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Dr. Grey AI

Peptide

Cosyntropin (Cortrosyn/Synacthen)

Cosyntropin is a synthetic ACTH(1-24) peptide. FDA-approved for diagnosis of adrenocortical insufficiency. The 250mcg ACTH stimulation test is the gold standard diagnostic test. Meta-analysis shows 97% sensitivity at 95% specificity for primary adrenal insufficiency. Less immunogenic than full ACTH due to absence of amino acids 25-39. Half-life 15 minutes with peak cortisol at 30-60 minutes.

Research notice. This page is for education and research. Peptides may not be FDA-approved for human use and may only be legally available for research. Talk to a qualified clinician before considering any peptide.

Best evidence
Grade A
Conditions studied
1
Outcomes
7
Graded outcomes
4111

Evidence by condition

  • Strong
  • Moderate
  • Limited
  • Very limited

1 condition, plus general outcomes

Hypoadrenalism

Hypoadrenalism: outcomes studied for Cosyntropin (Cortrosyn/Synacthen)
GradeOutcomeEffectSizeStudiesPeopleStudies list
Cortisol Stimulation

Normal response: cortisol ≥18 mcg/dL (500 nmol/L) at 30-60 minutes. Reliable stimulation of adrenal cortex in healthy individuals.

Changes; see studiesLarge effect20 studies

Studies that measured cortisol stimulation

and 10 more in the citations list

Safety Profile

Less immunogenic than natural ACTH. Rare hypersensitivity reactions. Well-tolerated diagnostic procedure used for decades.

Improves (the measure goes up)Large effect11 studies

Studies that measured safety profile

and 1 more in the citations list

Diagnostic Sensitivity (Primary AI)

97% sensitivity at 95% specificity for primary adrenal insufficiency. Meta-analysis of multiple studies confirms high diagnostic accuracy.

Improves (the measure goes up)Large effect10 studies

Studies that measured diagnostic sensitivity (primary ai)

Diagnostic Accuracy (Secondary AI)

57-61% sensitivity for secondary AI. Better for ruling in than ruling out. Low-dose (1mcg) may be superior (AUC 0.94 vs 0.85).

Improves (the measure goes up)Moderate effect10 studies

Studies that measured diagnostic accuracy (secondary ai)

General

General: outcomes studied for Cosyntropin (Cortrosyn/Synacthen)
GradeOutcomeEffectSizeStudiesPeopleStudies list
Kidney Function

23 human trials and systematic reviews support this finding. Evidence includes systematic reviews/meta-analyses. Human clinical trial data available.

Improves (the measure goes up)Moderate effect12 studies

Studies that measured kidney function

and 2 more in the citations list

Immune Function

3 human trials support this finding. Human clinical trial data available.

Improves (the measure goes up)Small effect5 studies

Studies that measured immune function

Blood Glucose Control

2 human trials support this finding. Human clinical trial data available.

Improves (the measure goes down)Small effect5 studies

Studies that measured blood glucose control

Key findings

  • Cortisol StimulationHypoadrenalismChanges; see studies
  • Safety ProfileHypoadrenalismImproves (the measure goes up)
  • Diagnostic Sensitivity (Primary AI)HypoadrenalismImproves (the measure goes up)

