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ACTH (Cosyntropin/Cortrosyn)24 residuesSYSMEHFRWGKPVGKKRRPVKVYPEach bubble = one amino acid. Size = residue mass. Color = chemical class.Also known as: ACTH, corticotropin, cosyntropin
Over 400 PubMed papers and six decades of clinical use make cosyntropin one of the most validated diagnostic tools in all of endocrinology. This synthetic 24-amino-acid fragment of ACTH triggers a measurable cortisol surge within 30 minutes, telling clinicians whether the adrenal glands can do their job. The full 39-amino-acid version, sold as HP Acthar Gel, carries FDA approval for infantile spasms, MS flares, and nephrotic syndrome. Cosyntropin isn't a research peptide or biohacking tool. It's a prescription diagnostic agent used in clinic settings, with a single standardized dose (250 mcg) that hasn't changed in decades.
Four hundred twenty-four PubMed-indexed papers, a 2023 patient-level meta-analysis (Kazlauskaite et al., PMC10045406), and decades of routine hospital use. That's the evidence base behind the cosyntropin stimulation test. Adrenocorticotropic hormone (ACTH, also known as corticotropin; CAS 9002-60-2) is a 39-amino-acid peptide produced by corticotroph cells in the anterior pituitary gland. Cosyntropin (brand name Cortrosyn) is the synthetic 24-amino-acid N-terminal fragment. It retains full biological activity at the melanocortin-2 receptor (MC2R) on adrenal cortical cells. The test itself is simple. A clinician injects 250 mcg intravenously or intramuscularly, draws cortisol at baseline, 30 minutes, and 60 minutes. Peak cortisol at or above 18 mcg/dL means the adrenals are functioning. Anything below that threshold raises a red flag for Addison's disease or secondary adrenal insufficiency. Beyond diagnostics, the full-length ACTH molecule appears in HP Acthar Gel, a repository corticotropin preparation derived from porcine pituitary extract. Acthar carries FDA approval for infantile spasms (first-line per AAP guidelines), MS exacerbations, nephrotic syndrome, and more than a dozen other inflammatory conditions. Its price tag, roughly $45,600 per vial, makes it one of the most expensive drugs in the United States. Reddit mentions for cosyntropin sit near zero. There is no community peptide protocol. This is a clinical compound prescribed by endocrinologists, neurologists, and nephrologists. The plasma half-life is approximately 15 minutes, meaning it clears the body before the diagnostic blood draw at 60 minutes is even complete.
ACTH binds to the melanocortin-2 receptor (MC2R), a G protein-coupled receptor found primarily on cells in the adrenal cortex zona fasciculata and zona reticularis. MC2R is unusual among melanocortin receptors because ACTH is its only known endogenous agonist. The receptor also requires a chaperone protein called MRAP1 (melanocortin-2 receptor accessory protein) to reach the cell surface. Without MRAP1, MC2R gets trapped in the endoplasmic reticulum and degraded. Once ACTH locks onto MC2R, the receptor activates the stimulatory G-protein (Gs). Gs turns on adenylyl cyclase, which converts ATP into cyclic AMP. Rising cAMP levels activate protein kinase A (PKA). PKA then phosphorylates two key enzymes in the steroidogenic pathway: StAR protein and CYP11A1 (cytochrome P450 side-chain cleavage enzyme). Together, these drive the rate-limiting conversion of cholesterol into pregnenolone. The downstream result is cortisol, corticosterone, and adrenal androgen production. ACTH-related melanocortin peptides also activate MC1R, MC3R, MC4R, and MC5R on immune cells (macrophages, lymphocytes, dendritic cells). This explains why Acthar Gel produces anti-inflammatory effects independent of cortisol. Those non-steroidogenic effects include suppression of NF-kB signaling and reduced pro-inflammatory cytokine release.
Cosyntropin is one of the most validated diagnostic tools in endocrinology, with over 400 PubMed-indexed papers spanning decades. The 250 mcg stimulation test is the international standard for evaluating adrenal reserve. A 2023 patient-level meta-analysis found the low-dose test (1 mcg) has better sensitivity for detecting secondary adrenal insufficiency than the standard 250 mcg dose, but the standard dose remains the clinical default due to simplicity and reproducibility. Acthar Gel therapeutic efficacy is well-documented for infantile spasms (first-line per AAP guidelines), MS exacerbations, and nephrotic syndrome, but its advantages over cheaper corticosteroid alternatives are debated.
