Evidence Grade A — Regulatory approved. 662 published studies. 41 registered clinical trials.
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Cosyntropin (sold as Cortrosyn) is not a treatment — it is a diagnostic tool. It is the standard reagent used in the ACTH stimulation test, one of the most commonly performed hormone tests, which checks whether the adrenal glands can produce cortisol normally. Doctors use it to diagnose adrenal insufficiency and to evaluate patients who have been on long-term steroid medications.
Cosyntropin is also known by these brand and alternate names:
662 published studies: 508 human, 51 animal, 7 in-vitro, 63 reviews
Cosyntropin is marketed as Cortrosyn (approved approximately 1970). It is the standard tool for the ACTH stimulation test, one of the most commonly performed endocrine diagnostic procedures. A standard 250 mcg dose is given by injection, with blood cortisol measured at 30 and 60 minutes. A normal response is typically defined as a stimulated cortisol level above 18–20 mcg/dL.
A low-dose (1 mcg) protocol has been studied as a potentially more sensitive test for detecting partial adrenal insufficiency, though the standard 250 mcg dose remains the established clinical practice. Cosyntropin is one of the few peptide compounds used purely for diagnosis rather than treatment.
Cosyntropin mimics the body's natural ACTH by stimulating the adrenal glands to produce cortisol. In a healthy person, a dose of cosyntropin triggers a rapid and substantial rise in cortisol within 30–60 minutes. If the adrenal glands fail to respond adequately (cortisol does not rise above the expected threshold), this indicates adrenal insufficiency — the adrenal glands cannot produce enough cortisol, whether due to primary adrenal failure or prolonged suppression from steroid medications.
Cosyntropin's clinical utility is well established and uncontroversial. The standard test protocol involves injecting 250 mcg and measuring blood cortisol at 30 and 60 minutes — a normal response confirms the adrenal glands are working. The main ongoing clinical discussion concerns what cortisol level counts as a "pass," since newer laboratory methods produce different numbers than older platforms, leading some guidelines to suggest lower thresholds. A low-dose version of the test (1 mcg instead of 250 mcg) has been studied as potentially more sensitive for detecting partial adrenal problems, but the standard dose remains the established practice. No significant research programmes are investigating cosyntropin itself — it is a mature diagnostic tool.
PeptideTrace tracks 41 registered clinical trials for Cosyntropin sourced from ClinicalTrials.gov.
Subclinical Primary Aldosteronism in Diabetes At-Risk for Kidney Disease
Updated Diagnostic Cortisol Values for Adrenal Insufficiency
Positron Emission Tomography (PET) Imaging of Cholesterol Trafficking: Clinical Evaluation of [18F]FNP-59 in Normal Human Subjects (Groups 2, 3 & 4)
Defining the Mechanisms Underlying Adrenal Insufficiency in Cirrhosis
Corticotropin Stimulation in Adrenal Venous Sampling for Patients With Primary Aldosteronism(ADOPA)
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Cosyntropin is a synthetic peptide consisting of the first 24 amino acids of the native 39-amino-acid adrenocorticotropic hormone (ACTH). This N-terminal fragment retains full biological activity at the melanocortin-2 receptor (MC2R) while eliminating the C-terminal residues (25–39) responsible for most of ACTH's immunogenic epitopes.
Cosyntropin binds MC2R on adrenal cortex zona fasciculata cells, activating the Gs/cAMP/PKA pathway to stimulate cortisol biosynthesis from cholesterol via the steroidogenic cascade (CYP11A1, CYP17A1, CYP21A2, CYP11B1). It is used exclusively as a diagnostic agent—the ACTH stimulation test measures the adrenal cortex's ability to produce cortisol in response to exogenous ACTH, distinguishing primary from secondary adrenal insufficiency.
Cosyntropin is marketed as Cortrosyn. Originally approved approximately 1970. Used for the ACTH stimulation test: 250 mcg IV or IM injection with cortisol measurement at 30 and 60 minutes. A normal response is defined as a stimulated cortisol level of ≥18–20 μg/dL (assay-dependent). A low-dose (1 mcg) protocol is sometimes used for greater sensitivity in detecting partial secondary adrenal insufficiency, though this is off-label and not universally endorsed.
Linaclotide is marketed as Linzess (approved August 2012). It is taken as a daily oral capsule on an empty stomach, at least 30 minutes before the first meal. The recommended dose is 290 mcg for IBS-C and 72 or 145 mcg for chronic constipation. In clinical trials, approximately 34% of IBS-C patients met the composite improvement endpoint compared to 17% on placebo. Diarrhoea is the most common side effect (approximately 20%) and the leading reason for discontinuation. Linaclotide has a boxed warning against use in children under 6 years due to deaths in young mice, though no such events have been reported in humans. It competes with plecanatide (which targets the same pathway) and other IBS-C treatments.
Elamipretide (Forzinity) was approved by the FDA for Barth syndrome based on the TAZPOWER trial. The randomised crossover phase (12 patients) did not meet its primary endpoints, but the open-label extension (168 weeks) demonstrated durable improvements in walking distance and muscle strength that formed the basis for approval. Barth syndrome affects approximately 1 in 300,000–400,000 births. A larger Phase III trial in primary mitochondrial myopathy (218 patients, MMPOWER-3) did not meet its primary endpoint, and the drug was not approved for that broader indication. Elamipretide remains approved exclusively for Barth syndrome. See also SS-31 (#158) for the research compound context.
Glucagon has been available as an emergency injection since the 1960s and remains the standard rescue treatment for severe hypoglycaemia. Recent innovation has focused on making it easier to administer in emergencies. Baqsimi, approved in 2019, was the first needle-free option as a nasal powder. Gvoke, also approved in 2019, eliminated the need to mix and reconstitute the medication before injection — a significant advance since severe hypoglycaemia often impairs the ability to follow complex preparation steps. Dasiglucagon (Zegalogue), a next-generation stable liquid glucagon approved in 2021, further improved on the convenience of rescue administration. Beyond emergency rescue, glucagon's receptor is now a major research target — dual and triple agonists combining glucagon receptor activity with GLP-1 (such as survodutide and retatrutide) are in advanced clinical trials for obesity and metabolic disease.
This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before making decisions about your health.
