What does the Adrenocorticotropic Hormone (ACTH) stimulation test consist of?

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From the Guidelines

The ACTH stimulation test consists of measuring cortisol levels before and after administering synthetic ACTH (cosyntropin) to evaluate adrenal gland function, typically involving a baseline blood sample, an injection of 250 micrograms of cosyntropin, and additional blood samples at 30 and 60 minutes to measure cortisol response. The test is used to diagnose adrenal insufficiency, including primary and secondary adrenal insufficiency, and patients should avoid taking glucocorticoids before the test if possible, as they can interfere with results 1.

Key Components of the Test

  • Baseline blood sample to measure cortisol levels
  • Injection of 250 micrograms of cosyntropin (Synacthen or Cortrosyn) either intravenously or intramuscularly
  • Additional blood samples collected at 30 and 60 minutes after the injection to measure cortisol response
  • Normal response: cortisol levels rise significantly above baseline (typically to >18-20 μg/dL or >500 nmol/L), indicating proper adrenal function

Important Considerations

  • The test works by mimicking the body's natural stress response, where ACTH from the pituitary stimulates the adrenal cortex to produce cortisol
  • A diminished cortisol response suggests impaired adrenal function that requires further investigation and potential treatment
  • The high-dose (250-μg) ACTH stimulation test is considered superior to other existing diagnostic tests for primary adrenal insufficiency, with peak cortisol levels below 18 μg/dl indicating adrenal insufficiency 1
  • The task force suggested using the high-dose rather than the low-dose ACTH test for the diagnosis of CIRCI due to easier practical modalities and comparable accuracy 1

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Overview of the Adrenocorticotropic Hormone (ACTH) Stimulation Test

The ACTH stimulation test is used to evaluate adrenal function and diagnose adrenal insufficiency. The test involves administering synthetic ACTH, also known as cosyntropin, to stimulate the adrenal glands to produce cortisol.

Components of the ACTH Stimulation Test

  • The test typically involves administering a dose of synthetic ACTH, which can range from 1 microg to 250 microg, depending on the specific protocol being used 2, 3, 4.
  • Blood samples are collected before and after administration of the ACTH to measure cortisol levels 2, 3, 5, 6, 4.
  • The test can be performed using different routes of administration, including intravenous and intramuscular injection 3, 4.

Interpretation of Test Results

  • A cortisol level below a certain threshold, such as 18 μg/dL or 500 nmol/L, after 30 or 60 minutes indicates impaired adrenocortical reserve 2, 3, 5, 6.
  • Newer specific cortisol assays may have lower thresholds for a normal response, such as 14-15 μg/dL 5.
  • Basal cortisol levels can also be used to diagnose adrenal insufficiency, but may have poor sensitivity compared to ACTH-stimulated cortisol levels 3.

Special Considerations

  • The test may not be suitable for patients with recent pituitary injury or those receiving high-dose glucocorticoid therapy 2, 6.
  • The effective time frame for the test may be limited in patients receiving high-dose glucocorticoid therapy, with some studies suggesting that the test may be used within the first 3 days after initiation of therapy 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Intramuscular ACTH stimulation test for assessment of adrenal function.

The Journal of the Association of Physicians of India, 2013

Research

Adrenocorticotropic hormone stimulation test during high-dose glucocorticoid therapy.

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 2009

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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