What disease process is diagnosed using the Cosyntropin (Adrenocorticotropic hormone, ACTH) stimulation test?

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From the Guidelines

The cosyntropin stimulation test is primarily used to diagnose adrenal insufficiency, particularly primary adrenal insufficiency (Addison's disease) and secondary adrenal insufficiency. This test evaluates the ability of the adrenal glands to respond to adrenocorticotropic hormone (ACTH) by measuring cortisol levels before and after administration of synthetic ACTH (cosyntropin) 1.

Key Points

  • In the standard test, blood samples are collected at baseline and 30-60 minutes after intravenous or intramuscular injection of 250 mcg of cosyntropin.
  • A normal response shows cortisol levels rising to at least 18-20 mcg/dL after stimulation, with one study suggesting that peak cortisol levels below 18 μg/dl at 30 or 60 min indicate adrenal insufficiency 1.
  • The test is valuable because symptoms of adrenal insufficiency can be nonspecific, and baseline cortisol measurements alone may be misleading due to diurnal variation.
  • Recent glucocorticoid use can affect test results, so medication history should be considered when interpreting results.
  • The high-dose (250-μg) ACTH stimulation test remains the most popular diagnostic test for adrenal insufficiency, although the low-dose (1-μg) ACTH test has similar diagnostic accuracy 1.

Diagnosis

The cosyntropin stimulation test is used to diagnose primary adrenal insufficiency (Addison's disease) and secondary adrenal insufficiency (pituitary dysfunction). In primary adrenal insufficiency, both baseline and stimulated cortisol levels are low, while in secondary adrenal insufficiency, baseline cortisol may be low but with some response to stimulation, though typically below normal thresholds.

Clinical Considerations

It's essential to consider the clinical context when interpreting test results, as recent glucocorticoid use or other medications can affect cortisol levels. Additionally, the test should not delay treatment in patients with suspected acute adrenal crisis, as prompt administration of hydrocortisone and saline infusion is crucial in these cases 1.

From the FDA Drug Label

Cosyntropin for injection is indicated, in combination with other diagnostic tests, for use as a diagnostic agent in the screening of adrenocortical insufficiency in adults and pediatric patients. The Cosyntropin stimulation test is used to diagnose adrenocortical insufficiency 2.

  • The test involves administering cosyntropin and measuring the response of the adrenal cortex.
  • Adrenocortical insufficiency can be suggested by stimulated plasma cortisol levels of less than 18 mcg/dL at 30- or 60-minutes post cosyntropin administration 2.

From the Research

Cosyntropin Stimulation Test

The cosyntropin stimulation test is used to diagnose adrenal insufficiency, a condition where the adrenal glands do not produce enough cortisol and/or aldosterone hormones.

  • The test involves administering a synthetic form of adrenocorticotropic hormone (ACTH), called cosyntropin, and measuring the response of the adrenal glands by checking the level of cortisol in the blood 3, 4, 5.
  • The test can be used to diagnose both primary and secondary adrenal insufficiency, although the low-dose cosyntropin stimulation test is more sensitive for diagnosing secondary adrenal insufficiency in nonstressed patients 3.
  • Different cortisol assays may have different cutoff values for a normal response to the cosyntropin stimulation test, and using assay-specific cutoffs can help reduce misclassification and overtreatment of patients with suspected adrenal insufficiency 4, 5.

Adrenal Insufficiency Diagnosis

The diagnosis of adrenal insufficiency can be challenging, and the cosyntropin stimulation test is one of the tools used to assess adrenal function.

  • The test is considered the best available test for establishing the diagnosis of secondary adrenal insufficiency, with a cortisol level determined at 30 minutes after stimulation and a cutoff level of 18 to 20 microg/dL in nonstressed patients 3.
  • However, the use of the cosyntropin test in critical illness is less well established, and its role in guiding steroid therapy in critical illness is not supported by current evidence 6.
  • Other tests, such as the overnight dexamethasone suppression test, may be used to assess adrenal function in certain situations, such as suspected hypercortisolism (Cushing's syndrome) 7.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Diagnosing adrenal insufficiency: which test is best--the 1-microg or the 250-microg cosyntropin stimulation test?

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 2008

Research

New Diagnostic Cutoffs for Adrenal Insufficiency After Cosyntropin Stimulation Using Abbott Architect Cortisol Immunoassay.

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 2022

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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