addison's disease). A supraphysiologic dose of cosyntropin maximally stimulates the adrenal cortex. Failure to produce an adequate cortisol response confirms impaired adrenal reserve. This test is also used to evaluate secondary adrenal insufficiency from chronic corticosteroid use or pituitary disease, though sensitivity for secondary AI is lower.

Dose: 250 mcg cosyntropin IV bolus or IM
Protocol: Draw baseline cortisol (time 0), administer cosyntropin, draw cortisol at 30 and 60 minutes
Normal response: Peak cortisol greater than 18 mcg/dL (500 nmol/L) at either 30 or 60 minutes
Duration: Single test — not a treatment protocol
Notes: Perform in the morning (7-9 AM) when baseline cortisol is expected to be at its diurnal peak. Do not administer exogenous glucocorticoids on the morning of the test (hydrocortisone must be held for at least 12 hours; dexamethasone does not cross-react with most cortisol assays). Patients on oral contraceptives may have falsely elevated cortisol-binding globulin, increasing total cortisol levels.

Adrenal Insufficiency Diagnosis (Low-Dose Cosyntropin Test)

The low-dose test uses a physiologic level of cosyntropin to detect subtler degrees of adrenal insufficiency, particularly secondary adrenal insufficiency from prolonged corticosteroid use or pituitary disease. Because the standard 250 mcg dose can stimulate partially atrophied adrenals to produce a borderline-passing cortisol response, the 1 mcg dose may unmask mild HPA axis suppression.

Dose: 1 mcg cosyntropin IV bolus (must be prepared by serial dilution)
Protocol: Draw baseline cortisol, administer 1 mcg IV, draw cortisol at 20 and 30 minutes
Normal response: Peak cortisol greater than 18 mcg/dL (500 nmol/L)
Duration: Single test
Notes: IV route only — IM absorption is too variable at this low dose. Diluted solution must be prepared fresh and administered within 30 minutes because cosyntropin adsorbs to plastic syringes and tubing. Some centers use plastic syringes pre-flushed with albumin to minimize adsorption. The low-dose test is not universally accepted as superior and is not recommended as the sole diagnostic test by the Endocrine Society.

Infantile Spasms (West Syndrome)

Acthar Gel is one of two first-line treatments for infantile spasms (the other being vigabatrin). Clinical trials have demonstrated superiority of ACTH over oral corticosteroids for cessation of spasms and normalization of the EEG pattern (hypsarrhythmia). This is considered one of the strongest evidence-based indications for repository corticotropin.

Dose: 150 USP units/m2/day IM, divided into two daily doses
Timing: Two-week treatment course, followed by a two-week taper
Frequency: Twice daily IM injections
Duration: 2 weeks full dose, 2 weeks taper (4 weeks total)
Notes: Requires close monitoring: blood pressure, blood glucose, electrolytes, growth parameters, and infection surveillance. Immunizations with live vaccines must be deferred during treatment. Parents should be educated on signs of infection, as immunosuppression increases risk. Response is typically assessed by EEG at 2 weeks.

Nephrotic Syndrome & MS Exacerbations

Acthar Gel is used for nephrotic syndrome refractory to conventional immunosuppressive therapy, and as an alternative to IV methylprednisolone for acute MS relapses. The mechanism may extend beyond simple cortisol stimulation — ACTH acts on melanocortin receptors expressed on immune cells (MC1R, MC3R, MC5R), providing direct anti-inflammatory and immunomodulatory effects independent of adrenal cortisol production.

Dose (nephrotic syndrome): 80 USP units IM or SC, twice weekly
Dose (MS exacerbations): 80-120 USP units IM daily for 2-3 weeks
Frequency: Per indication — see above
Duration: Nephrotic syndrome: 6 months typical; MS: 2-3 weeks per exacerbation
Notes: Monitor blood pressure, blood glucose, serum potassium, weight, and signs of infection throughout treatment. Acthar Gel carries the same adverse effect profile as systemic corticosteroid therapy. Proteinuria and renal function should be tracked in nephrotic syndrome. Consider PJP (Pneumocystis jirovecii pneumonia) prophylaxis for prolonged courses.

