What are the cut-off values for Adrenocorticotropic hormone (ACTH) stimulation tests?

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Last updated: April 11, 2025View editorial policy

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From the Guidelines

The ACTH stimulation test cutoff values should be set at a peak cortisol level below 18 μg/dl at 30 or 60 min to indicate adrenal insufficiency, as confirmed by the Endocrine Society guideline. The ACTH stimulation test is used to evaluate adrenal function by measuring the response of the adrenal glands to adrenocorticotropic hormone stimulation. According to the latest guideline from the Endocrine Society, cited in the 2017 Intensive Care Medicine study 1, the high-dose (250-μg) ACTH stimulation test is superior to other existing diagnostic tests to establish the diagnosis of primary adrenal insufficiency.

  • The test involves administering cosyntropin (250 μg) and measuring the serum cortisol level at 30 or 60 minutes after administration.
  • A normal response is typically a serum cortisol level greater than 18 μg/dl at 30 or 60 minutes after ACTH administration, as stated in the guideline 1.
  • For the low-dose 1 μg test, the same cutoff values generally apply, as suggested by a single-center randomized trial comparing low-dose ACTH stimulation test with total random cortisol for diagnosis of adrenal insufficiency in adults with septic shock 1.
  • It's essential to note that recent glucocorticoid use can suppress results, so patients should avoid taking steroids before testing when possible, and morning baseline cortisol levels are also measured to exclude or suggest adrenal insufficiency.
  • The Surviving Sepsis Campaign guidelines suggest not using the ACTH stimulation test to select patients with septic shock that may be treated with hydrocortisone, but this does not affect the cutoff values for the test itself, as mentioned in the study 1.

From the Research

ACTH Stim Tests Cut Off Values

  • The cut off values for ACTH stim tests vary depending on the assay used, with studies suggesting lower thresholds for monoclonal antibody-based immunoassays compared to older polyclonal antibody-based assays 2, 3.
  • A study using the Abbott Architect immunoassay recommended a threshold of 14.6 μg/dL for cortisol at 60 minutes after ACTH stimulation, with a sensitivity of 92% and specificity of 96% 2.
  • Another study proposed new cortisol cutoffs for the Elecsys II, Access, and LC-MS/MS assays, with values ranging from 14.5 to 14.8 μg/dL at 30 minutes after stimulation 3.
  • The use of a lower dose of ACTH (1 μg) has been suggested as a more sensitive test for central adrenal insufficiency, with a cortisol level below 500 nmol/L after 30 minutes indicating impaired adrenocortical reserve 4.
  • A study evaluating the diagnostic performance of serum delta cortisol from ACTH stimulation tests proposed cut-off levels of Δ < 1.8 µg/dL and Δ > 11.8 µg/dL for 30-minute delta cortisol, yielding high sensitivity and specificity > 90% 5.
  • Re-assessment of the cut-off value for the low-dose ACTH stimulation test suggested a cut-off of 401.5 nmol/L, which decreased the number of false positive results while maintaining high sensitivity 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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