How to perform an Adrenocorticotropic Hormone (ACTH) stimulation test for Congenital Adrenal Hyperplasia (CAH) diagnosis in an adult taking estrogen patches?

From the Guidelines

To perform an ACTH stimulation test for CAH diagnosis in an adult taking estrogen patches, the patient should continue wearing the patches during testing as they won't significantly affect results, and the test should be conducted using a high-dose (250-μg) ACTH stimulation test, which is the most popular diagnostic test for adrenal insufficiency, as suggested by the Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017 guidelines 1. The test should be conducted in the morning after an overnight fast. First, a baseline blood sample is drawn to measure cortisol and 17-hydroxyprogesterone (17-OHP) levels. Then, 250 mcg of synthetic ACTH (cosyntropin/Synacthen) is administered intravenously or intramuscularly. Additional blood samples are collected at 30 and 60 minutes post-injection to measure cortisol and 17-OHP responses.

• Key points to consider:
  • The high-dose ACTH test is easy to perform and safe, with comparable accuracy to the low-dose test, as shown in a meta-analysis of 30 studies involving 1209 adults and 228 children 1.
  • In CAH, particularly 21-hydroxylase deficiency, the 17-OHP level will show an exaggerated response compared to normal individuals.
  • The test evaluates the adrenal glands' ability to produce cortisol in response to ACTH stimulation.
  • Patients should inform their healthcare provider about all medications they're taking, as some might interfere with test results, although estrogen patches generally don't need to be discontinued 1.
• Important considerations:
  • Proper interpretation requires consideration of the specific CAH variant suspected and the patient's clinical presentation.
  • Other medications like glucocorticoids may need adjustment before testing, but estrogen patches can be continued as they do not significantly affect the test results 1.

From the FDA Drug Label

Advise patients to stop taking estrogen-containing drugs four to six weeks before cosyntropin for injection testing [seeDosage and Administration (2.1), Warnings and Precautions (5.2), and Drug Interactions (7)].

• Estrogen: May elevate plasma total cortisol levels Stop estrogen containing drugs 4 to 6 weeks before cosyntropin for injection testing to allow cortisol binding globulin levels to return to levels within the reference range.

To perform an Adrenocorticotropic Hormone (ACTH) stimulation test for Congenital Adrenal Hyperplasia (CAH) diagnosis in an adult taking estrogen patches, the patient should stop taking estrogen-containing drugs 4 to 6 weeks before the cosyntropin for injection testing. This allows cortisol binding globulin levels to return to levels within the reference range, ensuring accurate test results 2 2.

From the Research

Performing an ACTH Stimulation Test for CAH Diagnosis in Adults Taking Estrogen Patches

To perform an Adrenocorticotropic Hormone (ACTH) stimulation test for Congenital Adrenal Hyperplasia (CAH) diagnosis in an adult taking estrogen patches, consider the following steps:

• The ACTH stimulation test is used to evaluate adrenal gland function, particularly in diagnosing CAH and adrenal insufficiency 3.
• Estrogen therapy may affect cortisol levels, but there is limited information on its impact on the ACTH stimulation test.
• The test involves administering synthetic ACTH (cosyntropin) and measuring cortisol levels at baseline and after stimulation 4, 5.
• The normal cortisol response to ACTH stimulation is typically considered to be ≥18 μg/dL (500 nmol/L) using older serum cortisol assays 4.
• However, newer specific cortisol assays may have lower thresholds for a normal response, ranging from 13.2 to 14.6 μg/dL 4, 5.
• It is essential to consider the type of assay used and the clinical presentation of the patient when interpreting the results of the ACTH stimulation test 6.

Special Considerations for Adults Taking Estrogen Patches

• There is no direct evidence on how estrogen patches affect the ACTH stimulation test results.
• However, it is known that high-dose glucocorticoid therapy can suppress the cortisol response to ACTH stimulation, and this effect may be seen within 3-4 days of therapy initiation 7.
• Similarly, estrogen therapy may potentially affect cortisol levels, but its impact on the ACTH stimulation test is unclear.
• Clinicians should be aware of the potential effects of estrogen therapy on cortisol levels and interpret the test results in the context of the patient's clinical presentation and medical history.

Key Points to Consider

• The ACTH stimulation test is a valuable tool for diagnosing CAH and adrenal insufficiency.
• Newer specific cortisol assays may have lower thresholds for a normal response.
• Estrogen therapy may potentially affect cortisol levels, but its impact on the ACTH stimulation test is unclear.
• Clinicians should consider the type of assay used, the patient's clinical presentation, and medical history when interpreting the test results 4, 5, 6, 3, 7.