Medical Supervision Required: All ACTH applications — diagnostic and therapeutic — require administration by or under the supervision of a licensed healthcare provider. The cosyntropin stimulation test requires proper blood draw timing and laboratory interpretation. Acthar Gel therapy requires ongoing monitoring for adverse effects of hypercortisolism. These are not self-administered protocols.

ACTH Administration Guide

Cosyntropin Stimulation Test (IV or IM)

Patient preparation: Schedule test for morning (7-9 AM); hold hydrocortisone for at least 12 hours; patient should be fasting or have had a light breakfast
Establish IV access and draw baseline cortisol and ACTH levels (time 0)
Reconstitute cosyntropin: Add 1 mL normal saline to the 250 mcg vial; swirl gently
Administer 250 mcg IV push (over 2 minutes) or IM into the deltoid
Draw cortisol at 30 minutes post-injection
Draw cortisol at 60 minutes post-injection
Interpret results: Peak cortisol greater than 18 mcg/dL = normal adrenal response; below this threshold suggests adrenal insufficiency

Acthar Gel (IM or SC Injection)

Remove Acthar Gel from refrigerator 15-20 minutes before injection to allow warming to room temperature (gel is viscous when cold)
Draw the prescribed dose using an 18-21 gauge needle (gel consistency requires a larger bore for drawing)
Switch to a 22-25 gauge needle for injection
Select injection site: Gluteal region (IM) or abdominal subcutaneous tissue; rotate sites between injections
Clean the site with alcohol and allow to dry
For IM: Insert needle at 90-degree angle into the upper outer quadrant of the gluteus; inject slowly (the gel is viscous)
For SC: Pinch skin, insert at 45-degree angle into abdominal tissue; inject slowly
Apply gentle pressure with gauze after withdrawal; do not massage the injection site

Administration Notes

Cosyntropin (diagnostic): Single administration — no injection rotation needed
Acthar Gel (therapeutic): Rotate injection sites; the gel can cause local tissue irritation with repeated injections at the same site
Acthar Gel viscosity: The gelatin matrix makes the preparation thick; drawing with a larger-gauge needle and injecting with a standard gauge is standard practice
Do not administer IV: Acthar Gel is for IM or SC use only — never administer intravenously

ACTH Treatment Duration & Protocols

ACTH treatment duration varies significantly by indication. Diagnostic use is a single test. Therapeutic use ranges from short courses (MS exacerbations) to extended protocols (nephrotic syndrome). All therapeutic courses require gradual tapering to avoid adrenal suppression from abrupt withdrawal.

Indication	Duration	Taper	Notes
Cosyntropin stimulation test	Single administration	None required	Diagnostic test only; no ongoing treatment
Infantile spasms	2 weeks full dose + 2 weeks taper	Gradual over 2 weeks	May repeat if spasms recur; second course same protocol
MS exacerbations	2-3 weeks	Taper over 1-2 weeks	Per-relapse treatment; not for chronic MS management
Nephrotic syndrome	Up to 6 months	Gradual taper guided by proteinuria response	Duration based on clinical response; monitor renal function
Rheumatologic conditions	Variable (days to weeks)	Taper based on response	Short courses for acute flares (e.g., gout); longer for chronic conditions

ACTH in Clinical Combination Protocols

ACTH is not "stacked" in the traditional research peptide sense. However, it is used alongside other medications in structured clinical protocols. The following combinations reflect established medical practice rather than experimental stacking.

ACTH + Vigabatrin (Infantile Spasms Protocol)

In infantile spasms, ACTH and vigabatrin are the two first-line treatments. Some treatment algorithms use them sequentially (ACTH first, vigabatrin if ACTH fails, or vice versa), while others combine them upfront for refractory cases. The combination targets different mechanisms: ACTH modulates the HPA axis and has broad immunomodulatory effects, while vigabatrin irreversibly inhibits GABA transaminase, increasing brain GABA levels.

Agent	Dose	Route	Role
ACTH (Acthar Gel)	150 USP units/m2/day	IM (divided BID)	Primary therapy for spasm cessation
Vigabatrin	50-150 mg/kg/day	Oral (divided BID)	First-line alternative or combination agent

Combination use should only occur under pediatric neurology supervision. Vigabatrin carries a risk of irreversible visual field defects and requires ophthalmologic monitoring through the REMS program.

