Corticorelin
A single-dose test drug that tells a pituitary cause of Cushing's syndrome from a tumour elsewhere
Corticorelin ovine triflutate is the sheep version of corticotropin-releasing hormone, the hypothalamic signal that makes the pituitary release ACTH. Sold as Acthrel, it is given as one intravenous dose during a test for ACTH-dependent Cushing's syndrome: pituitary tumours usually respond with a rise in ACTH and cortisol, tumours elsewhere usually do not. FDA approved it in 1996. It is a diagnostic, not a treatment.
What is it?
In Cushing's syndrome caused by excess ACTH, the key question is where the ACTH comes from: a pituitary adenoma, which is Cushing's disease, or an ectopic tumour such as a lung carcinoid. Pituitary adenomas usually still respond to CRH, so an injection of corticorelin that raises ACTH and cortisol points to the pituitary. Ectopic tumours usually do not respond.
The test performs well in large series. In 323 patients at the US National Institutes of Health, the CRH test had a diagnostic accuracy of 91% against 75% for the high-dose dexamethasone suppression test, and a rise in cortisol of at least 40% was the most specific finding, with a positive predictive value of 99%. A European series of 469 patients found similar cut-offs useful, and a 2026 analysis argued that a clearly positive test can spare some patients petrosal sinus sampling. An older study found positive ACTH responses in 89% of patients with pituitary disease, and a short version reading ACTH at 15 minutes performed nearly as well: a rise of at least 43% gave 83% sensitivity and 94% specificity, and combined with a positive high-dose dexamethasone test it excluded an ectopic source in every case.
It is used beyond Cushing's disease. After pituitary surgery, it identified adrenal insufficiency with 78% sensitivity, a little below a simple morning cortisol. Thresholds for the stimulated cortisol peak can sort who needs steroid replacement: above 17.5 µg/dL no one did, below 10 everyone did. In adrenal disease, a response to CRH in bilateral macronodular hyperplasia predicted success of removing one gland, and after dexamethasone, bilateral incidentalomas often responded where single ones did not.
The dexamethasone-CRH combination is also used in psychiatric research as a probe of the stress axis; in one study, depressed women with or without childhood adversity responded no differently from healthy women.
Corticorelin also helps imaging: in a trial of 18F-FDG PET, giving it raised tumour uptake and revealed adenomas not visible on the baseline scan. According to the Acthrel label, it is contraindicated after a hypersensitivity reaction to ovine corticorelin, and its adverse effects are dose-dependent, which is why doses are limited to 1 microgram per kilogram. Several of the studies on this page used human rather than ovine CRH, so their cut-offs may not transfer exactly to Acthrel.
Mechanism of Action
Corticorelin is ovine corticotropin-releasing hormone, given once to see whether the pituitary answers with ACTH.
CRH receptor
Stimulates pituitary corticotrophs to release ACTH, and cortisol follows.
Pituitary vs ectopic
Pituitary adenomas usually respond; ectopic ACTH tumours usually do not.
Short-lived
Half-life with a fast 11.6-minute and a slow 73-minute phase (Acthrel label 12.3).
Published Research
These are clinical studies of the CRH test, read from their PubMed abstracts.
323 patients: CRH test vs 8 mg dexamethasone
The CRH test had a diagnostic accuracy of 91% against 75% for the high-dose dexamethasone test; a cortisol rise of at least 40% had a positive predictive value of 99%.
469 patients with ACTH-dependent Cushing's syndrome
A 30-minute ACTH rise of at least 31% separated pituitary from ectopic disease with 83% sensitivity and 85% specificity, and a cortisol rise of at least 12% gave 82% sensitivity.
64 patients with pituitary-dependent disease
89% had a positive ACTH response and 88% a positive cortisol response; one patient with an ectopic tumour had a false-positive cortisol response.
CRH-enhanced PET for pituitary adenomas
Corticorelin raised adenoma uptake on 18F-FDG PET and revealed six adenomas not visible on the baseline scan, including two of five that MRI had missed.
Can it replace petrosal sampling?
In patients with ACTH-dependent Cushing's syndrome, an ACTH rise of at least 50% after CRH identified Cushing's disease with 87% sensitivity and 95% specificity (positive predictive value 99%); the authors propose pituitary surgery without petrosal sinus sampling when the test is positive.
A 15-minute version
An ACTH rise of at least 43% at 15 minutes after human CRH best separated Cushing's disease from ectopic ACTH (sensitivity 83%, specificity 94%); combined with a positive high-dose dexamethasone test, it excluded ectopic disease in every case.
Predicting adrenalectomy success
In 23 patients with primary bilateral macronodular adrenal hyperplasia, 74% were in remission a median of 115 months after removing one adrenal gland; an ACTH rise of more than 50% on a human CRH test beforehand predicted remission.
After pituitary surgery
In 156 patients tested early after pituitary tumour surgery, the CRH test had 78% sensitivity and 90% specificity for adrenal insufficiency at follow-up, slightly below a single basal cortisol (86% and 92%).
Who needs steroid replacement
In patients assessed for central adrenal insufficiency, none of 106 with a CRH-stimulated cortisol peak of 17.5 µg/dL or more needed replacement, while all 64 with a peak below 10 µg/dL did; between the two, DHEA-S helped decide.