Kazlauskaite et al. 2023, "ACTH Stimulation Test for the Diagnosis of Secondary Adrenal Insufficiency: Light and Shadow" (PMC10045406): patient-level meta-analysis showing low-dose test superiority for secondary AI detection
The standard 250 mcg dose provides supraphysiologic stimulation that may mask mild or early secondary adrenal insufficiency: a known limitation. The low-dose (1 mcg) protocol isn't FDA-approved and requires dilution of the 250 mcg vial, introducing preparation variability. Acthar Gel's superiority over IV methylprednisolone for MS is not established: the high price tag makes the cost-benefit analysis unfavorable for many indications.
There is effectively no community use of cosyntropin as a research peptide. Reddit mentions are near zero. This is a clinical diagnostic agent administered by doctors in clinic settings: it has no application in the peptide optimization community. Acthar Gel patient communities exist (primarily for infantile spasms and MS), but discussion centers on cost, insurance battles, and side effects, not self-directed protocols.
Scientific data is extensive for cosyntropin as a diagnostic tool and Acthar Gel as a therapeutic agent. There is no community peptide use to align with: this is a clinical-only compound. The "community" that exists (Acthar Gel patients) interacts with this drug exclusively through physician prescriptions, not self-directed protocols.
| Level | Dose / Injection | Frequency |
|---|---|---|
| Beginner | 250mcg | Single dose |
| Moderate | 250mcg | Single dose |
| Aggressive | 250mcg | Single dose |
Cosyntropin comes in a 0.25 mg vial. Reconstitute with 1 mL of normal saline (0.9% NaCl), not bacteriostatic water. The manufacturer is specific about this. You'll draw up the entire 1 mL for the full 250 mcg diagnostic dose. There's no partial dosing for adults. The timing matters more than most people realize. Morning testing (8-9 AM) is preferred because cortisol follows a diurnal rhythm; afternoon testing can produce misleading baseline values. Draw your baseline cortisol before touching the cosyntropin. Then collect at both 30 and 60 minutes. Some patients with intact adrenal function peak late, and calling it a failure based on one timepoint is a common diagnostic error. Stop glucocorticoids on the day of testing. Estrogen-containing drugs need a 4-6 week washout because they raise cortisol-binding globulin. Miss that detail and you'll get a falsely raised total cortisol reading. Use reconstituted cosyntropin immediately. Don't store it. Don't batch it. One vial, one test, one patient.
Cosyntropin is primarily used as a single diagnostic dose rather than cycled therapy. For therapeutic corticotropin (Acthar Gel), typical protocols are 2-3 weeks for MS exacerbations with gradual taper, or individualized schedules for chronic conditions. Tapering is mandatory after courses exceeding one week to prevent adrenal crisis from HPA axis suppression.
Cosyntropin is a single diagnostic dose: cycling doesn't apply. For therapeutic Acthar Gel, treatment courses are time-limited (2-3 weeks for MS, 4 weeks for infantile spasms) specifically to avoid sustained HPA axis suppression. The "2 weeks on / 2 weeks off" cycling data in the database entry refers to Acthar Gel infantile spasm protocols, not cosyntropin. Courses longer than 1 week require a tapering protocol: never stop abruptly. Chronic use (nephrotic syndrome, rheumatology) uses lower twice-weekly dosing to reduce adrenal suppression risk.
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Expected: Definitive assessment of adrenal reserve. Normal response: cortisol rises to ≥18-20 mcg/dL. Subnormal response indicates adrenocortical insufficiency requiring further workup (ACTH level to distinguish primary vs secondary AI).
Monitor: Cortisol assay at baseline, 30 min, 60 min. Some guidelines recommend measuring both timepoints: patients failing at 30 min may pass at 60 min.
Remove the flip-off seal from the cosyntropin 0.25 mg vial.
Using a sterile syringe, inject 1 mL of 0.9% sodium chloride (normal saline) into the vial. Swirl gently until dissolved. The solution should be clear and colorless.
Draw baseline serum cortisol before proceeding.
For IV administration, push slowly over 2 minutes. For IM, inject into the deltoid or gluteal muscle using a 22-25 gauge needle.
Start a timer at the moment of injection.
Draw serum cortisol at 30 minutes post-injection and again at 60 minutes. Label tubes clearly with draw times.