ACTH + Immunosuppressive Therapy (Nephrotic Syndrome)

In refractory nephrotic syndrome, Acthar Gel may be used as an alternative to or in sequence with conventional immunosuppressants such as calcineurin inhibitors (tacrolimus, cyclosporine), mycophenolate, or rituximab. ACTH provides both cortisol-dependent anti-inflammatory effects and direct melanocortin-mediated effects on podocytes, which may help reduce proteinuria through a mechanism distinct from standard immunosuppression.

Agent	Dose	Route	Role
ACTH (Acthar Gel)	80 USP units BIW	IM or SC	Steroid-sparing immunomodulation
Tacrolimus or Cyclosporine	Per nephrology protocol	Oral	Calcineurin-dependent immunosuppression

Concurrent immunosuppression increases infection risk. PJP prophylaxis, monitoring of drug levels, and regular assessment of renal function and proteinuria are essential.

Cosyntropin Test + CRH Test (Extended HPA Axis Evaluation)

For distinguishing primary from secondary adrenal insufficiency, some endocrinologists use the cosyntropin stimulation test in combination with a CRH (corticotropin-releasing hormone) stimulation test. The cosyntropin test evaluates adrenal reserve directly, while the CRH test evaluates the pituitary's ability to secrete ACTH in response to hypothalamic stimulation. Together, they can localize the level of HPA axis dysfunction.

Test	Dose	Route	Measures
Cosyntropin stimulation	250 mcg	IV	Adrenal cortisol response (reserve)
CRH stimulation	1 mcg/kg or 100 mcg	IV	Pituitary ACTH response

CRH testing is less commonly performed due to limited availability of synthetic CRH (corticorelin ovine). These tests are performed on separate days and interpreted by an endocrinologist to determine whether adrenal insufficiency is primary (adrenal), secondary (pituitary), or tertiary (hypothalamic).

All clinical combinations require physician supervision and are not appropriate for self-administration. Browse the Peptide Directory for information on other peptides in clinical use.

Safety, Side Effects & Contraindications

Important Safety Information: ACTH stimulates cortisol production. All adverse effects of exogenous corticosteroids apply to therapeutic ACTH use, particularly with Acthar Gel. Short-term diagnostic use (single cosyntropin stimulation test) has an excellent safety profile. Chronic or repeated therapeutic use carries significant risk and requires close monitoring.

Cosyntropin Stimulation Test (Diagnostic — Single Dose)

Generally very well tolerated:

Mild flushing at the injection site — transient
Rare hypersensitivity reactions (urticaria, pruritus) — very uncommon
Anaphylaxis — extremely rare but documented; have epinephrine available
Transient tachycardia or feeling of warmth — occasional

Key point: A single diagnostic dose of cosyntropin carries minimal risk. Adverse reactions are rare and almost always mild. Patients with known hypersensitivity to cosyntropin or any component should not receive the test.

Acthar Gel (Therapeutic — Repeated/Chronic Use)

Common (reflects cortisol elevation and immunosuppression):

Hyperglycemia — blood glucose elevation; may unmask or worsen diabetes
Fluid retention and edema — sodium and water retention
Hypertension — from mineralocorticoid effects
Hypokalemia — potassium wasting from aldosterone stimulation
Weight gain — from fluid retention and increased appetite
Mood changes — irritability, insomnia, euphoria, or depression
Immunosuppression — increased susceptibility to infections
Injection site reactions — pain, induration, abscess (especially IM)

Serious (with prolonged use):

Cushing syndrome — iatrogenic hypercortisolism with chronic use
Adrenal suppression — HPA axis suppression requiring tapering
Osteoporosis — bone density loss with prolonged courses
Peptic ulcer disease — increased risk, especially with concurrent NSAIDs
Opportunistic infections — PJP, fungal infections, reactivation of tuberculosis
Growth suppression in children — monitor growth parameters during therapy