Bilateral adrenal incidentalomas
After dexamethasone suppression, CRH produced an ACTH and cortisol response in 41.3% of patients with bilateral adrenal incidentalomas but only 2.6% with a single one.
DEX/CRH test in depression
In a study of depressed and healthy women with and without childhood adversity, free salivary cortisol responses to the dexamethasone-CRH test did not differ between groups.
Dosing Data
Acthrel is a single intravenous diagnostic dose, with ACTH and cortisol sampled before and after the injection.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the Acthrel label.
Contraindications & Cautions
From the label; a clinician decides.
Legal Status
Corticorelin is an FDA-approved diagnostic agent.
Frequently Asked Questions
?What is corticorelin used for?
A diagnostic test in ACTH-dependent Cushing's syndrome, to tell a pituitary source of ACTH from a tumour elsewhere. It is given once, intravenously, under supervision.
?How accurate is the CRH test?
In 323 NIH patients its diagnostic accuracy was 91%, better than the high-dose dexamethasone test's 75%.
?Is corticorelin a treatment?
No. It is approved only as a diagnostic agent.
?Can the CRH test replace petrosal sinus sampling?
Sometimes. A 2026 analysis found a clearly positive test (ACTH rise of at least 50%) identified pituitary Cushing's disease with a 99% positive predictive value and proposed surgery without sampling in that case; a negative test still needs further work-up.
?Is it used after pituitary surgery?
Yes, to check for adrenal insufficiency. In 156 patients it had 78% sensitivity and 90% specificity, slightly below a single morning cortisol.
?Does it work for adrenal tumours?
It can help: in bilateral macronodular adrenal hyperplasia, an ACTH response to CRH predicted remission after removing one adrenal gland, and bilateral incidentalomas responded far more often than single ones.
?How is the test done?
A single intravenous dose of 1 microgram per kilogram, with blood taken for ACTH and cortisol before and at set times after the injection.
References
- [fda-pi] Ferring. ACTHREL (corticorelin ovine triflutate for injection), US prescribing information: indication, contraindication (hypersensitivity to ovine corticorelin), dose-dependent adverse effects. DailyMed version of November 12, 2021; read September 30, 2026.
- [pubmed] Elenius H, et al. "Ovine CRH Stimulation and 8 mg Dexamethasone Suppression Tests in 323 Patients With ACTH-Dependent Cushing's Syndrome." J Clin Endocrinol Metab, 2023;109(1):e182-e189. PMID: 37531629.
- [pubmed] Detomas M, et al. "Outcome of CRH stimulation test and overnight 8 mg dexamethasone suppression test in 469 patients with ACTH-dependent Cushing's syndrome." Front Endocrinol (Lausanne), 2022;13:955945. PMID: 36277711.
- [pubmed] Natt N, et al. "The ovine corticotropin-releasing hormone stimulation test in the differential diagnosis of adrenocorticotropic hormone-dependent cushing's syndrome." Endocr Pract, 1997;3(3):130-4. PMID: 15251472.
- [pubmed] Boyle J, et al. "CRH stimulation improves (18)F-FDG-PET detection of pituitary adenomas in Cushing's disease." Endocrine, 2019;65(1):155-165. PMID: 31062234.
- [fda] FDA. Drugs@FDA (openFDA): ACTHREL, BLA 020162, approved May 23, 1996. Read September 30, 2026.
- [pubmed] Losa M, et al. "A positive corticotropin-releasing hormone test may obviate the need for petrosal sinus sampling in patients with cushing's disease." J Endocrinol Invest, 2026;49(5):1039-1047. PMID: 41493525.
- [pubmed] Ritzel K, et al. "ACTH after 15 min distinguishes between Cushing's disease and ectopic Cushing's syndrome: a proposal for a short and simple CRH test." Eur J Endocrinol, 2015;173(2):197-204. PMID: 25953828.
- [pubmed] Tizianel I, et al. "Corticotropin-releasing hormone test predicts the outcome of unilateral adrenalectomy in primary bilateral macronodular adrenal hyperplasia." J Endocrinol Invest, 2024;47(3):749-756. PMID: 37796369.
- [pubmed] de Vries F, et al. "Early postoperative HPA-axis testing after pituitary tumor surgery: reliability and safety of basal cortisol and CRH test." Endocrine, 2020;67(1):161-171. PMID: 31556005.
- [pubmed] Mitsui Y, et al. "An attempt to create a treatment algorithm of central adrenal insufficiency using CRH test, DHEA-S and clinical evaluation." J Med Invest, 2022;69(3.4):287-293. PMID: 36244782.
- [pubmed] Vassiliadi DA, et al. "Abnormal Responsiveness to Dexamethasone-Suppressed CRH Test in Patients With Bilateral Adrenal Incidentalomas." J Clin Endocrinol Metab, 2015;100(9):3478-85. PMID: 26147608.
- [pubmed] Spitzer C, et al. "The dexamethasone corticotropin releasing hormone test in healthy and depressed women with and without childhood adversity." Psychoneuroendocrinology, 2018;87:147-151. PMID: 29080551.
Sources & Citations
Studies were read from their PubMed abstracts; the Acthrel label (DailyMed version of November 12, 2021) was read September 30, 2026.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.