Normal result: peak cortisol at or above 18-20 mcg/dL at either timepoint.
For Acthar Gel (therapeutic use): administer IM or subcutaneously. Infantile spasms protocol calls for 150 U/m2/day divided into two injections. MS exacerbation dosing runs 80-120 units once daily for 2-3 weeks. Rotate injection sites for repeated dosing.
Storage: cosyntropin vials store at room temperature (15-30 degrees C). Protect from light. Acthar Gel requires cold chain storage per Mallinckrodt labeling.
Falsely elevate cortisol during diagnostic testing. For therapeutic Acthar Gel, concurrent glucocorticoids create additive immunosuppression and Cushingoid risk.
Do not combineIncrease cortisol-binding globulin, falsely elevating total cortisol measurements. Stop 4-6 weeks before cosyntropin testing.
Can interfere with cortisol assay results during stimulation testing.
Contraindicated during therapeutic Acthar Gel use due to immunosuppressive effects: risk of disseminated infection.
Do not combinePricing updated 2026-04-09
Acthar Gel's chronic side effect profile looks a lot like what happens when you flood the body with cortisol, because that's exactly what it does. Cushingoid features (moon face, central weight gain, abdominal striae) develop in most patients by week two of daily dosing. This isn't a rare side effect. It's an expected pharmacologic consequence of sustained ACTH stimulation. Hyperglycemia is the second concern that warrants real attention. ACTH-driven cortisol elevation raises blood glucose enough to unmask diabetes in predisposed patients. Blood glucose monitoring during any Acthar Gel course longer than a few days isn't optional. Hypokalemia represents a less obvious but potentially dangerous risk. Mineralocorticoid effects from adrenal stimulation cause potassium wasting. The risk compounds when patients are also taking amphotericin B or loop diuretics. Weekly serum potassium checks are standard during therapeutic courses. For the single diagnostic dose of cosyntropin (250 mcg), adverse effects are far less dramatic. Hypersensitivity reactions occur infrequently. Anaphylaxis is rare but documented even on first exposure, which is why every cosyntropin stimulation test requires epinephrine on hand and IV access established before the injection. Published side effects from the single diagnostic dose include bradycardia, tachycardia, transient hypertension, peripheral edema, and injection-site rash. These are uncommon and typically self-limited. Chronic Acthar Gel use carries additional risks: fluid retention, increased infection susceptibility, osteoporosis with prolonged courses, cataracts, peptic ulceration, mood disturbances (ranging from insomnia to frank psychosis), and skin hyperpigmentation from melanocortin receptor activation. Neutralizing antibody formation has been reported with prolonged administration. Abrupt discontinuation after courses longer than one week can precipitate adrenal crisis. This is not a theoretical risk. HPA axis suppression from exogenous ACTH is predictable and dose-dependent. Tapering protocols are mandatory. If morning cortisol falls below 10 mcg/dL after completing a course, hydrocortisone bridging may be necessary until the axis recovers. Pregnancy is contraindicated for therapeutic corticotropin. Animal studies showed embryocidal effects. Breastfeeding requires caution since ACTH-stimulated cortisol elevation may affect nursing infants.
Verify ACTH (Cosyntropin/Cortrosyn) dosing and safety with a second opinion
Cosyntropin (Cortrosyn) is a fully FDA-approved pharmaceutical product manufactured under GMP conditions by Amphastar Pharmaceuticals. Acthar Gel is manufactured by Mallinckrodt. Neither product is typically sourced from compounding pharmacies or research chemical suppliers. Counterfeiting risk is negligible because these are hospital/clinic supply items dispensed through regulated pharmaceutical channels.
| Test | When | Target |
|---|---|---|
| Serum cortisol (baseline, 30 min, 60 min) | During cosyntropin stimulation test | ≥18-20 mcg/dL peak |
| Blood glucose | During and after Acthar Gel therapeutic courses | Fasting <126 mg/dL |
| Serum potassium | Weekly during Acthar Gel therapy | 3.5-5.0 mEq/L |
| Blood pressure | Each visit during Acthar Gel therapy | <140/90 mmHg |
| Morning cortisol (post-treatment) | After completing an Acthar Gel course >1 week | ≥10 mcg/dL (AM draw) |
The entire point of the diagnostic test: determines adrenal reserve adequacy
Chronic ACTH stimulation elevates cortisol, which raises blood glucose. Can unmask diabetes.