Contraindications

Known hypersensitivity to cosyntropin or porcine proteins (Acthar Gel is porcine-derived)
Systemic fungal infections — immunosuppression may exacerbate
Active or latent tuberculosis — screen before initiating Acthar Gel
Ocular herpes simplex — risk of corneal perforation
Recent surgery or GI perforation — corticosteroid effects impair wound healing
Congestive heart failure — fluid retention may worsen cardiac status
Uncontrolled hypertension — mineralocorticoid effects raise blood pressure
Pregnancy (Acthar Gel) — potential teratogenic effects; diagnostic cosyntropin is Category C
Live vaccines — do not administer during immunosuppressive therapy

Monitoring Requirements

Blood glucose: Baseline and regular monitoring — daily during initiation of Acthar Gel
Blood pressure: Monitor at each clinical visit
Electrolytes: Serum potassium, sodium — weekly during initial therapy
Infection surveillance: Monitor for signs of infection; low threshold for workup
Bone density: Consider DEXA scan for courses exceeding 3 months
Ophthalmologic exam: Baseline and periodic for long-term use (cataracts, glaucoma risk)

Regulatory Status

FDA-approved: Cosyntropin (Cortrosyn) for diagnostic testing; Acthar Gel (repository corticotropin) for infantile spasms, nephrotic syndrome, MS exacerbations, and select rheumatologic conditions
Prescription required: Both cosyntropin and Acthar Gel are prescription medications
WADA status: ACTH is prohibited at all times under S2 (Peptide Hormones) on the WADA Prohibited List

Common ACTH Testing & Dosing Mistakes

Not holding hydrocortisone before the cosyntropin stimulation test — Exogenous hydrocortisone will be measured by the cortisol assay, producing a falsely normal result. Hydrocortisone must be held for at least 12 hours (some protocols require 24 hours) before the test. Dexamethasone does not cross-react with most cortisol assays and can be used as a bridge if needed.
Performing the cosyntropin test in the afternoon — Cortisol follows a diurnal rhythm, peaking in the early morning. Afternoon testing may produce lower baseline cortisol levels that do not reflect true adrenal reserve. Standard practice is to perform the test between 7-9 AM for optimal interpretability.
Using the low-dose (1 mcg) test without proper serial dilution — The 1 mcg dose requires precise serial dilution from the 250 mcg vial. Inaccurate dilution produces unreliable results. Additionally, cosyntropin adsorbs to plastic surfaces — the diluted solution must be prepared fresh and administered within 30 minutes. Using a pre-diluted solution that has been sitting produces falsely low stimulation.
Interpreting a passing cosyntropin test as ruling out secondary adrenal insufficiency — The standard 250 mcg test can stimulate partially atrophied adrenals to produce a borderline-passing response even when the HPA axis is suppressed. A normal result on the 250 mcg test does not definitively exclude secondary adrenal insufficiency, especially in the early stages of pituitary disease or shortly after discontinuing chronic corticosteroids.
Abruptly discontinuing Acthar Gel without tapering — Therapeutic ACTH administration suppresses the endogenous HPA axis. Abrupt withdrawal can precipitate adrenal crisis — a life-threatening condition characterized by hypotension, hypoglycemia, and cardiovascular collapse. All courses of Acthar Gel longer than 1-2 weeks require a gradual taper.
Failing to monitor blood glucose during Acthar Gel therapy — ACTH stimulates cortisol production, which raises blood glucose through gluconeogenesis and insulin resistance. Hyperglycemia is one of the most common adverse effects of Acthar Gel. Diabetic patients may require insulin dose adjustments. Non-diabetic patients may develop new-onset hyperglycemia requiring treatment.
Treating ACTH as a self-administered research peptide — Unlike many peptides in the research space, ACTH and cosyntropin are prescription medications with well-defined clinical indications and significant adverse effect profiles. Self-administration without medical oversight risks unmonitored cortisol elevation, electrolyte disturbances, immunosuppression, and HPA axis suppression. All ACTH applications require physician supervision.
Administering Acthar Gel intravenously — Acthar Gel is a repository (depot) formulation in a gelatin matrix designed for slow absorption from IM or SC injection sites. IV administration of the gel is contraindicated and dangerous. Only reconstituted cosyntropin (Cortrosyn) is appropriate for IV administration.

Frequently Asked Questions

What is the cosyntropin stimulation test?

