Cosyntropin
Also known as: Tetracosactide, Synacthen, Cortrosyn, ACTH 1-24, Tetracosactide acetate, Nasacthin
Synthetic ACTH analogue (corticotropin peptide)
What it is
Doctors use cosyntropin to test whether the adrenal glands are working properly. It is a short synthetic version of the body's own ACTH hormone and is given by injection in a hospital or clinic. People being evaluated for unexplained fatigue, low blood pressure, or suspected adrenal disease are the most common patients tested.
The scientific side
cosyntropin is a synthetic 24-amino acid peptide that replicates the biologically active N-terminal fragment of endogenous adrenocorticotropic hormone (ACTH). The StatPearls reference (PMID 32310400) describes its mechanism directly: cosyntropin binds to ACTH receptors on the adrenal cortex and stimulates the gland to produce cortisol. By measuring serum cortisol levels before and after cosyntropin administration, clinicians can determine whether the adrenal glands respond appropriately to ACTH stimulation. This makes cosyntropin valuable for diagnosing primary adrenal insufficiency (Addison disease) and certain forms of secondary or tertiary adrenal insufficiency arising from hypothalamic-pituitary dysfunction. Several abstracts illustrate how this mechanism translates into clinical practice. In the post-adrenalectomy setting (PMID 42816228), a normal cortisol response to cosyntropin confirms intact residual adrenal reserve, while a blunted response identifies patients who need glucocorticoid replacement. In immune checkpoint inhibitor-induced hypophysitis (PMIDs 42713228, 42827725), a blunted cortisol response to cosyntropin, combined with low ACTH levels, confirms secondary adrenal insufficiency caused by pituitary damage rather than primary adrenal failure. In patients with mild autonomous cortisol secretion co-occurring with primary aldosteronism, cosyntropin stimulation unmasks differences in steroid metabolite output that are not apparent at baseline (PMID 42203076). A cardiometabolic cohort study (PMID 42819023) further showed that subjects with ACTH-independent hypercortisolism paradoxically had higher stimulated cortisol after cosyntropin, identifying a unique biochemical phenotype. The low-dose Synacthen stimulation test, using 1 µg rather than the standard 250 µg, appears capable of detecting central adrenal insufficiency because subnormal adrenal reserve is unmasked by a smaller ACTH stimulus; the 40-minute cortisol time-point provided the most reliable single measurement in a large pediatric cohort (PMID 42043277). Subcutaneous administration produces steroid responses statistically comparable to intramuscular injection (PMID 39862361), and tetracosactide frozen in plastic syringes for up to approximately two years retains biological activity equivalent to freshly prepared material (PMID 42315192).
Class: Synthetic ACTH analogue (corticotropin peptide)
Administration & storage
- Administration
- Intravenous (IV) bolus — most common route in published clinical studies (PMIDs 42816228422030764202217942813006)Intramuscular (IM) — used interchangeably with IV in many protocols; subcutaneous tetracosactide 250 µg produced statistically comparable steroid profiles to IM tetracosactide 250 µg in a randomized study of 60 healthy women (PMID 39862361)Subcutaneous (SC) — validated as a reliable alternative; PMID 39862361 confirmed comparable stimulated steroid levels versus IM routeIntranasal — a novel intranasal formulation (Nasacthin) is under clinical trial evaluation (STARLIT-3 studyPMID 41644156) as a non-invasive alternative to IV Synacthen; not yet standard of care
- Storage
- Tetracosactide acetate stored frozen in plastic syringes at -20°C for up to approximately 1.8 years was shown to retain biological activity equivalent to freshly prepared material in a prospective veterinary crossover study (PMID 42315192). Clinical pharmacopeial guidance recommends refrigeration (2–8°C) for standard prepared solutions; the frozen syringe approach represents a practical option during supply shortages per study authors.