Mineralocorticoid effects cause potassium wasting: hypokalemia risk increases with concurrent amphotericin B or diuretics
Fluid retention and mineralocorticoid effects raise blood pressure
Assesses HPA axis recovery after exogenous ACTH suppression. Low morning cortisol indicates ongoing adrenal suppression requiring continued physiologic replacement.
Diagnostic: Cortisol begins rising within minutes of cosyntropin injection. Initial adrenal response measurable by 30 minutes post-dose.
Diagnostic: Peak cortisol response typically reached at 30-60 minutes. Normal response is cortisol ≥18-20 mcg/dL confirming adequate adrenal reserve.
Therapeutic (Acthar Gel): Clinical improvement in infantile spasms and MS exacerbations typically observed within the first 1-2 weeks of daily dosing.
Therapeutic: Full treatment effect realized. Begin tapering protocols to prevent adrenal suppression and rebound symptoms.
0-30 minutes (Diagnostic): Cortisol starts climbing within minutes of the cosyntropin injection. By 30 minutes, the adrenal response is measurable. This first blood draw gives an early read on whether the glands are responding. Cosyntropin's 15-minute half-life means it's already clearing the bloodstream at this point. 30-60 minutes (Diagnostic): Peak cortisol typically lands in this window. Anything at or above 18-20 mcg/dL confirms the adrenals have adequate reserve. Patients report the test itself as straightforward and painless. By 60 minutes, the cosyntropin has cleared plasma entirely. 1-2 weeks (Acthar Gel Therapeutic): Clinical improvement typically appears within the first two weeks of daily dosing. Parents of infants with West syndrome report dramatic spasm reduction early in this window. MS patients have more variable onset; some feel relief within days while others need the full course. Expect fluid retention, mood changes, increased appetite, insomnia, and raised blood glucose during this phase. 2-4 weeks (Acthar Gel Therapeutic): Full treatment effect is realized. Mandatory taper begins to prevent adrenal crisis and rebound. Cushingoid features have appeared in most patients by now (moon face, weight gain). Parents and MS patients describe the taper phase as challenging since symptoms can fluctuate. Hyperglycemia, hypokalemia, infection risk, and mood swings are common during this period.
Cortisol begins rising within minutes of cosyntropin injection. Measurable cortisol increase at 30 minutes. Target: ≥18 mcg/dL.
N/A: not community-used. Patients report the test itself is straightforward and painless.
Peak cortisol typically reached. Normal response ≥18-20 mcg/dL confirms adequate adrenal reserve. Cosyntropin has cleared plasma by this point (t½ ~15 min).
N/A: the test is over. Results interpreted by the ordering physician.
Infantile spasms: cessation or significant reduction expected within 2 weeks. MS exacerbations: symptom improvement beginning within days to 1 week.
Parents of infants with West syndrome report dramatic spasm reduction in the first 1-2 weeks. MS patients report variable onset: some improve within days, others take the full course.
Full treatment effect realized. Begin mandatory taper to prevent adrenal crisis and rebound.
Cushingoid features appear in most patients by this point (moon face, weight gain). Parents and MS patients report the taper phase as challenging: symptoms can fluctuate.
Source: FDA label and clinical pharmacology references; cosyntropin plasma half-life ~15 minutes
Loading the interactive decay curve.
Cosyntropin (Cortrosyn) holds full FDA approval as a diagnostic agent for screening adrenocortical insufficiency. It is manufactured by Amphastar Pharmaceuticals under GMP conditions and dispensed through regulated pharmaceutical channels. Generic cosyntropin is available at comparable pricing. HP Acthar Gel (repository corticotropin injection) is separately FDA-approved by Mallinckrodt Pharmaceuticals for over a dozen indications including infantile spasms, MS exacerbations, and nephrotic syndrome. It holds grandfathered FDA status with no generic equivalent due to its unique porcine-derived formulation. ACTH is explicitly listed on the WADA Prohibited List under S2.2.2 (Corticotrophins and Their Releasing Factors). It is banned both in-competition and out-of-competition. This covers cosyntropin, tetracosactide, and repository corticotropin. Documented doping cases exist in professional cycling. Neither cosyntropin nor Acthar Gel is available from compounding pharmacies or research peptide vendors. These are manufactured pharmaceutical products requiring a prescription. This content is for informational purposes only and does not constitute medical advice.
Peptide Schedule Research TeamReviewed Apr 20265 Citations