The cosyntropin stimulation test is the gold-standard diagnostic test for adrenal insufficiency. A synthetic ACTH analog (cosyntropin, 250 mcg) is administered IV or IM, and blood cortisol levels are measured at baseline, 30 minutes, and 60 minutes. A peak cortisol response greater than 18 mcg/dL (500 nmol/L) indicates normal adrenal function. A subnormal response suggests adrenal insufficiency and warrants further evaluation.

What is the difference between the 250 mcg and 1 mcg cosyntropin tests?

The standard 250 mcg dose provides supraphysiologic adrenal stimulation and is the recommended first-line test. The 1 mcg low-dose test more closely approximates physiologic ACTH levels and may detect milder degrees of adrenal insufficiency, particularly secondary AI from chronic corticosteroid use. However, the low-dose test requires precise serial dilution, is more technically demanding, and is not universally accepted as superior. Most endocrinologists use the 250 mcg test as the primary screening tool.

What is Acthar Gel and how does it differ from cosyntropin?

Acthar Gel (repository corticotropin injection) is a purified preparation of porcine-derived ACTH in a gelatin matrix that provides prolonged absorption from the injection site. Unlike cosyntropin (a synthetic 24-amino-acid ACTH fragment used for one-time diagnostic testing), Acthar Gel is used therapeutically for conditions including infantile spasms, nephrotic syndrome, and MS exacerbations. Acthar Gel is given IM or SC, never IV, and contains the full-length ACTH molecule along with other POMC-derived peptides.

What is a normal cortisol response to the cosyntropin test?

A peak cortisol level greater than 18 mcg/dL (500 nmol/L) at either the 30-minute or 60-minute blood draw is considered a normal response, indicating adequate adrenal reserve. Some laboratories and newer assays use a slightly lower cutoff (15-16 mcg/dL) depending on the specific cortisol assay platform. Always reference your laboratory's specific cutoff values and discuss results with an endocrinologist.

Can I self-administer ACTH or cosyntropin?

No. ACTH and cosyntropin are prescription medications that should only be administered under medical supervision. The cosyntropin stimulation test requires properly timed blood draws and laboratory interpretation by an endocrinologist. Acthar Gel therapy requires ongoing monitoring of blood glucose, blood pressure, electrolytes, and infection surveillance. Self-administration carries risks of unmonitored cortisol elevation, electrolyte imbalances, and HPA axis suppression.

What are the main side effects of ACTH therapy?

For the diagnostic cosyntropin test (single dose), side effects are minimal — mild flushing or transient discomfort at the injection site. For therapeutic Acthar Gel (repeated dosing), side effects mirror those of systemic corticosteroid therapy: hyperglycemia, fluid retention, hypertension, hypokalemia, weight gain, mood changes, immunosuppression, and increased infection risk. Prolonged use can cause iatrogenic Cushing syndrome, osteoporosis, and adrenal suppression requiring gradual tapering.

What is the half-life of ACTH?

Endogenous ACTH and synthetic cosyntropin have a plasma half-life of approximately 15 minutes. This is why the diagnostic cosyntropin test measures cortisol response rather than ACTH levels — the peptide is rapidly cleared, but its effect on adrenal cortisol production persists for 60+ minutes. Acthar Gel is formulated in a gelatin matrix specifically to slow absorption and provide sustained ACTH levels over hours, making it suitable for therapeutic use.

Is ACTH FDA-approved?

Yes, in specific formulations and for specific indications. Cosyntropin (Cortrosyn) is FDA-approved for the diagnostic assessment of adrenal function. Acthar Gel (repository corticotropin injection) is FDA-approved for infantile spasms, nephrotic syndrome, MS exacerbations, and several rheumatologic conditions. These are among the few peptides with full FDA approval for therapeutic use.

What medications should be held before a cosyntropin stimulation test?

Hydrocortisone must be held for at least 12-24 hours before the test, as it cross-reacts with cortisol assays. Prednisone and prednisolone should also be held, though they have variable cross-reactivity depending on the assay. Dexamethasone does not cross-react with most cortisol assays and can be used as a glucocorticoid bridge if needed. Oral contraceptives increase cortisol-binding globulin, which can elevate total cortisol levels and produce falsely reassuring results. Discuss all current medications with the ordering physician.