Legal & regulatory status
FDA-approved diagnostic agent (Cortrosyn) for use in the ACTH stimulation test to assess adrenocortical function. Described as the standard-of-care dynamic test in multiple clinical studies (PMIDs: 32310400, 42816228,…
ACTH and its synthetic analogues including cosyntropin are prohibited in-competition under the WADA Prohibited List (S2 Peptide Hormones, Growth Factors, Related Substances and Mimetics). No specific clinical trial data…
Marketed as Synacthen (tetracosactide) in Canada for adrenal function testing; referenced in clinical literature under both trade names (PMIDs: 42813006, 41580757).
What it's studied for
- Diagnosis of primary adrenal insufficiency (Addison disease) Established clinical standard
- Diagnosis of secondary and tertiary adrenal insufficiency Established clinical use with nuance — high-dose test less sensitive for central causes
- Assessment of adrenal function after unilateral adrenalectomy Retrospective institutional data — establishes practical decision algorithm
- Evaluation for congenital adrenal hyperplasia (non-classical 21-hydroxylase deficiency) — 17-hydroxyprogesterone stimulation Retrospective pediatric cohort — established clinical practice
- Diagnosis of relative adrenal insufficiency in decompensated liver disease Prospective cohort — clinically meaningful outcome data
- Evaluation of cortisol secretion co-occurring with primary aldosteronism (MACS-PA) Prospective multicenter study
- Screening for adrenal insufficiency in people living with HIV Cross-sectional study — limited sample, specific population
Safety signals
- Hypersensitivity and allergic reactions (including anaphylaxis risk)
- Transient local injection-site reactions
- Precipitation of adrenal crisis if test is performed in severely deficient patients without prior glucocorticoid cover
- False-negative stimulation test results with high-dose (250 µg) protocol in partial central adrenal insufficiency
- Assay-dependent variability in cortisol threshold interpretation — risk of over- or under-diagnosis
- Pharmacodynamic interference from prior glucocorticoid exposure (adrenal atrophy)
- Potential for abnormal test results reflecting underlying severe illness rather than true adrenal pathology (relative adrenal insufficiency in critical illness)
All studies (10)
Frequently asked
What is the cosyntropin stimulation test used for?
The cosyntropin stimulation test is used by doctors to check whether the adrenal glands are producing enough cortisol. Cosyntropin is injected and blood cortisol is measured before and afterward; a normal rise indicates healthy adrenal function. It is most often performed when a doctor suspects adrenal insufficiency, including Addison disease or pituitary-related cortisol deficiency. See PMIDs 32310400 and 42559695 for clinical reference.
What dose is used in the test?
Most standard hospital protocols use 250 µg of cosyntropin given intravenously or intramuscularly, with cortisol measured at baseline and at 30 and/or 60 minutes. A lower 1 µg dose is sometimes used when the doctor specifically wants to detect subtle pituitary-related adrenal problems; studies suggest the 40-minute cortisol reading is most reliable at this dose. Dose selection and interpretation should always be made by a physician. See PMIDs 32310400, 42043277, and 41679895.
Can the test be done by injection under the skin rather than into a vein?
Research has shown that subcutaneous injection of 250 µg tetracosactide produces adrenal steroid responses that are statistically comparable to intramuscular injection in healthy adults. However, intravenous and intramuscular routes remain the routes used in most published clinical guidelines, and any change in testing route should be discussed with the ordering physician. See PMID 39862361.
How long can cosyntropin (tetracosactide) be stored?
A veterinary study found that tetracosactide stored frozen in plastic syringes at -20°C for a median of approximately 1.8 years retained biological activity equivalent to freshly prepared material. Standard clinical guidance recommends refrigeration at 2–8°C for prepared solutions. Patients and clinicians should always follow the manufacturer's labeled storage instructions. See PMID 42315192.
Can immune checkpoint inhibitor cancer drugs cause problems that the cosyntropin test would catch?
Yes. Case reports describe immune checkpoint inhibitor-induced hypophysitis as a cause of secondary adrenal insufficiency that can be confirmed with the cosyntropin stimulation test. A blunted cortisol response combined with inappropriately low ACTH levels points to pituitary rather than primary adrenal failure. Any cancer patient on these medications who develops unexplained fatigue, low blood pressure, or hyponatremia should be evaluated promptly by an endocrinologist. See PMIDs 42713228 and 42827725.