What is the cosyntropin (adrenocorticotropic hormone stimulation test)?

The Cosyntropin Test: A Diagnostic Tool for Adrenal Insufficiency

The cosyntropin test is a diagnostic procedure that uses synthetic adrenocorticotropic hormone (ACTH) to evaluate adrenal gland function by measuring cortisol response, primarily used to screen for adrenal insufficiency in adults and pediatric patients. 1

Test Mechanism and Purpose

• Cosyntropin is a synthetic version of ACTH containing the first 24 amino acids of natural ACTH, which exhibits the full corticosteroidogenic activity of natural ACTH while having minimal immunologic activity 1
• The test works by stimulating the adrenal cortex to produce cortisol, mimicking the body's natural response to ACTH 1
• It is specifically indicated for use as a diagnostic agent in screening for adrenocortical insufficiency, in combination with other diagnostic tests 1
• The test helps distinguish between primary adrenal insufficiency (adrenal gland failure) and secondary adrenal insufficiency (pituitary gland failure) 2

Standard Test Protocol

• Prior to testing, certain medications should be discontinued:

  • Glucocorticoids and spironolactone should be stopped on the day of testing 1
  • Long-acting glucocorticoids may need to be stopped for a longer period 1
  • Estrogen-containing drugs should be stopped 4-6 weeks before testing 1

• The standard protocol involves:

  • For adults: 0.25 mg cosyntropin administered intravenously or intramuscularly 1
  • For pediatric patients: 0.125 mg for children under 2 years, 0.25 mg for ages 2-17 1
  • Blood samples are collected at baseline and at 30 and 60 minutes after cosyntropin administration 1, 3

Interpretation of Results

• Normal response is typically defined as a peak cortisol level above 18-20 μg/dL in non-stressed patients 4
• In critically ill patients, a cortisol level less than 25 μg/dL or an increment of less than 9 μg/dL from baseline may indicate adrenal insufficiency 4
• The test performs well for primary adrenal insufficiency with high sensitivity (97% at 95% specificity) 2
• For secondary adrenal insufficiency, the test has lower sensitivity (57% at 95% specificity) 2

Clinical Applications

• The test is valuable in diagnosing adrenal insufficiency in patients with hypo-osmolar hyponatremia, as adrenal insufficiency can present similarly to SIADH 5
• It's used to evaluate suspected hypophysitis (inflammation of the pituitary gland), particularly in patients receiving immune checkpoint inhibitor therapy 6
• The test helps distinguish primary from secondary adrenal insufficiency by evaluating the relationship between ACTH and cortisol levels 5

Test Variations

• Low-dose cosyntropin test (1 μg) has been studied as an alternative to the standard 250 μg dose 4, 7
• Some studies suggest the low-dose test may be more sensitive for detecting secondary adrenal insufficiency 4
• However, for primary adrenal insufficiency, the standard high-dose test is generally sufficient 2, 4
• Recent evidence suggests that a single 60-minute cortisol measurement may be sufficient for screening purposes, with 99.7% concordance with the traditional three-sample approach 3

Important Considerations and Precautions

• Hypersensitivity reactions, including anaphylaxis, have been reported with cosyntropin use 1
• Test results may be inaccurate in patients taking medications that affect cortisol or cortisol binding globulin levels 1
• In cases of suspected adrenal crisis, treatment should not be delayed for diagnostic testing 5
• The test is contraindicated in patients with a history of hypersensitivity to cosyntropin or its excipients 1

Clinical Pitfalls to Avoid

• Don't rely solely on electrolyte abnormalities for diagnosis, as hyponatremia may be only marginally reduced and hyperkalemia is present in only about 50% of cases 5
• When treating secondary adrenal insufficiency with concurrent hypothyroidism, always start corticosteroids several days before thyroid hormone to prevent precipitating adrenal crisis 5
• Be aware that the test has lower sensitivity for secondary adrenal insufficiency, so additional testing may be needed if clinical suspicion remains high 2