Studies cited

32 studies from PubMed

  1. Examining aldosterone plasma concentration alterations post-ACTH stimulation in healthy subjects: a systematic literature review and meta-analysis on ACTH's role in aldosterone secretion.Hormones (Athens, Greece), 2024 · PMID 39052132
  2. Salivary corticosterone measurement in large-billed crows by enzyme-linked immunosorbent assay.The Journal of veterinary medical science, 2023 · PMID 36418081
  3. New Cutoffs for the Biochemical Diagnosis of Adrenal Insufficiency after ACTH Stimulation using Specific Cortisol AssaysJ Endocr Soc, 2021 · PMID 33631762
  4. Cortisol levels in blood and hair of unanesthetized grizzly bears (Ursus arctos) following intravenous cosyntropin injection.Veterinary medicine and science, 2021 · PMID 33978314
  5. Cosyntropin for the Treatment of Refractory Postdural Puncture Headache in Pediatric Patients: A Retrospective Review.The Clinical journal of pain, 2020 · PMID 31789828
  6. Pitfalls in the interpretation of the cosyntropin stimulation test for the diagnosis of adrenal insufficiencyCurr Opin Endocrinol Diabetes Obes, 2019 · PMID 30855285
  7. Diagnostic accuracy of basal cortisol level to predict adrenal insufficiency in cosyntropin testing: results from an observational cohort study with 804 patientsEndocr Pract, 2017 · PMID 28938409
  8. Total and free cortisol levels during 1 μg, 25 μg, and 250 μg cosyntropin stimulation tests compared to insulin tolerance test: results of a randomized, prospective, pilot study.Endocrine, 2017 · PMID 28730418
  9. ACTH Stimulation Tests for the Diagnosis of Adrenal Insufficiency: Systematic Review and Meta-AnalysisJ Clin Endocrinol Metab, 2016 · PMID 26649617
  10. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice GuidelineJ Clin Endocrinol Metab, 2016 · PMID 27270475
  11. Cosyntropin as a diagnostic agent in the screening of patients for adrenocortical insufficiencyClin Pharmacol, 2010 · PMID 20122035
  12. Normal hypothalamic-pituitary-adrenal axis by high-dose cosyntropin testing in patients with abnormal response to low-dose cosyntropin stimulation: a retrospective review.Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 2010 · PMID 19833587
  13. Is the cosyntropin test redundant in the acutely ill patient suspected of adrenal insufficiency? A case report and literature review.Tennessee medicine : journal of the Tennessee Medical Association, 2010 · PMID 20961018
  14. H.P. Acthar Gel and Cosyntropin Review: Clinical and Financial ImplicationsP T, 2009 · PMID 19654226
  15. Hypothalamic-pituitary-adrenal axis assessment in healthy term neonatal foals utilizing a paired low dose/high dose ACTH stimulation test.Journal of veterinary internal medicine, 2009 · PMID 19192152
  16. Performance of low-dose ACTH stimulation test in patients suspected of secondary adrenal insufficiencyJ Clin Endocrinol Metab, 2008 · PMID 19088152
  17. Autoimmune polyglandular syndrome, type II.American family physician, 2007 · PMID 17375512
  18. Can 1 microg of cosyntropin be used to evaluate adrenal insufficiency in critically ill patients?The Annals of pharmacotherapy, 2005 · PMID 15741424
  19. Adrenal function in critically ill patients: how to test? When to treat?Cleveland Clinic journal of medicine, 2005 · PMID 15929456
  20. The short corticotropin stimulation test revisited: new normal reference range using Immulite 2000Clin Chem Lab Med, 2004 · PMID 15181101
  21. High-dose and low-dose cosyntropin stimulation tests for diagnosis of adrenal insufficiency.Annals of internal medicine, 2004 · PMID 14970166
  22. Serum concentrations of cortisol, sex hormones of adrenal origin, and adrenocortical steroid intermediates in healthy dogs following stimulation with two doses of cosyntropin.American journal of veterinary research, 2004 · PMID 15631026
  23. Comparison of low and high dose corticotropin stimulation tests in patients with pituitary diseaseJ Clin Endocrinol Metab, 2003 · PMID 12519857
  24. Diagnosis of adrenal insufficiency.Annals of internal medicine, 2003 · PMID 12899587
  25. Prevalence of abnormal adrenocortical function in human immunodeficiency virus infection by low-dose cosyntropin test.International journal of STD & AIDS, 2001 · PMID 11779371
  26. Comparison between low-dose and high-dose ACTH stimulation tests for adrenal insufficiencyJ Clin Endocrinol Metab, 1997 · PMID 9329348
  27. A low dose ACTH test for assessment of hypothalamic-pituitary-adrenal functionClin Endocrinol (Oxf), 1996 · PMID 8636269
  28. Severe hyperkalemia in two patients with diabetes after cosyntropin administration.Journal of diabetes and its complications, 1992 · PMID 1472747
  29. Enhanced adrenal sensitivity to exogenous cosyntropin (ACTH alpha 1-24) stimulation in major depression. Relationship to dexamethasone suppression test results.Archives of general psychiatry, 1987 · PMID 3030218
  30. Cosyntropin stimulation in adrenal vein testing for aldosteronoma.The Western journal of medicine, 1985 · PMID 2983501
  31. The use of a cosyntropin stimulation test to predict adrenal suppression in renal transplant patients being withdrawn from prednisone.Transplantation, 1983 · PMID 6308859
  32. Combined dexamethasone suppression and cosyntropin (synthetic ACTH) stimulation test in the dog: new approach to testing of adrenal gland function.American journal of veterinary research, 1980 · PMID 6255830