Is ACTH used as a research peptide like BPC-157 or other popular peptides?

No. Unlike research peptides such as BPC-157, Ipamorelin, or DSIP, ACTH is an established pharmaceutical with FDA-approved clinical indications. It is not used in the biohacking or research peptide community for self-experimentation. ACTH stimulates cortisol production, and chronic cortisol elevation carries serious health risks including immunosuppression, metabolic dysfunction, and HPA axis suppression. There is no legitimate use case for self-administered ACTH outside of medical supervision.

Key Takeaways

ACTH is a 39-amino-acid pituitary hormone; cosyntropin (ACTH 1-24) is its synthetic diagnostic analog that retains full biological activity
The standard cosyntropin stimulation test (250 mcg IV/IM) is the gold-standard diagnostic test for adrenal insufficiency — normal response is cortisol greater than 18 mcg/dL at 30 or 60 minutes
The low-dose test (1 mcg IV) may detect milder secondary adrenal insufficiency but requires precise serial dilution and immediate use
Acthar Gel (repository corticotropin) is FDA-approved for infantile spasms, nephrotic syndrome, MS exacerbations, and select rheumatologic conditions
This is a clinical/diagnostic peptide — not a research peptide for self-administration; all applications require physician supervision
Therapeutic ACTH carries the same adverse effect profile as systemic corticosteroids: hyperglycemia, hypertension, fluid retention, immunosuppression
Never abruptly discontinue Acthar Gel — tapering is required to prevent adrenal crisis from HPA axis suppression
ACTH acts on MC2R to stimulate adrenal cortisol production, but also has direct immunomodulatory effects via MC1R, MC3R, and MC5R on immune cells
The diagnostic cosyntropin test (single dose) has an excellent safety profile; therapeutic Acthar Gel requires close monitoring of blood glucose, blood pressure, electrolytes, and infection risk
ACTH is prohibited at all times by WADA under S2 (Peptide Hormones) — athletes subject to testing must avoid all forms

This article is for educational and informational purposes only. ACTH (cosyntropin) and Acthar Gel are FDA-approved prescription medications that must be prescribed and supervised by a licensed healthcare provider. Do not self-administer ACTH. All diagnostic testing requires proper laboratory interpretation by a qualified endocrinologist. See our Medical Disclaimer.

References:

Bornstein SR, Allolio B, Arlt W, et al. "Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society clinical practice guideline." J Clin Endocrinol Metab. 2016;101(2):364-389.
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.
Dickstein G, Shechner C, Nicholson WE, et al. "Adrenocorticotropin stimulation test: effects of basal cortisol level, time of day, and suggested new sensitive low dose test." J Clin Endocrinol Metab. 1991;72(4):773-778.
Baram TZ, Mitchell WG, Tournay A, et al. "High-dose corticotropin (ACTH) versus prednisone for infantile spasms: a prospective, randomized, blinded study." Pediatrics. 1996;97(3):375-379.
Hogan J, Bomback AS, Mehta K, et al. "Treatment of idiopathic FSGS with adrenocorticotropic hormone gel." Clin J Am Soc Nephrol. 2013;8(12):2072-2081.
Simsarian JP, Saunders C, Smith DM. "Five-day regimen of intramuscular or subcutaneous self-administered adrenocorticotropic hormone gel for acute exacerbations of multiple sclerosis." Drug Des Devel Ther. 2011;5:467-475.
Catania A, Gatti S, Colombo G, Lipton JM. "Targeting melanocortin receptors as a novel strategy to control inflammation." Pharmacol Rev. 2004;56(1):1-29.
Fleseriu M, Hashim IA, Engelman DH, et al. "Impact of assay methodology on cortisol measurement and interpretation of cosyntropin stimulation testing." Endocr Pract. 2022;28(4):432-441.

Next Steps

Dosage Calculator — Get reconstitution math for cosyntropin vial preparation and serial dilution.
Thymosin Alpha-1 Guide — Another immune-modulating peptide with clinical applications — compare mechanisms and protocols.
Peptide Directory — Browse all peptides with research summaries and dosing data.

ACTH (Cosyntropin) Dosage Guide: Clinical Protocols, Diagnostic Testing & Safety (2026)